Various Types Of Arthritis Research Articles

Curcumin and its protective and therapeutic uses

Curcumin is a yellow orange powder, which is extracted from the turmeric plant (Curcuma longa). Curcumin is the principal curcuminoid of the turmeric (C. longa). Curcumin was first isolated in 1815 and its chemical structure was determined by Roughley and Whiting in 1973. It has been identified as 1,6-heptadiene-3,5-dione-1,7-bis (4-hydroxy-3-methoxyphenyl)-(1e,6e) or diferuloylmethane. Turmeric has been listed as “generally recognized as safe” (GRAS) as a coloring and flavoring agent in food by the US Food and Drug Administration (FDA). As per WHO, as an additive the daily acceptable dose of curcumin for humans has been defined as 0–3 mg/kg body weight. Curcumin can be administered by different routes as topical, oral, and inhalational. Curcumin inserts deep into the cell membrane in a manner similar to cholesterol. Curcumin has a high lipophilic character, and body fat has a high percentage of bound curcumin. The systemic bioavailability of orally administered curcumin is low in humans and only traces of it have been found in the liver and portal circulation. Piperine has been reported to increase the bioavailability of curcumin. Recently, it has been reported that newly developed nanoparticulate curcumin has better bioavailability. There is a growing list of disease conditions that can be treated by curcumin. Curcumin has been found to have therapeutic effects in wound healing and in various types of arthritis, cardiovascular diseases, diabetes, pulmonary diseases, Parkinson’s disease, and in Alzheimer’s disease. Curcumin has been reported to have potential role in the treatment of atherosclerosis, arthritis, chronic anterior uveitis, colon cancer, familial adenomatous polyposis, hypercholesteremia, inflammatory bowel disease, pancreatic cancer, pancreatitis, psoriasis, ulcerative colitis, and even HIV.

Regulation of tumour necrosis factor signalling: live or let die.

Tumour necrosis factor (TNF) is a pro-inflammatory cytokine that has important roles in mammalian immunity and cellular homeostasis. Deregulation of TNF receptor (TNFR) signalling is associated with many inflammatory disorders, including various types of arthritis and inflammatory bowel disease, and targeting TNF has been an effective therapeutic strategy in these diseases. This Review focuses on the recent advances that have been made in understanding TNFR signalling and the consequences of its deregulation for cellular survival, apoptosis and regulated necrosis. We discuss how TNF-induced survival signals are distinguished from those that lead to cell death. Finally, we provide a brief overview of the role of TNF in inflammatory and autoimmune diseases, and we discuss up-to-date and future treatment strategies for these disorders.

An Analysis of Different Types of Arthritis with Joint Effusions among Kashmiri Population in a Tertiary Care Hospital.

Introduction: Arthritis is the initial manifestation of many joint disorders. Synovial fluid analysis helps in this aspect.Objective: To analyse the gross, microscopic and biochemical variations in the synovial fluid in various causes of joint effusions and to assess the synovial fluid cytology with biochemical parameters in various types of arthritis to increase the accuracy of diagnosis.Materials and Methods: In the present cross sectional study. Gross examination was done to find total volume, clarity, viscosity of the synovial fluid and it was equally divided into two halves. One half of synovial fluid was send for biochemical analysis and the other half for microscopic examination.Results: Out of 477 synovial fluid samples analysed. Total leucocyte count was found to be highest in septic arthritis and lowest in osteoarthritis. Neutrophils were highest in septic arthritis (95%) and lowest in osteoarthritis (24%). Sugar level in synovial fluid was highest in osteoarthritis and gouty arthritis (70-90 mg/dL each) and lowest in septic arthritis. Proteins were highest in rheumatoid arthritis and traumatic arthritis (4.1-6.5 gm/dL and 4.2-6.4 gm/dL respectively) and lowest in osteoarthritis (1.2-2.4 gm/dL). Out of 290 positive cases in synovial C-reactive protein levels, the highest were found in rheumatoid arthritis (130), rheumatoid factor was found positive in 143 cases while it was negative in 127 cases of osteoarthritis.Conclusion: Biochemical analysis of synovial fluid for proteins and sugar contributes in diagnosis of different types of arthritis. RF in synovial fluid proves to be of value in diagnosis of monoarticular arthritis.

