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Musculoskeletal disorders (MSDs) are medical condition mostly caused by work related occupations and working environment, affecting patients’ muscles, joints, tendons, ligaments and nerves and developing over time. A community sample of 73 females and 32 males aged 85 and over underwent a standardised examination at home. Musculoskeletal pain was reported by 57% of those interviewed(1).
Types of Musculo-Skeletal disorders in elder(2)
1. Osteoarthritis
2. Gout
3. Rheumatoid Arthritis
4. Polymalagia Arthritis
5. Cervical myleopathy and spinal canal stenosis
6. Osteoporosis
7. Low back pain
8. Fibromyalgia
Rheumatoid Arthritis
Rheumatoid Arthritis is defined a chronic disorder as a result of inflammation, affecting mostly the flexible (synovial) joints and tissues and organs in the body. The disease affects more women than men and generally occurs after the ages of 40, causing diminished quality of life of many elders(1). According to CDC, Musculoskeletal disorders (MSDs) affects over 52 millions of adults in the US alone, including 294,000 children under age 18 with some form of arthritis or rheumatic conditions(2). Rheumatoid Arthritis can induced bone loss through elevating bone resorption without increasing bone formation(4). A cross-sectional population-based study of 1042 patients with rheumatoid arthritis showed that RA patients had an increased risk of death from various causes(4a).
Signs and Symptoms
1. The feet and joints
Patient with rheumatoid arthritis (RA) often associate to valgus deformities of the feet and deformities of gait due to body function in effort to support the collapsing longitudinal arch of the foot(3). According to Dr. Brooks F and Dr. Hariharan K., feet demortities, effecting over 90% of the patient, behind only the hand, leading to painful callosities and dislocation of the metatarsophalangeal joints(5). Because of its severity, regardless to "....pharmacological management of rheumatoid arthritis and its impact upon disease progression, forefoot deformity and pain remain common manifestations requiring reconstruction from orthopadic surgeons" Dr. Amin A. and the reaserch team at the Royal National Orthopaedic Hospital, said(6).
In fact, the prevalence of deformations of hands, feet and gait can be seen among patient with rheumatoid arthritis among aging population may be depending to the severity and time factors which can lead to enormous pain and swelling of the ankle of which correlated weakly but statistically significantly with limitation and disability(7). The Jyväskylä Central Hospital, suggested that radiographic damage of hand and foot joints, and the number of tender and swollen joints are frequent found in patient with Rheumatoid Arthritis(8)(9).
2. The gait
Dr. Weiss RJ. and the research team at the Karolinska Institutet, showed that the kinematic and kinetic gait changes in rheumatoid arthritis (RA) patients are the result of a significant reduction in joint motions, joint moments, such as decreased hip flexion-extension range, hip abduction, knee flexion-extension range,...(9). The valgus deformities of the feet in patient withRA may be the main contribution to deformities of gait, including revealed decreases in velocity, stride length, and single-limb-support time(10). Used as characterise dysfunction of the lower limb and foot in people, gait also expressed its effects mainly in RA's patient with conditions of of a slower walk, longer double support time, and avoidance of extreme positions(11).
2. The gait
Dr. Weiss RJ. and the research team at the Karolinska Institutet, showed that the kinematic and kinetic gait changes in rheumatoid arthritis (RA) patients are the result of a significant reduction in joint motions, joint moments, such as decreased hip flexion-extension range, hip abduction, knee flexion-extension range,...(9). The valgus deformities of the feet in patient withRA may be the main contribution to deformities of gait, including revealed decreases in velocity, stride length, and single-limb-support time(10). Used as characterise dysfunction of the lower limb and foot in people, gait also expressed its effects mainly in RA's patient with conditions of of a slower walk, longer double support time, and avoidance of extreme positions(11).
3. The hands
The affects of deformation of RA's hands can be described through the defects of bone ankylosis as a result of bone damage of the prolonged onset of the disease(12). These deformities of hand and wrist and small peripheral joints (such as fingers and wrist) due to chronic inflammation can be treated by transelectrical nerve stimulation, the University of Ottawa suggested(14).
According to the joint study lead by the University of Warwick, strengthening and stretching have been found effectively in reduced pain and dysfunction of the hands and/or wrists in RA patient with stable medication for at least 3 months(13)
The affects of deformation of RA's hands can be described through the defects of bone ankylosis as a result of bone damage of the prolonged onset of the disease(12). These deformities of hand and wrist and small peripheral joints (such as fingers and wrist) due to chronic inflammation can be treated by transelectrical nerve stimulation, the University of Ottawa suggested(14).
According to the joint study lead by the University of Warwick, strengthening and stretching have been found effectively in reduced pain and dysfunction of the hands and/or wrists in RA patient with stable medication for at least 3 months(13)
4. The Muscle strength
The effects of muscle strength in patient with RA may contribute to the prevalence of functional limitations physically of that cdan effects daily living and quality of life. Dr. Häkkinen A and the research team at Jyväskylä Central Hospital, suggested that 2-year program of strength training showed a statistically significant improvement in clinical disease activity parameters, walking speed and physical function(15). Some researchers suggested that muscle strength was found inversely and independently associated with all-cause mortality, including the levels of physical activity or even cardiorespiratory fitness(16).
Dr. Brodin N and Dr. Swärdh said"... short-term land-based aerobic and strengthening exercise on moderate to high intensity results in positive effects on oxygen uptake and muscular strength, but not pain,..." (17).of that may be necessary for patient with RA.
5. Rheumatoid nodules
Rheumatoid nodules, lump on the skin, closed to the joint have been found to affect the joints of patients with rheumatoid nodules(18). Treatment of rheumatoid nodules are necessary in odd cases if the patient are experiencing pain or interference of mechanical function, according to Dr. Tilstra JS and Dr.Lienesch DW.(19). Use of methotrexate (MTX) in patient with RA may accelerate the occurance of nodulosis in the fingers. but nodules will be resolved after methotrexate was discontinued and recurred after methotrexate was reintroduced(20).
5. Conjunctival nodule
Although is rare in patients with rheumatoid arthritis, the appreance of the nodules may exhibit the
severity of the underlying disease, according to the Tehran University of Medical Sciences(21), including Pityriasis Lichenoides et Varioliformis Acuta(22), Epstein-Barr virus(23)
Although is rare in patients with rheumatoid arthritis, the appreance of the nodules may exhibit the
severity of the underlying disease, according to the Tehran University of Medical Sciences(21), including Pityriasis Lichenoides et Varioliformis Acuta(22), Epstein-Barr virus(23)
6. Morning stiffness
Morning stiffness, as a marker of inflammatory activity in reflecting functional disability and pain is a very common symptoms of patients in early rheumatoid arthritis(24). Use of glucocorticoid is found effectively in pain relief over 70 percent of patient with RA(25).
According to the Charité University Medicine, in a 12-week, multicentre, randomised, double-blind trial, 288 patients with active rheumatoid arthritis, treatment of modified-release prednisone exhibited a clinically relevant reduction of morningstiffness of the joint in comparison of immediate-release prednisone(26).
Morning stiffness, as a marker of inflammatory activity in reflecting functional disability and pain is a very common symptoms of patients in early rheumatoid arthritis(24). Use of glucocorticoid is found effectively in pain relief over 70 percent of patient with RA(25).
According to the Charité University Medicine, in a 12-week, multicentre, randomised, double-blind trial, 288 patients with active rheumatoid arthritis, treatment of modified-release prednisone exhibited a clinically relevant reduction of morningstiffness of the joint in comparison of immediate-release prednisone(26).
7. Quality of life
7.1. Physical disability
Although psychological distress and physical disability have been decreased with the cautious approach with respect to prescribing medication and physical exercise progressed toward RA patient(27), but tools necessary to measure RA disease activity are often incomplete, imprecise, or rely on a combination of physician and patient subjective evaluations(28)
Dr. Motl RW and Dr. McAuley E.said" The rationale and the associated onset of chronic disease conditions that influence function, disability, and quality of life (QOL) is embedded in the "Graying of America""(29), including patient with RA.
7.2. Concurrent psychiatric disorders
Concurrent psychiatric disorders, such as depression or anxiety in patient with Rheumatoid Arthritis is found to associate to poor quality of life, according to Dr. Mok C, and the scientists at the Tuen
Mun Hospital(30). Patients with RA is found to associate to Neurologic (N) and psychiatric (P) syndromes including depression and anxiety and symptoms of cognitive dysfunction, etc.,....of that induced poorer quality of life, according to the Lby the SF-36 and fatigue by a 10 point Likert scale(32).
Dr. Arnold LM said" Chronic widespread pain is associated with several medical and psychiatric disorders,....,careful and comprehensive differential diagnosis must be performed to ensure a correct diagnosis before an appropriate treatment can be selected"(31).
The Causes
7.1. Physical disability
Although psychological distress and physical disability have been decreased with the cautious approach with respect to prescribing medication and physical exercise progressed toward RA patient(27), but tools necessary to measure RA disease activity are often incomplete, imprecise, or rely on a combination of physician and patient subjective evaluations(28)
Dr. Motl RW and Dr. McAuley E.said" The rationale and the associated onset of chronic disease conditions that influence function, disability, and quality of life (QOL) is embedded in the "Graying of America""(29), including patient with RA.
7.2. Concurrent psychiatric disorders
Concurrent psychiatric disorders, such as depression or anxiety in patient with Rheumatoid Arthritis is found to associate to poor quality of life, according to Dr. Mok C, and the scientists at the Tuen
Mun Hospital(30). Patients with RA is found to associate to Neurologic (N) and psychiatric (P) syndromes including depression and anxiety and symptoms of cognitive dysfunction, etc.,....of that induced poorer quality of life, according to the Lby the SF-36 and fatigue by a 10 point Likert scale(32).
Dr. Arnold LM said" Chronic widespread pain is associated with several medical and psychiatric disorders,....,careful and comprehensive differential diagnosis must be performed to ensure a correct diagnosis before an appropriate treatment can be selected"(31).
The Causes
Rheumatoid arthritis is caused by immune dysfunction in attacking its own tissues, causing severe damage and inflammation of the joints, especially in the progresses to destruction of cartilage and bone. The causes of auto immune disorder is unknown, but some researchers expected the following.
1. Abnormal autoimmune response
Scientists in the study of Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis suggested that patients with abnormal gene expressions of interleukin (IL) -37,(32a), miR-573 on IL-6 production(33) and microRNA-203(34),... are associated to increased risk of rheumatoid arthritis.
Dr. Lee HM and the research team at the Osaka University said" Abnormal regulatory networks in the immune response and one marrow (BM) cells from RA patients, indicating that the BM is pathologically involved in RA"(35).
2. Abnormal lipid profile
Abnormal lipid profile in many cases is associated to the metabolic syndrome risk, especially in patient with type II diabetes(36). The University of California suggested that patient with rheumatoid arthritis are found to have a high expression of low-density lipoprotein (LDL) cholesterol driven by increases in cholesterol ester catabolism(37). Dr. Xue C and the research team at the People's Hospital of Peking University showed that the association of rheumatoid arthritis and an abnormal lipid profile may be contributed as a result of increased inflammation markers and autoimmune antibodies(38) or inflammatory changes in HDL-C and Lp(a) metabolisms(39).
1. Abnormal autoimmune response
Scientists in the study of Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis suggested that patients with abnormal gene expressions of interleukin (IL) -37,(32a), miR-573 on IL-6 production(33) and microRNA-203(34),... are associated to increased risk of rheumatoid arthritis.
Dr. Lee HM and the research team at the Osaka University said" Abnormal regulatory networks in the immune response and one marrow (BM) cells from RA patients, indicating that the BM is pathologically involved in RA"(35).
2. Abnormal lipid profile
Abnormal lipid profile in many cases is associated to the metabolic syndrome risk, especially in patient with type II diabetes(36). The University of California suggested that patient with rheumatoid arthritis are found to have a high expression of low-density lipoprotein (LDL) cholesterol driven by increases in cholesterol ester catabolism(37). Dr. Xue C and the research team at the People's Hospital of Peking University showed that the association of rheumatoid arthritis and an abnormal lipid profile may be contributed as a result of increased inflammation markers and autoimmune antibodies(38) or inflammatory changes in HDL-C and Lp(a) metabolisms(39).
3. Genetic susceptibility
Certain genetic variations inherited from a parent, may be involved in the expression of RA patient, some research insisted. The Immunochip custom SNP array of 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers found that people with certain gene of loci are found to have an increased risk of rheumatoid arthritis(40).
Certain genetic variations inherited from a parent, may be involved in the expression of RA patient, some research insisted. The Immunochip custom SNP array of 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers found that people with certain gene of loci are found to have an increased risk of rheumatoid arthritis(40).
Genetic association of CCR5 promoter polymorphism also seems to play an important role in determining different forms of rheumatoid arthritis(41), according to the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. In fact, over expression of Aiolos polymorphisms(42), LRP3 rs35829419 polymorphism(43), Interleukin-6 promoter haplotypes(44),... are all found to induced certain human diseases, including rheumatoid arthritis.
4. Inflammatory and infectious connections
Chronic inflammation of the joint can result of thickens the synovium, of that affect the cartilage and bone within the joint. Dr. Liao F. and the the research team at the Wuhan University said" Rheumatoid arthritis (RA) is a common, systemic autoimmune disease which leads to destruction of the joint architecture and consequent disability"(46). According to Epidemiological studies, the prevalence of RA affects about 5% of the population are aged 50 years or older, involved the connection of infectious etiology with a complex inflammatory response(45).
T helper 17 cells (Th17), a major effector cells in several chronic inflammatory states, correlated with local and systemic parameters of inflammation may also be a causative link to the expression of patient with RA(47)
Chronic inflammation of the joint can result of thickens the synovium, of that affect the cartilage and bone within the joint. Dr. Liao F. and the the research team at the Wuhan University said" Rheumatoid arthritis (RA) is a common, systemic autoimmune disease which leads to destruction of the joint architecture and consequent disability"(46). According to Epidemiological studies, the prevalence of RA affects about 5% of the population are aged 50 years or older, involved the connection of infectious etiology with a complex inflammatory response(45).
T helper 17 cells (Th17), a major effector cells in several chronic inflammatory states, correlated with local and systemic parameters of inflammation may also be a causative link to the expression of patient with RA(47)
1. Age
The prevalence of Rheumatoid arthritis is proportional with the progression of age. The University of Twente study suggests age is independently associated with the levels of both acute phase reactants in early RA.(48).
In a study of 950 RA patients, the median age at the time of onset of RA according to age of the young-onset RA (YORA) and late-onset RA (LORA) is 58(49).
According to the joint study lead by the Leiden University Medical Center, Zone, expression of gene IL7R gene expression associates with longevity and healthy ageing are also found to involved risk of immune-related disease, such as RA and reduced health(50).
2. Gender and body mass index
If you are women and overweight, you are at increased risk to develop Rheumatoid Arthritis(51)(52)(54), probably due to the association between body composition BMI and inflammatory activity of in rheumatoid arthritis(55). The Korea study suggests, Middle- and old-aged women accounted for the majority of the Korean RA population, of which interfere with daily activity and employment rate(53).
3. Race
Genome-wide association studies and meta-analysis indicate that several genes/loci are consistently associated with rheumatoid arthritis (RA) in European and Asian populations(40). In treatment of RA, Dr. Constantinescu F and the research team at the Virginia Commonwealth University said " (there is) racial disparities in treatment preferences for rheumatoid arthritis(56). The University of Nebraska, Omaha suggests 52 percent of African American subjects were found to be risk averse compared with 12% of the white subjects. Race remained strongly associated with risk aversion in RA(57).
4. Smoking
Smoking is considered as one of the environment risk factor in involvement of Rheumatoid arthritis (RA) development and severity(58). The Danish study insisted that smoking exhibits other risk factors including IgM-rheumatoid factor, anti-CCP and shared epitopes in contribution to the early onset of rheumatoid arthritis(59). In fact, the medical literature was reviewed from 1985 to 2001 with the assistance of a MEDLINE showed that cigarette smoking has been increasingly shown in epidemiologic and case-control studies to be an important risk factor for both the incidence and severity of RA, especially in seropositive men. The poor habit also induce mutations or alterations in p53, a suppressor gene found in patients with RA(60).
5. Family history
Rheumatoid arthritis (RA) is associated to greater risk in the first degree relatives in familial clustering, mothers confer susceptibility to RA on their offspring more often than fathers(61). According to the data on patients with RA were ascertained through the nationwide Swedish Patient Register of 88,639, the clinical Swedish Rheumatology Quality Register of 11,519, risk of RA are same in both sex but Familial factors is found to be overlap between seropositive RA and seronegative RA(62).
6. Vaccines
Certain vaccines may cause Rheumatoid Arthritis(65). But there is no statistically significant association between exposure to vaccine and onset of RA, according to the Kaiser Permanente Vaccine Study Center(64).
7. Other risk factors
Dr. Oliver JE and Dr. Silman AJ. in the study risk factors are that lead to the development of rheumatoid arthritis (RA). suggest diets high in caffeine, low in antioxidants, high in red meat, changes in the female hormonal environment such as in pregnancy, breastfeeding and the use of the oral contraceptive (OC) pill, cigarette smoking and passive inhalation of smoke may also contribute to an increased risk of RA(63).
Rheumatoid arthritis (RA) is associated to greater risk in the first degree relatives in familial clustering, mothers confer susceptibility to RA on their offspring more often than fathers(61). According to the data on patients with RA were ascertained through the nationwide Swedish Patient Register of 88,639, the clinical Swedish Rheumatology Quality Register of 11,519, risk of RA are same in both sex but Familial factors is found to be overlap between seropositive RA and seronegative RA(62).
Certain vaccines may cause Rheumatoid Arthritis(65). But there is no statistically significant association between exposure to vaccine and onset of RA, according to the Kaiser Permanente Vaccine Study Center(64).
7. Other risk factors
Dr. Oliver JE and Dr. Silman AJ. in the study risk factors are that lead to the development of rheumatoid arthritis (RA). suggest diets high in caffeine, low in antioxidants, high in red meat, changes in the female hormonal environment such as in pregnancy, breastfeeding and the use of the oral contraceptive (OC) pill, cigarette smoking and passive inhalation of smoke may also contribute to an increased risk of RA(63).
The Diagnosis
If you are experience certain subtle symptoms, such as achy joints or a morning stiffness, etc,....you may be at the early stage onset of rheumatoid arthritis. If your doctor suspect that have develop RA because of some RA symptoms such as such as warmth, swelling and pain in the joints, after physical exam, certain blood tests may be necessary, including
1. Erythrocyte sedimentation rate
ESR is a a common hematology test to calculate the rate of red blood cells sediment in a period of one hour. According to Dr. Wolfe F said " ESR is sensitive to immunoglobulins and rheumatoid factor (RF),... but a a poorer measure of inflammation"(64a) and may be effected by other factors. Other clinical findings, the individual's health history, and results from laboratory tests are necessary, such as C-reactive protein(64a) to rule out a suspected diagnosis for the confirmation of the result. Dr Sokka T and Dr. Pincus T. normal ESR and CRPC-reactive protein, are seen in a substantial proportion of patients with RA.(65a)If you are experience certain subtle symptoms, such as achy joints or a morning stiffness, etc,....you may be at the early stage onset of rheumatoid arthritis. If your doctor suspect that have develop RA because of some RA symptoms such as such as warmth, swelling and pain in the joints, after physical exam, certain blood tests may be necessary, including
1. Erythrocyte sedimentation rate
2. C-reactive protein
A group of "acute phase reactants" protein produced by liver and found in patient with rheumatoid arthritis.,tends to elevate in case of inflammation. According to the Copenhagen University Hospital, oral nonsteroidal antiinflammatory drugs (NSAIDs) does not effects the levels of protein but may be constituted to the influence of NSAIDs on cardiovascular complications in patient with RA(66).
3. Test for Anemia
According to statistic, the prevalence of mild anemia characterized by low serum iron concentration ranged between 33% and 60% are found in patient with rheumatoid arthritis(67), such as aplastic anemia and iron deficiency anemia. In fact, patient with combination of RA and amenia are mostly experience severe forms of joint disease and improvement of anemia is found to contribute to over all quality of life (QOL) and response to RA therapy(67).
According to statistic, the prevalence of mild anemia characterized by low serum iron concentration ranged between 33% and 60% are found in patient with rheumatoid arthritis(67), such as aplastic anemia and iron deficiency anemia. In fact, patient with combination of RA and amenia are mostly experience severe forms of joint disease and improvement of anemia is found to contribute to over all quality of life (QOL) and response to RA therapy(67).
4. Anti-cyclic citrullinate d peptide (anti-CCP antibodies)
Cyclic citrullinated peptides (CCP) in most cases is ordered in conjunction with the test of rheumatoid factor in patient with RA. The positive find of anti-citrullinated peptide/protein antibodies may contribute to the presence of the early event in the disease(68). Dr van Venrooij WJ and the research team at the Radboud University said"...., the presence of these antibodies was highly predictive of and specific for RA, and illustrating the importance of ACPA"(69).
5. Rheumatoid factor
Rheumatoid factor test is a blood test to measure the antibody in patient with rheumatoid arthritis.
The study of 71 patients with rheumatoid arthritis and 25 control subjects. AIF-1 is found to associated with the pathogenesis of RA involved in the immunological process underlying RA(70).
Cyclic citrullinated peptides (CCP) in most cases is ordered in conjunction with the test of rheumatoid factor in patient with RA. The positive find of anti-citrullinated peptide/protein antibodies may contribute to the presence of the early event in the disease(68). Dr van Venrooij WJ and the research team at the Radboud University said"...., the presence of these antibodies was highly predictive of and specific for RA, and illustrating the importance of ACPA"(69).
5. Rheumatoid factor
Rheumatoid factor test is a blood test to measure the antibody in patient with rheumatoid arthritis.
The study of 71 patients with rheumatoid arthritis and 25 control subjects. AIF-1 is found to associated with the pathogenesis of RA involved in the immunological process underlying RA(70).
Others such as elevation of interleukin-7 receptor (IL-7Ralpha)(71), interleukin-18(72),.... also involve in the presence of RA.
6. X ray
6. X ray
X ray may be important to determine the changes of bone mineral density. Patient with RA are found to have an lower BMD of that can lead to increased risk of major fracture and hip fracture(73). The family notebook suggested the relative change of Rheumatoid Arthritis found in X ray according to Dr. Kirwan J and Dr. Byron M, Watt I. include soft tissue swelling, joint space narrowing and erosive damage(74).
Misdiagnosis and Delay diagnosis
1. Polyarticular gout
1. Polyarticular gout
Polyarticular gout, a inflammatory condition with painful crystals forming in the joints has been found to be misdiagnosed as Rheumatoid Arthritis in elderly of that can constitute to poor treatment as well as failure to recognize underlying renal insufficiency, and increased cardiac risks(75), according to the Albert Einstein College of Medicine.
2. Hypercalcemia and Lytic Bone Lesions Masquerading Inflammatory Arthritis
According to the Mashhad University of Medical Sciences, a 50-year-old woman with hypercalcemia, lytic bone lesions and inflammatory arthritis of both hands was misdiagnosed as rheumatoid arthritis due to the presence of perparathyroidism in rheumatologic manifestations(76).
3. Systemic sclerosis
Systemic sclerosis (SSc) is an autoimmune disease of the connective tissue may be misdiagnosed as rheumatoid arthritis. According to the Dr. Horimoto AM and Dr. Costa IP, arthritis, clinically observed, may be a feature often found in patient with Systemic sclerosis, often leading to early misdiagnosis with rheumatoid arthritis (RA)(77).
Jaccoud's arthropathy (JA), a clinical situation foundt mostly in patient withsystemic lupus erythematosus (SLE) is found to be misdiagnosed as RA, due to swan neck," ulnar deviation and "Z-thumb which overlap with symptoms of patient with RA, according to the joint study lead by the Universidade Federal da Bahia, Salvador(78).
In fact, according to the joint study by the University of Texas Southwestern Medical Center and Victoria Hospital, the misdiagnosis of the atypical Infections versus Inflammatory Conditions of the Hand due to some similarity to inflammatory conditions regarding their clinical and imaging finding is rare but delay diagnosis can increase risk of severe bone and joint destruction, and higher morbidity(79).
The Complications
4. Carpal tunnel syndrome
Carpal tunnel syndrome is defined as a condition of pressure on the nerve in the wrist that supplies Carpal tunnel syndrome caused by volar dislocation of the lunate, associated with median nerve neuropathy has found in a patient with rheumatoid arthritis(87).
5. Scabies
Scabies is highly contagious skin disease caused by an infestation by the itch mite Sarcoptes is found to be another complication of medication use cause of disease(89).
6. Dry eye syndrome and Sjogren’s syndrome
According to 61 patients with rheumatoid arthritis recruited at Siriraj Hospital during March 2009-September 2010. the prevalence of secondary Sjogren's syndrome and dry eye were found with astonished rate of 28%(90). The awareness and detection of dry eye syndrome and secondary Sjogren’s syndrome in rheumatoid arthritis may has constituted the importantevaluation of their severity and proper management(91), the Mahidol University suggested.
7. Cerebral vasculitis
Cerebral vasculitis is a condition of inflammation of blood vessel wall involving the nervous system.
The diseases also share some characteristics with RA such as elevated levels of white blood cells, erythrocyte sedimentation rate, C-reactive protein, IgG-rheumatoid factor and immune complex(92). Dr. Ohno T and the reaserch team at the Ohtsu Red Cross Hospital reported that methotrexate is found effectively in treatment of long lasting rheumatoid cerebral vasculitis(93).
8. Other complications
According to 10 relevant studies out of 2326 bibliographic citations found by the University of Palermo, complication associate to RA, include ericardial effusion (OR 10.7; 95% CI 5.0-23.0), valvular nodules (OR 12.5; 95% CI 2.8-55.4), tricuspidal valve insufficiency (OR 5.3; 95% CI 2.4-11.6), aortic valve stenosis (OR 5.2; 95% CI 1.1-24.1), mitral valve insufficiency (OR 3.4; 95% CI 1.7-6.7), aortic valve insufficiency (OR 1.7; 95% CI 1.0-2.7), combined valvular alterations (OR 4.3; 95% CI 2.3-8.0), mitral valve thickening and/or calcification (OR 5.0; 95% CI 2.0-12.7), aortic valve thickening and/or calcification (OR 4.4; 95% CI 1.1-17.4), valvular thickening and/or calcification (OR 4.8; 95% CI 2.2-10.5), and mitral valve prolapse (OR 2.2; 95% CI 1.2-4.0)(88).
The Diseases associated to Rheumatoid Arthritis(Comorbidities)
1. Cardiovascular disease (CVD)
Cardiovascular disease (CVD), one the most leading cause of death in US, in particular Coronary artery disease, is found to associate to patient with RA(95). Dr.Goodson N said" Cardiovascular death is........ responsible for approximately half the deaths observed in RA(95). The study of 54 patients with RA :87% were women, with a mean age of 51 and 92% with rheumatoid factor positive showed that high homocysteine concentration is correlate to highest risk of CVD in RA patient(96).
Recent study by Dr. Kumar N and Armstrong DJ. insisted that traditional risk factors such as homocysteine, oxidised low-density lipoprotein, high-sensitivity C-reactive protein and leptin may contribute to the growing rates CVD death in RA patient(97).
2. Infections
The chronic, debilitating, autoimmune nature of RA affected directly or indirectly in almost all organ systems of RA patient, have shown to induced risk of infection(98) which is found to be responsible for death of 25% of RA patients(99). According to the joint study lead by Tampere University, in total of 10,994 patient-years, 341 serious infections were found in patient with RA(100).
3. Mental health issues
According to the study by National Institute for Science and Technology high prevalence of anxiety and depression and even suicide ideation has been found to associated to patient with RA(101) probably due to inflict of medicine(101). Dr. Rouse PC and the research team at the joint study lead by the University of Birmingham, Birmingham, suggested that depression is one most concern and positive psychological well-being in RA patients(102).
Dr. Ryan and Dr. McGuire B insisted that chronic pain associated to PA may constitute to psychological symptoms of depression and anxiety in patients with RA(103).
4. Cancers
Use of TNF-alpha antagonists for treatment of inflammatory diseases may associate to risk of cancer, particular lung cancer(104). According Dr. Buchbinder R and the research team lead by the Monash University, "Malignancy incidence was low in this RA cohort and biologic exposure did not increase the risk of malignancy. Melanoma risk was increased in both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status, and possibly methotrexate exposure, may be responsible"(105).
The do’s and do not’s list
The progression of RA as of other chronic diseases in most cases induced complications constitute the expressions of other diseases, especially of the adverse effects of certain medication use.
1. Osteoporosis
The condition of gradually loss of bone mineral density due to aging has found to be associate to the complication of rheumatoid arthritis. It mat be result of bone weakening induced by the progression of the disease.
Dr Lee SG, and the research team at the Pusan National University School of Medicine, suggest, the prevalence of osteoporosis in the RA patients was 1.9 times higher than in healthy subjects. Glucocorticoid use for treatment of osteoporosis was a risk factor for generalized bone loss in female RA patients(80). In the study of Italian Study Group on Bone Mass in patient with Rheumatoid Arthritis, Dr. Insignia L and his team concluded "... osteoporosis and its dramatic complications in RA the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids"(81).
