Musculo-Skeletal Disorders - Polymalagia Arthritis by

Kyle J. Norton

Musculoskeletal disorders (MSDs) is 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. A major restriction of joint movement range was frequent in the shoulder but uncommon in other joints. A shoulder disorder was found in 27% of subjects, rheumatoid arthritis in 1% and osteoarthritis (OA) of the hand, hip, and knee in five, seven, and 18% of subjects, respectively. Disability was frequent: a walking distance of < 500 m was found in 60% and ADL dependency in 40% of the group. Factors related to one or both of these disability measures included female gender, hip and knee OA, impaired vision, cognitive impairment and neurological disease(1). IV. Polymalagia Arthritis Polymalagia Arthritis is defined as a condition a common inflammatory rheumatic disease which cause pain, stiffness and tenderness in large muscles, including muscles shoulders and pelvic girdleas a result of the presence of a synovitis in proximal joints and periarticular structures, causing musculoskeletal symptoms in PMR. A. Signs and Symptoms 1. In the study in Assessment and management of polymyalgia rheumatica in older adults, Dr. Kennedy-Malone LM, and Dr. Enevold GL. at the University of North Carolina School of Nursing in Greensbor, showed that Polymyalgia rheumatica (PMR) is a periarticular rheumatic condition characterized by pain and stiffness, primarily in the neck, shoulders, hips, and pelvic girdle. Temporal arteritis (TA) or giant cell arteritis, the most common primary vasculitis in older adults, is found in approximately 10% to 30% of people who have PMR. Left untreated, TA can result in sudden, irreversible blindness. Geriatric nurses need to familiarize themselves with these disorders to accurately assess and manage people with them(3). 2. Other symptoms include

a. Fever and lumbar pain There is a report of a71-year-old man consulted our Department of Orthopedics for fever and lumbar pain, which initially developed in early September 2000. Administration of NSAIDs resulted in the disappearance of lumbar pain. However, fever persisted. Administration of NSAIDs resulted in the disappearance of lumbar pain. However, fever persisted. The Creactive protein (CRP) level was persistently high. Therefore, on October 5, 2000, the patient was referred to our department. At the outpatient clinic, a detailed examination was performed. However, the etiology could not be determined. Repeated administration of NSAIDs resulted in pyretolysis, and the dose of NSAIDs was decreased from January 31, 2001. Severe fever appeared again, and inflammatory reaction also exacerbated. On March 11, 2001, muscular pain involving the bilateral shoulders and forearms suddenly developed. For diagnostic treatment, administration of prednisolone (PSL) at 10 mg/day was started. Muscular pain rapidly disappeared(4). b. In the study of Polymyalgia rheumatica(PMR), Dr. Kwiatkowska B,and Dr. Filipowicz-Sosnowska A. at the Eleonora Reicher Rheumatology Institute, Warszawa, Poland indicated that PMR is a rheumatic disease which mainly affects the elderly, and is seldom diagnosed in patients <50 years of age. The prevalence of polymyalgia rheumatica is approximately 16.8 to 53.7 per 100,000 of the population >50 years of age. Patients may present with spiking fever, malaise, fatigue, weight loss and other features suggesting inflammation, which in each case requires differential diagnosis from malignancies(5). Others indicated that Polymyalgia rheumatica is a common disease affecting the elderly population. Symptoms and signs are often nonspecific, including pain and stiffness in the proximal muscles, anorexia, fatigue, depression, weight loss, fever and temporal headaches(6). c. Etc. B. Causes and Rick factors B1. Causes The cause of PMR is not well understood, but researchers believe it is a result of the abnormal inflammatory activity of inflammatory cells and proteins of the immune system due to the presence of a synovitis in proximal joints and periarticular structures. 1. Genetic factors In the study to evaluate HLA-DRB1 associations in patients with

polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in the Spanish population, showed that he HLA-DRB1 alleles associated with susceptibility for developing PMR and GCA are different. Whether PMR with low ESR represents a different clinical subset of the disease should be clarified in a larger sample of patients. HLA-DRB1 genes might predict the presence of relapses in PMR, but they do not seem to be indicators of severe disease in GCA patients(7). 2. Environmental contagious factors In the review personal and published observations of giant cell (temporal) arteritis (GCA) or polymyal-gia rheumatica (PMR) with familial or conjugal aggregation and emphasise on epidemiological, clinical and genetic features of such cases, showed that familial aggregation of GCA and PMR accumulated data pointing to a genetic predisposition. However, environmental contagious factors could have trigger synchronous disease onset in up to one-fourth of the cases(8). 3. Giant cell arteritis Giant cell arteritis (GCA) is an inflammatory vasculopathy that involves large- and medium-sized arteries and can cause vision loss, stroke and aneurysms. GCA occurs in people aged >50 years and is more common in women. A higher incidence of the disease is observed in populations from Northern European countries. Polymyalgia rheumatica (PMR) is a periarticular inflammatory process manifesting as pain and stiffness in the neck, shoulders and pelvic girdle. PMR shares the same pattern of age and sex distribution as GCA. The pathophysiology of PMR and GCA is not completely understood, but the two conditions may be related and often occur concurrently(9) 4. Etc. B.2. Risk factors 1. Aging If you are over 50 years of age, you are at increased risk of Polymalagia Arthritis (PMR). Polymyalgia rheumatica is a rheumatic disease which mainly affects the elderly, and is seldom diagnosed in patients <50 years of age. The prevalence of polymyalgia rheumatica is approximately 16.8 to 53.7 per 100,000 of the population >50 years of age(10). 2. Diet In the study to investigate the association of red meat and other specific