“Four legs instead of two” – perspectives on a Nordic walking-based walking programme among people with arthritis

Purpose: Nordic Walking (NW) is growing in popularity among people with arthritis. The aim of this study was to explore the perspectives of participants with arthritis on a NW-based walking programme including factors contributing to sustained participation in the programme. Methods: Three semi-structured focus groups were conducted with a total of 27 participants with various types of arthritis. The groups consisted of participants who completed a NW-based walking programme in the previous 4 years. Only participants who had sustained involvement in the walking group were included. Groups were audio-recorded, transcribed verbatim and thematic analysis was performed. Results: Participants reported that the walking programme offered numerous benefits. Two distinct themes emerged: (1) “four legs instead of two legs” and (2) “a support group”. Theme 1 incorporates the physical, psychological and educational benefits that stem from involvement in a walking group while Theme 2 incorporates the benefits of social support in group-based activity. Conclusion: Several benefits of a NW-based walking programme from the perspectives of individuals with arthritis who engage in group-based walking programmes were identified. The benefits may encourage sustained participation and justify the promotion of NW as an intervention for people with arthritisImplications for RehabilitationConsidering how to sustain exercise participation is important to ensure continued benefits from physical activity participationA community-based Nordic walking-based walking programme for people with arthritis improved exercise knowledge and confidence to exerciseGroup exercise is valuable in providing support and motivation to continue exercising.

Pharmacology in the musculoskeletal system

Musculoskeletal diseases (also called rheumatic diseases) are a major cause of morbidity throughout the world ( World Health Organization (WHO), 2003 ); they encompass a wide spectrum of disorders that are propagated by a plethora of biological factors. There are over 200 such rheumatic diseases that span from various types of arthritis to systemic connective tissue diseases ( European League Against Rheumatism (EULAR), 2009 ). They constitute a diverse group of conditions from those of acute onset and short duration (e.g. gout, tendonitis and bursitis) to chronic progressive disorders such as osteoarthritis, rheumatoid arthritis and systemic lupus erythematosus. Rheumatic diseases represent an important social and economic problem inflicting enormous costs on health and social care systems. In Europe, nearly 25% of adults are affected by long-standing musculoskeletal problems that limit daily activities ( Lidgren et al, 2005 ). By virtue of their inconsistent pathophysiology; each musculoskeletal disease demands a different approach to its management in the clinic. Therefore, there is no single medication or treatment that is optimal for everyone. In many rheumatic diseases pain is a common symptom and its management is one of the most important aspects of patient care.

English

A lot of research on the prevalence of arthritis in India population has been carried out. However no studies on the genetic relationships within groups of arthritic patients in India have been reported. The current study focuses on analyzing the genetic diversity between patients suffering from the various types of arthritis with reference to factors inducing its onset. A total of 36 patients suffering from different types of arthritis were analyzed with reference to the age, gender, BMI, family history, hemoglobin and thyroid profile. The variation in the genetic profile was also analyzed using the RAPD technique. Data analysis showed patients suffering from arthritis to be at a greater risk of thyroid disorders, however the type of arthritis played a significant role. A distinct correlation between the genetic variation and presence of arthritis including its type was observed.

P280 - Faecal calprotectin remains stable in inactive Crohn's disease patients

P280 - Faecal calprotectin remains stable in inactive Crohn's disease patients

P281 - The prevalence of antibodies against cyclic citrullinated peptide (anti-CCP) is low in patients with inflammatory bowel disease with or without arthritis

P281 - The prevalence of antibodies against cyclic citrullinated peptide (anti-CCP) is low in patients with inflammatory bowel disease with or without arthritis

Elevated expression of caspase-3 inhibitors, survivin and xIAP correlates with low levels of apoptosis in active rheumatoid synovium.

IntroductionTumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a tumour necrosis factor (TNF) family member capable of inducing apoptosis in many cell types.MethodsUsing immunohistochemistry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) and real-time PCR we investigated the expression of TRAIL, TRAIL receptors and several key molecules of the intracellular apoptotic pathway in human synovial tissues from various types of arthritis and normal controls. Synovial tissues from patients with active rheumatoid arthritis (RA), inactive RA, osteoarthritis (OA) or spondyloarthritis (SpA) and normal individuals were studied.ResultsSignificantly higher levels of TRAIL, TRAIL R1, TRAIL R2 and TRAIL R4 were observed in synovial tissues from patients with active RA compared with normal controls (p < 0.05). TRAIL, TRAIL R1 and TRAIL R4 were expressed by many of the cells expressing CD68 (macrophages). Lower levels of TUNEL but higher levels of cleaved caspase-3 staining were detected in tissue from active RA compared with inactive RA patients (p < 0.05). Higher levels of survivin and x-linked inhibitor of apoptosis protein (xIAP) were expressed in active RA synovial tissues compared with inactive RA observed at both the protein and mRNA levels.ConclusionsThis study indicates that the induction of apoptosis in active RA synovial tissues is inhibited despite stimulation of the intracellular pathway(s) that lead to apoptosis. This inhibition of apoptosis was observed downstream of caspase-3 and may involve the caspase-3 inhibitors, survivin and xIAP.

Tumor necrosis factor α drives cadherin 11 expression in rheumatoid inflammation

Cadherin 11 expressed on fibroblast-like synoviocytes (FLS) plays a key role in normal synovial architecture. The purpose of this study was to examine the expression of cadherin 11 in human synovitis. Cadherin 11 expression in synovial biopsy samples from patients with various types of arthritis and in lung biopsy samples from patients with interstitial pneumonitis (IP) was examined by immunostaining. The regulation of cadherin 11 expression in human FLS was assessed by quantitative reverse transcription-polymerase chain reaction analysis and Western blotting. Therapeutic modulation of synovial cadherin 11 was assessed before and after effective antiinflammatory therapy. Abundant staining for cadherin 11 was seen in the intimal lining layer and the synovial sublining in inflamed tissues, with discrete staining in noninflammatory osteoarthritic (OA) tissues. The pattern and degree of immunostaining were similar in tissues from patients with rheumatoid arthritis (RA), nonpsoriatic spondylarthritis (SpA), psoriatic arthritis (PsA), and inflammatory OA. Clear staining for cadherin 11 was also observed in lung tissues from RA-associated IP and idiopathic IP patients, but was very limited in normal lung tissue. Cadherin 11 staining correlated strongly with the degree of inflammatory infiltration of the tissue, as well as with the C-reactive protein level and the erythrocyte sedimentation rate in RA patients. In vitro, cadherin 11 expression by FLS was consistently up-regulated by tumor necrosis factor alpha (TNFalpha) at the protein, but not the messenger RNA, level. Cadherin 11 staining in vivo was strongly down-regulated by prednisone treatment in RA patients and by TNFalpha blockade in SpA patients. Cadherin 11 expression is regulated by mediators of inflammation, such as TNFalpha. Since cadherin 11 plays an important role in cartilage destruction in experimental arthritis, down-modulation of cadherin 11 by potent antiinflammatory therapies in humans with arthritis may contribute to halting cartilage damage.

Molecular mechanisms of cartilage destruction: Mechanics, inflammatory mediators, and aging collide

Destruction and loss of articular cartilage is a central feature in most forms of arthritis including the most common form, osteoarthritis (OA). The pathobiologic differences among the various types of arthritis relate, at least in part, to differences in mechanisms driving cartilage destruction. Often forms of arthritis are divided into “inflammatory” and “noninflammatory,” where “inflammatory” arthritis is meant to indicate cellular inflammation resulting from an influx of various activated leukocytes into the joint which mediate destruction, while “noninflammatory” arthritis indicates a lack of significant inflammatory cell invasion and is often described as “degenerative arthritis.” However, as we discover more about the basic mechanisms behind “noninflammatory” or “degenerative arthritis,” it is becoming clear that these are misnomers.