2. Lymphoproliferative diseases
The use of Methotrexate (MTX) as a first choice of medicine for treatment of RA has been found to induced complication of MTX-related lymphoproliferative diseases (MTX-LPDs). The joint study by the Niigata Rheumatic Center suggests the cytological examinations of the synovial fluid followed by knee operation are important and effective for early diagnosis of MTX-LPD(82). The study 589 RA outpatients examined at the National Center for Global Health and Medicine in the period from January 1990 to October 2010 conducted by the Osaka University Graduate School of Medicine also supported of the above claim and expressed the concern of the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids.(83).
1. Osteoporosis
The condition of gradually loss of bone mineral density due to aging has found to be associate to the complication of rheumatoid arthritis. It mat be result of bone weakening induced by the progression of the disease.
Dr Lee SG, and the research team at the Pusan National University School of Medicine, suggest, the prevalence of osteoporosis in the RA patients was 1.9 times higher than in healthy subjects. Glucocorticoid use for treatment of osteoporosis was a risk factor for generalized bone loss in female RA patients(80). In the study of Italian Study Group on Bone Mass in patient with Rheumatoid Arthritis, Dr. Insignia L and his team concluded "... osteoporosis and its dramatic complications in RA the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids"(81).
2. Lymphoproliferative diseases
The use of Methotrexate (MTX) as a first choice of medicine for treatment of RA has been found to induced complication of MTX-related lymphoproliferative diseases (MTX-LPDs). The joint study by the Niigata Rheumatic Center suggests the cytological examinations of the synovial fluid followed by knee operation are important and effective for early diagnosis of MTX-LPD(82). The study 589 RA outpatients examined at the National Center for Global Health and Medicine in the period from January 1990 to October 2010 conducted by the Osaka University Graduate School of Medicine also supported of the above claim and expressed the concern of the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids.(83).
3. Neurologic complications
According to Dr. Bhattacharyya S and Dr. Helfgott SM, insisted that patient with RA in many cases have found to associate to neurologic complications because of its inflammatory origins and affect on nervous system (84). Recent study of 2624 patients treated with rituximab for rheumatoid arthritis RA and other autoimmune diseases, the late-onset neutropenia was observed in 40 patients with 25 of RA of which contributed to risk of 1.3% of patients(85). Other support of above includes the study by the
The Ipswich Hospital NHS Trust, of which insisted that Late-onset neutropenia (LON) occurs infrequently after treatment with RTX, but can present with infection(86).
The Ipswich Hospital NHS Trust, of which insisted that Late-onset neutropenia (LON) occurs infrequently after treatment with RTX, but can present with infection(86).
4. Carpal tunnel syndrome
Carpal tunnel syndrome is defined as a condition of pressure on the nerve in the wrist that supplies Carpal tunnel syndrome caused by volar dislocation of the lunate, associated with median nerve neuropathy has found in a patient with rheumatoid arthritis(87).
5. Scabies
Scabies is highly contagious skin disease caused by an infestation by the itch mite Sarcoptes is found to be another complication of medication use cause of disease(89).
6. Dry eye syndrome and Sjogren’s syndrome
According to 61 patients with rheumatoid arthritis recruited at Siriraj Hospital during March 2009-September 2010. the prevalence of secondary Sjogren's syndrome and dry eye were found with astonished rate of 28%(90). The awareness and detection of dry eye syndrome and secondary Sjogren’s syndrome in rheumatoid arthritis may has constituted the importantevaluation of their severity and proper management(91), the Mahidol University suggested.
7. Cerebral vasculitis
Cerebral vasculitis is a condition of inflammation of blood vessel wall involving the nervous system.
The diseases also share some characteristics with RA such as elevated levels of white blood cells, erythrocyte sedimentation rate, C-reactive protein, IgG-rheumatoid factor and immune complex(92). Dr. Ohno T and the reaserch team at the Ohtsu Red Cross Hospital reported that methotrexate is found effectively in treatment of long lasting rheumatoid cerebral vasculitis(93).
8. Other complications
According to 10 relevant studies out of 2326 bibliographic citations found by the University of Palermo, complication associate to RA, include ericardial effusion (OR 10.7; 95% CI 5.0-23.0), valvular nodules (OR 12.5; 95% CI 2.8-55.4), tricuspidal valve insufficiency (OR 5.3; 95% CI 2.4-11.6), aortic valve stenosis (OR 5.2; 95% CI 1.1-24.1), mitral valve insufficiency (OR 3.4; 95% CI 1.7-6.7), aortic valve insufficiency (OR 1.7; 95% CI 1.0-2.7), combined valvular alterations (OR 4.3; 95% CI 2.3-8.0), mitral valve thickening and/or calcification (OR 5.0; 95% CI 2.0-12.7), aortic valve thickening and/or calcification (OR 4.4; 95% CI 1.1-17.4), valvular thickening and/or calcification (OR 4.8; 95% CI 2.2-10.5), and mitral valve prolapse (OR 2.2; 95% CI 1.2-4.0)(88).
The Diseases associated to Rheumatoid Arthritis(Comorbidities)
The simultaneous presence of chronic Rheumatoid Arthritis with other diseases or conditions, include cardiovascular diseases (CVD), cancer, osteoporosis, and depression with often underrecognized in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis (PsO)(94).according to the joint study lead by Notre-Dame Hospital.
1. Cardiovascular disease (CVD)
Cardiovascular disease (CVD), one the most leading cause of death in US, in particular Coronary artery disease, is found to associate to patient with RA(95). Dr.Goodson N said" Cardiovascular death is........ responsible for approximately half the deaths observed in RA(95). The study of 54 patients with RA :87% were women, with a mean age of 51 and 92% with rheumatoid factor positive showed that high homocysteine concentration is correlate to highest risk of CVD in RA patient(96).
Recent study by Dr. Kumar N and Armstrong DJ. insisted that traditional risk factors such as homocysteine, oxidised low-density lipoprotein, high-sensitivity C-reactive protein and leptin may contribute to the growing rates CVD death in RA patient(97).
2. Infections
The chronic, debilitating, autoimmune nature of RA affected directly or indirectly in almost all organ systems of RA patient, have shown to induced risk of infection(98) which is found to be responsible for death of 25% of RA patients(99). According to the joint study lead by Tampere University, in total of 10,994 patient-years, 341 serious infections were found in patient with RA(100).
3. Mental health issues
According to the study by National Institute for Science and Technology high prevalence of anxiety and depression and even suicide ideation has been found to associated to patient with RA(101) probably due to inflict of medicine(101). Dr. Rouse PC and the research team at the joint study lead by the University of Birmingham, Birmingham, suggested that depression is one most concern and positive psychological well-being in RA patients(102).
Dr. Ryan and Dr. McGuire B insisted that chronic pain associated to PA may constitute to psychological symptoms of depression and anxiety in patients with RA(103).
4. Cancers
Use of TNF-alpha antagonists for treatment of inflammatory diseases may associate to risk of cancer, particular lung cancer(104). According Dr. Buchbinder R and the research team lead by the Monash University, "Malignancy incidence was low in this RA cohort and biologic exposure did not increase the risk of malignancy. Melanoma risk was increased in both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status, and possibly methotrexate exposure, may be responsible"(105).
5. Gastrointestinal ulcer
Use of Non-steroidal anti-inflammatory drugs (NSAIDs) for treatment of RA is frequently associated to gastrointestinal (GI) ulcers and complications of ulcers(106). The Tokyo Women's Medical University study suggests the prevalence of upper gastrointestinal (UGI) ulcer in patient with RA is also related to Helicobacter pylori and the association of H. pylori infectionas well as the intake of nonsteroidal anti-inflammatory drug (NSAID), according to a cohort of Japanese patients with rheumatoid arthritis (RA)(107).
The Prevention and Management
The do’s and do not’s list
The aim of the do and do not list is to find the common strategy with the use of natural remedies to prevent the early onset of RA and protect against the progression and pregressive symptoms of rheumatoid arthritis. Dr. Combe B said in the study of early rheumatoid arthritis: strategies for prevention and management"... A very early use of effective disease-modifying anti-rheumatic drugs (DMARDs) is a key point in patients at risk of developing persistent and erosive arthritis" and " Information and education for patients, as well as some non-pharmacological interventions, can be proposed as treatment adjuncts. Finally, the reduction or stopping of smoking, which could prevent the development and progression of early RA, is the only prevention tool currently available"
In herbal medicine, disease-modifying anti-rheumatic drugs (DMARDs) may be replaced with the intake of anti inflammatory foods.
1. Reduce intake of saturated and trans fat and increase intake of omega 3 fatty acids
Omega-3 FAs imay protect against the development of RA-related autoimmunity in pre-clinical RA, according to a nested case-control study (109). But according to Dr. Devaraj S. and the research team at the UC Davis Medical Center, oonly limit study showed the effects of dietary fatty acids (ie, oleic acid and alpha-linolenic acid) reduce biomarkers of inflammation, null effects in fish oil(110).
According to results of over 13 double-blind, placebo-controlled studies involving a total of more than 500 people suggest that omega-3 fatty acids may improve symptoms of rheumatoid arthritis.
Intake of high amount of saturated fat and trans fay can increase the production of inflammatory cytokines(111).
2. Increase intake of fruit and vegetable
In a cross-sectional study of 1200 Puerto Rican adults aged 45-75 y, intake variety of fruits and vegetable but not quantity appears to be important in reducing inflammation(113). The healthy Mediterranean-type diet rich in fish, fruit and vegetables and low in saturated fats showed to contribute to over all health including complications of RA and RA itself(114).
3. Avoid high glycemic index diets
High glycemic index diets, which have low fiber content and are rich in trans fat cause the activation of the immune system, leading to excessive production of pro-inflammatory mediators(116). Dr. Kremer JM and Dr. Bigaouette J. of American diet in patients with RA said" Patients with RA ingest too much total fat and too little PUFA and fiber. Their diets are deficient in pyridoxine, zinc and magnesium vs the RDA and copper and folate vs the TAD"(115). Increase intake of fruits, vegetables, and whole grain consumption seem to be associated with the improvement in subclinical inflammatory condition(116).
High glycemic index diets, which have low fiber content and are rich in trans fat cause the activation of the immune system, leading to excessive production of pro-inflammatory mediators(116). Dr. Kremer JM and Dr. Bigaouette J. of American diet in patients with RA said" Patients with RA ingest too much total fat and too little PUFA and fiber. Their diets are deficient in pyridoxine, zinc and magnesium vs the RDA and copper and folate vs the TAD"(115). Increase intake of fruits, vegetables, and whole grain consumption seem to be associated with the improvement in subclinical inflammatory condition(116).
4. Maintaining body weight
According to the joint study lead by the Philadelphia VA Medical Center and University of Pennsylvania, a low body mass index (BMI) has been associated with accelerated mortality in patients with rheumatoid arthritis (RA) and obesity showed no support a biologically protective role in RA patients(117). Patients with high BMI have lower mortality than thinner patients(118).
5. Reduced intake of pro inflammatory foods
Foods sugar, dairy products, red meat and processed, meat, alcohol, artificial ingredients, refined products, etc. induced the production of pro inflammatory cytokine is associated to the expression and progression of Rheumatoid Arthritis(120) as Dr. Seaman DR. said" Nearly all degenerative diseases have the same underlying biochemical etiology, that is, a diet-induced proinflammatory state" and "treatment program must also include nutritional protocols to reduce the proinflammatory state"(119).
Foods sugar, dairy products, red meat and processed, meat, alcohol, artificial ingredients, refined products, etc. induced the production of pro inflammatory cytokine is associated to the expression and progression of Rheumatoid Arthritis(120) as Dr. Seaman DR. said" Nearly all degenerative diseases have the same underlying biochemical etiology, that is, a diet-induced proinflammatory state" and "treatment program must also include nutritional protocols to reduce the proinflammatory state"(119).
6. Increase in take of anti inflammatory foods
such as fresh vegetables and fruits, seeds and sprouts whole grain, fish, turkey, chicken, legumes, etc.
A high vegetable diet and fish oil are found to associate to reduce inflammation and progression of RA. Dr. Adam O and the research team at the Medizinische Klinik Innenstadt der LMU suggested that auch diet improved tender and swollen joints decreased caused by expression of pro inflammatory cytokines(121). Others in the study of 49 patients with active rheumatoid arthritis completed a 24-week, showed the intake of fish oil with olive oil is also associated with certain changes in immune function, probably through the health benefits from the presence of omega-3 fatty acids in olive(122).
such as fresh vegetables and fruits, seeds and sprouts whole grain, fish, turkey, chicken, legumes, etc.
A high vegetable diet and fish oil are found to associate to reduce inflammation and progression of RA. Dr. Adam O and the research team at the Medizinische Klinik Innenstadt der LMU suggested that auch diet improved tender and swollen joints decreased caused by expression of pro inflammatory cytokines(121). Others in the study of 49 patients with active rheumatoid arthritis completed a 24-week, showed the intake of fish oil with olive oil is also associated with certain changes in immune function, probably through the health benefits from the presence of omega-3 fatty acids in olive(122).
7. Stop smoking
Smoking are associated with increased of Rheumatoid Arthritis as it is considered as the most important extrinsic risk factors for the development and severity of Rheumatoid Arthritis, causing over expression of oxidative stress, inflammation, autoantibody formation and epigenetic changes(124).
According to the data of 2,800 adult patients included in the BARFOT early RA between 1992 and 2005study in Sweden. stop smoking after onset of RA did not change the poor prognosis of smokers with RA but reduced risk cardiovascular mortality and morbidity and the association of smoking with vasculitis and noduli in RA(123).
Smoking are associated with increased of Rheumatoid Arthritis as it is considered as the most important extrinsic risk factors for the development and severity of Rheumatoid Arthritis, causing over expression of oxidative stress, inflammation, autoantibody formation and epigenetic changes(124).
According to the data of 2,800 adult patients included in the BARFOT early RA between 1992 and 2005study in Sweden. stop smoking after onset of RA did not change the poor prognosis of smokers with RA but reduced risk cardiovascular mortality and morbidity and the association of smoking with vasculitis and noduli in RA(123).
8. Occupations
If you are in occupation of increased risk of Rheumatoid Arthritis(RA), such as farmers, upholsterers, lacquerers, concrete workers, and hair-dressers, you should take all precaution if necessary(124).
According to the Department of Occupational Health, Karolinska Hospital, in a register based cohort study of a total of 375,035 men and 140,139 women concluded "there were rather small differences in the relative risk of RA in different exposure groups and different occupations"(125).
If you are in occupation of increased risk of Rheumatoid Arthritis(RA), such as farmers, upholsterers, lacquerers, concrete workers, and hair-dressers, you should take all precaution if necessary(124).
According to the Department of Occupational Health, Karolinska Hospital, in a register based cohort study of a total of 375,035 men and 140,139 women concluded "there were rather small differences in the relative risk of RA in different exposure groups and different occupations"(125).
9. Moderate exercise
Moderate exercise such as yoga(127)(128), taichi(128), qi kong(128),.....enhances immune function in fighting against inflammatory and infectious disease outcomes(128).
In the study of habitual physical activity levels of 29 female patients with RA, researchers at the joint study lead by University of the Witwatersrand showed that the exercise improved bone density and induced protective effects on bone health(126).
In animal model,
The Diet
The Diet reduced risk of over expression of pro inflammatory cytokine is always important to prevent the early onset and patient with progression of the rheumatoid arthritis.
1. Organic Soy
Intake of soy protein can enhance the protective effect against Rheumatoid Arthritis(129). Genistein, an isoflavone derivative found in soy suppressed the proinflammatory cytokine production, through inhibiting the expression of accumulation of reactive oxygen species (ROS)(130).
In animal model with with collagen-induced arthritis (CIA),, genistein, daidzein, and soy protein found in organic soy, restore the paraoxonase and arylesterase activity as well as malondialdehyde (MDA) level fo that have a related improvement of patient with Rheumatoid Arthritis(131).Moderate exercise such as yoga(127)(128), taichi(128), qi kong(128),.....enhances immune function in fighting against inflammatory and infectious disease outcomes(128).
In the study of habitual physical activity levels of 29 female patients with RA, researchers at the joint study lead by University of the Witwatersrand showed that the exercise improved bone density and induced protective effects on bone health(126).
In animal model,
The Diet
The Diet reduced risk of over expression of pro inflammatory cytokine is always important to prevent the early onset and patient with progression of the rheumatoid arthritis.
1. Organic Soy
Intake of soy protein can enhance the protective effect against Rheumatoid Arthritis(129). Genistein, an isoflavone derivative found in soy suppressed the proinflammatory cytokine production, through inhibiting the expression of accumulation of reactive oxygen species (ROS)(130).
2. Green tea
Green tea uss as a precious drink in social activities in many culture has been found to prevent the onset of rheumatoid arthritis and protect against the progression of the diseases due tom aging, via its antioxidant property(132). In animal models, green tea aqueous extract improve over function of rat with rheumatoid arthritis through significantly decreasing and down-regulating the systemic production of pro-inflammatory cytokines and the expression of chemokine receptor-5 in synovial tissues(133). Dr. Ahmed S. said "Green tea's active ingredient, epigallocatechin 3-gallate (EGCG), ....one of the leading plant-derived molecules studied for its potential health benefits,........I summarize the findings from some of the most significant preclinical studies with EGCG in arthritic diseases(134).
3. Olive oil
Olive oil when used conjunction with fish oil is found to prevent the early development and protect against progression the diseases in patient with RA, in our earlier research(135). In other study of a total 145 RA patients and 188 control subjects, regular intake of of both cooked vegetables and olive oil was inversely and independently associated with risk of RA, probably through the consumption of n-3 fatty acids and nutrients effects(136). Dr. Rosillo MÁ and the research team lead by the University of Seville showed that phenolic compounds found in the extra virgin olive oil (EVOO) inhibited the levels of proinflammatory cytokines and prostaglandin E2 in the joint as well as down-regulation of the arthritic process(137).
4. Salmon
Salmon containing high amount Omega 3 fatty acid which is found to decrease the risk of RA(138).
Salmon cartilage proteoglycan (PG), in animal model is found effective in suppressed excess inflammation in different mouse inflammatory diseases, including rheumatoid arthritis, through attenuated collagen-induced arthritis (CIA) pathogenesis by modulating immune response and local production inflammatory cytokines and chemokines in the joints(139).Salmon calcitonin, a hormone found in salmon and used as spray for treatment of osteoporosis exhibited anti inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA), according to the School of Food Science and Environmental Health(140).
5. Ginger
Ginger (Zingiber officinale), one of traditional herbal medicine and spicy used in many Asian culture today, is being used as an anti-inflammatory in Chinese and Ayurvedic medicine. Crude dichloromethane extract from ginger, contained essential oils and more polar compounds, was found more efficacious in preventing both joint inflammation and destruction, according to Dr. Funk JL and scientists at the University of Arizona(141)).
Dr. Al-Nahain A and the research team at the University of Development Alternative said"..., phytochemicals( found in ginger) can form the basis of discovery of new drugs, which not only can provide symptomatic relief but also may provide total relief from RA by stopping RA-induced bone destruction"(142)
The Phytochemicals
1. Curcumin
Curcumin is a phytochemical found abundantly in Turmeric, principal curcuminoid of the popular Indian spice
1.1. Anti-inflammatory agent
1.1. Antioxidants
Curcumin, one of most powerful antioxidant found in foods was found epidemiologically as a proven antioxidant for its anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects(145). The antioxidant is also considered as a novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease by the Western Sydney University(146).
In rheumatoid arthritis patients, oral administration of curcumin sginificantly improved the American College of Rheumatology (ACR) DAS scores in reduction in tenderness and swelling of joint and and other arthritic conditions(147) such as dramatic amelioration of arthritis symptoms(148).
In rheumatoid arthritis patients, oral administration of curcumin sginificantly improved the American College of Rheumatology (ACR) DAS scores in reduction in tenderness and swelling of joint and and other arthritic conditions(147) such as dramatic amelioration of arthritis symptoms(148).
2. Gingerol
Gingerole, is also known as gingerol, a phytochemical of Flavonoids (polyphenols) found in fresh ginger.
2.1. Antioxidants and Anti-inflammatory effects
Crude ginger and rosemary extracts showed to inhibit the production of pro-inflammatory cytokines due ot its function as an inflammatory mediators with high antioxidant activity(149). The comparison of different ginger constituents, such as [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol, 6-Shogaol has found to be most potent antioxidant and anti-inflammatory phytochemical due the presence of alpha,beta-unsaturated ketone moiety(150).Gingerole, is also known as gingerol, a phytochemical of Flavonoids (polyphenols) found in fresh ginger.
2.1. Antioxidants and Anti-inflammatory effects
Dr. Masuda Y. and the research team at the Osaka City University said" antioxidants isolated from the rhizomes of ginger,....the antioxidant activity might be due to not only radical scavenging activity of antioxidants but also their affinity of the antioxidants to the substrates"(151).
In rheumatoid arthritis, Epigallocatechin-3-gallate (EGCG) may have a beneficiary effects for treatment of RA due to its suppressed autoimmune arthritis activity(160), also through vary antioxidant and anti inflammatory pathways.
The Antioxidant
2.2. Rheumatoid arthritis
In rheumatoid arthritis, ginger-turmeric rhizomes mixture on animal model, may be effective against rheumatoid arthritis (RA) severity and complications, through the mediation of decreasing the systemic inflammation that occur at the appearance of polyarthritis, oxidative stress and dyslipidemia(152). According to DR. Ramadan G1 and the research team at the King Faisal University, the anti-inflammatory/anti-oxidant activity of ginger is less potent than turmeric but constitute to some beneficial effects against rheumatoid arthritis onset/progression(153).
3. Quercetin
Quercetin is a member of flavonoids, found in fruits, vegetables, leaves and grains with anti inflammatory and antioxidant property(154)(155). which have been found effectively in reduce the early onset and stop the progression of rheumatoid arthritis.
In rat adjuvant arthritis, an oral daily dose of 150 mg/kg b.w. of quercetin for 28 days,quercetin lowered levels of pro inflammatory cytokines, interleukin-1β, C-reactive protein, and monocyte chemotactic protein-1 and restored plasma antioxidant capacity(156), . Dr.Ji JJ and the research team at the Dalian Medical University, suggested that quecetin may be a potent agent for treatment of symptoms of RA such as disabling joint disease involved hands, wrists, feet and other small joints, through its anti inflammatory and antioxidant effects(157).Quercetin is a member of flavonoids, found in fruits, vegetables, leaves and grains with anti inflammatory and antioxidant property(154)(155). which have been found effectively in reduce the early onset and stop the progression of rheumatoid arthritis.
4. Epigallocatechin-3-gallate (EGCG)
Epigallocatechin-3-gallate (EGCG) found in green tea has been found to process antitumor,anti-Alzheimer, and anti-aging properties throguh epidemiological studies(158). According to the joint study lead by the Zhejiang University, Epigallocatechin-3-gallate (EGCG) improved anti-oxidant defense enzyme, reduced mitochondrial oxidative stress, through its antioxidants and inflammatory effects which may contribute to the treatment of rheumatoid arthritis(159).In rheumatoid arthritis, Epigallocatechin-3-gallate (EGCG) may have a beneficiary effects for treatment of RA due to its suppressed autoimmune arthritis activity(160), also through vary antioxidant and anti inflammatory pathways.
Antioxidants found abundantly in fruits and vegetables can enhance the immune system fighting against forming of free radicals causes of irregular cell growth and foreign invasion of inflammation and infection.
1. Vitamin C
Vitamin C, one of most powerful free radical scavengers, played an important role in prevention of domino effects of imbalance of estrogen may be a potent antioxidant effectively in normalization of the impaired oxidant/antioxidant system and delayed complication of RA(161). Dr, Al-Okbi SY in the study of elevated oxidative stress and inflammatory biomarkers suggested that vitamin C can be used as as complementary medicine to manage rheumatoid arthritis due to its anti-inflammatory and antioxidant activities(162).
But Dr. Rosenbaum CC and the research team at the the Bethesda North Hospital Pharmacy iunsisted that more high quality research are necessary before supplements including vitamin C can be effectively and safely recommended to reduce nonsteroidal antiinflammatory drug or steroid usage"(163)
2. Vitamin E
Low intake of vitamin E and selenium have been found to the RA elder patient(166).Vitamin E, another free radical scavenger may also be effective for patient with RA due to its positive effect on autoimmune disease by decreasing proinflammatory cytokines and lipid mediator(164). Dr. Aryaeian N. in the investigation of the effectiveness of supplements in RA, showed that the procession of property in promoted immunity and involvement of inflammatory parameters may put vitamin E in front of other rheumatoid arthritis (RA)management supplements(165).
3. Glucosamine
Glucosamine, a compound of the simple sugar glucose and the amino acid glutamine, is a precursor for glycosaminoglycans may be another antioxidant used for management of symptoms of patient with RA, according to the study of 25 patients in the glucosamine group and 26 patients in the placebo group(167). Dr. Matsuno H. and the research team at the Matsuno Clinic for Rheumatic Diseases, said" (oral administration of) glucosamine-chondroitin-quercetin glucoside (GCQG) for 3 months showed a significant improvement in pain symptoms, daily activities (walking and climbing up and down stairs), and visual analogue scale, and changes in the synovial fluid properties"(168) in patient of OA and RA. Further more, the supplement also found to consist the therapeutic potential for arthritis by exerting antioxidative and immunomodulatory effects(169).
4. Methylsulfonylmethane
Methylsulfonylmethane (MSM), an antioxidant with organosulfur compound has shown to involve in reduced the progression of inflammatory processes in RA patient(170). The Jazan University study in the comparison of the effectiveness of Echinacea extract and composite glucosamine, chondroitin and methyl sulfonyl methane supplements, showed that both ingredient exhibit anti inflammation, oedema and mild proliferation of synovial cells activities, through reduced cartilage damage and bone density of that may be a promising light on arthritis treatment(171)
The Treatment
A. In conventional medicine perspective
The aim of treatment is to stop the progression and relieve the symptoms of the diseases
1. Non Medication
1.1. Physical therapy
A. In conventional medicine perspective
The aim of treatment is to stop the progression and relieve the symptoms of the diseases
1. Non Medication
1.1. Physical therapy
Physical therapy with functions of re mediated impairments and promoted mobility, used conjunction with others including education, medical treatment,and occupational therapy may play an essential role for management of RA(172). In the treatment of patient with RA using the Whole-body cryotherapy (WBC) in supplement to physical therapy, Dr. combination and the research team at the joint study lead by the University School of Physical Education in Poznań said" (The combined therapies showed )improvement in pain, disease activity, fatigue, time of walking, and the number of steps over a distance of 50 m,...... similar significant reduction in IL-6 and TNF-α level (the inflammatory cytokines),...regardless of the kind of the applied physical procedure in patient with RA(173).
1.2. Relaxation therapy and biofeedback training
Relaxation and temperature biofeedback training as an adjunctive therapy has showed to alleviate both pain and stress-related symptoms as well as improvement of pain, tension, and sleep patterns. In fact, the therapy are found to induced higher physical/functional indices in comparison to physical therapy(174). Dr. Astin JA. and the research team at the University of Maryland School of Medicine suggested that psychological interventions such as relaxation, biofeedback, cognitive-behavioral therapy, may form an important part in may be important adjunctive therapies in the medical management of RA, especially for patients who have had the illness for shorter duration(175).In fact, a systematic review and meta-analysis of randomized controlled trials, also showed that psychological intervention improved both depressive symptoms and anxiety among patients with RA(176).
Relaxation and temperature biofeedback training as an adjunctive therapy has showed to alleviate both pain and stress-related symptoms as well as improvement of pain, tension, and sleep patterns. In fact, the therapy are found to induced higher physical/functional indices in comparison to physical therapy(174). Dr. Astin JA. and the research team at the University of Maryland School of Medicine suggested that psychological interventions such as relaxation, biofeedback, cognitive-behavioral therapy, may form an important part in may be important adjunctive therapies in the medical management of RA, especially for patients who have had the illness for shorter duration(175).In fact, a systematic review and meta-analysis of randomized controlled trials, also showed that psychological intervention improved both depressive symptoms and anxiety among patients with RA(176).
1.3. Low level laser therapy
Low level laser therapy may be beneficiary in modulated inflammatory response both in early as well as in late progression stages of RA, through its effects in significantly improved mononuclear inflammatory cells(177) as well as modulating inflammatory mediators (IL-1β, IL-6)(178). The study of 132 patients at the age varying from 18 to 85 years presenting with rheumatoid arthritis by Dr.Kulova LA, and Dr. Burduli NM also found thatn the therapy showed an improvement of the endothelial function and the microcirculation indices in patient with rheumatoid arthritis(179). But according to a randomized double-blind controlled trial laser therapy using low-level aluminum gallium arsenide was not effective at the wavelength, dosage, and power studied for the treatment of hands among patients with rheumatoid arthritis(180).
Low level laser therapy may be beneficiary in modulated inflammatory response both in early as well as in late progression stages of RA, through its effects in significantly improved mononuclear inflammatory cells(177) as well as modulating inflammatory mediators (IL-1β, IL-6)(178). The study of 132 patients at the age varying from 18 to 85 years presenting with rheumatoid arthritis by Dr.Kulova LA, and Dr. Burduli NM also found thatn the therapy showed an improvement of the endothelial function and the microcirculation indices in patient with rheumatoid arthritis(179). But according to a randomized double-blind controlled trial laser therapy using low-level aluminum gallium arsenide was not effective at the wavelength, dosage, and power studied for the treatment of hands among patients with rheumatoid arthritis(180).