dietary components in predicting the development of inflammatory polyarthritis, DR. Pattison DJ, and the research team at the University of Manchester, indicated that high level of red meat consumption may represent a novel risk factor for inflammatory arthritis or may act as a marker for a group of persons with an increased risk from other lifestyle causes(11). 3. Smoking In the study to examined the influence of smoking on disease outcome at 3 years among patients newly presenting with inflammatory polyarthritis (IP), indicated that Despite smokers being more likely to develop nodules and to be RF positive, current smokers did not have higher levels of radiologic damage, and had fewer swollen joints. We hypothesize that this could be due to either the effect of cigarette smoking on the inflammatory response or other factors (e.g., reduced physical activity in smokers) which may limit joint inflammation and damage(12). 4. Gender If you are women, you are at increased risk to develop Polymalagia Arthritis 5. Race Rheumatic diseases are common in China. In the study to clarify prevalence rates of common rheumatic diseases in China, using the World Health Organization-International League of Associations for Rheumatology COPCORD (Community Oriented Program for Control of Rheumatic Diseases) protocol and those that did not employ this protocol but were published in recognized journals were identified and analyzed. showed that the prevalence of rheumatic complaints varied with the locality surveyed. The prevalence of OA is comparable with that in Western countries but varies in terms of joint involvement. The prevalence of ankylosing spondylitis is similar to that in Caucasians. Except in Taiwan, the prevalence of RA in China is lower than that in developed countries. The prevalence of hyperuricemia and gout increased after the 1980s, but it remains lower than that in developed countries(13). 6. Etc. C. Complications 1. Visual complications

There is a report of Four case histories are reported in which patients with polymyalgia rheumatica (polymyalgia arteritic) developed evidence of cranial arteritis (in one case two years and in one six months) following withdrawal of steroid therapy after apparent cure(14). 2. Stroke Polymyalgia rheumatica (PMR) is a relatively common rheumatic disease, particularly in the elderly. Vasculitis is associated with PMR and theoretically makes such patients susceptible to vascular events such as stroke, according to study of researchers at the Taipei Medical University(15) 3. Low back pain and MRI-abnormalities Abnormalities in shoulder and hip joints are most common, but signs of cervical and lumbar interspinous bursitis might also be found in patients with PMR(16). 4. Cervical interspinous bursitis Cervical interspinous bursitis is a likely basis for discomfort in the neck of patients with PMR. The prominent inflammatory involvement of cervical bursae supports the hypothesis that PMR is a disorder of prominent involvement of extra-articular synovial structures. MRI evidence of interspinous cervical bursitis was found in all patients with PMR, and in three patients with fibromyalgia, in two with psoriatic spondylitis and one with cervical osteoarthritis(17). 5. Renal failure Renal involvement in PMR is extremely rare and very few cases of AA amyloidosis secondary to PMR have been described in literature. Dr. Javaid MM, and research team at the King's College Hospital NHS Foundation Trust, rpeort a case of a case of a patient with history PMR who developed nephrotic range proteinuria and rapidly deteriorating renal function secondary to AA amyloidosis within 18 months of the onset of symptoms of PMR. This case reinforces the association of PMR with secondary AA amyloidosis and highlights the importance of monitoring renal function in patients with PMR(18). 6. Perforated colonic diverticular disease Patients with polymyalgia may have perforated colonic diverticular disease which mimics their rheumatic pathology. In such cases steroid therapy,

which is the mainstay of polymyalgia therapy, can be detrimental. Primary and hospital practitioners are encouraged to be vigilant regarding nonspecific gastrointestinal symptoms and consider alternative diagnoses in those patients whose symptoms do not resolve with standard therapy, as this can lead to an overall better outcome(19) 7. Metastatic lymphoma There is a report of A 48-year-old HIV-positive woman presented with progressive pain and stiffness of both shoulders and hips. She was given the diagnosis of polymyalgia rheumatica (PMR) due to high erythrocyte sedimentation rate. However, a 1-week course of prednisolone failed to improve her symptoms. She later discovered a breast lump of which histopathological tissue was consistent with a diffuse large B-cell lymphoma. Whole body bone scan revealed multiple bony metastases(20). 8. Cancer Patients hospitalized for PMR and GCA had a marginally increased risk of cancer, with the highest risk noted for the first year after hospitalization. However, for specific cancers, such as skin cancer and leukaemia, the increases were still significant for patients diagnosed later than 1 year after hospitalization(21) 9. Etc. D. Diagnosis There is no specific test to diagnose polymyalgia rheumatica. The practice guideline for general practitioners (GPs) on polymyalgia rheumatica and temporal arteritis was published in February 2010 by the Dutch College of General Practitioners. This guideline provides GPs with recommendations for the diagnosis and treatment of polymyalgia rheumatica. After other disorders have been excluded, the diagnosis of 'polymyalgia rheumatica' is made in patients over the age of 50 who have bilateral pain in the neck and shoulder girdle and/or hip girdle that has lasted for longer than 4 weeks, morning stiffness that lasts longer than 60 minutes and an ESR > 40 mm in the first hour(22). Other researchers suggested that Diagnosis of rheumatologic disorders in the elderly is often complicated by the primary care clinician's inability to differentiate among similar manifestations of rheumatologic disorders, the presence of comorbid conditions, and symptoms attributed simply to aging. A major consequence of the aches and pains associated with rheumatologic disorders, including polymyalgia