470 Efficacy of nemorubicin (MMDX) administered with iodinated oil via hepatic artery (IHA) to patients with unresectable primary hepatocellular carcinoma (HCC): phase II trial

The genus Rosa (roses) has long been used in traditional or folk medicine worldwide for the treatment of various types of arthritis including rheumatoid arthritis and osteoarthritis. The active constituents of Rosa spp., such as flavonoids, triterpenoids, and phytosterols, could act on different targets in the NF-κB signalling pathway, inhibit pro-inflammatory enzymes (e.g. MMPs and COX-2), lower the production of inflammatory cytokines and chemokines (e.g. TNF-α, IL-1β, IL-6, CCL5), and reduce oxidative stress, which in turn suppress inflammatory processes. Preclinical and clinical studies have demonstrated that these species possess analgesic, anti-arthritic, anti-inflammatory, anti-oxidative and bone-preserving activities. This review presents comprehensive overview of the mode and mechanism of action of various extracts, preparations, and active constituents from this genus. The dynamic beneficial effects of the products prepared from this genus in arthritis management are summarized. The Rosa genus is a treasure waiting for further exploration by researchers interested in the development of safe and effective anti-arthritic agents.

Arthritis in hemochromatosis or iron storage disease.

Hemochromatosis is a common autosomal recessive condition characterized by increased iron absorption and tissue deposition. Recognition of this condition is important because phlebotomy can be life saving. This review examines recent studies of articular manifestations in hemochromatosis and the frequency of hemochromatosis genes in the general population and in selected patients with various types of arthritis. Genetic mutations in the HFE gene are present in most patients with hemochromatosis. Several studies have shown a higher frequency of homozygous or heterozygous HFE mutations in individuals with various types of arthritis compared with unselected populations. Although important, the lack of characterization of arthritis in the controls of these studies limits their impact. One recent study compared arthritis symptoms in individuals with HFE mutations, newly identified through a large screening program, with individuals lacking such mutations from the same population. Individuals with hemochromatosis genotypes reported a higher frequency of some arthritis symptoms than did controls. Although these differences were not statistically significant, the low number of individuals with hemochromatosis genotypes limited the statistical power of this study. Arthritis symptoms are common in individuals with hemochromatosis and can have a significant impact on their quality of life. Although the genetic defect associated with hemochromatosis is common in whites, the frequency with which these genotypes cause clinical disease remains unclear. More detailed study of arthritis symptoms and signs over time in individuals with and without mutations in the HFE gene is necessary to determine the contribution of HFE genes to arthritis in the population.

The Oriental medicine "Cool-Cool (Cool-X-A)" inhibits inflammatory cytokine production and migration in mast cells.

Plant medications have been applied to treat pains from various types of arthritis in Korea. Rheumatoid arthritis (RA) is well known to be a chronic autoimmune/inflammatory disease that leads to progressive joint damage and cartilage destruction. Accumulation and activation of mast cells have been demonstrated in rheumatoid synovial tissue. Because infiltrated mast cells and their mediators may contribute to the initiation and progression of the inflammatory process and matrix degradation of RA, we tested the inhibitory effects of "Cool-Cool" (CC, Cool-X-A), an Oriental medication, on the production and migration of major inflammatory cytokines in mast cells. CC was treated in vitro before activation of human mast cell line (HMC-1) with phorbol 12-myristate 13-acetate, and the cytotoxicity of CC was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assay. CC had no cytotoxic effects on HMC-1 cell viability. The inhibitory effects on cytokine production were monitored by enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR). CC inhibited not only the secretion but also the expression of TNF-alpha and IL-8 in HMC-1 cells. CC also suppressed migration of mast cells induced by stem cell factor. These findings may help in understanding the mechanism of action of this herbal medication, leading to the control of mast cells in inflammatory conditions like RA.