1.4. Occupational therapy
According to the Canadian association of occupation therapy, it is form of treatment to solve the problems that interfere with your ability to do the things that are important to you. It can also prevent a problem or minimize its effects(181). According to the Netherlands Institute for Health Services Research, in controlled (randomized and non-randomized) and other than controlled studies (OD) addressing OT for RA patients showed that occupation therapy improved outcome on functional ability, social participation and/or health related quality of life(182). Rheumatologically, occupation therapy in many cases has successfully improved and maintained functional capacity, prevented progression of deformities, ......... of that may require for the engagement of the individual in meaningful occupations, favoring autonomy and independence in self-care activities, employment, educational, social and leisure(183)
1.5. Prosorba column apheresis therapy (PCT)
Prosorba column apheresis therapy (PCT), a medical device containnig purified staphylococcal protein A covalently bound to a silica matrix has been used in many medical centers for treatment severerheumatoid arthritis (RA) since its approval in 1999(184) with some promising result(185).
The therapy showed a 52% improvement in joint tenderness, 40% improvement in swelling, 42% improvement in patient's pain, 38% improvement in patient's global response, and 48% improvement in physician's global scores 76% of responders, according to the study by Cypress Bioscience(184).
Prosorba column apheresis therapy (PCT), a medical device containnig purified staphylococcal protein A covalently bound to a silica matrix has been used in many medical centers for treatment severerheumatoid arthritis (RA) since its approval in 1999(184) with some promising result(185).
The therapy showed a 52% improvement in joint tenderness, 40% improvement in swelling, 42% improvement in patient's pain, 38% improvement in patient's global response, and 48% improvement in physician's global scores 76% of responders, according to the study by Cypress Bioscience(184).
2. Medication
Medication or combined medication are used to stop the progression and relieve the symptoms of the diseases may include
2.1. Medication for reduced symptoms
Nonsteroidal anti-inflammatory drugs (NSAIDs)can be bought as over counter medicine for reduced pain and inflammation for patient with rheumatoid arthritis with an incidence of significant upper GI toxic effects, according to a total of 8059 patients (>/=18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA)(186). Dr. Wienecke T and Dr. Gøtzsche PC. in the comparison of NSAIDs and Paracetamol for treatment of RA said " There is a need for a large trial, with appropriate randomisation, double-blinding, test of the success of the blinding, and with explicit methods to measure and analyse pain and adverse effects"(187) due to favorable of onsteroidal anti-inflammatory drugs (NSAIDs) in general population.
Medication or combined medication are used to stop the progression and relieve the symptoms of the diseases may include
2.1. Medication for reduced symptoms
Nonsteroidal anti-inflammatory drugs (NSAIDs)can be bought as over counter medicine for reduced pain and inflammation for patient with rheumatoid arthritis with an incidence of significant upper GI toxic effects, according to a total of 8059 patients (>/=18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA)(186). Dr. Wienecke T and Dr. Gøtzsche PC. in the comparison of NSAIDs and Paracetamol for treatment of RA said " There is a need for a large trial, with appropriate randomisation, double-blinding, test of the success of the blinding, and with explicit methods to measure and analyse pain and adverse effects"(187) due to favorable of onsteroidal anti-inflammatory drugs (NSAIDs) in general population.
2.2. Medication for interfering the disease progression
a. Corticosteroids
a. Corticosteroids
Corticosteroid, a class a class of chemicals including the steroid hormones medication prednisone, prednisolone and methyprednisolone have been used in conventional medicine for quick treatment of inflammatory diseases such as rheumatoid arthritis, through reduced in activity and expression as a result of oxidative/nitrative stress(188). The University de Montréal joint study of 838 patient indicated the effectiveness of corticosteroids for treatment of inflammation of RA may accompany with increased hazard of infection(189), risk for the development of secondary osteoporosis(190) and dyslipidemia and hypertension(192). adrenal suppression, bone loss, skin thinning, increased cataract formation, decreased linear growth in children, metabolic changes, and behavioral abnormalities(191).
DMARDs, a disease-modifying antirheumatic drug such as methotrexate, hydroxycholorquine, sulfasalazine, leflunomide used by conventional doctor to modify the course of the disease(RA in this case) by releasing 4 h later to coincide with the rise of nocturnal inflammatory cytokines associated with development of symptoms of RA(192). According to the report of Dr. Sitzia J and Dr. Huggins L. the adverse effects of DMARDs may include alopecia, fatigue, weight gain with fatigue and nausea to be the "most troublesome" problems, followed by difficulty sleeping and sore eyes(193), as well as other incidences of gastrointestinal side effects(194).
c. Biologics
Biologics including abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, infliximab, golimumab and rituximab works with similar effects as DMARDs but more quickly in blocking a specific step in the inflammation process, such as blocking the activation of T cells(197), B cells(198), pro inflammatory cytokines(199),...... have found significantly improved outcomes for patients with rheumatoid arthritis(195), through reducing the signs and symptoms of RA, slowing radiographic progression of joint destruction, and improving physical function and quality of life in patients with RA(196).
d. JAK inhibitors
JAK inhibitors, the medication used in conventional doctors for inhibition of the activity of one or more of the Janus kinase family of enzymes, involving function in cytokine receptor signalling pathway, through interaction with signal transducers(transmission of molecularsignals from a cell's exterior to its interior) and activators of transcription proteins(a sequence-specific DNA-binding factor in controlling the rate of transcription of genetic information from DNA to messenger RNA)(200) is also known as a new subcategory of DMARDs. Dr. Norman P. said" JAK inhibitors differ in isoform specificity profiles, with good efficacy achievable by selective inhibition of either JAK1 (filgotinib or INCB-039110) or JAK3 (decernotinib)' of that contrite to the effective treatment of patient with rheumatoid arthritis)(201). According to the University of Occupational and Environmental Health, use of Tofacitinib, a new class of DMARDs orally available exhibited a strong clinical efficacy similar to biologic DMARDs through inhibited multiple cytokines and signaling pathways at clinical doses that are in contrast to biological DMARDs(202).
Here, we quoted the criteria of medication or combined medication is used to stop the progression and relieve the symptoms of RA by Dr. da Mota LM, and scientists at the Universidade de Brasília
1) The therapeutic decision should be shared with the patient;
2) Immediately after the diagnosis, a disease-modifying antirheumatic drug (DMARD) should be prescribed, and the treatment adjusted to achieve remission;
3) Treatment should be conducted by a rheumatologist;
4) The initial treatment includes synthetic DMARDs;
5) Methotrexate is the drug of choice;
6) Patients who fail to respond after two schedules of synthetic DMARDsshould be assessed for the use of biologic DMARDs;
7) Exceptionally, biologic DMARDs can be considered earlier;
8) Anti-TNF agents are preferentially recommended as the initial biologic therapy; 9) after therapeutic failure of a first biologic DMARD, other biologics can be used;
10) Cyclophosphamide and azathioprine can be used in severe extra-articular manifestations;
11) Oral corticoid is recommended at low doses and for short periods of time;
12) Non-steroidal anti-inflammatory drugs should always be prescribed in association with a DMARD; 13) clinical assessments should be performed on a monthly basis at the beginning of treatment;
14) Physical therapy, rehabilitation, and occupational therapy are indicated;
15) Surgical treatment is recommended to correct sequelae;
16) Alternative therapy does not replace traditional therapy;
17) Family planning is recommended;
18) The active search and management of comorbidities are recommended;
19) The patient’s vaccination status should be recorded and updated;
20) Endemic-epidemic transmissible diseases should be investigated and treated.
3. Surgery
Surgery in some cases may be necessary to relieve severe pain and extensive joint deformities and with patient do not response to non and medical treatment. According to the Wrightington Hospital NHS Trust, in the study of postoperative infection or surgical complications occurring within one year of surgery in patient with RA found that the surgical procedure induced 27% of infection and complication for patient with different in the intake of Methotrexate(204), a synthetic compound used for treatment of some forms of cancers.
B. Treatment in herbal and traditional Chinese medicine
B.1.2. Exercise
Exercise, today is less popular leisure-time activity in many countries throughout the Western world, especially in the youth due to promotion of information collection through mobile phone. Exercise as medicine has been found to benefit to many forms of chronic diseases, including rheumatoid arthritis(210). Dr. Pedersen BK and Dr.Saltin B. Said" Considerable knowledge has accumulated in recent decades concerning the significance of physical activity in the treatment of a number of diseases,....... muscle, bone and joint diseases"(211).
Arobic capacity and/or muscle strength training(212), physical training exercise(213) are recommended as routine practice in patients with RA. In fact, according to the Bowman Gray School of Medicine, therapeutic exercise performance in patient with rheumatoid arthritis have shown in improving aerobic capacity, strengthening muscles, improving endurance and increasing flexibility(214).
1. 1. Garlic
Garlic (Allium sativum) is a species in the onion genus, belongings to family Amaryllidaceae, native to central Asia, used popularly in traditional and Chinese medicine to treat common cold and flu(228), strengthen immunity(228), etc....The clinical trial of alisate--a garlic preparation produced in Russia showed the effectiveness of alisate used compunction with other and monotherapy in reduced symptoms of RA with little side effects(227). Dr. Majewski M. said" aged garlic extract (AGE), have a clear and significant biological effect in immune system improvement,...Clinically,garlic has been evaluated for a number of purposes, including treatment of .....rheumatoid arthritis,..."(228)
1.2. Ginger
Ginger (Zingiber officinale) used in many Eastern culture as a cooking spice is best in the West for its treatment againts morning sickness in early stage of pregnancy. The herbal medicine is also found to relieve pain induced by inflammation due to its effects in inhibited pro inflammatory cytokines(229) of that may be beneficiary as pharmaceutical ingredient for treatment of Rheumatoid arthritis(230) when used in combination with others herbal medicine. DR. Al-Nahain A and the research team at the University of Development Alternative said, "(Ginger) not only can provide symptomatic relief but also may provide total relief from RA by stopping RA-induced bone destruction"(231).
1.3. Turmeric
Turmeric is a perennial plant used as spice in Indian and as herbal medicine for strengthening the overall energy of the body, relieving gas, dispelling worms, improving digestion, regulating menstruation, dissolving gallstones, etc.(232) may be a potential candidate for treatment of rheumatoid arthritis due of its phytochemical curcumin imilar to methotrexate(233). Dr. Ramadan G and Dr. El-Menshawy O. said, "mixture of ginger and turmeric rhizomes powder (1 : 1) suspended in distilled water (GTaq) in alleviating both articular and extra-articular manifestations in rat adjuvant-induced arthritis (AIA),.....may be effective against RA severity and complications"(234), probably due to the mixture anti-inflammatory and anti-oxidant properties(235).
1.4. Green tea
Green tea , a precious drink in traditional Chinese and many culture in Southeast Asia cultures used exceptional in socialization for more than 4000 thousand years has been found to consist the property of suppressed autoimmune arthritis(238) through its phytochemical epigallocatechin-3-Gallate
(EGCG) in upregulation of the Nrf-2 antioxidant pathway in -mediated immunoregulation and ameliorated experimental arthritis in animal study(236).
Dr. Riegsecker S and the research team at the University of Toledo said," (The) potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis,.........., extensive clinical evidence of the 'synovial inflammation-systemic inflammation' link and the benefits of EGCG in regulating cytokine-driven inflammation in the pathogenesis of RA and its CV complication"(237).
1.5. Cooked tomato
Tomato, the edible vegetable is best known for its phytochemical lycopene found in skin for treatment of prostate health(239)(240). According to the University of Kerala, lycopene (all-trans) found in tomato may be a better natural source with increased activity and without side effects in the treatment of anti-inflammatory diseases, in the study on type II collagen induced arthritis in Sprague Dawley rats(241). In a total of 184,643 US women followed in the Nurses' Health Study and Nurses' Health Study II cohorts in 1980-2004 study showed that intake of antioxidants including lycopene, may protect against development of rheumatoid arthritis or systemic lupus erythematosus by combating oxidative stress(242).
1.2. Magnesium
Dr. Minton K. in the study of mutation of Mutation of the magnesium transporter 1 (MAGT1) gene has been found to associate to immunodeficiency due to reduced levels of magnesium(258), inducing severe chronic viral infections and inflammations(259). Deficiency of magnesium is found in patient with RA(253), routine dietary supplementation with multivitamins and trace elements is appropriate in this population(253), Dr. Kremer JM1, Bigaouette J. suggested. The Ankara University study expressed only slight and statistically insignificant reductions of plasma and erythrocyte Mg levels of the RA patients showed when compared to controls, with a positive correlations between erythrocyte SOD activity and Mg level(260).
1.3. Selenium
Selenium, is found to be one of most powerful antioxidant in enhancing immune system in fighting against inflammatory and immune-related diseases, including anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic inflammatory disorders mainly through its incorporation into selenoproteins(261). Low serum Se concentration is found to associate in patient with RA(262). But according to the Free University of Brussels, in a in a double blind multi-centric placebo-controlled study showed no clinical benefit selenium treatment on RA but a significant improvement in arm movements and health feeling(263).
1.4. Zinc
Recent study showed that lower than normal serum levels of Zinc (Cu) has found in patients with rheumatoid arthritis(254).
1.5. Pyridoxine
Dietary pyridoxine showed to improve immune responses(267) and reduced the expression of pro inflammatory cytokines of that may relate to the early onset of rheomatoid arthritis(268) but the deficiency was not severe enough to affect the immune system, according to the Instituto Nacional de Ciencias Médicas y Nutricion(269). Dr Chiang EP. and the research team of the National Chung-Hsing University said, " Suboptimal vitamin B6 status seen in rheumatoid arthritis can be corrected by 50 mg pyridoxine supplementation for 30 days,.... but (The pyridoxine supplementation) did not suppress pro-inflammatory cytokine production in patients with rheumatoid arthritis"(270).
2.3. Vitamin E
Vitamin A similar to vitamin A are found to consist a clinical outcomes and oxidative stress (274)which has been found to play an important role in the inflammation and parthenogenesis of RA(283).
According to studies, diets containing fish oil and vitamin E not only showed a significant pain reduction in patients but also induced a positive effect on autoimmune disease by decreasing proinflammatory cytokines and lipid mediator(280). In the rat model of collagen-induced arthritis (CIA), oral adminsitration of δ-tocotrienol (10 mg/kg) induced a significant impact in lowering paw edema, through it anti inflammatory effects(281).
In Rheumatoid Arthritis, omega-3 fatty acid supplementation improved physical functioning, physical role, bodily pain, general health, vitality, social functioning, grip strength, morning stiffness,....in comparison to the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in patient of rheumatoid arthritis(301).
B.5. The Miracle Topical Remedy
Certain topical remedies used in traditional or folk medicine have found effective on attenuate persistent symptoms of rheumatoid arthritis
1. Capsaicin cream
Furthermore combined treatment with ginger and stimulation at zusanli (ST 36) showed a significantly greater improvements in RA symptoms, laboratory outcomes, and gastrointestinal
symptom scores in comparison to anti-rheumatic drugs (ARDs), and acupoint stimulation at zusanli (ST 36) alone(343).
Dr. Hoffman T said," Ginger: an ancient remedy and modern miracle drug,.. (showed) "unclear" for treating rheumatoid arthritis, osteoarthritis, or joint and muscle pain)" (345), but Dr. Grzanna R and the research team at the RMG Biosciences, said,"ginger modulates biochemical pathways activated in chronic inflammation"(346).
2. Primrose oil
Primrose oil is a popular herbal medicine used herbal remedy used for treatment of numerous conditions, including pain relief and may be next potential target with pharmaceutical value in treatment of RA through its anti-angiogenic, anti-inflammatory, and anti-oxidant activities(347)
With a rich source of omega-6 essential fatty acids, primrose oil may be effective "use in the treatment of systemic diseases marked by chronic inflammation, such as atopic dermatitis and rheumatoid arthritis" Dr.Bayles B and Dr. Usatine R. said(348).
The study of forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs showed that primrose oil express a significant reduction in morning stiffness and pain and mild improvement in rheumatoid arthritis(349).
3. Willow bark
5. Devil’s claw
Devil’s claw is also one most popular herb used in alternative medicine for treatment of patient suffering from rheumatoid arthritis, probably through anti inflammatory activity and oxidative activity(359).
Dr. Wegener T. said, " Extracts of the secondary tubers of Devil's Claw , (showed)an improvement of motility and a reduction of pain sensation in several clinical studies,......Pharmacological experiments have shown analgesic, antiphlogistic and antiinflammatory actions,..(due to) its most important constituents iridoid glycosides"(360).
In the study of investigation of the efficacy of selected complementary and alternative medicine (CAM) therapies for pain from arthritis and related conditions, devil's claw, may be the best choice for relieved pain of rheumatoid arthritis (RA), but Dr. Soeken KL suggested that additional high quality research is necessary for its validation(361).
8. Coriander
10. Green Tea
Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years.
11. Turmeric
Turmeric, a cooking spice used in many culture in South East Asian, especially in India, also has been used as herbal medicine over thousands of year(373). Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, reduced inappropriate inflammatory responses through expression in inhibiting cell proliferation and metastasis and downregulating various factors, including the inflammatory cytokines and pathway(372) in animal model.
In acute and chronic inflammation, including Rheumatoid Arthritis, curcumin showed to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action, such as down-regulation of inflammatory transcription factors, cytokines,......related to expression of RA(374).
12. Bromelain
Bromelain, a group of protein digesting enzymes found in pineapples (Ananas comosus) used in traditional medicine as inflammatory agent and to treat pains, strains, and muscle aches and pains and ease back pain and chronic joint pain, skin diseases, etc.(467,376), through its the anti-inflammatory and analgesic properties may be the next potential target of pharmaceutical agent to reduce symptoms of rheumatoid arthritis(377). In the comparison for the effectiveness of cyclosporin A (5 mg/kg/day and 10 mg/kg/day orally); a mixture of enzymes containing pure substances (bromelain, trypsin, rutin) in the same ratio as in Phlogenzym (PHL, 150 mg/kg, twice daily, the mixture combined with cyclosporin A significantly inhibited both inflammation and destructive arthritis-associated changes, the Research Institute of Rheumatic Diseases suggested(378).
Furthermore, according to Dr. Bazzichi L and the research team at University of Pisa, bromelain may have a potential in activate autoreactive B cells induced the role of autoimmunity in the pathogenesis of rheumatoid arthritis, as self-perpetuing disorder(379).
Furthermore, application of Keishibukuryogan has shown to decreased tender joint count, swollen joint count and DAS(28) decreased significantly with CRP and inflammatory cytokines remained unchanged(391) in RA 's patient.
Furhtermore, the study from DR. Nanjundaiah SM and research team at the University of Maryland School of Medicine also found that the herbal formula expressed inhibition of symptoms of RA through a significant reduction in the levels of chemokines (RANTES, MCP-1, MIP-1α, and GRO/KC), MMPs (MMP 2 and 9), as well as cytokines (IL-6 and IL-17) by by suppressing the mediators of immune pathology(395)
Surgery in some cases may be necessary to relieve severe pain and extensive joint deformities and with patient do not response to non and medical treatment. According to the Wrightington Hospital NHS Trust, in the study of postoperative infection or surgical complications occurring within one year of surgery in patient with RA found that the surgical procedure induced 27% of infection and complication for patient with different in the intake of Methotrexate(204), a synthetic compound used for treatment of some forms of cancers.
B. Treatment in herbal and traditional Chinese medicine
B.1. Life style modification according herbal and TCM medicine specialist
Life style modification has shown to be beneficiary for patients with Rheumatoid Arthritis to improve musculoskeletal and bone health and reduce disability. Dr. Jones G. and the research team at the joint study lead by University of Tasmania said" Lifestyle is of considerable importance in the first two and there is emerging evidence for rheumatoid arthritis despite it not traditionally being considered a lifestyle disease"(205). Modern herbal and TCM medicine specialists may suggest the following
B.1.1. Maintain balance weight
Maintain healthy weigh is important not only for reduce cost of treatment according to the study of retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service(206) but also attenuate the risk of motility in patient with rheumatoid arthritis(207).
Dr. Baker JF and the research team at the joint study lead by Philadelphia VA Medical Center and University of Pennsylvania said" . Weight loss at an annualized rate of ≥3 kg/m(2) was associated with the greatest risk of death (HR 2.49, 95% CI 1.73-3.57, P < 0.001). Low BMI (<20 kg/m(2) ) in patients with a history of obesity (>30 kg/m(2) ) was associated with the greatest risk (HR 8.52, 95% CI 4.10-17.71, P < 0.001)(208).
In fact, many scientists have concerned for the rapidly increasing prevalence of obesity may contribute to recent increase in the incidence of rheumatoid arthritis(RA)(209).
Life style modification has shown to be beneficiary for patients with Rheumatoid Arthritis to improve musculoskeletal and bone health and reduce disability. Dr. Jones G. and the research team at the joint study lead by University of Tasmania said" Lifestyle is of considerable importance in the first two and there is emerging evidence for rheumatoid arthritis despite it not traditionally being considered a lifestyle disease"(205). Modern herbal and TCM medicine specialists may suggest the following
B.1.1. Maintain balance weight
Maintain healthy weigh is important not only for reduce cost of treatment according to the study of retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service(206) but also attenuate the risk of motility in patient with rheumatoid arthritis(207).
Dr. Baker JF and the research team at the joint study lead by Philadelphia VA Medical Center and University of Pennsylvania said" . Weight loss at an annualized rate of ≥3 kg/m(2) was associated with the greatest risk of death (HR 2.49, 95% CI 1.73-3.57, P < 0.001). Low BMI (<20 kg/m(2) ) in patients with a history of obesity (>30 kg/m(2) ) was associated with the greatest risk (HR 8.52, 95% CI 4.10-17.71, P < 0.001)(208).
In fact, many scientists have concerned for the rapidly increasing prevalence of obesity may contribute to recent increase in the incidence of rheumatoid arthritis(RA)(209).
B.1.2. Exercise
Exercise, today is less popular leisure-time activity in many countries throughout the Western world, especially in the youth due to promotion of information collection through mobile phone. Exercise as medicine has been found to benefit to many forms of chronic diseases, including rheumatoid arthritis(210). Dr. Pedersen BK and Dr.Saltin B. Said" Considerable knowledge has accumulated in recent decades concerning the significance of physical activity in the treatment of a number of diseases,....... muscle, bone and joint diseases"(211).
Arobic capacity and/or muscle strength training(212), physical training exercise(213) are recommended as routine practice in patients with RA. In fact, according to the Bowman Gray School of Medicine, therapeutic exercise performance in patient with rheumatoid arthritis have shown in improving aerobic capacity, strengthening muscles, improving endurance and increasing flexibility(214).
B.1.3. Quite smoking
Smoking is a risk factor for RA,and heavy smokers, according to the Kobe University Graduate Schoolof Medicine(217)(218)
Smoking has been found to induce many forms of lung disease, and cancer,. According to statistic, smoking cause death of over 83% of patient with lung cancer. Recent study suggested of the associated of lung diseases suchas bronchiectasis and unexplained dyspnea as predictor for the future development of rheumatoid arthritis, due to inflammation induced by external triggers (such as smoking) (215).
In a total of 857 patients, for determination of the effects of cigarette smoking in RA disease severity,pack years of cigarette smoking was significantly associated with rheumatoid factor seropositivity and radiographic erosions but less severe radiographic disease seemed to be more strongly associated with cigarette smoking than more severe disease(216).
B.1.4. Reduced intake of coffee
Coffee, one of many flavor drink in many culture may be associate to risk of rheumatoid arthritis, as coffee drunk daily was found directly proportional to the prevalence of RF positivity in dose depend-manner, according to the National Public Health Institute in a cohort of 18 981 men and women who had neither arthritisnor a history of it at the baseline examination in 1973-76. Up to late 1989(218). Recent study by the University of Alabama at Birmingham also suggested that decaffeinated coffee intake is independently and positively associated with RA onset(219).
Other studies insisted of little evidence of an association between coffee, decaffeinated coffee, or tea consumption and the risk of RA among women, including the Harvard Medical School, and Brigham and Women's Hospital(220).
B.1.5. Moderate alcohol drinking
Intake of moderate alcohol has been found to induce diseases protection. According to the Brigham and Women's Hospital and Harvard Medical School, long term moderate alcohol drinking are also associate to reduce risk of RA(221) and study of 34,141 women born between 1914 and 1948, followed up from 1 January 2003 to 31 December 2009 by the Institute of Environmental Medicine(222).
Smoking is a risk factor for RA,and heavy smokers, according to the Kobe University Graduate Schoolof Medicine(217)(218)
Smoking has been found to induce many forms of lung disease, and cancer,. According to statistic, smoking cause death of over 83% of patient with lung cancer. Recent study suggested of the associated of lung diseases suchas bronchiectasis and unexplained dyspnea as predictor for the future development of rheumatoid arthritis, due to inflammation induced by external triggers (such as smoking) (215).
In a total of 857 patients, for determination of the effects of cigarette smoking in RA disease severity,pack years of cigarette smoking was significantly associated with rheumatoid factor seropositivity and radiographic erosions but less severe radiographic disease seemed to be more strongly associated with cigarette smoking than more severe disease(216).
B.1.4. Reduced intake of coffee
Coffee, one of many flavor drink in many culture may be associate to risk of rheumatoid arthritis, as coffee drunk daily was found directly proportional to the prevalence of RF positivity in dose depend-manner, according to the National Public Health Institute in a cohort of 18 981 men and women who had neither arthritisnor a history of it at the baseline examination in 1973-76. Up to late 1989(218). Recent study by the University of Alabama at Birmingham also suggested that decaffeinated coffee intake is independently and positively associated with RA onset(219).
Other studies insisted of little evidence of an association between coffee, decaffeinated coffee, or tea consumption and the risk of RA among women, including the Harvard Medical School, and Brigham and Women's Hospital(220).
B.1.5. Moderate alcohol drinking
Intake of moderate alcohol has been found to induce diseases protection. According to the Brigham and Women's Hospital and Harvard Medical School, long term moderate alcohol drinking are also associate to reduce risk of RA(221) and study of 34,141 women born between 1914 and 1948, followed up from 1 January 2003 to 31 December 2009 by the Institute of Environmental Medicine(222).
B.2. Psychological intervention
Psychological intervention may be useful to reduce depression, anxiety and other symptoms in patient with RA due to associate to pain, distress and disability and reduced quality of life style in chronic pain patients, the University College London suggested(223). Dr. Matcham F and the research team at the joint study lead by King's College London said" The most consistent relationship was found between mood and fatigue, with low mood frequently associated with increased fatigue. Some evidence also highlighted the relationship between RA-related cognitions (such as RA self-efficacy) and fatigue, and non-RA-cognitions (such as goal ownership) and fatigue(224), as there is a psychological correlates of fatigue in rheumatoid arthritis.
B.3. Diet modification according herbal and TCM medicine specialist
1. Top foods to reduce risk of inflammation
Foods with anti pro inflammatory cytokines can be helpful to prevent and to protect against early
onset of rheumatoid arthritis. "Low grade inflammation has been found to play a pathophysiological role in RA" Dr. Jeppesen J. said (225) as the proinflammatory cytokines may affect synoviocyte proliferation caused by elevated interleukin-21 (IL-21) IL-21-induced proliferation and secretion of TNF-α and IL-6(226).
Foods with anti pro inflammatory cytokines can be helpful to prevent and to protect against early
onset of rheumatoid arthritis. "Low grade inflammation has been found to play a pathophysiological role in RA" Dr. Jeppesen J. said (225) as the proinflammatory cytokines may affect synoviocyte proliferation caused by elevated interleukin-21 (IL-21) IL-21-induced proliferation and secretion of TNF-α and IL-6(226).
Garlic (Allium sativum) is a species in the onion genus, belongings to family Amaryllidaceae, native to central Asia, used popularly in traditional and Chinese medicine to treat common cold and flu(228), strengthen immunity(228), etc....The clinical trial of alisate--a garlic preparation produced in Russia showed the effectiveness of alisate used compunction with other and monotherapy in reduced symptoms of RA with little side effects(227). Dr. Majewski M. said" aged garlic extract (AGE), have a clear and significant biological effect in immune system improvement,...Clinically,garlic has been evaluated for a number of purposes, including treatment of .....rheumatoid arthritis,..."(228)
1.2. Ginger
Ginger (Zingiber officinale) used in many Eastern culture as a cooking spice is best in the West for its treatment againts morning sickness in early stage of pregnancy. The herbal medicine is also found to relieve pain induced by inflammation due to its effects in inhibited pro inflammatory cytokines(229) of that may be beneficiary as pharmaceutical ingredient for treatment of Rheumatoid arthritis(230) when used in combination with others herbal medicine. DR. Al-Nahain A and the research team at the University of Development Alternative said, "(Ginger) not only can provide symptomatic relief but also may provide total relief from RA by stopping RA-induced bone destruction"(231).