rheumatica (PMR), is the impedance of activities of daily living, potentially leading to a loss of independence. PMR is common in the elderly. Often coexisting with PMR, temporal arteritis can lead to complications, including blindness, stroke, or cardiac sequelae. Timely detection and appropriate treatment of PMR in the elderly may improve quality of life, as well as deter irreversible problems. Patient education also has an important role(23). If you are suspected to develop Polymalagia Arthritis, after a general physical exam, including the examination of shoulder motion, or swelling of the joints in the wrists, hands, etc., certain tests may be necessary 1. Blood test(24) a. Erythrocyte sedimentation rate (ESR) is the blood test to exam the red blood cells in a test tube. he higher the ESR value is an indication of inflammation. b. C-reactive protein (CRP) Blood test measures the levels of C-reactive protein (CRP) produced by the liver in response to an injury or infection and people with polymyalgia rheumatic. c. Blod test for thrombocytes Patient with polymyalgia rheumatica have an unusually high number of thrombocytosis. On the other hand, People with anemic polymyalgia rheumatica have a lower number of red blood cells than normal. d. Rheumatoid factor (RF) RF is an antibody, a protein made by the immune system presented in the blood of people with rheumatoid arthritis, but not in the blood of people with polymyalgia rheumatica. 2. Biopsy Polymyalgia rheumatica is often associated with giant cell arteritis with biopsy by taking a small sample from the scalp artery in the emporal artery and examined under a microscope in a laboratory. Patients suspected of giant cell arteritis or polymyalgia rheumatica are often referred to the otolaryngologist for temporal artery biopsy. These patients may initially present to the otolaryngologist with symptoms referable to the head and neck(25). 3. Etc. E. Preventions In conventional medicine, there is no known way to prevent Polymalagia Arthritis, although progression of the disease usually can be stopped or

slowed by early, aggressive treatment. Since Polymalagia Arthritis is caused by inflammation pain, stiffness and tenderness in large muscles, including muscles shoulders and pelvic girdleas a result of the presence of a synovitis in proximal joints and periarticular structures. Diet with high in anti inflammatory and immunity enhancing foods, antioxidants and phytochemicals may provide protection and reduced risk of the disease. E.1. The do's and do not's list 1. Reduce intake of saturated and trans fat and increase intake of omega 3 fatty acids Although Limited studies have shown that certain dietary fatty acids (ie, oleic acid and alpha-linolenic acid) reduce biomarkers of inflammation. Most of the studies with fish oil supplementation have shown null effects, and conflicting results have been reported with saturated and trans fatty acids(26). Intake of high amount of saturated fat and trans fay can increase the production of inflammatory cytokines. Also There is reasonably strong evidence that omega-3 fatty acids may help people with rheumatoid arthritis. The 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. One of the ways it appears to work is by decreasing the production of inflammatory chemicals(27). 2. Increase intake of increasing the ratio of (n-3):(n-6) PUFA Coinciding with this increase in the ratio of (n-6):(n-3) PUFA are increases in chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer's disease (AD). By increasing the ratio of (n-3):(n-6) PUFA in the Western diet, reductions may be achieved in the incidence of these chronic inflammatory diseases(28). 2. Increase intake of fruit and vegetable In a cross-sectional study of 1200 Puerto Rican adults aged 45-75 y, we assessed FV intake with a food-frequency questionnaire, Dr. Bhupathiraju SN, and Dr.Tucker KL. at the Tufts University, showed that FV variety, but not quantity, appears to be important in reducing inflammation. Although the results are suggestive, larger studies are needed to confirm a possible association with CHD risk score(29). 3. Avoid high glycemic index diets Other studies suggested that the consumption of 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 and the reduction of the anti-inflammatory ones. Although the results are controversial, healthy dietary intakes with the reduction in fat intake (especially trans and saturated fat) and the increase in fruits, vegetables, and whole grain consumption seem to be associated with the improvement in subclinical inflammatory condition(30). 4. Reduced intake of pro inflammatory foods, such as sugar, dairy products, red meat and processed, meat, alcohol, artificial ingredients, refined products, etc. 5. Increase in take of anti inflammatory foods, such as fresh vegetables and fruits, seeds and sprouts whole grain, fish, turkey, chicken, legumes, etc. 6. Stop smoking As smoking are associated with increased of Polymalagia Arthritis. 7. Moderate exercise Moderate exercise enhances immune function in fighting against inflammation and increase the blood circulation to provide nutrients to the body's organs need 8. Etc. E.2. Foods to prevent Polymalagia Arthritis(PMR) 1. Soy In the study to examine the role of TK activity on the expression of the inducible nitric oxide (NO) synthase (iNOS), found that TK inhibition by genistein had no effect on the expression or nuclear translocation of the transcription factors interferon regulatory factor-1 and nuclear factor-KB, respectively, both of which have been implicated in transcriptional regulation of the human iNOS gene. Nuclear run-on analysis demonstrated that the effect of genistein on iNOS messenger RNA expression was not at the level of transcription, suggesting that posttranscriptional regulation of iNOS messenger RNA might be TK dependent. Isoflavones, such as genistein, are useful tools to dissect regulatory pathways in vitro and in vivo and may have potential use as novel antiinflammatory therapeutic agents(31). 2. Green tea Green tea contains more amount of antioxidants than any drinks or food with