Analysis of temporomandibular joint synovial fluid using Fourier transform/infrared spectroscopy

Purpose: In recent years infrared spectroscopy has been increasingly used for the analytical determination of biologic fluids and tissues. With the help of this method it was possible to investigate the various types of arthritis affecting the knee joint, among others. The aim of our study was to show that infrared spectroscopy can also be used as a method to analyze the synovial fluid of the temporomandibular joint to differentiate between inflammatory and noninflammatory disorders. Materials and Methods: Using Fourier transform/infrared spectroscopy analysis, comparable absorption spectra with characteristic signals in the corresponding range of wavelength were shown and used to prove pathologic alterations in the synovial fluid. Samples of 22 patients with arthritis of the temporomandibular joint and 12 patients with noninflammatory internal derangement were investigated and compared with each other. Results: Our measurements presented a distinct intensity difference between the absorption spectra of patients who had arthritis and those without signs of an inflammatory change but with an internal derangement as control specimens. Due to the small number of undiluted samples it was not possible to follow up with a multivariant analysis, necessary for a differential diagnostic evaluation between the individual types of arthritis. Conclusions: A certain differentiation between arthritic and noninflamed temporomandibular joints can be noted with infrared spectroscopy of the synovial fluid. This represents a valuable option for minimally invasive diagnostic proof of inflammation in cases of joint disorders. © 2002 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 60:1302-1306, 2002

Inducible nitric oxide synthase is expressed in joints of goats in the late stage of infection with caprine arthritis encephalitis virus.

We have studied the expression of the inducible form of nitric oxide synthase (iNOS) in joints of goats infected with the caprine arthritis encephalitis virus (CAEV). Nitric oxide generated by iNOS is thought to play an important role in the pathogenesis of various types of arthritis, especially rheumatoid arthritis (RA) in humans. Surprisingly, iNOS immunoreactivity was found only in joints of long-term infected goats with severe clinical arthritis, whereas-despite the presence of high numbers of inflammatory cells in the synovial tissue-no iNOS immunoreactivity was detected in mildly arthritic and in short-term experimentally infected goats. Most iNOS-positive cells expressed neither MHC class II nor CD68, which suggests that they were fibroblast-like synoviocytes. In situ hybridization studies showed that there was no correlation between iNOS immunoreactivity and detectable virus expression in the joint. In addition, infection of macrophages in vitro-the major host cells of CAEV in vivo-did not lead to increased iNOS mRNA expression. In response to stimulation, similar levels of iNOS expression were observed in infected and in uninfected macrophages. These findings suggest that the expression of iNOS is a feature of late-stage chronic arthritis and is not involved in the development of the inflammatory lesions. Both the lack of co-localization of iNOS protein and viral transcripts in the joint and the finding that CAEV does not stimulate the expression of iNOS in vitro further suggest that iNOS is not directly induced by the virus or the anti-viral immune response in the joint, that it may well, however, be involved in tissue remodelling or scar formation.

Tripterygium wilfordii Hook F extract suppresses proinflammatory cytokine-induced expression of matrix metalloproteinase genes in articular chondrocytes by inhibiting activating protein-1 and nuclear factor-kappaB activities.

The major pathologic manifestations of rheumatoid arthritis (RA) and osteoarthritis (OA) are joint inflammation and articular cartilage resorption by proinflammatory cytokine-stimulated matrix metalloproteinases (MMPs) and aggrecanases. The Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) is effective for treatment of various types of arthritis. However, mechanisms and targets of its actions are poorly understood. Anti-inflammatory activities of the extracts of this plant were previously attributed to inhibition of cyclooxygenase-2 mRNA and prostaglandin E(2) synthesis. Here, we show that in primary human femoral head osteoarthritic and normal bovine chondrocytes, TWHF partially or completely inhibited mRNA and protein expression of tumor necrosis factor-alpha, interleukin (IL)-1, and IL-17-inducible MMP-3 and MMP-13. This agent also inhibited cytokine-stimulated MMP-3 protein expression in human synovial fibroblasts. A dose range of 2.5 to 10 ng/ml of TWHF was effectively inhibitory for IL-1. Pretreatment for 30 min or 1 h (but not 2-10 h) after IL-1 treatment with TWHF inhibited MMP-3 RNA induction. The inhibitory doses had no adverse effect on the viability of chondrocytes. Mechanistic studies revealed no impact on the activation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase mitogen-activated protein kinases. Instead, TWHF partially inhibited DNA binding capacity of cytokine-stimulated activating protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) transcription factors. Therefore, besides its anti-inflammatory activity, this agent may also be effective in blocking cartilage matrix resorption by MMPs by impairing AP-1 and NF-kappaB binding activities. Thus, TWHF extract contains novel inhibitors of MMP expression that may be of therapeutic potential in arthritis and other conditions associated with increased MMPs.