1.3. Turmeric
Turmeric is a perennial plant used as spice in Indian and as herbal medicine for strengthening the overall energy of the body, relieving gas, dispelling worms, improving digestion, regulating menstruation, dissolving gallstones, etc.(232) may be a potential candidate for treatment of rheumatoid arthritis due of its phytochemical curcumin imilar to methotrexate(233). Dr. Ramadan G and Dr. El-Menshawy O. said, "mixture of ginger and turmeric rhizomes powder (1 : 1) suspended in distilled water (GTaq) in alleviating both articular and extra-articular manifestations in rat adjuvant-induced arthritis (AIA),.....may be effective against RA severity and complications"(234), probably due to the mixture anti-inflammatory and anti-oxidant properties(235).
1.4. Green tea
Green tea , a precious drink in traditional Chinese and many culture in Southeast Asia cultures used exceptional in socialization for more than 4000 thousand years has been found to consist the property of suppressed autoimmune arthritis(238) through its phytochemical epigallocatechin-3-Gallate
(EGCG) in upregulation of the Nrf-2 antioxidant pathway in -mediated immunoregulation and ameliorated experimental arthritis in animal study(236).
Dr. Riegsecker S and the research team at the University of Toledo said," (The) potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis,.........., extensive clinical evidence of the 'synovial inflammation-systemic inflammation' link and the benefits of EGCG in regulating cytokine-driven inflammation in the pathogenesis of RA and its CV complication"(237).
1.5. Cooked tomato
Tomato, the edible vegetable is best known for its phytochemical lycopene found in skin for treatment of prostate health(239)(240). According to the University of Kerala, lycopene (all-trans) found in tomato may be a better natural source with increased activity and without side effects in the treatment of anti-inflammatory diseases, in the study on type II collagen induced arthritis in Sprague Dawley rats(241). In a total of 184,643 US women followed in the Nurses' Health Study and Nurses' Health Study II cohorts in 1980-2004 study showed that intake of antioxidants including lycopene, may protect against development of rheumatoid arthritis or systemic lupus erythematosus by combating oxidative stress(242).
2. The miracle Salmon calcitonin
Salmon, is a highly nutrition with best source of Omega 3 fatty acids found in fish for human consumption born in fresh water, migrate to the deep ocean, then travel thousands of miles in the deep sea cold water throughout their life cycle and within to five years returning to the exacted location where they were born to reproduce and die.
Nutrients
1. Protein
2. Omega-3 fatty acids
3. B vitamins
4. Vitamin D
5. Astaxanthin
is a potent antioxidant that stimulates the development of healthy fish nervous systems and enhances the fish's fertility and growth rate.
6. Selenium
7. Tryptophan
8. Magnesium
9. Phosphorus
10. Etc.
Intake of salmon calcitonin, a hormone extract from salmon or a synthetic polypeptide of the same sequence found in salmon, has shown to attenuate the pathogenesis of rheumatoid arthritis (RA, through reduced expression of a key of (orphan nuclear receptor, NR4A2) redulator and potential biomarker for inflammation(243). Dr. Tascioglu F and the research team at the Osmangazi University Faculty of Medicine, said." alendronate and intranasal salmon calcitonin (sCT) treatments,...produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids"(244). Furthermore, according to the multicenter study of 32 women with RA, intranasal salmon calcitonin (sCT) prevented bone loss at the proximal femur in patients with active RA induced by intake of low dose glucocorticoids for 12 months(245).
Salmon proteoglycan prepared from salmon nasal cartilage under nondenaturing conditions showed to improve autoimmune disease caused by chronic inflammation of connective tissues, through modulating immune response of splenocytes to CII stimulation and local production inflammatory cytokines and chemokines in the joints, the research lead by Dr. Yoshimura S. suggested.(246)
Salmon, is a highly nutrition with best source of Omega 3 fatty acids found in fish for human consumption born in fresh water, migrate to the deep ocean, then travel thousands of miles in the deep sea cold water throughout their life cycle and within to five years returning to the exacted location where they were born to reproduce and die.
Nutrients
1. Protein
2. Omega-3 fatty acids
3. B vitamins
4. Vitamin D
5. Astaxanthin
is a potent antioxidant that stimulates the development of healthy fish nervous systems and enhances the fish's fertility and growth rate.
6. Selenium
7. Tryptophan
8. Magnesium
9. Phosphorus
10. Etc.
Intake of salmon calcitonin, a hormone extract from salmon or a synthetic polypeptide of the same sequence found in salmon, has shown to attenuate the pathogenesis of rheumatoid arthritis (RA, through reduced expression of a key of (orphan nuclear receptor, NR4A2) redulator and potential biomarker for inflammation(243). Dr. Tascioglu F and the research team at the Osmangazi University Faculty of Medicine, said." alendronate and intranasal salmon calcitonin (sCT) treatments,...produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids"(244). Furthermore, according to the multicenter study of 32 women with RA, intranasal salmon calcitonin (sCT) prevented bone loss at the proximal femur in patients with active RA induced by intake of low dose glucocorticoids for 12 months(245).
Salmon proteoglycan prepared from salmon nasal cartilage under nondenaturing conditions showed to improve autoimmune disease caused by chronic inflammation of connective tissues, through modulating immune response of splenocytes to CII stimulation and local production inflammatory cytokines and chemokines in the joints, the research lead by Dr. Yoshimura S. suggested.(246)
3. The miracle of Olive oil
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.
Olive Oil: Fat Content
1. Saturated fats
a. Palmitic acid
b. Stearic acid
c. Arachidic acid
d. ehenic acid
e. Myristic acid
f. Lignoceric acid
2. Unsaturated fat3. Monounsaturated fats
a. Oleic acid
b. Palmitoleic acid
3. Polyunsaturated fats
a. Linoleic acid
b. Linolenic acid
Monounsaturated fatty acids found abundantly in extra virgin olive oil has found to inhibit proinflammatory cytokines in inducing the decreases lubricin expression and predisposes to cartilage degeneration(247). Intake of olive oil, according to the University of Athens Medical School and University of Seville, showed to reduce risk of risk of rheumatoid arthritis (RA) due to the effects of n-3 fatty acids through the antioxiant activity(248) as well as preventing inflammatory response and cartilage matrix degradation in murine collagen-induced rheumatoid arthritis(249), respectively.
Furthermore, in animal models of acute inflammation and rheumatoid arthritis, hydroxytyrosol, a phytochemical found in virgin olive oil, a primary source of fat in the Mediterranean diet, inhibited significant impact on chronic inflammation and acute inflammatory processes, through its antioxidant and anti-inflammatory properties, recent study suggested.(250).
In deed, dr. González Cernadas L and the research team at the Unidad de Fisioterapia Basada en la Evidencia del Departamento de Fisioterapia de la Universidad de A Coruña said," some dietetic elements (polyunsaturated fatty acids, mediterranean diet and antioxidants) with inflammatory markers reduction and oxidative stress inhibition have anti-inflammatory effects and decrease AR disease activity"(251)
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.
Olive Oil: Fat Content
1. Saturated fats
a. Palmitic acid
b. Stearic acid
c. Arachidic acid
d. ehenic acid
e. Myristic acid
f. Lignoceric acid
2. Unsaturated fat3. Monounsaturated fats
a. Oleic acid
b. Palmitoleic acid
3. Polyunsaturated fats
a. Linoleic acid
b. Linolenic acid
Monounsaturated fatty acids found abundantly in extra virgin olive oil has found to inhibit proinflammatory cytokines in inducing the decreases lubricin expression and predisposes to cartilage degeneration(247). Intake of olive oil, according to the University of Athens Medical School and University of Seville, showed to reduce risk of risk of rheumatoid arthritis (RA) due to the effects of n-3 fatty acids through the antioxiant activity(248) as well as preventing inflammatory response and cartilage matrix degradation in murine collagen-induced rheumatoid arthritis(249), respectively.
Furthermore, in animal models of acute inflammation and rheumatoid arthritis, hydroxytyrosol, a phytochemical found in virgin olive oil, a primary source of fat in the Mediterranean diet, inhibited significant impact on chronic inflammation and acute inflammatory processes, through its antioxidant and anti-inflammatory properties, recent study suggested.(250).
In deed, dr. González Cernadas L and the research team at the Unidad de Fisioterapia Basada en la Evidencia del Departamento de Fisioterapia de la Universidad de A Coruña said," some dietetic elements (polyunsaturated fatty acids, mediterranean diet and antioxidants) with inflammatory markers reduction and oxidative stress inhibition have anti-inflammatory effects and decrease AR disease activity"(251)
B.3. The Preventive Minerals and Vitamins
1. Minerals for Immunity
Strengthen immunity plays an important role in regulating the free radical and other form of irregular cell growth causes of inflammation and auto immune diseases as well as attenuating the foreigner invasion. According to the study maintaining normal levels of Copper, Selenium and Zinc have found to improve immune function against morbidity, decrease antibody production, infection, impaired natural killing cells, etc......(252) in animal study. Also according to Dr. Kremer JM and Bigaouette J., deficiency of pyridoxine, zinc, copper, and magnesium may induce rheumatoid arthritis expression(253).
1. Minerals for Immunity
Strengthen immunity plays an important role in regulating the free radical and other form of irregular cell growth causes of inflammation and auto immune diseases as well as attenuating the foreigner invasion. According to the study maintaining normal levels of Copper, Selenium and Zinc have found to improve immune function against morbidity, decrease antibody production, infection, impaired natural killing cells, etc......(252) in animal study. Also according to Dr. Kremer JM and Bigaouette J., deficiency of pyridoxine, zinc, copper, and magnesium may induce rheumatoid arthritis expression(253).
1.1. Copper
Epidemiological studies suggested that levels of copper may be influence to the risk of rheumatoid arthritis has produced inconclusive results, it probably due to the disease orgination(254)(255). According to the relevant published data were retrieved through PubMed, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) before September 20, 2014 of 1444 RA cases and 1241 healthy controls, above normal serum levels of copper (Cu) has found in patients with rheumatoid arthritis(254). Dr Li J and the research team at the joint study lead by Sichuan University, suggested patient with rheumatoid arthritis with B-lymphocyte dysfunction are associated to lower levels of copper, selenium and zinc levels(255). Other study insisted that the alternation of copper concentration may be a result of the changes of the immunoregulatory cytokines(256). Dr Percival SS said,"The immune system requires copper to perform several functions,.....interleukin 2 is reduced and T cell proliferation are reduced in copper deficiency"(257).
Epidemiological studies suggested that levels of copper may be influence to the risk of rheumatoid arthritis has produced inconclusive results, it probably due to the disease orgination(254)(255). According to the relevant published data were retrieved through PubMed, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) before September 20, 2014 of 1444 RA cases and 1241 healthy controls, above normal serum levels of copper (Cu) has found in patients with rheumatoid arthritis(254). Dr Li J and the research team at the joint study lead by Sichuan University, suggested patient with rheumatoid arthritis with B-lymphocyte dysfunction are associated to lower levels of copper, selenium and zinc levels(255). Other study insisted that the alternation of copper concentration may be a result of the changes of the immunoregulatory cytokines(256). Dr Percival SS said,"The immune system requires copper to perform several functions,.....interleukin 2 is reduced and T cell proliferation are reduced in copper deficiency"(257).
1.2. Magnesium
Dr. Minton K. in the study of mutation of Mutation of the magnesium transporter 1 (MAGT1) gene has been found to associate to immunodeficiency due to reduced levels of magnesium(258), inducing severe chronic viral infections and inflammations(259). Deficiency of magnesium is found in patient with RA(253), routine dietary supplementation with multivitamins and trace elements is appropriate in this population(253), Dr. Kremer JM1, Bigaouette J. suggested. The Ankara University study expressed only slight and statistically insignificant reductions of plasma and erythrocyte Mg levels of the RA patients showed when compared to controls, with a positive correlations between erythrocyte SOD activity and Mg level(260).
1.3. Selenium
Selenium, is found to be one of most powerful antioxidant in enhancing immune system in fighting against inflammatory and immune-related diseases, including anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic inflammatory disorders mainly through its incorporation into selenoproteins(261). Low serum Se concentration is found to associate in patient with RA(262). But according to the Free University of Brussels, in a in a double blind multi-centric placebo-controlled study showed no clinical benefit selenium treatment on RA but a significant improvement in arm movements and health feeling(263).
1.4. Zinc
Recent study showed that lower than normal serum levels of Zinc (Cu) has found in patients with rheumatoid arthritis(254).
Deficiency of zinc is found to increase immune response through activation of increasing immune cell and inducing pro inflammatory ccytokines IL6(264), especially in aging population(265). who are vulnerable for the aging degenerative chronic diseases of rheumatoid arthritis(266).
1.5. Pyridoxine
Dietary pyridoxine showed to improve immune responses(267) and reduced the expression of pro inflammatory cytokines of that may relate to the early onset of rheomatoid arthritis(268) but the deficiency was not severe enough to affect the immune system, according to the Instituto Nacional de Ciencias Médicas y Nutricion(269). Dr Chiang EP. and the research team of the National Chung-Hsing University said, " Suboptimal vitamin B6 status seen in rheumatoid arthritis can be corrected by 50 mg pyridoxine supplementation for 30 days,.... but (The pyridoxine supplementation) did not suppress pro-inflammatory cytokine production in patients with rheumatoid arthritis"(270).
2. Top vitamins for rheumatoid arthritis
Free radical scavengers such as vitamins plays an essential role in reduced risk of rheumatoid arthritis
due to their effects in attenuate the expression of free radical and pro inflammatory cytokines(271)(272)
2.1. Vitamin A
According to the Imam Reza Hospital of Tabriz University of Medical Sciences, antioxidant including vitamin A are found to consist a clinical outcomes and oxidative stress in RA(274).
Patient with rheumatoid arthritis are accompanied with the over expression of the levels of serum leptin and other related cytokines, Dr. Xiong RB and the research team at the Southern Medical Universit said, " VitA.....significantly reduced the levels of leptin, TNF-α, IL-6 and CRP and the ESR(Pro inflammatory cytokines) and significantly increased the levels of IL-10 ( limiting autoimmunity and inflammatory responses),.... (of that) may provide a novel approach for the treatment of RA"(273).. All-trans retinoic acid (ATRA), a biologic key metabolite of vitamin A, showed to suppress the clinical and histologic signs of arthritis in the collagen-induced arthritis (CIA) mice model through downregulated the expression of RANK and prevented white blood cell from differentiating into osteoclasts, causing RA( 275).
Free radical scavengers such as vitamins plays an essential role in reduced risk of rheumatoid arthritis
due to their effects in attenuate the expression of free radical and pro inflammatory cytokines(271)(272)
2.1. Vitamin A
According to the Imam Reza Hospital of Tabriz University of Medical Sciences, antioxidant including vitamin A are found to consist a clinical outcomes and oxidative stress in RA(274).
Patient with rheumatoid arthritis are accompanied with the over expression of the levels of serum leptin and other related cytokines, Dr. Xiong RB and the research team at the Southern Medical Universit said, " VitA.....significantly reduced the levels of leptin, TNF-α, IL-6 and CRP and the ESR(Pro inflammatory cytokines) and significantly increased the levels of IL-10 ( limiting autoimmunity and inflammatory responses),.... (of that) may provide a novel approach for the treatment of RA"(273).. All-trans retinoic acid (ATRA), a biologic key metabolite of vitamin A, showed to suppress the clinical and histologic signs of arthritis in the collagen-induced arthritis (CIA) mice model through downregulated the expression of RANK and prevented white blood cell from differentiating into osteoclasts, causing RA( 275).
2.2. Vitamin C
Dietary vitamin C did significantly influence on growth performance and immune response, according to epidemiological studies(276)(277).
Dietary vitamin C did significantly influence on growth performance and immune response, according to epidemiological studies(276)(277).
Maintaining the balance between pro oxidant and antioxidant levels such as vitamin C and uric acid are important to prevent the insult of free radicals in rheumatoid arthritis, according Dr. Mahajan M and the research team at the Govt. Medical College suggested(278).
Dr Al-Okbi SY said" the majority of nutraceuticals studied possess beneficial effect toward chronic inflammatory diseases,.....anti-inflammatory and antioxidant nutraceuticals may serve as complementary medicine for the management of RA(279).
Dr Al-Okbi SY said" the majority of nutraceuticals studied possess beneficial effect toward chronic inflammatory diseases,.....anti-inflammatory and antioxidant nutraceuticals may serve as complementary medicine for the management of RA(279).
2.3. Vitamin E
Vitamin A similar to vitamin A are found to consist a clinical outcomes and oxidative stress (274)which has been found to play an important role in the inflammation and parthenogenesis of RA(283).
According to studies, diets containing fish oil and vitamin E not only showed a significant pain reduction in patients but also induced a positive effect on autoimmune disease by decreasing proinflammatory cytokines and lipid mediator(280). In the rat model of collagen-induced arthritis (CIA), oral adminsitration of δ-tocotrienol (10 mg/kg) induced a significant impact in lowering paw edema, through it anti inflammatory effects(281).
2.4. Vitamin D
Vitamin D receptor (VDR), best known for its function in variety of metabolic disorders and in regulation of inflammation, is found to associate to the risk of RA(284), through its expression on reduced risk for FLS-mediated cartilage and bone invasion and erosions by attenuating the pro inflammatory cytokines induced osteoclasts. Vitamin D deficiency is common in rheumatoid arthritis (RA) of which induced pain, fatigue, and limited physical activity as well as poor quality of life(285).
Dr. Kostoglou-Athanassioul and the research team at the Red Cross Hospital, said," vitamin D deficiency is highly prevalent in patients with RA, .......may be linked to disease severity in RA. As vitamin D deficiency has been linked to diffuse musculoskeletal pain, these results have therapeutic implications"(286).
Vitamin D receptor (VDR), best known for its function in variety of metabolic disorders and in regulation of inflammation, is found to associate to the risk of RA(284), through its expression on reduced risk for FLS-mediated cartilage and bone invasion and erosions by attenuating the pro inflammatory cytokines induced osteoclasts. Vitamin D deficiency is common in rheumatoid arthritis (RA) of which induced pain, fatigue, and limited physical activity as well as poor quality of life(285).
Dr. Kostoglou-Athanassioul and the research team at the Red Cross Hospital, said," vitamin D deficiency is highly prevalent in patients with RA, .......may be linked to disease severity in RA. As vitamin D deficiency has been linked to diffuse musculoskeletal pain, these results have therapeutic implications"(286).
2.5. Vitamin K
Vitamin K, another vitamin is found to plays an important role as an anti-inflammatory nutrient in bone metabolism(287). According to the cross-sectional study of a total of 158 female RA patients (mean age 62.5 years), oral administration VitK2 significant decreased serum CRP, and inhibited the proliferation of fibroblast-like synoviocytes (FLSs) and the development of collagen-induced arthritis (CIA). in a dose-dependent manner(288)
Vitamin K, another vitamin is found to plays an important role as an anti-inflammatory nutrient in bone metabolism(287). According to the cross-sectional study of a total of 158 female RA patients (mean age 62.5 years), oral administration VitK2 significant decreased serum CRP, and inhibited the proliferation of fibroblast-like synoviocytes (FLSs) and the development of collagen-induced arthritis (CIA). in a dose-dependent manner(288)
B.4. The Important supplements for rheumatoid arthritis
1. Glucosamine
Glucosamine, a compound of the simple sugar glucose and the amino acid glutamine, is a precursor for glycosaminoglycans(194,289), a major component of joint cartilage(195,290). In a randomized placebo-controlled study of 51 rheumatoid arthritis (RA) patients: 25 patients in the glucosamine group and 26 patients in the placebo group, Glucosamine hydrochloride at a daily dose of 1,500 mg showed to improve some symptomatic effects on RA(291).
The orally administered combination of a glucosamine-chondroitin-quercetin glucoside (GCQG) supplement also exerted a special effect on improving the synovial fluid properties in OA patients, according to the Matsuno Clinic for Rheumatic Diseases(292). Furthermore, a novel glucosamine analogue also showed to inhibit the development of RA through exerting antioxidative and immunomodulatory effects(293).
1. Glucosamine
Glucosamine, a compound of the simple sugar glucose and the amino acid glutamine, is a precursor for glycosaminoglycans(194,289), a major component of joint cartilage(195,290). In a randomized placebo-controlled study of 51 rheumatoid arthritis (RA) patients: 25 patients in the glucosamine group and 26 patients in the placebo group, Glucosamine hydrochloride at a daily dose of 1,500 mg showed to improve some symptomatic effects on RA(291).
The orally administered combination of a glucosamine-chondroitin-quercetin glucoside (GCQG) supplement also exerted a special effect on improving the synovial fluid properties in OA patients, according to the Matsuno Clinic for Rheumatic Diseases(292). Furthermore, a novel glucosamine analogue also showed to inhibit the development of RA through exerting antioxidative and immunomodulatory effects(293).
2. Omega 3 fatty acids
Omega-3 fatty acids found abundantly in cold water fish, algae and seeds and nuts of plant has shown to exhibit the prevention of different pathologies, such as cardiovascular, psychiatric, neurological, dermatological and rheumatological disorders(297), including RA. Dr. Shafaghat A said," The hexane extract from the flower, leaf, stem, and seed contained 39.1%, 43.2%, 29.0%, and 37.6% of omega-3 fatty acids, ... possess considerable antioxidant activity(298) of that may be helpful in attenuate the oxidative stress in induction of RA.
Dr. Jeromson S. and the research team at the University of Stirling suggested that Omega 3 fatty acid also plays an essential role in Skeletal Muscle Health(299) in inhibition of pro inflammatory cytokines(300) which has a direct influence to the onset of rheumatoid arthritis.B.5. The Miracle Topical Remedy
Certain topical remedies used in traditional or folk medicine have found effective on attenuate persistent symptoms of rheumatoid arthritis
Topical Capsaicin cream used for treatment of soft tissue with a pharmaceutical name of Finalgon®(420), has been shown effectively to reduced symptoms of pain of 80% of patient with rheumatoid arthritis in a double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA)(301a). Dr. Rumsfield JA and Dr. West DP. Said," Although capsaicin is clinically used as an external analgesic for temporary relief of neuralgia, it has also been widely used as a research tool to study peripheral pain"(302). of that may be reason for the topical is recommended for treatment in patient with RA in modern herbal and TCM practitioners.
2. Avocado soybean unsaponifiables (ASU)
Avocado soybean unsaponifiables (ASU) is a natural vegetable extract composed of one-third avocado oil and two-thirds soybean oil, may be used effectively for treatment of knee osteoarthritis to replace the use of analgesics and nonsteroidal antiinflammatory drugs (NSAIDs), according to the a three-month, prospective, randomized, double-blind, placebo-controlled, parallel-group trial(372,294)).
In rat model, administration of avocado/soybean unsaponifiable (ASU), reduced bone resorption, expression of TRAP and RANKL through its positive effect on bone repair following ligature-induced periodontitis(295). Dr. Pirotta M said," Despite support for some of the most popular CAM therapies for pain from arthritis-related conditions, additional high quality research is needed for other therapies, especially for herbals and homeopathy"(296).
B.6. The alternative Electrostimulation
Electrostimulation has been applied to acupuncture to treat pain associate to the clips from the therapeutic device, are attached to the needles. This type of alternative application also was found in Ancient Egyptians and later the Greeks and Romans, dates back to thousands of years BC for treatment of pain, muscle dysfunction and sarcopenia(303).
Dr. Men'shikova IV. in the comment of combination of modern physiotherapeutic methods in rehabilitation said,"(Use of electrostimulation of smooth muscle) All patients(with RA) reported alleviation of pain and oedema in the affected joint. The rehabilitation period was 2-5 days shorter than after the traditional treatment(304).
In support to the above study, the School of Rehabilitation Sciences, University of Ottawa, in the review of randomized controlled trials (RCTs) and controlled clinical trials (CCTs), case-control and cohort studies comparing ES against placebo or another active intervention in patients with RA showed that electrostimulation (ES) was shown to have a clinically beneficial effect on grip strength and fatigue resistance for RA patients with muscle atrophy of the hand but the evidences were limited due to low methodological quality of the trial included(305).Electrostimulation has been applied to acupuncture to treat pain associate to the clips from the therapeutic device, are attached to the needles. This type of alternative application also was found in Ancient Egyptians and later the Greeks and Romans, dates back to thousands of years BC for treatment of pain, muscle dysfunction and sarcopenia(303).
Dr. Men'shikova IV. in the comment of combination of modern physiotherapeutic methods in rehabilitation said,"(Use of electrostimulation of smooth muscle) All patients(with RA) reported alleviation of pain and oedema in the affected joint. The rehabilitation period was 2-5 days shorter than after the traditional treatment(304).
B.7. Other essential alternative medicne treatment
1.1. Ice therapy
Ice therapy, using the techniques of compression and elevation basic principles for treatment of acute soft tissue injury, if applied correctly with repeated application of 10 minutes for avoiding side effects, and preventing possible further injury(306). According to Dr. van den Bekerom MP and the research team at the Orthopaedic Research Center Amsterdam, treatment of pain, swelling, ankle mobility or range of motion, must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines(307).
Unfortunately, according to the study of University of Ottawa, thermotherapy, including hot and ice packs application is found a significant effects on arthritic hands of patient with rheumatoid arthritis and most studies(308).
In regard of thermotherapy used of heat and cold treatment, Dr. Oosterveld FG and Dr. Rasker JJ said,s" In general, locally applied heat increases and locally applied cold decreases the temperature of the skin, superficial and deeper tissues, and joint cavity. Most studies dealing with the effects of heat and cold on pain, joint stiffness, grip strength, and joint function in inflamed joints report beneficial effects" and " In vitro studies show that higher temperatures increase the breakdown of articular cartilage and tissues that contain collagen".(311)
Beside suggesting certain herbal medicine for treatment of osteoarthritis, modern herbal and TCM medicine doctors may also combine other natural treatment for alleviating symptoms of the disease
1. Use Ice or Heat Therapies1.1. Ice therapy
Ice therapy, using the techniques of compression and elevation basic principles for treatment of acute soft tissue injury, if applied correctly with repeated application of 10 minutes for avoiding side effects, and preventing possible further injury(306). According to Dr. van den Bekerom MP and the research team at the Orthopaedic Research Center Amsterdam, treatment of pain, swelling, ankle mobility or range of motion, must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines(307).
Unfortunately, according to the study of University of Ottawa, thermotherapy, including hot and ice packs application is found a significant effects on arthritic hands of patient with rheumatoid arthritis and most studies(308).
1.2. Heat therapy
Heat therapy, is another form of thermotherapy with the use of heat in therapy for pain relief by alternative rehabilitation specialists. The review of studied that met the criteria of 328 subjects, by the University of Ottawa, superficial moist heat is found effective for relieved joint swelling, pain, reduced medication intake, improved range of motion (ROM), grip strength, hand function but limited by methodological considerations such as the poor quality of trials(309). In support of the above, the research team lead by Dr. found that in 17 with symmetrical rheumatoid arthritis (RA) applied heat to 1 hand twice daily for 2 years, heat therapy improve joint swelling, joint tenderness and grip strength with daily heat therapy did not accelerate the proliferative lesion in RA(310).
Heat therapy, is another form of thermotherapy with the use of heat in therapy for pain relief by alternative rehabilitation specialists. The review of studied that met the criteria of 328 subjects, by the University of Ottawa, superficial moist heat is found effective for relieved joint swelling, pain, reduced medication intake, improved range of motion (ROM), grip strength, hand function but limited by methodological considerations such as the poor quality of trials(309). In support of the above, the research team lead by Dr. found that in 17 with symmetrical rheumatoid arthritis (RA) applied heat to 1 hand twice daily for 2 years, heat therapy improve joint swelling, joint tenderness and grip strength with daily heat therapy did not accelerate the proliferative lesion in RA(310).
And according to the traditional Chinese medicine, correlation between cold and hot pattern are related to different pathways, and the network of that might be used for identifying the pattern and classification in other diseases including subsets of RA(312).
2. Acupuncture
The most oldest form of medical treatment in traditional Chinese medicine has been known for its function in relief pain(383,313) and functional limitation(384,314) for chronic patient, including patient with moderate or severe chronic pain(383,313).
The Cochrane Field of Rehabilitation and Related Therapies and the Cochrane Musculoskeletal Review suggests the effectiveness of acupuncture as a rehabilitation of an adjunct therapy for the symptomatic treatment of rheumatoid arthritis showed to reduce symptomatic knee pain in patients with RA 24 hours and 4 months post treatment(315). According to Dr. Wang C and the research team at the Tufts Medical Center and Tufts University School of Medicine, acupuncture showed to decrease pain, significant reduced morning stiffness and inflammatory markers in comparison to controls in patients with rheumatoid arthritis(316).
In a total of 80 eligible patients, 36 patients with mean age of 58 study, electroacupuncture (EA) and traditional Chinese acupuncture (TCA) significantly reduced tender joints and improved physician's and patients global score but large scale trial are recommended in orderto clarify the existing evidence base on acupuncture for RA.(317).The most oldest form of medical treatment in traditional Chinese medicine has been known for its function in relief pain(383,313) and functional limitation(384,314) for chronic patient, including patient with moderate or severe chronic pain(383,313).