the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world. a. Immune system a. 1. In the investigation of the immunomodulatory effects of decaffeinated green tea extract in rain bow of the study of "Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss)" by Sheikhzadeh N, Nofouzi K, Delazar A, Oushani AK.(32), researchers found that showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout(32). a.2. In the investigation of Green tea and Arthritis of the study of "Green tea polyphenol epigallocatechin 3-gallate in arthritis" by Ahmed S., researcher indicated that although these findings provide scientific evidence of the anti-rheumatic activity of EGCG, further preclinical studies are warranted before phase clinical trials could be initiated with confidence for patients with joint diseases(33). 3. 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. a. Olive oil phenolics In the evaluation of the olive oil phenolics of the Mediterranean diet and its lower incidence of atherosclerosis, cardiovascular disease, and certain types of cancer, found that olive oil phenolics have positive effects on certain physiological parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet and cellular function, and antimicrobial activity, according to "Chemistry and health of olive oil phenolics" by Cicerale S, Conlan XA, Sinclair AJ, Keast RS.(34) b. Antioxidants and weight loss In the analyzing the influence of a Mediterranean dietary pattern on plasma total antioxidant capacity (TAC) found that Mediterranean diet, especially rich in virgin olive oil, is associated with higher levels of plasma antioxidant capacity. Plasma TAC is related to a reduction in body weight after 3 years

of intervention in a high cardiovascular risk population with a Mediterranean-style diet rich in virgin olive oil, according to "A 3 years follow-up of a Mediterranean diet rich in virgin olive oil is associated with high plasma antioxidant capacity and reduced body weight gain" by Razquin C, Martinez JA, Martinez-Gonzalez MA, Mitjavila MT, Estruch R, Marti A.(35) 4. Salmon a. Antioxidants In the research of the antioxidant effect of vitamin E after ingestion of salmon found that that megadoses of vitamin E, far from having prooxidative activity, actually increase the anti-oxidative capacity of the liver, especially after ingestion of salmon oil, according to "Effects of megadoses of dietary vitamin E on the antioxidant status of rats fed lard or salmon oil" by Flader D, Brandsch C, Hirche F, Eder K.(36) b. Selenium Salmon contains trace minerals selenium which is essential for the healthy function of the thyroid and immune system as it increases the antioxidant defense system by fighting against the forming of free radicals and reduce the risk of irregular cells growth causes of tumor and cancer, according to the study of "Selenium in the immune system" by Arthur JR, McKenzie RC, Beckett GJ.,(37) c. Omega 3 fatty acids Omega 3 fatty acids is necessary to maintain the ratio of good and bad cholesterol, thus reducing the risk of cholesterol inflammation according to the study of "In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation" by Wang S, Wu D, Lamon-Fava S, Matthan NR, Honda KL, Lichtenstein AH., posted in PubMed (IV) and forming of free radical in the heart cells, leading to heart diseases. It also reduces the risk of plaque forming in the arterial wall, thus also decreasing the risk of stoke, according to the study of "N-3 vs. saturated fatty acids: effects on the arterial wall" by Sudheendran S, Chang CC, Deckelbaum RJ., posted in PubMed (38). 5. Circuit fruits Circuit fruit contain high amount of Quercetin which can reduce the risk of Rheumatoid Arthritis as a result of anti inflammatory and antioxidant effects a. Anti-Inflammatory