Chronic nephrotoxicity of anti-inflammatory drugs used in the treatment of arthritis.

We determined the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and the prevalence of chronic renal impairment and renal papillary necrosis (RPN) in patients with various types of arthritis. Ninety-four patients with chronic arthritis who had consumed more than 1000 capsules and/or tablets of NSAIDs were studied. Renal profiles and radiological investigations such as intravenous urogram (IVU), ultrasonography (US) and computed tomography (CT) were performed to look for evidence of RPN. Twelve patients did not complete the study. Ten of the 82 patients who had completed the study (12.2%) had radiologic evidence of RPN. Five out of 53 patients (9.4%) with rheumatoid arthritis, three out of 11 patients (27.3%) with gouty arthritis and two out of seven patients (28.6%) with osteoarthritis had RPN. Renal impairment (serum creatinine levels of 125-451 mumol/l) was found in 20 patients (24.4%). The patients had consumed 1000-26,300 capsules and/or tablets over a period ranging from 1 yr to more than 30 yr. Patients with chronic arthritis who consume excessive amount of NSAIDs are at risk of developing RPN and chronic renal impairment.

Joint complaints in psoriasis patients.

Four hundred and fifty-nine psoriasis patients seen at the Department of Dermatology, Bowman Gray School of Medicine of Wake Forest University, responded to a questionnaire concerning current or past joint complaints. Of these, 17% reported a previous diagnosis of psoriatic arthritis, and over 53% had a current or past history of arthralgias. Additional information on those patients reporting arthralgias focused on the cutaneous sites of involvement with psoriasis and which joints were most likely to be involved in patients with various types of arthritis. Previous treatments for skin involvement with psoriasis were more aggressive in those patients with a diagnosis of psoriatic arthritis. A significant proportion of patients presenting to dermatologists for treatment of psoriasis have joint complaints, and the percentage of patients with psoriatic arthritis is greater than generally appreciated by non-dermatologists.

Is it mandatory to examine synovial fluids promptly after arthrocentesis?

Fifty synovial fluid (SF) samples from patients with various types of arthritis were examined promptly after joint aspiration and after storage at room temperature (22 degrees C) or at refrigerator temperature (4 degrees C) for 1 hour, 2 hours, 3 hours, 6 hours, 1 day, and 3 days, then weekly for 3 weeks and monthly for 2 months. We found that the leukocyte count (white blood cell [WBC] count) decreased within a few hours. In 4 SF samples from patients with mild inflammation (initial range 3,150-6,200 WBC/mm3), the WBC count decreased into a "noninflammatory" range (less than 2,000/mm3) within 5-6 hours. In 3 of 5 SF samples that on the first day were found to be laden with crystals of calcium pyrophosphate dihydrate (CPPD), the crystals were much less abundant and were difficult to recognize by the next day. CPPD crystals dissolved completely in all SF samples by 3-8 weeks of the study. Monosodium urate crystals remained detectable throughout the 8 weeks of study, but they became smaller, less birefringent, and less numerous with time. Clumps of apatite-like crystals persisted for several months. Most SF samples initially negative for apatite-like crystals remained negative over time. New, artifactual crystals, including alizarin red S-positive clumps or star-shaped arrays, plate-like structures, positively birefringent Maltese crosses, and hematoidin crystals, developed with time. Because of these observations, we urge prompt examination of SF specimens to avoid the problems of misdiagnosing borderline inflammatory fluids, missing CPPD crystals that dissolve with time, or over-interpreting the findings because of the new, artifactual crystals.