The Cochrane Field of Rehabilitation and Related Therapies and the Cochrane Musculoskeletal Review suggests the effectiveness of acupuncture as a rehabilitation of an adjunct therapy for the symptomatic treatment of rheumatoid arthritis showed to reduce symptomatic knee pain in patients with RA 24 hours and 4 months post treatment(315). According to Dr. Wang C and the research team at the Tufts Medical Center and Tufts University School of Medicine, acupuncture showed to decrease pain, significant reduced morning stiffness and inflammatory markers in comparison to controls in patients with rheumatoid arthritis(316).
In the discuss of the imbalance between T-helper 17 (Th17) cells and regulatory T (Treg) cells induced rheumatoid arthritis, use of electroacupuncture (EA) not only restores the balance of Th17/Treg cell but also expresses its anti-inflammatory effects through educed paw volumes, arthritis scores and inflammation scores(319) in collagen-induced arthritis (autoimmune disease ) rats(320).
In fact, poor quality of studies and conflicting evidence exists in placebo-controlled trials, in some cases are also found to accompany with certain inconsistency of its efficacy(318).
5. Hydrotherapy
Hydrotherapy, using water for the treatment of disease has shown some beneficiary for treating pain in patient with RA(329). In comparison to patient of RA with no treatment in the short term, hydrotherapy has a positive role in reducing pain and improving the health status of RA treated patients, through reducing pain, joint tenderness, mood and tension symptoms, and increasing grip strength(329), in knee range of movement (women only) as well as maintaining improvement in emotional and psychological state(330).
Oligomineral, homeothermic, low radioactive water hydrotherapy exhibited significant improvement of functional capacity, quality of life and positive influence on disease activity in the patients with RA, an study from Serbian suggested.
3. Massage Therapy
Massage therapy used in traditional Chinese medicine over thousands of year for treatment of osteoarthritis (OA)(392,321) was effective in reduced pain of mild to moderate juvenile rheumatoid arthritis through mediation of children's anxiety and stress hormone (cortisol) levels(322).
Furthermore, in a forty-two adults with rheumatoid arthritis, light pressure massage therapy improved grip strength following the first and last massage sessions, reduced pain and promoted range of motion in their wrist and large upper joints (elbows and shoulders) by the end of the one month period(324).
Massage therapy used in traditional Chinese medicine over thousands of year for treatment of osteoarthritis (OA)(392,321) was effective in reduced pain of mild to moderate juvenile rheumatoid arthritis through mediation of children's anxiety and stress hormone (cortisol) levels(322).
Furthermore, in a forty-two adults with rheumatoid arthritis, light pressure massage therapy improved grip strength following the first and last massage sessions, reduced pain and promoted range of motion in their wrist and large upper joints (elbows and shoulders) by the end of the one month period(324).
Dr. Field T said," Moderate pressure massage,....increased weight gain in preterm infants, reduced pain in different syndromes including fibromyalgia and rheumatoid arthritis, enhanced attentiveness, reduced depression and enhanced immune function (increased natural killer cells and natural killer cell activity).......(as well as) reduced depression, anxiety and heart rate, ...... increased vagal activity and decreased cortisol levels"(323)
4. Spa therapySpa therapy may be one the effective technique for treatment of lower back pain, according to some studies(392.321).
In patient with rheumatoid arthritis, spa therapy showed to relief symptoms of pain, stiffness and mobility(395,325) and is considered as one of the best RA rehabilitation in many double-blinded trials through its defectiveness in attenuated pain relief, analgesic drug consumption and pro inflammatory cytokines, improved quality of life, etc.(326)(327).
Unfortunately, according to Dr. Verhagen AP and the research team at the Erasmus Medical Center, in the review of two new studies and a total of nine studies involving 579 participants,.there is overall evidence to support that spa therapy is more effective than no treatment, that one type of bath is more effective than another(328).In patient with rheumatoid arthritis, spa therapy showed to relief symptoms of pain, stiffness and mobility(395,325) and is considered as one of the best RA rehabilitation in many double-blinded trials through its defectiveness in attenuated pain relief, analgesic drug consumption and pro inflammatory cytokines, improved quality of life, etc.(326)(327).
Hydrotherapy, using water for the treatment of disease has shown some beneficiary for treating pain in patient with RA(329). In comparison to patient of RA with no treatment in the short term, hydrotherapy has a positive role in reducing pain and improving the health status of RA treated patients, through reducing pain, joint tenderness, mood and tension symptoms, and increasing grip strength(329), in knee range of movement (women only) as well as maintaining improvement in emotional and psychological state(330).
Oligomineral, homeothermic, low radioactive water hydrotherapy exhibited significant improvement of functional capacity, quality of life and positive influence on disease activity in the patients with RA, an study from Serbian suggested.
6. Tai Chi
Tai chi, is an ancient form of mind-body technique used in Chinese with meditative movements that promote balance and healing of the mind and body(406, 331). But to use the technique for treatment of RA has produced conflict result.
According to the review of 4 trials including 206 participants, tai chi showed a statistically significant and clinically important improvements in ankle plantar flexion, benefits on lower extremity range of motion, in particular ankle range of motion, for people with RA but had no alternation of outcomes of disease activity(332). Contract to the study, Dr Lee MS and the research team at the Universities of Exeter & Plymouth, said, " Tai chi reported some positive findings for tai chi on disability index, quality of life, depression and mood for RA patients, (but) did not demonstrate effectiveness on pain reduction(333).
Other study in the assessment of patient with RA suggested that tai chi should be sued for treatment of people with a chronic debilitating disease such as RA due to its potential for physical and psychological improvements(334).
Tai chi, is an ancient form of mind-body technique used in Chinese with meditative movements that promote balance and healing of the mind and body(406, 331). But to use the technique for treatment of RA has produced conflict result.
According to the review of 4 trials including 206 participants, tai chi showed a statistically significant and clinically important improvements in ankle plantar flexion, benefits on lower extremity range of motion, in particular ankle range of motion, for people with RA but had no alternation of outcomes of disease activity(332). Contract to the study, Dr Lee MS and the research team at the Universities of Exeter & Plymouth, said, " Tai chi reported some positive findings for tai chi on disability index, quality of life, depression and mood for RA patients, (but) did not demonstrate effectiveness on pain reduction(333).
Other study in the assessment of patient with RA suggested that tai chi should be sued for treatment of people with a chronic debilitating disease such as RA due to its potential for physical and psychological improvements(334).
7. Yoga
An ancient form of medical technique originated from India, is become a popular multimodal mind-body exercise in the Western world for promoted flexibility, strength, endurance, and balance(412, 335). According to university research conducted at a medical clinic, Yoga significantly decreased Health Assessment Questionnaire (HAQ) disability index, decreased perception of pain and depression, and improved balance in women with rheumatoid arthritis(336) and hand grip strength in normal persons and in patients with rheumatoid arthritis(337) as well as inducing positive changes in psychological or physiological outcomes(338).
But in the review of Eight RCTs with a total of 559 subjects, Dr. Cramer H and the research team at the Klinik für Naturheilkunde und Integrative Medizin, Knappschafts-Krankenhaus said" ,...there was very low evidence (of yoga) for effects on pain and disability,.... only weak recommendations can be made for the ancillary use of yoga in the management of....... RA at this point"(339)
An ancient form of medical technique originated from India, is become a popular multimodal mind-body exercise in the Western world for promoted flexibility, strength, endurance, and balance(412, 335). According to university research conducted at a medical clinic, Yoga significantly decreased Health Assessment Questionnaire (HAQ) disability index, decreased perception of pain and depression, and improved balance in women with rheumatoid arthritis(336) and hand grip strength in normal persons and in patients with rheumatoid arthritis(337) as well as inducing positive changes in psychological or physiological outcomes(338).
But in the review of Eight RCTs with a total of 559 subjects, Dr. Cramer H and the research team at the Klinik für Naturheilkunde und Integrative Medizin, Knappschafts-Krankenhaus said" ,...there was very low evidence (of yoga) for effects on pain and disability,.... only weak recommendations can be made for the ancillary use of yoga in the management of....... RA at this point"(339)
B.8. Herbal and Traditional Chinese medicine
Many herbal medicine have been found effectively for reduction of symptoms and treatment for patient with osteoarthritis(340), including
Many herbal medicine have been found effectively for reduction of symptoms and treatment for patient with osteoarthritis(340), including
B.8.1. Individual herb
1. Ginger
Ginger has been used internally and externally for over a thousand years in China to manage all types of arthritis symptoms, through its effective in compress therapy(431, 342) and is considered as one of the pharmaceutical candidate for treatment of an autoimmune disease such as RA, particularly in elderly people(341). According to the King Faisal University, the effectiveness of ginger for treatment of RA probably due to its the anti-inflammatory/anti-oxidant activity in reduction of the progression of RA(344).Furthermore combined treatment with ginger and stimulation at zusanli (ST 36) showed a significantly greater improvements in RA symptoms, laboratory outcomes, and gastrointestinal
symptom scores in comparison to anti-rheumatic drugs (ARDs), and acupoint stimulation at zusanli (ST 36) alone(343).
Dr. Hoffman T said," Ginger: an ancient remedy and modern miracle drug,.. (showed) "unclear" for treating rheumatoid arthritis, osteoarthritis, or joint and muscle pain)" (345), but Dr. Grzanna R and the research team at the RMG Biosciences, said,"ginger modulates biochemical pathways activated in chronic inflammation"(346).
2. Primrose oil
With a rich source of omega-6 essential fatty acids, primrose oil may be effective "use in the treatment of systemic diseases marked by chronic inflammation, such as atopic dermatitis and rheumatoid arthritis" Dr.Bayles B and Dr. Usatine R. said(348).
3. Willow bark
A herbal medicine used over thousands of years for treatment as an anti-inflammatory, antipyretic, and analgesic advocate in many culture(433, 350) and may be a potential agent for inhibition of pro inflammatory cytokines(351)(352) due to its phytochemical polyphenols(351).
Unfortunately, according to randomized double-blind controlled trials, willow bark extract showed no relevant efficacy in patients with OA and with RA(353).
In support to above, study conducted by the Columbia University showed that ethanolic extracts from willow bark with daily doses up to 240 mg salicin over periods of up to six weeks exhibits no significant improvement in patients with rheumatoid arthritis(354).
Unfortunately, according to randomized double-blind controlled trials, willow bark extract showed no relevant efficacy in patients with OA and with RA(353).
In support to above, study conducted by the Columbia University showed that ethanolic extracts from willow bark with daily doses up to 240 mg salicin over periods of up to six weeks exhibits no significant improvement in patients with rheumatoid arthritis(354).
4. Stinging nettle
Stinging nettle also known as Urtica dioica, a herbal medicine with long history for the effectiveness in treating of musculoskeletal pain(355).
Dr. Yang CL and the research team at the The University of Hong Kong in the study of scientific basis of botanical medicine as alternative remedies suggested that Urtica dioica demonstrated a strong anti-inflammatory and anti-arthritic effects and may may provide new treatment opportunities for RA patients(356).
Stinging nettle leaf extracts, an Germany registered Germany for adjuvant therapy of rheumatic diseases by inhibiting the inflammatory cascade, including on NF-kappaB activation(358) in autoimmune diseases through its immunomodulating effect and mediating T helper cell derived cytokine patterns(357).
Stinging nettle also known as Urtica dioica, a herbal medicine with long history for the effectiveness in treating of musculoskeletal pain(355).
Dr. Yang CL and the research team at the The University of Hong Kong in the study of scientific basis of botanical medicine as alternative remedies suggested that Urtica dioica demonstrated a strong anti-inflammatory and anti-arthritic effects and may may provide new treatment opportunities for RA patients(356).
Stinging nettle leaf extracts, an Germany registered Germany for adjuvant therapy of rheumatic diseases by inhibiting the inflammatory cascade, including on NF-kappaB activation(358) in autoimmune diseases through its immunomodulating effect and mediating T helper cell derived cytokine patterns(357).
5. Devil’s claw
Devil’s claw is also one most popular herb used in alternative medicine for treatment of patient suffering from rheumatoid arthritis, probably through anti inflammatory activity and oxidative activity(359).
Dr. Wegener T. said, " Extracts of the secondary tubers of Devil's Claw , (showed)an improvement of motility and a reduction of pain sensation in several clinical studies,......Pharmacological experiments have shown analgesic, antiphlogistic and antiinflammatory actions,..(due to) its most important constituents iridoid glycosides"(360).
In the study of investigation of the efficacy of selected complementary and alternative medicine (CAM) therapies for pain from arthritis and related conditions, devil's claw, may be the best choice for relieved pain of rheumatoid arthritis (RA), but Dr. Soeken KL suggested that additional high quality research is necessary for its validation(361).
6. Licorice
Licorice, one of most common Chinese herb used frequently in conjunction with other herbs in many herbal formulas is found to associate to the therapeutic effects on rheumatoid arthritis (RA) treatment through its phytochemicals glycyrrhizin (GL) and glycyrrhetinic acid (GA) in suppressing the anti-inflammatory cytokines(the COX-2/TxA2 pathway). The herbal medicine also decreases the adverse effects of conventional medicine NSAIDs or DMARDs(362).
In a collagen-induced arthritis DBA1/J mice model, oral administration of crude ascidian tunicate glycans with licorice extracts (ATECL) exerted its potential therapeutic effects for the treatment of rheumatoid arthritis through the changes in inflammatory proteins and cytokines levels, reduced the matrix metalloproteinase-9 (MMP-9) protein and increased interleukin-10 (IL-10) levels(363). Glycyrol another constituent of licorice, also expressed it effects in exhibition of the alleviated cartilage and bone erosion and reduced levels of serum inflammatory cytokines, through the suppression of proinflammatory cytokines (NF-κB and NFAT transcriptional activities and inhibited IL-2 expression), DR. Fu Y and the research team at the Beijing Normal University suggested(364).Licorice, one of most common Chinese herb used frequently in conjunction with other herbs in many herbal formulas is found to associate to the therapeutic effects on rheumatoid arthritis (RA) treatment through its phytochemicals glycyrrhizin (GL) and glycyrrhetinic acid (GA) in suppressing the anti-inflammatory cytokines(the COX-2/TxA2 pathway). The herbal medicine also decreases the adverse effects of conventional medicine NSAIDs or DMARDs(362).
8. Coriander
A common spice use in Chinese cooking as well as herbal medicine for treatment of vary inflammatory diseases, high cholesterol levels, diarrhea, mouth ulcers, etc. may consist a therapeutic value to alleviated symptoms of chronic inflammatory diseases due to its nti-inflammatory and antioxidant nutraceuticals(365).
Dr. Nair v and the research team at the All India Institute of Medical Sciences, said," Coriandrum sativum (CS),... seed hydroalcoholic extract (CSHE),.. inhibition of joint swelling as compared to control animals in both, formaldehyde and CFA inducedarthritis,..... increase in serum TNF-α levels in the CSHE treated groups as compared to control, the synovial expression of macrophage derived pro-inflammatory cytokines/cytokine receptor was found to be lower in the CSHE treated groups as compared to control(366).
9. Hot Chilli (Capsaicin)
Topical capsaicin, a neuromodulators, may be used for reduced pain in patients with RA. However, it is associated with a significant side effect, Dr. Richards BL and the research team at the Royal Prince Alfred Hospital suggested(367).
A double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA) received capsaicin (a substance P depletor) or placebo for four weeks, 80% of the capsaicin-treated patients experienced a reduction in pain after two weeks of treatment and it is considered as a safe and effective treatment for arthritis including RA(368).Topical capsaicin, a neuromodulators, may be used for reduced pain in patients with RA. However, it is associated with a significant side effect, Dr. Richards BL and the research team at the Royal Prince Alfred Hospital suggested(367).
10. Green Tea
Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years.
In mouse model, epigallocatechin 3-gallate (EGCG), a polyphenol present in green tea, may be potential use for prevention and treatment of RA by suppressing serum type-II collagen-specific immunoglobulin (Ig) IgG2a, T cell proliferation and relative frequencies of CD4 T cells,(inflammatory cytokines) through upregulation of the Nrf-2 antioxidant pathway in EGCG-mediated immunoregulation(369).
Dr. Riegsecker S and the research team at the University of Toledo, the effectiveness of epigallocatechin 3-gallate (EGCG) for treatment of RA is its ability in attenuation of the increased cytokine release and abnormally high levels of acute reactive proteins (ARPs) such as C-reactive protein (CRP), the a connecting link of inflammation in induced RA dysfunction(370). Furthermore, EGCG has been shown to be anti-inflammatory and protective in several studies using animal models of inflammatory arthritis, may be due to its function in reduced expression of inflammatory cytokines through its antioxidant and anti inflammatory properties(371), the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University suggested.
11. Turmeric
Turmeric, a cooking spice used in many culture in South East Asian, especially in India, also has been used as herbal medicine over thousands of year(373). Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, reduced inappropriate inflammatory responses through expression in inhibiting cell proliferation and metastasis and downregulating various factors, including the inflammatory cytokines and pathway(372) in animal model.
In acute and chronic inflammation, including Rheumatoid Arthritis, curcumin showed to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action, such as down-regulation of inflammatory transcription factors, cytokines,......related to expression of RA(374).
Dr. Park C and the research team at the Dongeui University College of Oriental Medicine suggested that the effectiveness of curcumin for treatment of RA is due to its inhibited of prostaglandin E(2) through numeral pathways such as hyperplasia of the synovial fibroblasts(375).
12. Bromelain
Bromelain, a group of protein digesting enzymes found in pineapples (Ananas comosus) used in traditional medicine as inflammatory agent and to treat pains, strains, and muscle aches and pains and ease back pain and chronic joint pain, skin diseases, etc.(467,376), through its the anti-inflammatory and analgesic properties may be the next potential target of pharmaceutical agent to reduce symptoms of rheumatoid arthritis(377). In the comparison for the effectiveness of cyclosporin A (5 mg/kg/day and 10 mg/kg/day orally); a mixture of enzymes containing pure substances (bromelain, trypsin, rutin) in the same ratio as in Phlogenzym (PHL, 150 mg/kg, twice daily, the mixture combined with cyclosporin A significantly inhibited both inflammation and destructive arthritis-associated changes, the Research Institute of Rheumatic Diseases suggested(378).
Furthermore, according to Dr. Bazzichi L and the research team at University of Pisa, bromelain may have a potential in activate autoreactive B cells induced the role of autoimmunity in the pathogenesis of rheumatoid arthritis, as self-perpetuing disorder(379).
13. Boswellia serrata
Boswellia serrata used as incense in religious and cultural ceremonies and in medicine over thousands of year may be the potential source for treatment of RA through its abilities to inhibit proinflammatory cytokines and modulation of antioxidant status(380) as well as inhibition of TNF-α (a cell signaling protein (cytokine) involved in systemic inflammation) and nitric oxide (NO) production(381).
Dr. Ammon HP, said" autoimmune diseases - formation of oxygen radicals and proteases (for example elastase) play an important destructive role,......From the pharmacological properties of
Boswellia serrata extracts and boswellic acids(BEs and BA), it is not surprising that positive effects of BEs in some chronic inflammatory diseases including rheumatoid arthritis,..(382)Boswellia serrata used as incense in religious and cultural ceremonies and in medicine over thousands of year may be the potential source for treatment of RA through its abilities to inhibit proinflammatory cytokines and modulation of antioxidant status(380) as well as inhibition of TNF-α (a cell signaling protein (cytokine) involved in systemic inflammation) and nitric oxide (NO) production(381).
Dr. Ammon HP, said" autoimmune diseases - formation of oxygen radicals and proteases (for example elastase) play an important destructive role,......From the pharmacological properties of
14. Dan Shen
Dan Shen with the pharmaceutical name of Radix Salvia miltiorrhizae, is a bitter and slightly cold herb, used mainly in traditional Chinese medicine for tonifying blood(494,383) has expressed the therapeutic effect on RA through its constituent ryptotanshinone (CTS),(384) through the inhibition of NF-κB signaling, the pro inflammatory cytokines.
The joint study lead by the West China Second Hospital, Sichuan University, injection of Salvia miltiorrhiza, a water‑soluble agent, derived from Salvia miltiorrhiza (SM), restores apoptosis of fibroblast-like synoviocytes and Bax mRNA expression levels of which related to the expression of synovial hyperplasia in RA(385).
Dr Nicolin V and the research team in the study of Tanshinone VI, another phytochemicals isolated from Dan shen suggested that the preventive of osteoclast differentiation in bone resorption probably through Tanshinone VI effect in inhibiting RANKL expression and NFkB induction(386)Dan Shen with the pharmaceutical name of Radix Salvia miltiorrhizae, is a bitter and slightly cold herb, used mainly in traditional Chinese medicine for tonifying blood(494,383) has expressed the therapeutic effect on RA through its constituent ryptotanshinone (CTS),(384) through the inhibition of NF-κB signaling, the pro inflammatory cytokines.
The joint study lead by the West China Second Hospital, Sichuan University, injection of Salvia miltiorrhiza, a water‑soluble agent, derived from Salvia miltiorrhiza (SM), restores apoptosis of fibroblast-like synoviocytes and Bax mRNA expression levels of which related to the expression of synovial hyperplasia in RA(385).
B.9. The herbal formulas in herbal and traditional Chinese medicine
Rheumatoid arthritis (RA) is a common worldwide public health problem especially in China, many RA formula has been used in the clinic and some of these TCM formulas have been existed over thousands of years in ancient China(388) with potential mechanisms such as inhibited osteoclast proliferation, suppressed fibroblast, decreased the expression of inflammatory cytokines, blocking signal pathways, etc.).
Rheumatoid arthritis (RA) is a common worldwide public health problem especially in China, many RA formula has been used in the clinic and some of these TCM formulas have been existed over thousands of years in ancient China(388) with potential mechanisms such as inhibited osteoclast proliferation, suppressed fibroblast, decreased the expression of inflammatory cytokines, blocking signal pathways, etc.).
1. Kynurenic acid (KYNA)
Kynurenic acid (KYNA), an endogenous neuromodulator and neuroprotector consisting anti-inflammatory, anti-oxidative and pain reliving properties, may be a propential herbal formula for prevention and treatment of Rheumatoid Arthritis due to activity involved in the synovial fluid of patients with rheumatoid arthritis(387).
Kynurenic acid (KYNA), an endogenous neuromodulator and neuroprotector consisting anti-inflammatory, anti-oxidative and pain reliving properties, may be a propential herbal formula for prevention and treatment of Rheumatoid Arthritis due to activity involved in the synovial fluid of patients with rheumatoid arthritis(387).
2. Keishibukuryogan
Keishibukuryogan, is a formul for the improvement of blood circulation may be a potential herbal formula used a treatment for reduced symptoms of RA, through its antioxidant and anti inflammatory effects on vascular function(389). As one of the most frequently used Kampo medicines in Japan, the herbal formula also has been used as biomarker protein (haptoglobin alpha 1 chain) for discriminating responders from non-responders in applying KBG for treatment of RA's patient(390).Furthermore, application of Keishibukuryogan has shown to decreased tender joint count, swollen joint count and DAS(28) decreased significantly with CRP and inflammatory cytokines remained unchanged(391) in RA 's patient.
3. Huo-Luo-Xiao-Ling Dan
Huo-Luo-Xiao-Ling Dan, the herbal formula has been used in traditional Chinese medicine for pain relief, including rheumatoid arthritis. According to Dr. Yu H and research team at the University of Maryland School of Medicine, it also used for treatment for RA due to its affects on several pathways such as immune response ( T cell proliferative and cytokine responses)(393), inflammation( proinflammatory cytokines IL-17 and IL-1β (393), cellular proliferation and apoptosis, and metabolic processes of which related to the onset ond progression of the disease(392). In arthritic bone damage in adjuvant arthritis (AA) model of RA, Huo-luo-xiao-ling dan (HLXL) suppressed inflammatory arthritis and reduced bone and cartilage damage in the joints of arthritic Lewis rats, through protection against bone damage via inhibition of mediators of osteoclastic bone remodeling (394).Furhtermore, the study from DR. Nanjundaiah SM and research team at the University of Maryland School of Medicine also found that the herbal formula expressed inhibition of symptoms of RA through a significant reduction in the levels of chemokines (RANTES, MCP-1, MIP-1α, and GRO/KC), MMPs (MMP 2 and 9), as well as cytokines (IL-6 and IL-17) by by suppressing the mediators of immune pathology(395)
4. Phytodolor (STW 1)
Phytodolor, a fixed herbal formulation containing alcoholic extracts of aspen leaves and bark (Populus tremula), common ash bark (Fraxinus excelsior), and golden rod herb (Solidago virgaurea),
may consist a potential effect on relieving symptoms of rheumatoid arthritis, the Australian Catholic University study suggested(396). DR Huber B said, " ....daily dose of either 3 x 30 drops of Phytodolor N .... administered over 3 weeks, ... improvements obtained were identical to those in the group receiving in part considerably higher doses of NSAIDs and placebo"(397)
In fact, the effectiveness of the herbal formula use for treatment of different subtypes of rheumatic diseases, such as painful inflammatory or degenerative rheumatic diseases(398), probably due to its antiinflammatory, antioedematous, antioxidative and analgesic properties(398).
5. Wu-tou decoction
Wu-tou decoction, containg 5 active herbs, Radix Aconiti (Wu Tou), Herba Ephedrae (Ma Huang), Radix Astragali (Huang Qi), Raidix Paeoniae Alba (Bai Shao) and Radix Glycytthizae (Gan Cao), has been used in traditional Chinese medicine for treatment of rheumatoid arthritis (RA), probably through anti-inflammatory and antioxidant activities(399), including effected on the expression of MMP-1 and MMP-13 in the joint of CIA rats and in human fibroblast-likesynoviocytes of rheumatoid arthritis(400).
6. Other formula used for treatment of RA may include
6.1. SKI306X, is a herbal formula containing Clematis mandshurica (CM), Prunella vulgaris (PV), and Trichosanthes kirilowii (TK)used to relieve pain associated with an anti-inflammatory and analgesic effect, as well as delay the destruction of cartilage in rheumatoid arthritis(403).
6.2. Wen Luo Yin (WLY) used in traditional Chinese formula for treatment of scattering cold pathogen, draining dampness, freeing the flow of network vessels and relieving pains may be a next pharmaceutical therapeutic agent for treaament of RA as it inhibited inflammation, pannus formation, cartilage and bone destruction of inflamed joints in CIA rat model(402).
6.3. Wei-Ling-Xian, another anti-arthritic herbal formula may also be effective for treatment of RA due to its phytochemical clematichinenoside (AR-6)in inhibition of pro inflammatory cytokines(403).
6.4. Liang Miao San, the herbal formual composed of the herbs Rhizoma Atractylodis (Cangzhu) and Cotex Phellodendri (Huangbai), is another traditional Chinese medicine formula for rheumatoid arthritis (RA) treatment through expression of differential anti-inflammatory activities of its phytochemical sinomenine by modulating distinct intracellular signaling pathways in RA(404).