According to the study of `Antioxidant and Anti-Inflammatory Activities of Quercetin 7-O--D-Glucopyranoside from the Leaves of Brasenia schreberi.`by Legault J, Perron T, Mshvildadze V, Girard-Lalancette K, Perron S, Laprise C, Sirois P, Pichette A. (Source from Laboratory for Analysis and Separation of Plant Species (LASEVE), Universit du Qubec Chicoutimi , Chicoutimi, Qubec, Canada.), posted in PubMed, researchers found that some flavonoids have been reported to possess beneficial effects in cardiovascular and chronic inflammatory diseases associated with overproduction of nitric oxide. Quercetin-7-O--Dglucopyranoside possesses anti-inflammatory activity, inhibiting expression of inducible nitric oxide synthase and release of nitric oxide by lipopolysaccharide-stimulated RAW 264.7 macrophages in a dosedependent manner. Quercetin-7-O--D-glucopyranoside also inhibited overexpression of cyclooxygenase-2 and granulocyte macrophage-colonystimulating factor. b. Free radical scavenger In a study of `Dietary chromones as antioxidant agents-the structural variable.`by Dias MM, Machado NF, Marques MP. (Source from Research Unit "Molecular Physical Chemistry", University of Coimbra, Portugal.), posted in PubMed, researchers found that from the eighteen tested compounds, three-fisetin, luteolin and quercetin-are shown to act as effective antiradicals. Consistent structure-activity relationships (SARs) were established regarding the antioxidant role of this type of chromone-based system. 6. Turmeric Turmeric, principal curcuminoid of the popular Indian spice, a rhizomatous herbaceous perennial plant of the ginger family, Zingiberaceae, native to tropical South Asia. a. Anti inflammatory effects In a systematic review of the literature was to summarize the literature on the safety and anti-inflammatory activity of curcumin, found that curcumin has been demonstrated to be safe in six human trials and has demonstrated anti-inflammatory activity. It may exert its anti-inflammatory activity by inhibition of a number of different molecules that play a role in inflammation, according to "Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa)" by Chainani-Wu N (39) b. Antioxidants

In the research of a literature search (PubMed) of almost 1500 papers dealing with curcumin, most from recent years, with ll available abstracts were read and pproximately 300 full papers were reviewed, found that curcumin, a component of turmeric, has been shown to be non-toxic, to have antioxidant activity, and to inhibit such mediators of inflammation as NFkappaB, cyclooxygenase-2 (COX-2), lipooxygenase (LOX), and inducible nitric oxide synthase (iNOS). Significant preventive and/or curative effects have been observed in experimental animal models of a number of diseases, including arteriosclerosis, cancer, diabetes, respiratory, hepatic, pancreatic, intestinal and gastric diseases, neurodegenerative and eye diseases, "Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases" by Bengmark S. (40) 7. Etc. E.3. Phytochemicals to prevent Polymalagia Arthritis (PMR) 1. Green tea Polyphenols (-)-epigallocatechin-3-gallate (EGCG), the predominant green tea polyphenol which mimic its effects, inhibits enzyme activities and signal transduction pathways that play important roles in inflammation and joint destruction in arthritis. The use of EGCG as a possible chemopreventive agent with a potential to inhibit the development of arthritis. Here we review the biological effects of EGCG in an attempt to understand its pivotal molecular targets that directly affect the inflammation and joint destruction process for prevention and/or for the development of new therapeutics for arthritis in humans(41). 2. Curcumin In the study to to investigate the anti-inflammatory properties of BDMC33 and elucidate its underlying mechanism action in macrophage cells. showed that the inflammatory action of BDMC33 on activated macrophage-like cellular systems, which could be used as a future therapeutic agent in the management of chronic inflammatory diseases(42) 3. Resveratrol Resveratrol (RES), a well-known antioxidant and anti-inflammatory compound, is abundant in red wine and exerts numerous pharmacological effects, including hepatoprotection and cadioprotection(43)

4. Boswellic acid Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various chronic inflammatory diseases. The resinous part of Boswellia serrata possesses monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic acids and four major pentacyclic triterpenic acids i.e. -boswellic acid, acetyl--boswellic acid, 11-keto-boswellic acid and acetyl-11-keto--boswellic acid, responsible for inhibition of pro-inflammatory enzymes(44). 5. Cucurbitacins In the observations on the analgesic effects of WEDC by investigating its actions using the hot plate test and zymosan-induced writhing test in mice, as well as zymosan-induced arthritis in rats evaluating articular inflammatory pain, cell migration and determination of NO release into the joint exudate, showed that The oral treatment of the animals with WEDC (110 mg/kg) produced a significant, dose-dependent reduction of articular incapacitation and abdominal contortions in the writhing test. The same effect was not observed in the hot plate and rota-rod tests. WEDC also reduced nitrite release into the zymosan-inflamed joints. In the evaluation of COX activity, we observed that WEDC was able to selectively inhibit COX2 but not COX-1 activity in COS-7 cells. Moreover, WEDC treatment did not show gastrointestinal toxicity(45). 6. Etc. F. Treatments F.1. In conventional medicine perspective 1. Non Medication The aim of non medical treatment is to control painful myalgia, improve muscle stiffness, and relieve the symptoms of constitutional features of the disease. a. Fasting as part of a naturopathic treatment Fasting may be formed part of polymyalgia rheumatica (PMR) treat. According to the report of a 67-year-old woman with proven diagnosis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) was admitted to stationary treatment twice to receive a complex therapy with methods of natural medicine comprising fasting as its main treatment element(56) b. Diet therapy