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(34) Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation by Stanczyk J1, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, Gay R, Buckley CD, Tak PP, Gay S, Kyburz D.(PubMed)
(35) Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis as revealed by DNA microarray analysis by Lee HM1, Sugino H, Aoki C, Shimaoka Y, Suzuki R, Ochi K, Ochi T, Nishimoto N.(PubMed)
(36) What is the consequence of an abnormal lipid profile in patients with type 2 diabetes or the metabolic syndrome? by Windler E1(PubMed)
(37) Potential mechanisms leading to the abnormal lipid profile in patients with rheumatoid arthritis versus healthy volunteers and reversal by tofacitinib by Charles-Schoeman C1, Fleischmann R, Davignon J, Schwartz H, Turner SM, Beysen C, Milad M, Hellerstein MK, Luo Z, Kaplan IV, Riese R, Zuckerman A,McInnes IB.(PubMed)
(38) [Association between systemic inflammation and autoimmunity parameters and plasma lipid in patients withrheumatoid arthritis].[Article in Chinese]by Xue C1, Liu WL, Sun YH, Ding RJ, Hu DY.(PubMed)
(39) Lp(a) lipoprotein and lipids in patients with rheumatoid arthritis: serum levels and relationship to inflammation by Dursunoğlu D1, Evrengül H, Polat B, Tanriverdi H, Cobankara V, Kaftan A, Kiliç M.(PubMed)
(40) High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis by
Eyre S, Bowes J, Diogo D, Lee A, Barton A, Martin P, Zhernakova A, Stahl E, Viatte S, McAllister K, Amos CI, Padyukov L, Toes RE, Huizinga TW, Wijmenga C,Trynka G, Franke L, Westra HJ, Alfredsson L, Hu X, Sandor C, de Bakker PI, Davila S, Khor CC, Heng KK, Andrews R, Edkins S, Hunt SE, Langford C, Symmons D; Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate; Wellcome Trust Case Control Consortium, Concannon P, Onengut-Gumuscu S,Rich SS, Deloukas P, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Ärlsetig L, Martin J, Rantapää-Dahlqvist S, Plenge RM, Raychaudhuri S, Klareskog L,Gregersen PK, Worthington J.(PubMed)
(41) Genetic association of CCR5 promoter single nucleotide polymorphism in seronegative and seropositiverheumatoid arthritis by Lima G1, Furuzawa-Carballeda J, Ramos-Bello D, Jakez-Ocampo J, Pascual-Ramos V, Núñez-Alvarez CA, Granados J, Llorente L.(PubMed)
(42) Overexpression of Aiolos in Peripheral Blood Mononuclear Cell Subsets from Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis by Cai X1, Liu X1, Du S1, Xu X1, Liu A1, Ge X1, Qiao Y1, Jiang Y2,3.(PubMed)
(43) NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans by Zhang Q1, Fan HW1, Zhang JZ1, Wang YM1, Xing HJ1.(PubMed)
(44) Interleukin-6 promoter haplotypes are associated with etanercept response in patients with rheumatoid arthritis by Schotte H1, Schmidt H2, Gaubitz M3, Drynda S4, Kekow J4, Willeke P5, Schlüter B2.(PubMed)
(45) Rheumatoid arthritis and periodontitis - inflammatory and infectious connections. Review of the literature by Rutger Persson G1(PubMed)
(46) Porphyromonas gingivalis may play an important role in the pathogenesis of periodontitis-associatedrheumatoid arthritis by Liao F1, Li Z, Wang Y, Shi B, Gong Z, Cheng X.(PubMed)
(47) The potential role of Th17 in mediating the transition from acute to chronic autoimmune inflammation:rheumatoid arthritis as a model by Ferraccioli G1, Zizzo G.(PubMed)
(48) How age and sex affect the erythrocyte sedimentation rate and C-reactive protein in early rheumatoid arthritis by Siemons L1, Ten Klooster PM, Vonkeman HE, van Riel PL, Glas CA, van de Laar MA.(PubMed)
(49) Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study by Innala L, Berglin E, Möller B, Ljung L, Smedby T, Södergren A, Magnusson S, Rantapää-Dahlqvist S, Wållberg-Jonsson S.(PubMed)
(50) IL7R gene expression network associates with human healthy ageing by Passtoors WM1, van den Akker EB2, Deelen J3, Maier AB4, van der Breggen R1, Jansen R5, Trompet S6, van Heemst D7, Derhovanessian E8, Pawelec G8, van Ommen GJ9, Slagboom PE3, Beekman M3.(PubMed)
(51) Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA Study by Jawaheer D, Olsen J, Lahiff M, Forsberg S, Lähteenmäki J, da Silveira IG, Rocha FA, Magalhães Laurindo IM, Henrique da Mota LM, Drosos AA, Murphy E,Sheehy C, Quirke E, Cutolo M, Rexhepi S, Dadoniene J, Verstappen SM, Sokka T; QUEST-RA.(PubMed)
(52) Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study by Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F, Skakic V, Badsha H, Peets T, Baranauskaite A, Géher P, Ujfalussy I, Skopouli FN, Mavrommati M, Alten R, Pohl C, Sibilia J, Stancati A, Salaffi F, Romanowski W, Zarowny-Wierzbinska D, Henrohn D, Bresnihan B, Minnock P, Knudsen LS, Jacobs JW,Calvo-Alen J, Lazovskis J, Pinheiro Gda R, Karateev D, Andersone D, Rexhepi S, Yazici Y, Pincus T; QUEST-RA Group.(PubMed)
(53) Socioeconomic and employment status of patients with rheumatoid arthritis in Korea by Kwon JM1, Rhee J, Ku H, Lee EK.(PubMed)
(54) Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis by Qin B1, Yang M2,3, Fu H4, Ma N5, Wei T6, Tang Q7, Hu Z8, Liang Y9, Yang Z10, Zhong R11.(PubMed)
(55) Association between body composition and inflammatory activity in rheumatoid arthritis. A systematic review.[Article in English, Spanish]by Alvarez-Nemegyei J1, Buenfil-Relloy FA2, Pacheco-Pantoja EL3.(PubMed)
(56) Racial disparities in treatment preferences for rheumatoid arthritis by Constantinescu F1, Goucher S, Weinstein A, Fraenkel L.(PubMed)
(57) The association of race and ethnicity with disease expression in male US veterans with rheumatoid arthritis by Mikuls TR1, Kazi S, Cipher D, Hooker R, Kerr GS, Richards JS, Cannon GW.(PubMed)
(58) Smoking and rheumatoid arthritis by Chang K1, Yang SM2, Kim SH3, Han KH4, Park SJ5, Shin JI2.(PubMed)
(59) [Smoking--a risk factor for rheumatoid arthritis development].[Article in Danish] by Christensen AF1, Lindegaard HM, Junker P.(PubMed)
(60) Cigarette smoking and rheumatoid arthritis by Albano SA1, Santana-Sahagun E, Weisman MH.(PubMed)
(61) Family history as a risk factor for rheumatoid arthritis: a case-control study by Koumantaki Y1, Giziaki E, Linos A, Kontomerkos A, Kaklamanis P, Vaiopoulos G, Mandas J, Kaklamani E.(PubMed)
(62) Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age by Frisell T1, Holmqvist M, Källberg H, Klareskog L, Alfredsson L, Askling J.(PubMed)
(63) Risk factors for the development of rheumatoid arthritis by Oliver JE1, Silman AJ.(PubMed)
(64) Risk of rheumatoid arthritis following vaccination with tetanus, influenza and hepatitis B vaccines among persons 15-59 years of age by Ray P1, Black S, Shinefield H, Dillon A, Carpenter D, Lewis E, Ross P, Chen RT, Klein NP, Baxter R; Vaccine Safety Datalink Team.(PubMed)
(65) Can immunisation trigger rheumatoid arthritis? by D P Symmons and K Chakravarty(PubMed)
(64a) Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in patients with rheumatoid arthritis by Wolfe F1.(PubMed)
(65a) Erythrocyte sedimentation rate, C-reactive protein, or rheumatoid factor are normal at presentation in 35%-45% of patients with rheumatoid arthritis seen between 1980 and 2004: analyses from Finland and the United States by Sokka T1, Pincus T.(PubMed)
(66) Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis: a meta-analysis of randomized controlled trials by Tarp S1, Bartels EM, Bliddal H, Furst DE, Boers M, Danneskiold-Samsøe B, Rasmussen M, Christensen R.(PubMed)
(67) Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature by Wilson A1, Yu HT, Goodnough LT, Nissenson AR.(PubMed)
(68) Anti-CCP antibodies: the past, the present and the future by van Venrooij WJ1, van Beers JJ, Pruijn GJ.(PubMed)
(69) Anti-citrullinated protein antibodies (ACPA) in early rheumatoid arthritis by Suwannalai P1, Trouw LA, Toes RE, Huizinga TW(PubMed)
(70) Expression of allograft inflammatory factor-1 in peripheral blood monocytes and synovial membranes in patients with rheumatoid arthritis by Pawlik A1, Kotrych D2, Paczkowska E3, Roginska D3, Dziedziejko V4, Safranow K4, Machalinski B5.(PubMed)
(71) Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-induced immune activation in rheumatoid arthritis by Hartgring SA1, van Roon JA, Wenting-van Wijk M, Jacobs KM, Jahangier ZN, Willis CR, Bijlsma JW, Lafeber FP.(PubMed)
(72) Interferon-gamma-inducing activity of interleukin-18 in the joint with rheumatoid arthritis by Yamamura M1, Kawashima M, Taniai M, Yamauchi H, Tanimoto T, Kurimoto M, Morita Y, Ohmoto Y, Makino H.(PubMed)
(73) [Risk factors for bone mineral density changes in patients with rheumatoid arthritis and fracture risk assessment].[Article in Chinese] by Wang Y1, Hao YJ1, Deng XR1, Li GT1, Geng Y1, Zhao J1, Zhou W1, Zhang ZL1.(PubMed)
(74) The relationship between soft tissue swelling, joint space narrowing and erosive damage in hand X-rays of patients with rheumatoid arthritis by Kirwan J1, Byron M, Watt I.(PubMed)
(48) How age and sex affect the erythrocyte sedimentation rate and C-reactive protein in early rheumatoid arthritis by Siemons L1, Ten Klooster PM, Vonkeman HE, van Riel PL, Glas CA, van de Laar MA.(PubMed)
(49) Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study by Innala L, Berglin E, Möller B, Ljung L, Smedby T, Södergren A, Magnusson S, Rantapää-Dahlqvist S, Wållberg-Jonsson S.(PubMed)
(50) IL7R gene expression network associates with human healthy ageing by Passtoors WM1, van den Akker EB2, Deelen J3, Maier AB4, van der Breggen R1, Jansen R5, Trompet S6, van Heemst D7, Derhovanessian E8, Pawelec G8, van Ommen GJ9, Slagboom PE3, Beekman M3.(PubMed)
(51) Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA Study by Jawaheer D, Olsen J, Lahiff M, Forsberg S, Lähteenmäki J, da Silveira IG, Rocha FA, Magalhães Laurindo IM, Henrique da Mota LM, Drosos AA, Murphy E,Sheehy C, Quirke E, Cutolo M, Rexhepi S, Dadoniene J, Verstappen SM, Sokka T; QUEST-RA.(PubMed)
(52) Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study by Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F, Skakic V, Badsha H, Peets T, Baranauskaite A, Géher P, Ujfalussy I, Skopouli FN, Mavrommati M, Alten R, Pohl C, Sibilia J, Stancati A, Salaffi F, Romanowski W, Zarowny-Wierzbinska D, Henrohn D, Bresnihan B, Minnock P, Knudsen LS, Jacobs JW,Calvo-Alen J, Lazovskis J, Pinheiro Gda R, Karateev D, Andersone D, Rexhepi S, Yazici Y, Pincus T; QUEST-RA Group.(PubMed)
(53) Socioeconomic and employment status of patients with rheumatoid arthritis in Korea by Kwon JM1, Rhee J, Ku H, Lee EK.(PubMed)
(54) Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis by Qin B1, Yang M2,3, Fu H4, Ma N5, Wei T6, Tang Q7, Hu Z8, Liang Y9, Yang Z10, Zhong R11.(PubMed)
(55) Association between body composition and inflammatory activity in rheumatoid arthritis. A systematic review.[Article in English, Spanish]by Alvarez-Nemegyei J1, Buenfil-Relloy FA2, Pacheco-Pantoja EL3.(PubMed)
(56) Racial disparities in treatment preferences for rheumatoid arthritis by Constantinescu F1, Goucher S, Weinstein A, Fraenkel L.(PubMed)
(57) The association of race and ethnicity with disease expression in male US veterans with rheumatoid arthritis by Mikuls TR1, Kazi S, Cipher D, Hooker R, Kerr GS, Richards JS, Cannon GW.(PubMed)
(58) Smoking and rheumatoid arthritis by Chang K1, Yang SM2, Kim SH3, Han KH4, Park SJ5, Shin JI2.(PubMed)
(59) [Smoking--a risk factor for rheumatoid arthritis development].[Article in Danish] by Christensen AF1, Lindegaard HM, Junker P.(PubMed)
(60) Cigarette smoking and rheumatoid arthritis by Albano SA1, Santana-Sahagun E, Weisman MH.(PubMed)
(61) Family history as a risk factor for rheumatoid arthritis: a case-control study by Koumantaki Y1, Giziaki E, Linos A, Kontomerkos A, Kaklamanis P, Vaiopoulos G, Mandas J, Kaklamani E.(PubMed)
(62) Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age by Frisell T1, Holmqvist M, Källberg H, Klareskog L, Alfredsson L, Askling J.(PubMed)
(63) Risk factors for the development of rheumatoid arthritis by Oliver JE1, Silman AJ.(PubMed)
(64) Risk of rheumatoid arthritis following vaccination with tetanus, influenza and hepatitis B vaccines among persons 15-59 years of age by Ray P1, Black S, Shinefield H, Dillon A, Carpenter D, Lewis E, Ross P, Chen RT, Klein NP, Baxter R; Vaccine Safety Datalink Team.(PubMed)
(65) Can immunisation trigger rheumatoid arthritis? by D P Symmons and K Chakravarty(PubMed)
(64a) Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in patients with rheumatoid arthritis by Wolfe F1.(PubMed)
(65a) Erythrocyte sedimentation rate, C-reactive protein, or rheumatoid factor are normal at presentation in 35%-45% of patients with rheumatoid arthritis seen between 1980 and 2004: analyses from Finland and the United States by Sokka T1, Pincus T.(PubMed)
(66) Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis: a meta-analysis of randomized controlled trials by Tarp S1, Bartels EM, Bliddal H, Furst DE, Boers M, Danneskiold-Samsøe B, Rasmussen M, Christensen R.(PubMed)
(67) Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature by Wilson A1, Yu HT, Goodnough LT, Nissenson AR.(PubMed)
(68) Anti-CCP antibodies: the past, the present and the future by van Venrooij WJ1, van Beers JJ, Pruijn GJ.(PubMed)
(69) Anti-citrullinated protein antibodies (ACPA) in early rheumatoid arthritis by Suwannalai P1, Trouw LA, Toes RE, Huizinga TW(PubMed)
(70) Expression of allograft inflammatory factor-1 in peripheral blood monocytes and synovial membranes in patients with rheumatoid arthritis by Pawlik A1, Kotrych D2, Paczkowska E3, Roginska D3, Dziedziejko V4, Safranow K4, Machalinski B5.(PubMed)
(71) Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-induced immune activation in rheumatoid arthritis by Hartgring SA1, van Roon JA, Wenting-van Wijk M, Jacobs KM, Jahangier ZN, Willis CR, Bijlsma JW, Lafeber FP.(PubMed)
(72) Interferon-gamma-inducing activity of interleukin-18 in the joint with rheumatoid arthritis by Yamamura M1, Kawashima M, Taniai M, Yamauchi H, Tanimoto T, Kurimoto M, Morita Y, Ohmoto Y, Makino H.(PubMed)
(73) [Risk factors for bone mineral density changes in patients with rheumatoid arthritis and fracture risk assessment].[Article in Chinese] by Wang Y1, Hao YJ1, Deng XR1, Li GT1, Geng Y1, Zhao J1, Zhou W1, Zhang ZL1.(PubMed)
(74) The relationship between soft tissue swelling, joint space narrowing and erosive damage in hand X-rays of patients with rheumatoid arthritis by Kirwan J1, Byron M, Watt I.(PubMed)
(75) Misdiagnosis of rheumatoid arthritis in an elderly woman with gout by Sewell KL1, Petrucci R, Keiser HD(PubMed)
(76) Hypercalcemia and Lytic Bone Lesions Masquerading Inflammatory Arthritis Treated as Rheumatoid Arthritis by Salari M1, Aboutorabi RB2, Rezaieyazdi Z1(PubMed)
(77) [Overlap between systemic sclerosis and rheumatoid arthritis: a distinct clinical entity?][Article in Portuguese] by Horimoto AM1, Costa IP2.(PubMed)
(78) Severe Jaccoud's arthropathy in systemic lupus erythematosus by Santiago MB1,2, Galvão V3, Ribeiro DS3, Santos WD3, da Hora PR3, Mota AP3, Pimenta E3, Oliveira I4, Atta AM4, Reis MG5, Reis EA5, Lins C3(PubMed)
(79) Atypical Infections versus Inflammatory Conditions of the Hand: The Role of Imaging in Diagnosis by Soldatos T1, Omar H, Sammer D, Chhabra A.(PubMed)
(80) Increased frequency of osteoporosis and BMD below the expected range for age among South Korean women with rheumatoid arthritis by Lee SG1, Park YE, Park SH, Kim TK, Choi HJ, Lee SJ, Kim SI, Lee SH, Kim GT, Lee JW, Lee JH, Baek SH.(PubMed)
(81) A multicenter cross sectional study on bone mineral density in rheumatoid arthritis. Italian Study Group on Bone Mass in Rheumatoid Arthritis by Sinigaglia L1, Nervetti A, Mela Q, Bianchi G, Del Puente A, Di Munno O, Frediani B, Cantatore F, Pellerito R, Bartolone S, La Montagna G, Adami S.(PubMed)
(82) A case of rheumatoid arthritis with methotrexate related lymphoproliferative diseases of the knee by Abe A1, Wakaki K2, Ishikawa H1, Ito S1, Murasawa A1.(PubMed)
(83) Clinical characteristics and incidence of methotrexate-related lymphoproliferative disorders of patients withrheumatoid arthritis by Yoshida Y1, Takahashi Y, Yamashita H, Kano T, Kaneko H, Mimori A(PubMed)
(84) Neurologic complications of systemic lupus erythematosus, sjögren syndrome, and rheumatoid arthritis by Bhattacharyya S1, Helfgott SM2.(PubMed)
(85) Late-onset neutropenia after treatment with rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry by Salmon JH1, Cacoub P2, Combe B3, Sibilia J4, Pallot-Prades B5, Fain O6, Cantagrel A7, Dougados M8, Andres E9, Meyer O10, Carli P11, Pertuiset E12, Pane I13, Maurier F14, Ravaud P13, Mariette X15, Gottenberg JE16.(PubMed)
(86) Late-onset neutropenia in patients with rheumatoid arthritis after treatment with rituximab by Abdulkader R1, Dharmapalaiah C, Rose G, Shand LM, Clunie GP, Watts RA.(PubMed)
(87) Carpal tunnel syndrome caused by volar dislocation of the lunate in a patient with rheumatoid arthritis by Oka Y1, Tokunaga D, Fujiwara H, Hojo T, Takatori R, Kubo T.(PubMed)
(88) Heart involvement in rheumatoid arthritis: systematic review and meta-analysis by Corrao S1, Messina S, Pistone G, Calvo L, Scaglione R, Licata G.(PubMed)
(89) Scabies in a Patient with Rheumatoid Arthritis Treated with Adalimumab - A Case Report by Marković I, Pukšić S, Gudelj Gračanin A, Čulo MI, Mitrović J, Morović-Vergles J1.(PubMed)
(90) Prevalence of dry eye syndrome and Sjogren's syndrome in patients with rheumatoid arthritis by Kosrirukvongs P1, Ngowyutagon P, Pusuwan P, Koolvisoot A, Nilganuwong S.(PubMed)
(91) A study of the prevalence of sicca symptoms and secondary Sjögren's syndrome in patients with rheumatoid arthritis, and its association to disease activity and treatment profile by Haga HJ1, Naderi Y, Moreno AM, Peen E.(PubMed)
(92) [Multiple cerebral infarction associated with cerebral vasculitis in rheumatoid arthritis].[Article in Japanese]by Ohta K1, Tanaka M, Funaki M, Sakauchi M, Suzuki N.(PubMed)
(93) Recovery from rheumatoid cerebral vasculitis by low-dose methotrexate by Ohno T1, Matsuda I, Furukawa H, Kanoh T.(PubMed)
(80) Increased frequency of osteoporosis and BMD below the expected range for age among South Korean women with rheumatoid arthritis by Lee SG1, Park YE, Park SH, Kim TK, Choi HJ, Lee SJ, Kim SI, Lee SH, Kim GT, Lee JW, Lee JH, Baek SH.(PubMed)
(81) A multicenter cross sectional study on bone mineral density in rheumatoid arthritis. Italian Study Group on Bone Mass in Rheumatoid Arthritis by Sinigaglia L1, Nervetti A, Mela Q, Bianchi G, Del Puente A, Di Munno O, Frediani B, Cantatore F, Pellerito R, Bartolone S, La Montagna G, Adami S.(PubMed)
(82) A case of rheumatoid arthritis with methotrexate related lymphoproliferative diseases of the knee by Abe A1, Wakaki K2, Ishikawa H1, Ito S1, Murasawa A1.(PubMed)
(83) Clinical characteristics and incidence of methotrexate-related lymphoproliferative disorders of patients withrheumatoid arthritis by Yoshida Y1, Takahashi Y, Yamashita H, Kano T, Kaneko H, Mimori A(PubMed)
(84) Neurologic complications of systemic lupus erythematosus, sjögren syndrome, and rheumatoid arthritis by Bhattacharyya S1, Helfgott SM2.(PubMed)
(85) Late-onset neutropenia after treatment with rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry by Salmon JH1, Cacoub P2, Combe B3, Sibilia J4, Pallot-Prades B5, Fain O6, Cantagrel A7, Dougados M8, Andres E9, Meyer O10, Carli P11, Pertuiset E12, Pane I13, Maurier F14, Ravaud P13, Mariette X15, Gottenberg JE16.(PubMed)
(86) Late-onset neutropenia in patients with rheumatoid arthritis after treatment with rituximab by Abdulkader R1, Dharmapalaiah C, Rose G, Shand LM, Clunie GP, Watts RA.(PubMed)
(87) Carpal tunnel syndrome caused by volar dislocation of the lunate in a patient with rheumatoid arthritis by Oka Y1, Tokunaga D, Fujiwara H, Hojo T, Takatori R, Kubo T.(PubMed)
(88) Heart involvement in rheumatoid arthritis: systematic review and meta-analysis by Corrao S1, Messina S, Pistone G, Calvo L, Scaglione R, Licata G.(PubMed)
(89) Scabies in a Patient with Rheumatoid Arthritis Treated with Adalimumab - A Case Report by Marković I, Pukšić S, Gudelj Gračanin A, Čulo MI, Mitrović J, Morović-Vergles J1.(PubMed)
(90) Prevalence of dry eye syndrome and Sjogren's syndrome in patients with rheumatoid arthritis by Kosrirukvongs P1, Ngowyutagon P, Pusuwan P, Koolvisoot A, Nilganuwong S.(PubMed)
(91) A study of the prevalence of sicca symptoms and secondary Sjögren's syndrome in patients with rheumatoid arthritis, and its association to disease activity and treatment profile by Haga HJ1, Naderi Y, Moreno AM, Peen E.(PubMed)
(92) [Multiple cerebral infarction associated with cerebral vasculitis in rheumatoid arthritis].[Article in Japanese]by Ohta K1, Tanaka M, Funaki M, Sakauchi M, Suzuki N.(PubMed)
(93) Recovery from rheumatoid cerebral vasculitis by low-dose methotrexate by Ohno T1, Matsuda I, Furukawa H, Kanoh T.(PubMed)
(94) Evidence-based Recommendations for the Management of Comorbidities in Rheumatoid Arthritis, Psoriasis, and Psoriatic Arthritis: Expert Opinion of the Canadian Dermatology-Rheumatology Comorbidity Initiative by Roubille C1, Richer V1, Starnino T1, McCourt C1, McFarlane A1, Fleming P1, Siu S1, Kraft J1, Lynde C1, Pope J1, Gulliver W1, Keeling S1, Dutz J1, Bessette L1,Bissonnette R1, Haraoui B1.(PubMed)
(95) Coronary artery disease and rheumatoid arthritis by Goodson N1.(PubMed)
(96) Cardiovascular risk factors in Chilean patients with rheumatoid arthritis by Cisternas M1, Gutiérrez MA, Klaassen J, Acosta AM, Jacobelli S.(PubMed)
(97) Cardiovascular disease--the silent killer in rheumatoid arthritis by Kumar N1, Armstrong DJ.(PubMed)
(98) Comorbidities in rheumatoid arthritis by Michaud K1, Wolfe F.(PubMed)
(99) Rheumatoid Arthritis (RA)(CDC)
(100) Rates of serious infections and malignancies among patients with rheumatoid arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy by Aaltonen KJ1, Joensuu JT2, Virkki L2, Sokka T2, Aronen P2, Relas H2, Valleala H2, Rantalaiho V2, Pirilä L2, Puolakka K2, Uusitalo T2, Blom M2, Konttinen YT2,Nordström D2(PubMed)
(101) Anxiety, depression and suicidal ideation in patients with rheumatoid arthritis in use of methotrexate, hydroxychloroquine, leflunomide and biological drugs by Pinho de Oliveira Ribeiro N1, Rafael de Mello Schier A, Ornelas AC, Pinho de Oliveira CM, Nardi AE, Silva AC.(PubMed)
(102) Measuring the positive psychological well-being of people with rheumatoid arthritis: a cross-sectional validation of the subjective vitality scale by Rouse PC1, Veldhuijzen Van Zanten JJ2,3, Ntoumanis N4, Metsios GS5,6, Yu CA7, Kitas GD8,9, Duda JL10.(PubMed)
(103) Psychological predictors of pain severity, pain interference, depression, and anxiety in rheumatoid arthritispatients with chronic pain by Ryan S1, McGuire B2.(PubMed)
(104) Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis by Mercer LK1, Lunt M1, Low AL1, Dixon WG1, Watson KD1, Symmons DP1, Hyrich KL1; BSRBR Control Centre Consortium(PubMed)
(105) Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necrosis factor therapy: analysis of the Australian Rheumatology Association Database (ARAD) prospective cohort study by Buchbinder R1,2, Van Doornum S3, Staples M4,5, Lassere M6, March L7.(PubMed)
(106) Decreasing incidence of symptomatic gastrointestinal ulcers and ulcer complications in patients with rheumatoid arthritis by Steen KS1, Nurmohamed MT, Visman I, Heijerman M, Boers M, Dijkmans BA, Lems WF.(PubMed)
(107) Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal ulcer in patients with rheumatoid arthritis in Japan by Tanaka E1, Singh G, Saito A, Syouji A, Yamada T, Urano W, Nakajima A, Taniguchi A, Tomatsu T, Hara M, Saito T, Kamatani N, Yamanaka H.(PubMed)
(108) Early rheumatoid arthritis: strategies for prevention and management by Combe B1.(PubMed)
(109) Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study by Gan RW1, Young KA1, Zerbe GO2, Demoruelle MK3, Weisman MH4, Buckner JH5, Gregersen PK6, Mikuls TR7, O'Dell JR7, Keating RM8, Clare-Salzler MJ9,Deane KD3, Holers VM3, Norris JM10.(PubMed)
(109) Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study by Gan RW1, Young KA1, Zerbe GO2, Demoruelle MK3, Weisman MH4, Buckner JH5, Gregersen PK6, Mikuls TR7, O'Dell JR7, Keating RM8, Clare-Salzler MJ9,Deane KD3, Holers VM3, Norris JM10.(PubMed)
(110) The effect of weight loss and dietary fatty acids on inflammation by Devaraj S1, Kasim-Karakas S, Jialal I.(PubMed)
(111) 4 Natural Remedies for Rheumatoid Arthritis(About health)
(112) Critical review: vegetables and fruit in the prevention of chronic diseases by Boeing H1, Bechthold A, Bub A, Ellinger S, Haller D, Kroke A, Leschik-Bonnet E, Müller MJ, Oberritter H, Schulze M, Stehle P, Watzl B.(PubMed)
(113) Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults by Bhupathiraju SN1, Tucker KL.(PubMed)
(114) A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow by McKellar G1, Morrison E, McEntegart A, Hampson R, Tierney A, Mackle G, Scoular J, Scott JA, Capell HA.(PubMed)
(115) Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium by Kremer JM1, Bigaouette J.(PubMed)
(116) [Role of diet on chronic inflammation prevention and control - current evidences].[Article in Portuguese] by Geraldo JM1, Alfenas Rde C.(PubMed)
(117) Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis by Baker JF1, Billig E2, Michaud K3, Ibrahim S1, Caplan L4, Cannon GW5, Stokes A6, Majithia V7, Mikuls TR8.(PubMed)
(118) Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation by Escalante A1, Haas RW, del Rincón I.(PubMed)
(119) The diet-induced proinflammatory state: a cause of chronic pain and other degenerative diseases? by Seaman DR.(PubMed)
(120) Osteoarthritis and rheumatoid arthritis pannus have similar qualitative metabolic characteristics and pro-inflammatory cytokine response by Furuzawa-Carballeda J1, Macip-Rodríguez PM, Cabral AR.(PubMed)
(121) Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis by Adam O1, Beringer C, Kless T, Lemmen C, Adam A, Wiseman M, Adam P, Klimmek R, Forth W.(PubMed)
(122) Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects by Kremer JM1, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE, Sherman M.(PubMed)
(123) The Effect of Stopping Smoking on Disease Activity in Rheumatoid Arthritis (RA). Data from BARFOT, a Multicenter Study of Early RA by Andersson ML1, Bergman S, Söderlin MK.(PubMed)
(124) Rheumatoid arthritis and occupation by SNORRASON E.(PubMed)
(125) Occupation, occupational exposure to chemicals and rheumatological disease. A register based cohort study by Lundberg I1, Alfredsson L, Plato N, Sverdrup B, Klareskog L, Kleinau S.(PubMed)
(126) Habitual Physical Activity, Sedentary Behaviour and Bone Health in Rheumatoid Arthritis by Prioreschi A1, Makda MA2, Tikly M2, McVeigh JA1.(PubMed)
(111) 4 Natural Remedies for Rheumatoid Arthritis(About health)
(112) Critical review: vegetables and fruit in the prevention of chronic diseases by Boeing H1, Bechthold A, Bub A, Ellinger S, Haller D, Kroke A, Leschik-Bonnet E, Müller MJ, Oberritter H, Schulze M, Stehle P, Watzl B.(PubMed)
(113) Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults by Bhupathiraju SN1, Tucker KL.(PubMed)
(114) A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow by McKellar G1, Morrison E, McEntegart A, Hampson R, Tierney A, Mackle G, Scoular J, Scott JA, Capell HA.(PubMed)
(115) Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium by Kremer JM1, Bigaouette J.(PubMed)
(116) [Role of diet on chronic inflammation prevention and control - current evidences].[Article in Portuguese] by Geraldo JM1, Alfenas Rde C.(PubMed)
(117) Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis by Baker JF1, Billig E2, Michaud K3, Ibrahim S1, Caplan L4, Cannon GW5, Stokes A6, Majithia V7, Mikuls TR8.(PubMed)
(118) Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation by Escalante A1, Haas RW, del Rincón I.(PubMed)
(119) The diet-induced proinflammatory state: a cause of chronic pain and other degenerative diseases? by Seaman DR.(PubMed)
(120) Osteoarthritis and rheumatoid arthritis pannus have similar qualitative metabolic characteristics and pro-inflammatory cytokine response by Furuzawa-Carballeda J1, Macip-Rodríguez PM, Cabral AR.(PubMed)
(121) Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis by Adam O1, Beringer C, Kless T, Lemmen C, Adam A, Wiseman M, Adam P, Klimmek R, Forth W.(PubMed)
(122) Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects by Kremer JM1, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE, Sherman M.(PubMed)
(123) The Effect of Stopping Smoking on Disease Activity in Rheumatoid Arthritis (RA). Data from BARFOT, a Multicenter Study of Early RA by Andersson ML1, Bergman S, Söderlin MK.(PubMed)
(124) Rheumatoid arthritis and occupation by SNORRASON E.(PubMed)
(125) Occupation, occupational exposure to chemicals and rheumatological disease. A register based cohort study by Lundberg I1, Alfredsson L, Plato N, Sverdrup B, Klareskog L, Kleinau S.(PubMed)
(126) Habitual Physical Activity, Sedentary Behaviour and Bone Health in Rheumatoid Arthritis by Prioreschi A1, Makda MA2, Tikly M2, McVeigh JA1.(PubMed)
(127) Yoga as a method of symptom management in multiple sclerosis by Frank R1, Larimore J1.(PubMed)
(128) The effects of mind-body therapies on the immune system: meta-analysis by Morgan N1, Irwin MR2, Chung M3, Wang C1.(PubMed)
(129) Protective effect of soy protein on collagen-induced arthritis in rat by Mohammad Shahi M1, Rashidi MR, Mahboob S, Haidari F, Rashidi B, Hanaee J.(PubMed)
(130) Genistein suppresses tumor necrosis factor α-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor κB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells by Li J1, Li J2, Yue Y1, Hu Y1, Cheng W1, Liu R3, Pan X4, Zhang P1.(PubMed)
(131) Soy protein, genistein, and daidzein improve serum paraoxonase activity and lipid profiles in rheumatoid arthritisin rats by Mohammadshahi M1, Haidari F, Saei AA, Rashidi B, Mahboob S, Rashidi MR.(PubMed)
(132) Green Tea Epigallocatechin-3-Gallate Suppresses Autoimmune Arthritis Through Indoleamine-2,3-Dioxygenase Expressing Dendritic Cells and the Nuclear Factor, Erythroid 2-Like 2 Antioxidant Pathway by Min SY1, Yan M1, Kim SB2, Ravikumar S3, Kwon SR4, Vanarsa K3, Kim HY5, Davis LS1, Mohan C3.(PubMed)
(133) Anti-inflammatory activity of green versus black tea aqueous extract in a rat model of human rheumatoid arthritis by Ramadan G1, El-Beih NM1, Talaat RM2, Abd El-Ghffar EA1.(PubMed)
(134) Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise by Ahmed S1.(PubMed)
(135) The effect of olive oil and fish consumption on rheumatoid arthritis--a case control study by Linos A1, Kaklamanis E, Kontomerkos A, Koumantaki Y, Gazi S, Vaiopoulos G, Tsokos GC, Kaklamanis P.(PubMed)
(136) Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables? by Linos A1, Kaklamani VG, Kaklamani E, Koumantaki Y, Giziaki E, Papazoglou S, Mantzoros CS.(PubMed)
(137) Anti-inflammatory and joint protective effects of extra-virgin olive-oil polyphenol extract in experimental arthritis by Rosillo MÁ1, Alcaraz MJ2, Sánchez-Hidalgo M1, Fernández-Bolaños JG3,(PubMed)
(138) Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study. by Gan RW1, Young KA1, Zerbe GO2, Demoruelle MK3, Weisman MH4, Buckner JH5, Gregersen PK6, Mikuls TR7, O'Dell JR7, Keating RM8, Clare-Salzler MJ9,Deane KD3, Holers VM3, Norris JM10. Alarcón-de-la-Lastra C1, Ferrándiz ML4.(PubMed)
(139) Attenuation of collagen-induced arthritis in mice by salmon proteoglycan by Yoshimura S1, Asano K1, Nakane A1.(PubMed)
(140) An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis by Ryan SM1, McMorrow J, Umerska A, Patel HB, Kornerup KN, Tajber L, Murphy EP, Perretti M, Corrigan OI, Brayden DJ.(PubMed)
(141) Comparative effects of two gingerol-containing Zingiber officinale extracts on experimental rheumatoid arthritis by Funk JL1, Frye JB, Oyarzo JN, Timmermann BN.(PubMed)
(142) Zingiber officinale: A Potential Plant against Rheumatoid Arthritis by Al-Nahain A1, Jahan R2, Rahmatullah M1.(PubMed)
(143) Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation by Satoskar RR, Shah SJ, Shenoy SG.(PubMed)
(144) Curcumin Mimics the Neurocognitive and Anti-Inflammatory Effects of Caloric Restriction in a Mouse Model of Midlife Obesity by Sarker MR1, Franks S2, Sumien N1, Thangthaeng N1, Filipetto F2, Forster M1.(PubMed)
(145) Curcumin and Apigenin - novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease by Venigalla M1, Gyengesi E2, Münch G3(PubMed)
(146) Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease by Venigalla M1, Gyengesi E2, Sharman MJ3, Münch G4(PubMed)
(147) A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis by Chandran B1, Goel A.(PubMed)
(148) Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine by Yang Y1, Wu X2, Wei Z2, Dou Y2, Zhao D3, Wang T2, Bian D2, Tong B2, Xia Y2, Xia Y4, Dai Y5(PubMed)
(149) Evaluation of in vitro anti-inflammatory effects of crude ginger and rosemary extracts obtained through supercritical CO2 extraction on macrophage and tumor cell line: the influence of vehicle type by Justo OR1, Simioni PU2, Gabriel DL2, Tamashiro WM2, Rosa Pde T3, Moraes ÂM4.(PubMed)
(150) Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol by Dugasani S1, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN.(PubMed)
(151) Antioxidant properties of gingerol related compounds from ginger by Masuda Y1, Kikuzaki H, Hisamoto M, Nakatani N.(PubMed)
(152) Protective effects of ginger-turmeric rhizomes mixture on joint inflammation, atherogenesis, kidney dysfunction and other complications in a rat model of human rheumatoid arthritis by Ramadan G1, El-Menshawy O.(PubMed)
(153) Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis by Ramadan G1, Al-Kahtani MA, El-Sayed WM.(PubMed)
(154) Antioxidant and Anti-Inflammatory Activity Determination of One Hundred Kinds of Pure Chemical Compounds Using Offline and Online Screening HPLC Assay by Lee KJ1, Oh YC1, Cho WK1, Ma JY1.(PubMed)
(155) Radical-scavenging and Anti-inflammatory Activity of Quercetin and Related Compounds and Their Combinations Against RAW264.7 Cells Stimulated with Porphyromonas gingivalis Fimbriae. Relationships between Anti-inflammatory Activity and Quantum Chemical Parameters by Murakami Y1, Kawata A2, Ito S3, Katayama T2, Fujisawa S2(PubMed)
(156) Quercetin reduced inflammation and increased antioxidant defense in rat adjuvant arthritis by Gardi C1, Bauerova K2, Stringa B3, Kuncirova V4, Slovak L4, Ponist S4, Drafi F4, Bezakova L5, Tedesco I6, Acquaviva A3, Bilotto S6, Russo GL7.(PubMed)
(157) Quercetin: a potential natural drug for adjuvant treatment of rheumatoid arthritis by Ji JJ1, Lin Y, Huang SS, Zhang HL, Diao YP, Li K.(PubMed)
(158) Green tea polyphenols and their potential role in health and disease by Afzal M1, Safer AM, Menon M.(PubMed)
(159) Mitochondrial modulation by Epigallocatechin 3-Gallate ameliorates cisplatin induced renal injury through decreasing oxidative/nitrative stress, inflammation and NF-kB in micebyPan H1, Chen J2, Shen K3, Wang X1, Wang P1, Fu G1, Meng H1, Wang Y1, Jin B1.(PubMed)
(160) Green Tea Epigallocatechin-3-Gallate Suppresses Autoimmune Arthritis Through Indoleamine-2,3-Dioxygenase Expressing Dendritic Cells and the Nuclear Factor, Erythroid 2-Like 2 Antioxidant Pathway by Min SY1, Yan M1, Kim SB2, Ravikumar S3, Kwon SR4, Vanarsa K3, Kim HY5, Davis LS1, Mohan C3.(PubMed)
(161) Effect of green tea extract and vitamin C on oxidant or antioxidant status of rheumatoid arthritis rat model by Meki AR1, Hamed EA, Ezam KA(PubMed)
(162) Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis.
Al-Okbi SY1(PubMed)
(162) Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis.
Al-Okbi SY1(PubMed)
(163) Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis by Rosenbaum CC1, O'Mathúna DP, Chavez M, Shields K.(PubMed)
(164) Effects of diets containing fish oil and vitamin E on rheumatoid arthritis. by Tidow-Kebritchi S1, Mobarhan S.(PubMed)
(165) Effect of conjugated linoleic Acid, vitamin e, alone or combined on immunity and inflammatory parameters in adults with active rheumatoid arthritis: a randomized controlled trial. by Aryaeian N1, Djalali M2, Shahram F3, Djazayery A4, Eshragian MR5(PubMed)
(166)Intake of antioxidants in patients with rheumatoid arthritis by Silva BN1, Araújo ÍL1, Queiroz PM2, Duarte AL3, Burgos MG4.(PubMed)
(167) Effects of glucosamine administration on patients with rheumatoid arthritis by Nakamura H1, Masuko K, Yudoh K, Kato T, Kamada T, Kawahara T.(PubMed)
(168) Effects of an oral administration of glucosamine-chondroitin-quercetin glucoside on the synovial fluid properties in patients with osteoarthritis and rheumatoid arthritis by Matsuno H1, Nakamura H, Katayama K, Hayashi S, Kano S, Yudoh K, Kiso Y.(PubMed)
(169) The anti-arthritic and immune-modulatory effects of NHAG: a novel glucosamine analogue in adjuvant-induced arthritis by Shah SU1, Jawed H, Awan SI, Anjum S, Simjee SU.(PubMed)
(170) The "MESACA" study: methylsulfonylmethane and boswellic acids in the treatment of gonarthrosis by Notarnicola A1, Tafuri S, Fusaro L, Moretti L, Pesce V, Moretti B.(PubMed)
(171) The effectiveness of Echinacea extract or composite glucosamine, chondroitin and methyl sulfonyl methane supplements on acute and chronic rheumatoid arthritis rat model by Arafa NM1, Hamuda HM, Melek ST, Darwish SK.(PubMed)
(172) Juvenile rheumatoid arthritis: physical therapy and rehabilitation by Cakmak A1, Bolukbas N.(PubMed)
(173) Effects of Whole-Body Cryotherapy in Comparison with Other Physical Modalities Used with Kinesitherapy inRheumatoid Arthritis by Gizińska M1, Rutkowski R1, Romanowski W2, Lewandowski J3, Straburzyńska-Lupa A4.(PubMed)
(174) Rheumatoid arthritis: a study of relaxation and temperature biofeedback training as an adjunctive therapy by Achterberg J, McGraw P, Lawlis GF.(PubMed)
(175) Psychological interventions for rheumatoid arthritis: a meta-analysis of randomized controlled trials by Astin JA1, Beckner W, Soeken K, Hochberg MC, Berman B.(PubMed)
(176) Psychological interventions for rheumatoid arthritis: examining the role of self-regulation with a systematic review and meta-analysis of randomized controlled trials by Knittle K1, Maes S, de Gucht V.(PubMed)
(177) Low-level laser therapy in different stages of rheumatoid arthritis: a histological study by Alves AC1, de Carvalho PT, Parente M, Xavier M, Frigo L, Aimbire F, Leal Junior EC, Albertini R.(PubMed)
(178) Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation by Alves AC, Vieira R, Leal-Junior E, dos Santos S, Ligeiro AP, Albertini R, Junior J, de Carvalho P.(PubMed)
(179) [The influence of intravenous laser therapy on the endothelial function and the state of microcirculation in the patients presenting with rheumatoid arthritis].[Article in Russian] by Kulova LA, Burduli NM.(PubMed)
(180) Assessment of the effectiveness of low-level laser therapy on the hands of patients with rheumatoid arthritis: a randomized double-blind controlled trial by Meireles SM1, Jones A, Jennings F, Suda AL, Parizotto NA, Natour J.(PubMed)
(181) What is occupation therapy(Canadian association of occupation therapy)
(182) Occupational therapy for rheumatoid arthritis by Steultjens EM1, Dekker J, Bouter LM, van Schaardenburg D, van Kuyk MA, van den Ende CH.(PubMed)
(183) [Occupational therapy in rheumatoid arthritis: what rheumatologists need to know?].[Article in Portuguese] by de Almeida PH1, Pontes TB2, Matheus JP2, Muniz LF3, da Mota LM3.(PubMed)
(184) Effects of Prosorba column apheresis in patients with chronic refractory rheumatoid arthritis by
Roth S1(PubMed)
(175) Psychological interventions for rheumatoid arthritis: a meta-analysis of randomized controlled trials by Astin JA1, Beckner W, Soeken K, Hochberg MC, Berman B.(PubMed)
(176) Psychological interventions for rheumatoid arthritis: examining the role of self-regulation with a systematic review and meta-analysis of randomized controlled trials by Knittle K1, Maes S, de Gucht V.(PubMed)
(177) Low-level laser therapy in different stages of rheumatoid arthritis: a histological study by Alves AC1, de Carvalho PT, Parente M, Xavier M, Frigo L, Aimbire F, Leal Junior EC, Albertini R.(PubMed)
(178) Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation by Alves AC, Vieira R, Leal-Junior E, dos Santos S, Ligeiro AP, Albertini R, Junior J, de Carvalho P.(PubMed)
(179) [The influence of intravenous laser therapy on the endothelial function and the state of microcirculation in the patients presenting with rheumatoid arthritis].[Article in Russian] by Kulova LA, Burduli NM.(PubMed)
(180) Assessment of the effectiveness of low-level laser therapy on the hands of patients with rheumatoid arthritis: a randomized double-blind controlled trial by Meireles SM1, Jones A, Jennings F, Suda AL, Parizotto NA, Natour J.(PubMed)
(181) What is occupation therapy(Canadian association of occupation therapy)
(182) Occupational therapy for rheumatoid arthritis by Steultjens EM1, Dekker J, Bouter LM, van Schaardenburg D, van Kuyk MA, van den Ende CH.(PubMed)
(183) [Occupational therapy in rheumatoid arthritis: what rheumatologists need to know?].[Article in Portuguese] by de Almeida PH1, Pontes TB2, Matheus JP2, Muniz LF3, da Mota LM3.(PubMed)
(184) Effects of Prosorba column apheresis in patients with chronic refractory rheumatoid arthritis by
Roth S1(PubMed)
(185) A randomized double-blind sham-controlled trial of the Prosorba column for treatment of refractory rheumatoid arthritis by Gendreau RM1; Prosorba Clinical Trial Group(PubMed)
(186) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis andrheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study by Silverstein FE1, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS.(PubMed)
(187) Paracetamol versus nonsteroidal anti-inflammatory drugs for rheumatoid arthritis by Wienecke T1, Gøtzsche PC.(PubMed)
(188) How corticosteroids control inflammation: Quintiles Prize Lecture 2005 by Barnes PJ1.(PubMed)
(189) Use of corticosteroids in patients with rheumatoid arthritis treated with infliximab: treatment implications based on a real-world Canadian population by Haraoui B1, Jovaisas A2, Bensen WG3, Faraawi R3, Kelsall J4, Dixit S3, Rodrigues J5, Sheriff M6, Rampakakis E7, Sampalis JS7, Lehman AJ8, Otawa S8,Nantel F8, Shawi M8.(PubMed)
(190) Adverse effects of corticosteroids on bone metabolism: a review by Mitra R1.(PubMed)
(191) Adverse effects of inhaled corticosteroids by Hanania NA1, Chapman KR, Kesten S.(PubMed)
(191) Adverse effects of corticosteroids on the cardiovascular system by Sholter DE1, Armstrong PW.(PubMed)
(192) Delayed-release prednisone improves fatigue and health-related quality of life: findings from the CAPRA-2 double-blind randomised study in rheumatoid arthritis by Alten R1, Grahn A2, Holt RJ3, Rice P4, Buttgereit F5.(PubMed)
(193) Side effects of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy for breast cancer by Sitzia J1, Huggins L.(PubMed)
(194) Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis by Shea B1, Swinden MV2, Ghogomu ET2, Ortiz Z2, Katchamart W2, Rader T2, Bombardier C2, Wells GA2, Tugwell P2.(PubMed)
(195) Biologics in rheumatoid arthritis: where are we going? by Fechtenbaum M1, Nam JL, Emery P.(PubMed)
(196) Use of biologics in rheumatoid arthritis: where are we going? by Pucino F Jr1, Harbus PT, Goldbach-Mansky R.(PubMed)
(197) [Efficacy and safety of abatacept in patients with rheumatoid arthritis and no prior treatment with biologics].[Article in Spanish] by Escudero Contreras A1, Castro-Villegas MC, Hernández-Hernández MV, Díaz-González F.(PubMed)
(198) Complement activation and C3b deposition on rituximab-opsonized cells substantially blocks binding of phycoerythrin-labeled anti-mouse IgG probes to rituximab by Beum PV1, Kennedy AD, Li Y, Pawluczkowycz AW, Williams ME, Taylor RP.(PubMed)
(199) Infections and biological therapy in rheumatoid arthritis by Cunnane G1, Doran M, Bresnihan B.(PubMed)
(200) Transcription factors: An overview by David S. Latchman(Science direct)
(201) Selective JAK inhibitors in development for rheumatoid arthritis by Norman P1.(PubMed)
(202) Targeting the Janus kinases in rheumatoid arthritis: focus on tofacitinib by Yamaoka K1, Tanaka Y.(PubMed)
(203) Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery by Grennan DM1, Gray J, Loudon J, Fear S.(PubMed)
(204) 2012 Brazilian Society of Rheumatology Consensus for the treatment of rheumatoid arthritis.[Article in English, Portuguese] by da Mota LM1, Cruz BA, Brenol CV, Pereira IA, Rezende-Fronza LS, Bertolo MB, de Freitas MV, da Silva NA, Louzada-Júnior P, Giorgi RD, Lima RA, da Rocha Castelar Pinheiro G; Brazilian Society of Rheumatology.(PubMed)
(205) Lifestyle modifications to improve musculoskeletal and bone health and reduce disability--a life-course approach by Jones G1, Winzenberg TM2, Callisaya ML3, Laslett LL4.(PubMed)
(206) Cost analysis of biologic drugs in rheumatoid arthritis first line treatment after methotrexate failure according to patients' body weight.[Article in English, Spanish] by Román Ivorra JA1, Ivorra J1, Monte-Boquet E2, Canal C3, Oyagüez I4, Gómez-Barrera M5.(PubMed)
(207) Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation by Escalante A1, Haas RW, del Rincón I.(PubMed)
(208) Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis. by Baker JF1, Billig E2, Michaud K3, Ibrahim S1, Caplan L4, Cannon GW5, Stokes A6, Majithia V7, Mikuls TR8.(PubMed)
(209) Contribution of obesity to the rise in incidence of rheumatoid arthritis by Crowson CS1, Matteson EL, Davis JM 3rd, Gabriel SE.(PubMed)
(210) Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases by Pedersen BK1, Saltin B2.(PubMed)
(211) Evidence for prescribing exercise as therapy in chronic disease by Pedersen BK1, Saltin B.(PubMed)
(212) Dynamic exercise programs (aerobic capacity and/or muscle strength training) in patients with rheumatoid arthritis by Hurkmans E1, van der Giesen FJ, Vliet Vlieland TP, Schoones J, Van den Ende EC.(PubMed)
(213) Effects of a group-based exercise and educational program on physical performance and disease self-management in rheumatoid arthritis: a randomized controlled study by Breedland I1, van Scheppingen C, Leijsma M, Verheij-Jansen NP, van Weert E.(PubMed)
(214) Therapeutic exercise for rheumatoid arthritis and osteoarthritis by Semble EL1, Loeser RF, Wise CM.(PubMed)
(215) The lung in rheumatoid arthritis, cause or consequence? by Chatzidionisyou A1, Catrina AI.(PubMed)
(216) Cigarette smoking and rheumatoid arthritis severity by Saag KG1, Cerhan JR, Kolluri S, Ohashi K, Hunninghake GW, Schwartz DA.(PubMed)
(217) Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies by Sugiyama D1, Nishimura K, Tamaki K, Tsuji G, Nakazawa T, Morinobu A, Ku) .(PubMed)
(218) Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. by Heliövaara M1, Aho K, Knekt P, Impivaara O, Reunanen A, Aromaa A.magai S(PubMed)
(219) Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: results from the Iowa Women's Health Study by Mikuls TR1, Cerhan JR, Criswell LA, Merlino L, Mudano AS, Burma M, Folsom AR, Saag KG.(PubMed)
(220) Coffee consumption and risk of rheumatoid arthritis by Karlson EW1, Mandl LA, Aweh GN, Grodstein F.(PubMed)
(221) Alcohol consumption and risk of incident rheumatoid arthritis in women: a prospective study. by Lu B1, Solomon DH, Costenbader KH, Karlson EW.(PubMed)
(222) Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study by Di Giuseppe D1, Alfredsson L, Bottai M, Askling J, Wolk A.(PubMed)
(223) Psychological therapies for the management of chronic pain (excluding headache) in adults by Williams AC1, Eccleston C, Morley S.(PubMed)
(224) Psychological correlates of fatigue in rheumatoid arthritis: a systematic review by Matcham F1, Ali S2, Hotopf M3, Chalder T4.(PubMed)
(225) Low-grade chronic inflammation and vascular damage in patients with rheumatoid arthritis: don't forget "metabolic inflammation" by Jeppesen J.(PubMed)
(226) Interleukin-21 Induces Proliferation and Proinflammatory Cytokine Profile of Fibroblast-like Synoviocytes of Patients with Rheumatoid Arthritis by Xing R1, Yang L1, Jin Y1, Sun L1, Li C1, Li Z2, Zhao J1, Liu X1.(PubMed)
(227) [Garlic effectiveness in rheumatoid arthritis].[Article in Russian] by Denisov LN, Andrianova IV, Timofeeva SS.(PubMed)
(228) Allium sativum: facts and myths regarding human health by Majewski M.(PubMed)
(229) Influence of ginger and cinnamon intake on inflammation and muscle soreness endued by exercise in Iranian female athletes by Mashhadi NS1, Ghiasvand R, Askari G, Feizi A, Hariri M, Darvishi L, Barani A, Taghiyar M, Shiranian A, Hajishafiee M.(PubMed)
(230) Effect of sanhuangwuji powder, anti-rheumatic drugs, and ginger-partitioned acupoint stimulation on the treatment of rheumatoid arthritis with peptic ulcer: a randomized controlled study by Liu D, Guo M, Hu Y, Liu T, Yan J, Luo Y, Yun M, Yang M, Zhang J, Guo L.(PubMed)
(231) Zingiber officinale: A Potential Plant against Rheumatoid Arthritis by Al-Nahain A1, Jahan R2, Rahmatullah M1.(PubMed)
(232) Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition, Chapter 13Turmeric, the Golden Spice From Traditional Medicine to Modern Medicine by Sahdeo Prasad and Bharat B. Aggarwal(NCBI)
(233) The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats by Zheng Z1, Sun Y2, Liu Z1, Zhang M1, Li C1, Cai H3.(PubMed)
(234)Protective effects of ginger-turmeric rhizomes mixture on joint inflammation, atherogenesis, kidney dysfunction and other complications in a rat model of human rheumatoid arthritis by Ramadan G1, El-Menshawy O.(PubMed)
(235) Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis by Ramadan G1, Al-Kahtani MA, El-Sayed WM.(PubMed)
(236) Green Tea Epigallocatechin-3-Gallate Suppresses Autoimmune Arthritis Through Indoleamine-2,3-Dioxygenase Expressing Dendritic Cells and the Nuclear Factor, Erythroid 2-Like 2 Antioxidant Pathway by Min SY1, Yan M1, Kim SB2, Ravikumar S3, Kwon SR4, Vanarsa K3, Kim HY5, Davis LS1, Mohan C3.(PubMed)
(237) Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation inrheumatoid arthritis by Riegsecker S1, Wiczynski D, Kaplan MJ, Ahmed S.(PubMed)
(238) Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis by Al-Okbi SY1.(PubMed)
(239) A Phase II Randomized Trial of Lycopene-Rich Tomato Extract Among Men with High-Grade Prostatic Intraepithelial Neoplasia by Gann PH1, Deaton RJ1, Rueter EE1, van Breemen RB2, Nonn L1, Macias V1, Han M3, Ananthanarayanan V4.(PubMed)
(240) Lycopene/tomato consumption and the risk of prostate cancer: a systematic review and meta-analysis of prospective studies by Chen J1, Song Y, Zhang L.(PubMed)
(241) Anti-inflammatory activity of lycopene isolated from Chlorella marina on type II collagen induced arthritis in Sprague Dawley rats by Renju GL1, Muraleedhara Kurup G, Saritha Kumari CH.(PubMed)
(242) Antioxidant intake and risks of rheumatoid arthritis and systemic lupus erythematosus in women by Costenbader KH1, Kang JH, Karlson EW.(PubMed)
(243) An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis by Ryan SM1, McMorrow J, Umerska A, Patel HB, Kornerup KN, Tajber L, Murphy EP, Perretti M, Corrigan OI, Brayden DJ.(PubMed)
(244) The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin by Tascioglu F1, Colak O, Armagan O, Alatas O, Oner C.(PubMed)
(245) Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patients with active rheumatoid arthritis receiving low dose glucocorticoid therapy? by Kotaniemi A1, Piirainen H, Paimela L, Leirisalo-Repo M, Uoti-Reilama K, Lahdentausta P, Ruotsalainen P, Kataja M, Väisänen E, Kurki P.(PubMed)
(246) Attenuation of collagen-induced arthritis in mice by salmon proteoglycan by Yoshimura S1, Asano K1, Nakane A1.(PubMed)
(247) Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: an in vivo and in vitro study on lubricin expression by Musumeci G, Trovato FM, Pichler K, Weinberg AM, Loreto C, Castrogiovanni P.(PubMed)
(248) Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables? by Linos A1, Kaklamani VG, Kaklamani E, Koumantaki Y, Giziaki E, Papazoglou S, Mantzoros CS.(PubMed)
(249) Dietary extra-virgin olive oil prevents inflammatory response and cartilage matrix degradation in murine collagen-induced arthritis. by Rosillo MA1, Sánchez-Hidalgo M, Sánchez-Fidalgo S, Aparicio-Soto M, Villegas I, Alarcón-de-la-Lastra C.(PubMed)
(250) Protective effects of hydroxytyrosol-supplemented refined olive oil in animal models of acute inflammation andrheumatoid arthritis by Silva S1, Sepodes B2, Rocha J2, Direito R2, Fernandes A2, Brites D2, Freitas M3, Fernandes E3, Bronze MR1, Figueira ME4.(PubMed)
(251) [Importance of nutritional treatment in the inflammatory process of rheumatoid arthritis patients; a review].[Article in Spanish] by González Cernadas L1, Rodríguez-Romero B2, Carballo-Costa L2.(PubMed)
(252) Trace Minerals and Immunity in Beef Cattle by SQM
(253) Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium by Kremer JM1, Bigaouette J.(PubMed)
(254) Serum Levels of Copper and Zinc in Patients with Rheumatoid Arthritis: a Meta-analysis. by Xin L1, Yang X1, Cai G1, Fan D1, Xia Q1, Liu L1, Hu Y1, Ding N1, Xu S2, Wang L1, Li X1, Zou Y1, Pan F3.(PubMed)
(255) Effects of B-lymphocyte dysfunction on the serum copper, selenium and zinc levels of rheumatoid arthritispatients by Li J1, Liang Y2, Mao H3, Deng W4, Zhang J5.(PubMed)
(256) Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritisand osteoarthritis by Yazar M1, Sarban S, Kocyigit A, Isikan UE.(PubMed)
(257) Copper and immunity by Percival SS1(PubMed)
(258) Magnesium regulates antiviral immunity by Kirsty Minton(PubMed)
(259) MAGT1 by Genetic home reference
(260) Trace element and magnesium levels and superoxide dismutase activity in rheumatoid arthritis by Tuncer S1, Kamanli A, Akçil E, Kavas GO, Seçkin B, Atay MB.(PubMed)
(261) The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities by Huang Z1, Rose AH, Hoffmann PR.(PubMed)
(262) The Association Between Serum Selenium Levels with Rheumatoid Arthritis by Yu N1, Han F1, Lin X1, Tang C1, Ye J1, Cai X2.(PubMed)
(263) Selenium supplementation in rheumatoid arthritis investigated in a double blind, placebo-controlled trial by Peretz A1, Siderova V, Nève J.(PubMed)
(264) Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation by Wong CP1, Rinaldi NA, Ho E.(PubMed)
(265) Zinc and inflammatory/immune response in aging by Vasto S1, Mocchegiani E, Malavolta M, Cuppari I, Listì F, Nuzzo D, Ditta V, Candore G, Caruso C.(PubMed)
(266) Zinc and its role in immunity and inflammation by Bonaventura P1, Benedetti G1, Albarède F2, Miossec P3.(PubMed)
(267) Effects of dietary pyridoxine on immune responses in abalone, Haliotis discus hannai Ino by Chen H1, Mai K, Zhang W, Liufu Z, Xu W, Tan B.(PubMed)
(268) High dose dietary pyridoxine induces T-helper type 1 polarization and decreases contact hypersensitivity response to fluorescein isothiocyanate in mice by Kobayashi C1, Kurohane K, Imai Y.(PubMed)
(269) Biochemical deficiency of pyridoxine does not affect interleukin-2 production of lymphocytes from patients with Sjögren's syndrome by Tovar AR1, Gómez E, Bourges H, Ortíz V, Kraus A, Torres N.(PubMed)
(270) Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients withrheumatoid arthritis by Chiang EP1, Selhub J, Bagley PJ, Dallal G, Roubenoff R.(PubMed)
(271) Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis by Rosenbaum CC1, O'Mathúna DP, Chavez M, Shields K.(PubMed)
(272) The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials by Canter PH1, Wider B, Ernst E.(PubMed)
(272) The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials by Canter PH1, Wider B, Ernst E.(PubMed)
(273) Effects and mechanisms of vitamin A and vitamin E on the levels of serum leptin and other related cytokines in rats with rheumatoid arthritis by Xiong RB1, Li Q2, Wan WR1, Guo JQ1, Luo BD1, Gan L1.(PubMed)
(274) Beneficial role of antioxidants on clinical outcomes and erythrocyte antioxidant parameters in rheumatoid arthritis patients by Jalili M1, Kolahi S2, Aref-Hosseini SR3, Mamegani ME4, Hekmatdoost A5.(PubMed)
(275) Retinoic acid attenuates rheumatoid inflammation in mice by Kwok SK1, Park MK, Cho ML, Oh HJ, Park EM, Lee DG, Lee J, Kim HY, Park SH(PubMed)
(276) Effect of dietary vitamin C on the growth performance and innate immunity of juvenile cobia (Rachycentron canadum) by Zhou Q1, Wang L, Wang H, Xie F, Wang T.(PubMed)
(277) Effect of vitamin C supplements on cell-mediated immunity in old people by Kennes B, Dumont I, Brohee D, Hubert C, Neve P.(PubMed)
(278) Uric acid a better scavenger of free radicals than vitamin C in rheumatoid arthritis by Mahajan M1, Kaur S, Mahajan S, Kant R.(PubMed)
(279) Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis by Al-Okbi SY1(PubMed)
(280) Effects of diets containing fish oil and vitamin E on rheumatoid arthritis by Tidow-Kebritchi S1, Mobarhan S.(PubMed)
(281() Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis by Tulleken JE1, Limburg PC, Muskiet FA, van Rijswijk MH.(PubMed)
(282) Therapeutic efficacy of vitamin E δ-tocotrienol in collagen-induced rat model of arthritis by Haleagrahara N1, Swaminathan M2, Chakravarthi S3, Radhakrishnan A2.(PubMed)
(283) Beta-Carotene, Vitamin E, MDA, Glutathione Reductase and Arylesterase Activity Levels in Patients with ActiveRheumatoid Arthritis by Aryaeian N1, Djalali M, Shahram F, Jazayeri Sh, Chamari M, Nazari S.(PubMed)
(284) The vitamin D receptor regulates rheumatoid arthritis synovial fibroblast invasion and morphology. by Laragione T1, Shah A, Gulko PS.(PubMed)
(285) Vitamin D status and its association with quality of life, physical activity, and disease activity in rheumatoid arthritis patients by Raczkiewicz A1, Kisiel B, Kulig M, Tłustochowicz W.(PubMed)