Leucine-rich milk and whey proteins may be a potential treatment of age related loss of muscle mass and strength, according to the study of Dr, Bjrkman MP, and the rerearch team at Helsinki University Central Hospital(57). Other suggested that exercise and amino acid supplementation (AAS) together may be effective in enhancing not only muscle strength, but also combined variables of muscle mass and walking speed and of muscle mass and strength in sarcopenic women(58). c. Etc. 2. Medical treatment 2.1. Tocilizumab (TCZ) Tocilizumab (TCZ) is the first humanized interleukin-6 receptor-inhibiting monoclonal antibody developed to treat rheumatoid arthritis. a. In the study to assess the outcomes of 10 patients with relapsing/refractory GCA, TAK, or PMR treated with tocilizumab (TCZ), found that TCZ led to clinical and serological improvement in patients with refractory/relapsing GCA, TAK, or PMR. The demonstration of persistent large-vessel vasculitis at autopsy of one patient who had shown substantial response requires close scrutiny in larger studies(59). Other researchers in the study of ffficacy and safety of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (SJIA): tender 52-week data indicated that TENDER 1-year results demonstrate that TCZ is highly effective and generally well tolerated in pts with sJIA(60). b. Side Effects are not limit to b.1. Dizziness b.2. Headache b.3. Allergic effects, such as rash; hives; itching; difficulty breathing, etc. b.4. Skin changes b.5. Tiredness or weakness b.6. Etc. 2.2. Corticosteroids [CS] and nonsteroidal antiinflammatory drugs [NSAIDs]) 2.2.1.. Corticosteroids, a drug, a common presentation in primary care, and non-selective non-steroidal anti-inflammatory drugs (sometimes also referred to as traditional NSAIDs or tNSAIDs) and selective cyclo-

oxygenase 2 inhibitors (COX-2 inhibitors)(PMR) also be the first choice of treating of Polymalagia Arthritis, but the use of CS and NSAIDs in the treatment of PMR is associated with important long-term morbidity, according to Gabriel SE, Sunku J, Salvarani C, O'Fallon WM, Hunder GG., in the study of Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica(61). 2.2.2. Side effects a. Corticosteroids [CS] a.1. Corticosteroid withdrawal syndrome b.2. Hyperglycemia b.3. Insulin resistance b.4. Diabetes mellitus b.5. Osteoporosis b.6. Depression b.7. Colitis b.8. Etc. b. Nonsteroidal antiinflammatory drugs [NSAIDs] NSAIDs may cause large intestinal ulcers, bleeding, and perforation occasionally. It may cause relapse of classic inflammatory bowel disease and contribute to serious complications of diverticular disease (fistula and perforation). NSAIDs may occasionally cause small intestinal perforation, ulcers, and strictures requiring surgery. NSAIDs, however, frequently cause small intestinal inflammation, and the associated complications of blood loss and protein loss may lead to difficult management problems. The pathogenesis of NSAID enteropathy is a multistage process involving specific biochemical and subcellular organelle damage followed by a relatively nonspecific tissue reaction, according to Dr. Bjarnason I and the research team at King's College School of Medicine and Dentistry(61). 2.3. Etc. E.1. In Herbal medicine perspective 1. Comfrey Comfrey is a perennial Plant in the genus of Symphytum, belonging to the family Boraginaceae, native to Europe. It has been used in herbal and traditional medicine to ease excessive bleeding or on open wounds, relief

pain and swollen, treat circulation issues, reduce cholesterol, etc. In the investigation of the effect of a daily application of 6g Kytta-Salbe f (3 x 2 g) over a 3 week period with patients suffering from painful osteoarthritis of the knee with the complaints relating to osteoarthritis of the knee had persisted for 6.5 years found that the comfrey root extract ointment is well suited for the treatment of osteoarthritis of the knee. Pain is reduced, mobility of the knee improved and quality of life increased, according to "Efficacy of a comfrey root (Symphyti offic. radix) extract ointment in the treatment of patients with painful osteoarthritis of the knee: results of a double-blind, randomised, bicenter, placebo-controlled trial" by Grube B, Grnwald J, Krug L, Staiger C.(46) 2. Devil's claw Devil's claw also known as wood spider, is a plant of genus Harpagophytum in the family of Pedaliaceae, native to South Africa.The plant has been used as herb in traditional and herbal medicine to treat fever, rheumatoid arthritis, skin, gallbladder, pancreas, stomach and kidneys conditions, etc. 1. Antiinflammatory effects In the investigation of Harpagophytum procumbens (Hp) and it effect on inflammatory and degenerative disease, found that standardized ethanol Hp extract from Harpagophytum procumbensinhibits induction of proinflammatory gene expression, possibly by blocking the AP-1 pathway. This is novel evidence of a possible mechanism of action of this antiinflammatory drug, according to "Molecular Targets of the Antiinflammatory Harpagophytum procumbens (Devil's claw): Inhibition of TNF and COX-2 Gene Expression by Preventing Activation of AP-1." by Fiebich BL, Muoz E, Rose T, Weiss G, McGregor GP.(47) 2. Osteoarthritis a. In the observation of Harpagophytum procumbens and it effects on chronic inflammatory conditions such as Osteoarthritis found that Devil's Claw appeared effective in the reduction of the main clinical symptom of pain. The assessment of safety is limited by the small populations generally evaluated in the clinical studies. From the current data, Devil's Claw appears to be associated with minor risk (relative to NSAIDs), but further long-term assessment is required, according to the study of "Devil's Claw (Harpagophytum procumbens) as a treatment for osteoarthritis: a review of efficacy and safety" by Brien S, Lewith GT, McGregor G.(48) b. In the study of Devil's Claw (Harpagophytum procumbens) and it effects on osteoarthritis found that fourteen studies were identified: eight

observational studies; 2 comparator trials (1 open, the other randomized to assess clinical effectiveness); and 4 double-blinded, placebo-controlled, randomized controlled trials to assess efficacy. Many of the published trials lacked certain important methodological quality criteria. However, the data from the higher quality studies suggest that Devil's Claw appeared effective in the reduction of the main clinical symptom of pain, according to the study of "Devil's Claw (Harpagophytum procumbens) as a treatment for osteoarthritis: a review of efficacy and safety" by Brien S, Lewith GT, McGregor G.(49) 4. Degenerative diseases of the musculoskeletal system Extracts of the secondary tubers of Devil's Claw (Harpagophytum procumbens) and it degenerative painful rheumatism effects found that Pharmacological experiments have shown analgesic, antiphlogistic and antiinflammatory actions. Most important constituents are iridoid glycosides, which are supposed to contribute mainly to the observed effects. However, the entire extract has to be considered as active ingredient, according to"[Therapy of degenerative diseases of the musculoskeletal system with South African devil's claw (Harpagophytum procumbens DC)].[Article in German]" by Wegener T.(50) 5. Arthrosis of hip or knee In observation of Preparations made from the secondary tubers of Devil's claw (Harpagophytum procumbens) and it effects on rheumatic diseases (arthrosis and low back pain) found that a continuous improvement in typical clinical findings such as 45.5% for pain on palpation, 35% for limitation of mobility and 25.4% for joint crepitus. Only two cases of possible adverse drug reactions were reported (dyspeptic complaints and a sensation of fullness), according to "Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil's claw (Harpagophytum procumbens DC.)" by Wegener T, Lpke NP.(51) 6. Low back pain In the analyzing Harpagophytum procumbens and it osteoarthritis and low back pain effects found that the use of an aqueous extract of Harpagophytum procumbens at 60 mg harpagoside being non-inferior to 12.5 mg rofecoxib per day for chronic non-specific low-back pain (NSLBP) in the short term. Strong evidence exists for the use of an aqueous Harpagophytum extract at a daily dose equivalent of 50 mg harpagoside in the treatment of acute exacerbations of chronic NSLBP., according to the study of

"Harpgophytum procumbens for osteoarthritis and low back pain: a systematic review" by Gagnier JJ, Chrubasik S, Manheimer E.(52) 3. Valerian Valerian is a perennial flowering plant, in the genus Valeriana, belonging to the family Valerianaceae, native to Europe and parts of Asia. The herb has been used as a sedative and relaxing agent and to treat the liver, the urinary tract, the digestive tract problem, nerve conditions, etc. In the classification of V. officinalis extracts and its antioxidant properties against iron in hippocampal neurons in vitro, found that The effect of V. officinalis in deoxyribose degradation and reactive oxygen species (ROS) production was also investigated. In brain homogenates, V. officinalis inhibited thiobarbituric acid reactive substances induced by all pro-oxidants tested in a concentration dependent manner. Similarly, V. officinalis caused a significant decrease on the LPO in cerebral cortex and in deoxyribose degradation. QA-induced ROS production in cortical slices was also significantly reduced by V. officinalis, according to "In vitro antioxidant activity of Valeriana officinalis against different neurotoxic agents" by Sudati JH, Fachinetto R, Pereira RP, Boligon AA, Athayde ML, Soares FA, de Vargas Barbosa NB, Rocha JB.(53). The herb valerian may be useful as a mild sleep aid in clinical populations, such as persons with rheumatoid arthritis, according to the research team at the University of Virginia, School of Nursing(54) E.2. In traditional Chinese medicine perspective The aims of the Chinese herbal medicine formula is to enhance the immune system and promote kidney's Qi. Du huo Ji Sheng Tang (DHJST) a. In the study of Action Mechanisms of Du-Huo-Ji-Sheng-Tang on Cartilage Degradation in a Rabbit Model of Osteoarthritis, Dr. Chao-Wei Chen and the research team at the Shanghai Municipal Hospital of Traditional Chinese Medicine, showed that at the end of the sixth week after surgery, there was a significantly histological degeneration in the control group compared with the normal group. In the control group, the mean score for histological degeneration were further increases at 10th week, and there was a significantly lower mean score for histological degeneration in the DHJST group compared with the control group. To research the potential mechanism, the expression level of VEGF and HIF-1 were detected. The expression of VEGF mRNA and HIF-1 mRNA are low in normal group,

while the activities increase gradually in the control group. However, compared to that of the same time point model group, activity of VEGF and HIF-1 decreased significantly in DHJST group. In conclusion, DHJST exerts significant therapeutic effect on osteoarthritis rabbits, and mechanisms are associated with inhibition of VEGF and HIF-1 expression(57). b. Ingredients 1. Du Huo (Radix Angelicae Pubescentis) 2. Chuan Xiong (Rhizoma Chuanxiong) 3. Sang Ji Sheng (Herba Taxilli) 4. Ren Shen (Radix et Rhizoma Ginseng) 5. Du Zhong (Cortex Eucommiae) 6. Gan Cao (Rx et Rz Glycyrrhizae) 7. Niu Xi (Radix Cyathulae) 8. Dang Gui (Radix Angelicae Sinensis) 9. Xi Xin (Radix et Rhizoma Asari) 10. Bai Shao (Radix Paeoniae Alba) 11. Qin Jiao (Radix Gentianae Macrophyllae) 12. Sheng Di Huang (Radix Rehmanniae) 13. Fu Ling (Poriae) 14. Gui Xin (Cortex Rasus Cinnamomi) 15. Fang Feng (Radix Saposhnikoviae)(56) Natural Remedy For Arthritis, Gout, And Rheumatism Discover An Amazing, All-natural System That Literally Stops Arthritis, Gout, And Rheumatism In As Little As 7 Days. For common types of diseases of Ages of 50+, please visit http://medicaladvisorjournals.blogspot.ca/p/better-of-living-health-50over.html Sources (1) http://www.ncbi.nlm.nih.gov/pubmed/14528524 (2) http://health.yahoo.net/channel/musculoskeletal-disorders.html (3) http://www.ncbi.nlm.nih.gov/pubmed/11410767 (4) http://www.ncbi.nlm.nih.gov/pubmed/12462022 (5) http://www.ncbi.nlm.nih.gov/pubmed/19562970 (6) http://www.ncbi.nlm.nih.gov/pubmed/3388001

(7) http://www.ncbi.nlm.nih.gov/pubmed/15305244 (8) http://www.ncbi.nlm.nih.gov/pubmed/19646354 (9) http://www.ncbi.nlm.nih.gov/pubmed/21812500 (10) http://www.ncbi.nlm.nih.gov/pubmed/19562970 (11) http://www.ncbi.nlm.nih.gov/pubmed/15593211 (12) http://www.ncbi.nlm.nih.gov/pubmed/11229462 (13) http://www.ncbi.nlm.nih.gov/pubmed/18237382 (14) http://www.ncbi.nlm.nih.gov/pubmed/1223854 (15) http://www.ncbi.nlm.nih.gov/pubmed/22057203 (16) http://www.ncbi.nlm.nih.gov/pubmed/21262024 (17) http://www.ncbi.nlm.nih.gov/pubmed/18208867 (18) http://www.ncbi.nlm.nih.gov/pubmed/20969738 (19) http://www.ncbi.nlm.nih.gov/pubmed/20819228 (20) http://www.ncbi.nlm.nih.gov/pubmed/20686306 (21) http://www.ncbi.nlm.nih.gov/pubmed/20299378 (22) http://www.ncbi.nlm.nih.gov/pubmed/20482924 (23) http://www.ncbi.nlm.nih.gov/pubmed/11858317 (24) http://web.archive.org/web/20080623203621/http://www.mayoclinic.com/he alth/polymyalgia-rheumatica/DS00441/DSECTION=tests-and-diagnosis (25) http://www.ncbi.nlm.nih.gov/pubmed/3619280 (26) http://www.ncbi.nlm.nih.gov/pubmed/17045074 (27) http://altmedicine.about.com/od/arthritis/a/rheumatoid.htm (28) http://www.ncbi.nlm.nih.gov/pubmed/22570770 (29) http://www.ncbi.nlm.nih.gov/pubmed/22696854 (30) http://www.ncbi.nlm.nih.gov/pubmed/18820806 (31) http://www.ncbi.nlm.nih.gov/pubmed/19281374 (32) http://www.ncbi.nlm.nih.gov/pubmed/21985858 (33) http://www.ncbi.nlm.nih.gov/pubmed/20447316 (34) http://www.ncbi.nlm.nih.gov/pubmed/19093267 (35) http://www.ncbi.nlm.nih.gov/pubmed/19707219 (36) http://www.ncbi.nlm.nih.gov/pubmed/18577222 (37) http://www.ncbi.nlm.nih.gov/pubmed/12730442 (38) http://www.ncbi.nlm.nih.gov/pubmed/20207121 (39) http://www.ncbi.nlm.nih.gov/pubmed/12676044 (40) http://www.ncbi.nlm.nih.gov/pubmed/16387899 (41) http://www.ncbi.nlm.nih.gov/pubmed/20462508 (42) http://www.ncbi.nlm.nih.gov/pubmed/22489138 (43) http://www.ncbi.nlm.nih.gov/pubmed/22480310 (44) http://www.ncbi.nlm.nih.gov/pubmed/22457547

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