(286) Vitamin D and rheumatoid arthritis by Kostoglou-Athanassiou I1, Athanassiou P, Lyraki A, Raftakis I, Antoniadis C.(PubMed)
(287) Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial by Shishavan NG1, Gargari BP, Kolahi S, Hajialilo M, Jafarabadi MA, Javadzadeh Y.(PubMed)
(288) Vitamin K and rheumatoid arthritis by Okamoto H1(PubMed)
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(290)
(291) Effects of glucosamine administration on patients with rheumatoid arthritis by Nakamura H1, Masuko K, Yudoh K, Kato T, Kamada T, Kawahara T.(PubMed)
(292) Effects of an oral administration of glucosamine-chondroitin-quercetin glucoside on the synovial fluid properties in patients with osteoarthritis and rheumatoid arthritis by Matsuno H1, Nakamura H, Katayama K, Hayashi S, Kano S, Yudoh K, Kiso Y.(PubMed)
(293) The anti-arthritic and immune-modulatory effects of NHAG: a novel glucosamine analogue in adjuvant-inducedarthritis by Shah SU1, Jawed H, Awan SI, Anjum S, Simjee SU.(PubMed)
(294)
(295) Effect of avocado/soybean unsaponifiables on ligature-induced bone loss and bone repair after ligature removal in rats by Oliveira GJ1, Paula LG1, Souza JA1, Spin-Neto R2, Stavropoulos A3, Marcantonio RA1.(PubMed)
(296) Selected CAM therapies for arthritis-related pain: the evidence from systematic reviews by Soeken KL1.(PubMed)
(297) Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases: an overview. by Mazza M1, Pomponi M, Janiri L, Bria P, Mazza S.(PubMed)
(298) Antioxidant, antimicrobial activities and fatty acid components of flower, leaf, stem and seed of Hypericum scabrum by Shafaghat A1(PubMed)
(299) Omega-3 Fatty Acids and Skeletal Muscle Health by Jeromson S1, Gallagher IJ2, Galloway SD3, Hamilton DL4(PubMed)
(300) [Effects of lymphatic drainage and omega-3 polyunsaturated fatty acids on intestinal ischemia-reperfusion injury in rats].[Article in Chinese] by Zhou KG1, He GZ, Zhang R, Chen XF(PubMed)
(301) Role of omega-3 fatty acid supplementation with indomethacin in suppression of disease activity in rheumatoid arthritis by Das Gupta AB1, Hossain AK, Islam MH, Dey SR, Khan AL.(PubMed)
(301a) Treatment of arthritis with topical capsaicin: a double-blind trial by Deal CL1, Schnitzer TJ, Lipstein E, Seibold JR, Stevens RM, Levy MD, Albert D, Renold F.(PubMed)
(302) Topical capsaicin in dermatologic and peripheral pain disorders by Rumsfield JA1, West DP.(PubMed)
(303) Neuromuscular electrostimulation techniques: historical aspects and current possibilities in treatment of pain and muscle waisting by Heidland A1, Fazeli G, Klassen A, Sebekova K, Hennemann H, Bahner U, Di Iorio B.(PubMed)
(304) [Combination of modern physiotherapeutic methods in rehabilitation of patients with osteoarthrosis andrheumatoid arthritis after arthroscopic surgery on the knee joint].[Article in Russian] by Men'shikova IV.(PubMed)
(302) Topical capsaicin in dermatologic and peripheral pain disorders by Rumsfield JA1, West DP.(PubMed)
(303) Neuromuscular electrostimulation techniques: historical aspects and current possibilities in treatment of pain and muscle waisting by Heidland A1, Fazeli G, Klassen A, Sebekova K, Hennemann H, Bahner U, Di Iorio B.(PubMed)
(304) [Combination of modern physiotherapeutic methods in rehabilitation of patients with osteoarthrosis andrheumatoid arthritis after arthroscopic surgery on the knee joint].[Article in Russian] by Men'shikova IV.(PubMed)
(305) Electrical stimulation for the treatment of rheumatoid arthritis by Brosseau LU1, Pelland LU, Casimiro LY, Robinson VI, Tugwell PE, Wells GE.(PubMed)
(306) Ice therapy: how good is the evidence? by Mac Auley DC1.(PubMed)
(307) What is the evidence for rest, ice, compression, and elevation therapy in the treatment of ankle sprains in adults? by van den Bekerom MP1, Struijs PA, Blankevoort L, Welling L, van Dijk CN, Kerkhoffs GM.(PubMed)
(308) Thermotherapy for treating rheumatoid arthritis by Robinson V1, Brosseau L, Casimiro L, Judd M, Shea B, Wells G, Tugwell P.(PubMed)(309) Thermotherapy for treating rheumatoid arthritis by Welch V1, Brosseau L, Shea B, McGowan J, Wells G, Tugwell P.(PubMed)
(310) Rheumatoid arthritis: failure of daily heat therapy to affect its progression by Mainardi CL, Walter JM, Spiegel PK, Goldkamp OG, Harris ED Jr.(PubMed)
(311) Treating arthritis with locally applied heat or cold by Oosterveld FG1, Rasker JJ.(PubMed)
(307) What is the evidence for rest, ice, compression, and elevation therapy in the treatment of ankle sprains in adults? by van den Bekerom MP1, Struijs PA, Blankevoort L, Welling L, van Dijk CN, Kerkhoffs GM.(PubMed)
(308) Thermotherapy for treating rheumatoid arthritis by Robinson V1, Brosseau L, Casimiro L, Judd M, Shea B, Wells G, Tugwell P.(PubMed)(309) Thermotherapy for treating rheumatoid arthritis by Welch V1, Brosseau L, Shea B, McGowan J, Wells G, Tugwell P.(PubMed)
(310) Rheumatoid arthritis: failure of daily heat therapy to affect its progression by Mainardi CL, Walter JM, Spiegel PK, Goldkamp OG, Harris ED Jr.(PubMed)
(311) Treating arthritis with locally applied heat or cold by Oosterveld FG1, Rasker JJ.(PubMed)
(312) Correlation between cold and hot pattern in traditional Chinese medicine and gene expression profiles inrheumatoid arthritis by Jiang M1, Xiao C, Chen G, Lu C, Zha Q, Yan X, Kong W, Xu S, Ju D, Xu P, Zou Y, Lu A.(PubMed)
(313)
(314)
(315) Acupuncture and electroacupuncture for the treatment of rheumatoid arthritis by Casimiro L1, Barnsley L, Brosseau L, Milne S, Robinson VA, Tugwell P, Wells G.(PubMed)
(316) Acupuncture for pain relief in patients with rheumatoid arthritis: a systematic review by Wang C1, de Pablo P, Chen X, Schmid C, McAlindon T.(PubMed)
(317)Acupuncture in the treatment of rheumatoid arthritis: a double-blind controlled pilot study.
Tam LS1, Leung PC, Li TK, Zhang L, Li EK.(PubMed)
(313)
(314)
(315) Acupuncture and electroacupuncture for the treatment of rheumatoid arthritis by Casimiro L1, Barnsley L, Brosseau L, Milne S, Robinson VA, Tugwell P, Wells G.(PubMed)
(316) Acupuncture for pain relief in patients with rheumatoid arthritis: a systematic review by Wang C1, de Pablo P, Chen X, Schmid C, McAlindon T.(PubMed)
(317)Acupuncture in the treatment of rheumatoid arthritis: a double-blind controlled pilot study.
Tam LS1, Leung PC, Li TK, Zhang L, Li EK.(PubMed)
(318) A pilot study of acupuncture as adjunctive treatment of rheumatoid arthritis by Zanette Sde A1, Born IG, Brenol JC, Xavier RM.(PubMed)
(319) Electroacupuncture attenuates collagen-induced arthritis in rats through vasoactive intestinal peptide signalling-dependent re-establishment of the regulatory T cell/T-helper 17 cell balance by Zhu J1, Chen XY1, Li LB2, Yu XT3, Zhou Y1, Yang WJ1, Liu Z1, Zhao N1, Fu C1, Zhang SH4, Chen YF5.(PubMed)
(320) The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease by Afzali B1, Lombardi G, Lechler RI, Lord GM.(PubMed)
(321)
(322) Juvenile rheumatoid arthritis: benefits from massage therapy by Field T1, Hernandez-Reif M, Seligman S, Krasnegor J, Sunshine W, Rivas-Chacon R, Schanberg S, Kuhn C.(PubMed)
(323) Massage therapy research review by Field T1.(PubMed)
(324) Rheumatoid arthritis in upper limbs benefits from moderate pressure massage therapy by Field T1, Diego M, Delgado J, Garcia D, Funk CG.(PubMed)
(325)
(326) Long-term benefits of radon spa therapy in rheumatic diseases: results of the randomised, multi-centre IMuRa trial by Annegret F1, Thomas F.(PubMed)
(327) Long-term benefits of radon spa therapy in rheumatic diseases: results of the randomised, multi-centre IMuRa trial by Annegret F1, Thomas F.(PubMed)
(328) Balneotherapy (or spa therapy) for rheumatoid arthritis by Verhagen AP1, Bierma-Zeinstra SM, Boers M, Cardoso JR, Lambeck J, de Bie R, de Vet HC.(PubMed)
(329) The effectiveness of hydrotherapy in the management of rheumatoid arthritis: a systematic review by Al-Qubaeissy KY1, Fatoye FA, Goodwin PC, Yohannes AM.(PubMed)
(330) A randomized and controlled trial of hydrotherapy in rheumatoid arthritis by Hall J, Skevington SM, Maddison PJ, Chapman K.(PubMed)
(331) [Influence of balneophysical therapy on activity, functional capacity, and quality of life in patients withrheumatoid arthritis].[Article in Serbian] by Stojanović S, Dimić A, Stamenković B, Stanković A, Nedović J.(PubMed)
(332) Tai chi for treating rheumatoid arthritis. by Han A1, Robinson V, Judd M, Taixiang W, Wells G, Tugwell P.(PubMed)
(333) Tai chi for rheumatoid arthritis: systematic review by Lee MS1, Pittler MH, Ernst E.(PubMed)
(334) Tai Chi exercise and auricular acupressure for people with rheumatoid arthritis: an evaluation study by Lee HY1, Hale CA, Hemingway B, Woolridge MW.(PubMed)
(335)
(336) Functional and physiological effects of yoga in women with rheumatoid arthritis: a pilot study. by Bosch PR1, Traustadóttir T, Howard P, Matt KS.(PubMed)
(337) Improvement in hand grip strength in normal volunteers and rheumatoid arthritis patients following yogatraining by Dash M1, Telles S.(PubMed)
(338) Yoga as an alternative and complementary approach for arthritis: a systematic review by Sharma M1.(PubMed)
(339) Yoga for rheumatic diseases: a systematic review by Cramer H1, Lauche R, Langhorst J, Dobos G.(PubMed)
(340) Expert consensus on the treatment of rheumatoid arthritis with Chinese patent medicines by Zhao J1, Zha Q, Jiang M, Cao H, Lu A(PubMed)
(341) Zingiber officinale: A Potential Plant against Rheumatoid Arthritis by Al-Nahain A1, Jahan R2, Rahmatullah M1.(PubMed)
(342)
(343) Effect of sanhuangwuji powder, anti-rheumatic drugs, and ginger-partitioned acupoint stimulation on the treatment of rheumatoid arthritis with peptic ulcer: a randomized controlled study by Liu D, Guo M, Hu Y, Liu T, Yan J, Luo Y, Yun M, Yang M, Zhang J, Guo L.(PubMed).
(344) Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis by Rosenbaum CC1, O'Mathúna DP, Chavez M, Shields K.(PubMed)
(345 Ginger: an ancient remedy and modern miracle drug by Hoffman T1(PubMed)
(346) Ginger--an herbal medicinal product with broad anti-inflammatory actions vy Grzanna R1, Lindmark L, Frondoza CG.(PubMed)
(347) Evening primrose oil and celecoxib inhibited pathological angiogenesis, inflammation, and oxidative stress in adjuvant-induced arthritis: novel role of angiopoietin-1. by El-Sayed RM1, Moustafa YM, El-Azab MF.(PubMed)
(348) Evening primrose oil by Bayles B1, Usatine R.(PubMed)
(349) Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs by Brzeski M1, Madhok R, Capell HA.(PubMed)
(350)
(351) Inhibition of proinflammatory biomarkers in THP1 macrophages by polyphenols derived from chamomile, meadowsweet and willow bark by Drummond EM1, Harbourne N, Marete E, Martyn D, Jacquier J, O'Riordan D, Gibney ER.(PubMed)
(352) An in vivo study examining the antiinflammatory effects of chamomile, meadowsweet, and willow bark in a novel functional beverage by Drummond EM1, Harbourne N, Marete E, Jacquier JC, O'Riordan D, Gibney ER.(PubMed)
(353) Efficacy and safety of willow bark extract in the treatment of osteoarthritis and rheumatoid arthritis: results of 2 randomized double-blind controlled trials by Biegert C1, Wagner I, Lüdtke R, Kötter I, Lohmüller C, Günaydin I, Taxis K, Heide L(PubMed)
(354) A systematic review on the effectiveness of willow bark for musculoskeletal pain by Vlachojannis JE1, Cameron M, Chrubasik S.(PubMed)
(355) Patient consensus on mode of use of nettle sting for musculoskeletal pain by White AR1, Randall C, Harding G, Paterson C.(PubMed)
(356) Scientific basis of botanical medicine as alternative remedies for rheumatoid arthritis by Yang CL1, Or TC, Ho MH, Lau AS.(PubMed)
(357) Antirheumatic effect of IDS 23, a stinging nettle leaf extract, on in vitro expression of T helper cytokines by Klingelhoefer S1, Obertreis B, Quast S, Behnke B.(PubMed)
(358) Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF-kappaB by Riehemann K1, Behnke B, Schulze-Osthoff K.(PubMed)
(359) A review of the efficacy and safety of devil's claw for pain associated with degenerative musculoskeletal diseases, rheumatoid, and osteoarthritis by Denner SS1.(PubMed)
(360) [Therapy of degenerative diseases of the musculoskeletal system with South African devil's claw(Harpagophytum procumbens DC)].[Article in German] by Wegener T1(PubMed)
(361) Selected CAM therapies for arthritis-related pain: the evidence from systematic reviews by Soeken KL1.(PubMed)
(362) Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis by Huang QC1, Wang MJ2, Chen XM1, Yu WL2, Chu YL1, He XH1, Huang RY1.(PubMed)
(363) Ascidian tunicate extracts attenuate rheumatoid arthritis in a collagen-induced murine model. by Hong SH, Kwone JT, Lee JH, Lee S, Lee AY, Cho WY, Bat-Erdene M, Choi BD, Cho MH.(PubMed)
(364) Glycyrol suppresses collagen-induced arthritis by regulating autoimmune and inflammatory responses by Fu Y1, Zhou H1, Wang S1, Wei Q1.(PubMed)
(365) Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis by Al-Okbi SY1.(PubMed)
(366) Evaluation of disease modifying activity of Coriandrum sativum in experimental models by Nair V1, Singh S, Gupta YK.(PubMed)
(367) Neuromodulators for pain management in rheumatoid arthritis by Richards BL1, Whittle SL, Buchbinder R.(PubMed)
(368) Treatment of arthritis with topical capsaicin: a double-blind trial by Deal CL1, Schnitzer TJ, Lipstein E, Seibold JR, Stevens RM, Levy MD, Albert D, Renold F.(PubMed)
(360) [Therapy of degenerative diseases of the musculoskeletal system with South African devil's claw(Harpagophytum procumbens DC)].[Article in German] by Wegener T1(PubMed)
(361) Selected CAM therapies for arthritis-related pain: the evidence from systematic reviews by Soeken KL1.(PubMed)
(362) Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis by Huang QC1, Wang MJ2, Chen XM1, Yu WL2, Chu YL1, He XH1, Huang RY1.(PubMed)
(363) Ascidian tunicate extracts attenuate rheumatoid arthritis in a collagen-induced murine model. by Hong SH, Kwone JT, Lee JH, Lee S, Lee AY, Cho WY, Bat-Erdene M, Choi BD, Cho MH.(PubMed)
(364) Glycyrol suppresses collagen-induced arthritis by regulating autoimmune and inflammatory responses by Fu Y1, Zhou H1, Wang S1, Wei Q1.(PubMed)
(365) Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis by Al-Okbi SY1.(PubMed)
(366) Evaluation of disease modifying activity of Coriandrum sativum in experimental models by Nair V1, Singh S, Gupta YK.(PubMed)
(367) Neuromodulators for pain management in rheumatoid arthritis by Richards BL1, Whittle SL, Buchbinder R.(PubMed)
(368) Treatment of arthritis with topical capsaicin: a double-blind trial by Deal CL1, Schnitzer TJ, Lipstein E, Seibold JR, Stevens RM, Levy MD, Albert D, Renold F.(PubMed)
(369) Green Tea Epigallocatechin-3-Gallate Suppresses Autoimmune Arthritis Through Indoleamine-2,3-Dioxygenase Expressing Dendritic Cells and the Nuclear Factor, Erythroid 2-Like 2 Antioxidant Pathway by Min SY1, Yan M1, Kim SB2, Ravikumar S3, Kwon SR4, Vanarsa K3, Kim HY5, Davis LS1, Mohan C3.(PubMed)
(370) Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation inrheumatoid arthritis by Riegsecker S1, Wiczynski D, Kaplan MJ, Ahmed S.(PubMed)
(371) Green tea EGCG, T cells, and T cell-mediated autoimmune diseases by Wu D1, Wang J, Pae M, Meydani SN.(PubMed)
(372) The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats by Zheng Z1, Sun Y2, Liu Z1, Zhang M1, Li C1, Cai H3.(PubMed)
(370) Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation inrheumatoid arthritis by Riegsecker S1, Wiczynski D, Kaplan MJ, Ahmed S.(PubMed)
(371) Green tea EGCG, T cells, and T cell-mediated autoimmune diseases by Wu D1, Wang J, Pae M, Meydani SN.(PubMed)
(372) The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats by Zheng Z1, Sun Y2, Liu Z1, Zhang M1, Li C1, Cai H3.(PubMed)
(373) Clinical utility of curcumin extract by Asher GN1, Spelman K.(PubMed)
(374) Curcumin in inflammatory diseases. by Shehzad A1, Rehman G, Lee YS.(PubMed)
(375) Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients withrheumatoid arthritis by Park C1, Moon DO, Choi IW, Choi BT, Nam TJ, Rhu CH, Kwon TK, Lee WH, Kim GY, Choi YH.(PubMed)
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(377) Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults by Walker AF1, Bundy R, Hicks SM, Middleton RW.(PubMed)
(378) Inhibitory effect of enzyme therapy and combination therapy with cyclosporin A on collagen-induced arthritis by Rovenská E1, Svík K, Stancíková M, Rovenský J.(PubMed)
(379) Activation of murine autoreactive b cells by interleukin 1-like factors released from synovial inflammatory cells ofrheumatoid arthritis patients by Bazzichi L1, Soletti AL, Ciompi ML, Garzelli C.(PubMed)
(380) Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis by Umar S1, Umar K2, Sarwar AH3, Khan A4, Ahmad N5, Ahmad S5, Katiyar CK6, Husain SA7, Khan HA8.(PubMed)
(381) Inhibition of LPS-induced TNF-α and NO production in mouse macrophage and inflammatory response in rat animal models by a novel Ayurvedic formulation, BV-9238 by Dey D1, Chaskar S, Athavale N, Chitre D(PubMed)
(381) Inhibition of LPS-induced TNF-α and NO production in mouse macrophage and inflammatory response in rat animal models by a novel Ayurvedic formulation, BV-9238 by Dey D1, Chaskar S, Athavale N, Chitre D(PubMed)
(382) Modulation of the immune system by Boswellia serrata extracts and boswellic acids by Ammon HP1(PubMed)
(383)
(384) Therapeutic effect of Cryptotanshinone on collagen-induced arthritis in rats via inhibiting nuclear factor kappa B signaling pathway by Wang Y1, Wang S1, Li Y1, Jiang J1, Zhou C1, Li C1, Li D1, Lu L1, Liu P1, Huang M1, Shen X2.(PubMed)
(385) Salvia miltiorrhiza injection restores apoptosis of fibroblast-like synoviocytes cultured with serum from patients with rheumatoid arthritis by Liu QS1, Luo XY2, Jiang H2, Xing Y3, Yang MH2, Yuan GH2, Tang Z3, Wang H1(PubMed)
(386) Inhibition of bone resorption by Tanshinone VI isolated from Salvia miltiorrhiza Bunge by Nicolin V, Dal Piaz F, Nori SL, Narducci P, De Tommasi N.(PubMed)
(387) Kynurenic acid content in anti-rheumatic herbs by Zgrajka W1, Turska M2, Rajtar G3, Majdan M4, Parada-Turska J4.(PubMed)
(388) The treatment of rheumatoid arthritis using Chinese Medicinal Plants: From pharmacology to potential molecular mechanisms by Lü S1, Wang Q2, Li G3, Sun S4, Guo Y4, Kuang H5.(PubMed)
(389) Effects of keishibukuryogan on vascular function in adjuvant-induced arthritis rats by Nozaki K1, Goto H, Nakagawa T, Hikiami H, Koizumi K, Shibahara N, Shimada Y.(PubMed)
(390) Identification of a predictive biomarker for the beneficial effect of a Kampo (Japanese traditional) medicinekeishibukuryogan in rheumatoid arthritis patients by Ogawa K1, Kojima T, Matsumoto C, Kamegai S, Oyama T, Shibagaki Y, Muramoto H, Kawasaki T, Fujinaga H, Takahashi K, Hikiami H, Goto H, Kiga C, Koizumi K, Sakurai H, Shimada Y, Yamamoto M, Terasawa K, Takeda S, Saiki I.(PubMed)
(391) Keishibukuryogan (gui-zhi-fu-ling-wan), a Kampo formula, decreases disease activity and soluble vascular adhesion molecule-1 in patients with rheumatoid arthritis by Nozaki K1, Hikiami H, Goto H, Nakagawa T, Shibahara N, Shimada Y.(PubMed)
(392) Microarray analysis reveals the molecular basis of antiarthritic activity of huo-luo-xiao-ling dan by Yu H1, Lee DY, Nanjundaiah SM, Venkatesha SH, Berman BM, Moudgil KD(PubMed)
(392) Suppression of ongoing experimental arthritis by a chinese herbal formula (huo-luo-xiao-ling dan) involves changes in antigen-induced immunological and biochemical mediators of inflammation by Yang YH1, Rajaiah R, Lee DY, Ma Z, Yu H, Fong HH, Lao L, Berman BM, Moudgil KD.(PubMed)
(394) Chinese Herbal Formula Huo-Luo-Xiao-Ling Dan Protects against Bone Damage in Adjuvant Arthritis by Modulating the Mediators of Bone Remodeling by Nanjundaiah SM1, Lee DY, Berman BM, Moudgil KD.(PubMed)
(395) Modified huo-luo-xiao-ling dan suppresses adjuvant arthritis by inhibiting chemokines and matrix-degrading enzymes by Nanjundaiah SM1, Lee DY, Ma Z, Fong HH, Lao L, Berman BM, Moudgil KD.(PubMed)
(396) Herbal therapy for treating rheumatoid arthritis by Cameron M1, Gagnier JJ, Chrubasik S.(PubMed)
(397) [Therapy of degenerative rheumatic diseases. Need for additional analgesic medication with Phytodolor N].[Article in German] by Huber B1.(PubMed)
(398). Phytodolor--effects and efficacy of a herbal medicine by Gundermann KJ1, Müller J.(PubMed)
(399) Metabonomic study of Wu-tou decoction in adjuvant-induced arthritis rat using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry by Qi Y1, Li S2, Pi Z3, Song F3, Lin N4, Liu S5, Liu Z6.(PubMed)
(400) Uncovering pharmacological mechanisms of Wu-tou decoction acting on rheumatoid arthritis through systems approaches: drug-target prediction, network analysis and experimental validatio by Yanqiong Zhang,1 Ming Bai,2 Bo Zhang,3 Chunfang Liu,1 Qiuyan Guo,1 Yanqun Sun,1 Danhua Wang,1 Chao Wang,1Yini Jiang,1 Na Lin,b,1 and Shao Lia,1,2(PMC)
(401) Chemical profiling of Wu-tou decoction by UPLC-Q-TOF-MS by Qi Y1, Li S, Pi Z, Song F, Lin N, Liu S, Liu Z.(PubMed)
(402) Wen Luo Yin inhibits angiogenesis in collagen-induced arthritis rat model and in vitro by Liu C1, Kong X, Li X, Guo W, Zhang C, Sun Y, Su X, Liu X, Lu A, Lin N(PubMed)
(403) Anti-arthritic effects of clematichinenoside (AR-6) on PI3K/Akt signaling pathway and TNF-α associated with collagen-induced arthritis by Han W1, Xiong Y, Li Y, Fang W, Ma Y, Liu L, Li F, Zhu X.(PubMed)
(404) Anti-inflammatory activities of Chinese herbal medicine sinomenine and Liang Miao San on tumor necrosis factor-α-activated human fibroblast-like synoviocytes in rheumatoid arthritis by Chen DP1, Wong CK, Leung PC, Fung KP, Lau CB, Lau CP, Li EK, Tam LS, Lam CW.(PubMed)
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Back to General health http://kylejnorton.blogspot.ca/p/general-health.html
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Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Back to General health http://kylejnorton.blogspot.ca/p/general-health.html
Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca
