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ARTHRITIS: CLASSIFICATION, NATURE & CAUSE - A REVIEW. Sankar Mitra PhD *
Abstract and Figures
This article describes several common features about arthritis regarding nature, various forms and probable causes for its occurrence in a simplified manner. Typically, it is a collection of diseases together nomenclatured as " Arthritis ". Nearly 47 million people in the US alone are suffering from this disease. Globally, it imposes a huge financial burden. Considering medical condition, the disease exerts medium to severe problem at various bone-joints displaying inflammation as a common symptom which often turns serious, incapacitating the individuals through pain, swelling and inflexibility at those affected joints. Statistically, women over the menopausal stage fall as the major victims. Among the victims of either sex, about half suffers from Osteo arthritis (OA). Next in line, are those having the problem of Rheumatic arthritis (RA). Besides OA or RA, other categories of arthritis are also briefly illustrated in addition to their epidemiological survey. But the article emphasizes mainly on OA and RA for their severe role among the major population of sufferers. The likely reasons of developing calcification and its subsequent after-effect resulting in the progression of OA are discussed in semi-detail. Additionally, the role of autoimmune disorder along with its genetic predisposition which triggers the inflammation leading to RA is also included in the discussion. Simplistically, it is concluded that OA creates inflammation after wearing tearing of the cartilage tissue which is mechanically driven whereas RA is created out of the inflammation thereby imposing a problem. In that perspective RA is considered as an inflammatory autoimmune-disease
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... Interest regarding the involvement of inflammatory pathways particularly at cellular and molecular level is greatly increased, which in effect helps design numerous drugs for treating the inflammatory diseases like arthritis/ gout 4,5 . A long list of inflammatory pain mediators like, kinins or cytokines are known to act on specific targets causing the release of other intermediary ingredients at the inflamed sites exacerbating the problems 6 . ...
... It is established that free radicals can damage the joint cartilages by several ways: 1) They help degrade the proteoglycans, 2) The production of H 2 O 2 inhibits proteoglycan synthesis in chondrocytes by interfering ATP synthesis via the inhibition of glyceraldehyde-3phosphate dehydrogenase, 3) Production of NO promotes apoptosis in chondrocytes, 4) The ROS also activates NF-κβ and AP -1 to produce various inflammatory factors 4,43 . ...
... There are numerous causes behind this effect, aging, metabolic disorders, degenerative joint diseases, physical disturbances which also set the conditions for uncontrolled calcification. The high deposition level of Ca +2 in the form of calcium pyrophosphate di-hydrate [Ca 2 (PO 3 -O -PO 3 ) 4 4 ] is seen to be liable for setting the course of OA 5,67,68 . But whichever mechanism may be involved, due to the manifestation of stiffness it can no longer function as a shock absorber. ...
The article provides information regarding pharmacological and biochemical aspects of few herbs (Turmeric, Ginger, Capsicum, Devils' claw, Meadowsweet, Willow, Evening primrose, Juniper, Nettle and Boswellia) that are commonly used in treating arthritis and associated inflammations. All of them have substantialability to reduce pain and inflammation without the side effects. Distinctively, the herbs synthesize multiple phyto-chemicals that are chemically categorized as terpenes, flavins and tannins offering irrefutable impact on the patients providing significant relief. Advantageously, due to less side effects, the presence of multiple anti-inflammatory components insists patients to rely on herbs as a viable alternative in place of commercial therapeutic drugs available to control the arthritis. Many also use herbs as a supplement for additional therapeutic measure. It is proven that naturally occurring terpenes, sterols, flavins and polyphenols exert significant immune modulatory function to inhibit the inflammatory processes normally observed owing to the eruption of arthritis. So, by preventing the actions of NF-κβ and other associated factors these herbs control the arthritic problems. The co-presence of numerous ingredients in a single species often synergize the anti-inflammatory encounter while also preventing the generations of free radicals/ ROS which normally accelerate the inflammatory process. Intermittent assistance is occasionally provided by the few fatty acids within some herbs for their metabolic conversion to PGE1 or TXA1 adding additional preventive role. So less side effects along with the traditionally proven positive records ensure many to use herbs while managing the arthritic problems.
Arthritis is one of the most common disease states worldwide but is still publicly misunderstood and lacks engaging public awareness materials. Within the UK, the most prevalent types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). The two are commonly mistaken as the same disease but, in fact, have very different pathogenesis, symptoms and treatments. This chapter describes a study which aimed to assess whether an augmented reality (AR) application could be used to raise awareness about the difference between OA and RA.
Chondrocytes exposed to nitric oxide (NO) or antibody to Fas undergo cell death by apoptosis. This study examines structural
and functional properties of chondrocyte-derived apoptotic bodies. In NO treated cartilage, the dense pericellular matrix
that normally surrounds the cells is degraded and apoptotic bodies accumulate within and in the vicinity of the chondrocyte
lacunae. Functional analysis shows that apoptotic bodies isolated from NO-treated chondrocytes or cartilage produce pyrophosphate.
The levels of pyrophosphate produced by apoptotic bodies are increased by pretreatment of the chondrocytes with transforming
growth factor β and decreased by interleukin 1. Apoptotic bodies contain alkaline phosphatase and NTP pyrophosphohydrolase
activities and can precipitate calcium. These results suggest that chondrocyte-derived apoptotic bodies express functional
properties that may contribute to the pathologic cartilage calcification observed in aging and osteoarthritis.
Members of the CCN family of matricellular proteins are crucial for embryonic development and have important roles in inflammation, wound healing and injury repair in adulthood. Deregulation of CCN protein expression or activities contributes to the pathobiology of various diseases - many of which may arise when inflammation or tissue injury becomes chronic - including fibrosis, atherosclerosis, arthritis and cancer, as well as diabetic nephropathy and retinopathy. Emerging studies indicate that targeting CCN protein expression or signalling pathways holds promise in the development of diagnostics and therapeutics for such diseases. This Review summarizes the biology of CCN proteins, their roles in various pathologies and their potential as therapeutic targets.
The revised shared epitope (SE) concept in rheumatoid arthritis (RA) is based on the presence (S) or absence (X) of the SE RAA amino acid motif at positions 72 to 74 of the third hypervariable region of the various human leucocyte antigen (HLA)-DRB1 alleles. The purpose of this study was to investigate SE subtypes on the basis of the American College of Rheumatology 1987 revised criteria for the classification of RA in a cohort of South African RA patients (n = 143) and their association with clinical and circulating biomarkers of disease activity (autoantibodies, acute phase reactants and cytokines).
Genomic DNA was analysed using high-resolution recombinant sequence-specific oligonucleotide PCR typing of the HLA-DRB1 allele. Subtypes of the SE were classified according to the amino acids at positions 72 to 74 for the RAA sequence, and further sub-divided according to the amino acids at positions 70 and 71, which either contribute to (S2, S3P), or negate (S1, S3D) RA susceptibility. Disease activity was assessed on the basis of (1) Disease Activity Score in 28 joints using C-reactive protein (CRP), (2) rheumatoid factor (RF), (3) CRP and (4) serum amyloid A by nephelometry, anticyclic citrullinated peptide antibodies (aCCP) by an immunofluorometric procedure, and cytokines by multiplex bead array technology.
Of the 143 RA patients, 81 (57%) were homozygous (SS) and 50 (35%) were heterozygous (SX) for the SE alleles with significant overexpression of S2 and S3P (respective odds ratios (ORs) 5.3 and 5.8; P < 0.0001), and 12 (8%) were classified as no SE allele (XX). Both the SS and SX groups showed a strong association with aCCP positivity (OR = 10.2 and P = 0.0010, OR = 9.2 and P = 0.0028, respectively) relative to the XX group. Clinical scores and concentrations of the other biomarkers of disease activity (RF, CRP and T helper cell type 1 (Th1), Th2, macrophage and fibroblast cytokines) were also generally higher in the SS group than in the SX and XX groups.
RA susceptibility alleles investigated according to revised criteria for the classification of RA were significantly increased in South African RA patients and strongly associated with aCCP in particular as well as with circulating cytokines and disease severity.
Objective
The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA.
Methods
A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct “rheumatoid arthritis.”
Results
In the new criteria set, classification as “definite RA” is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0–5), serologic abnormality (score range 0–3), elevated acute-phase response (score range 0–1), and symptom duration (2 levels; range 0–1).
Conclusion
This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct “rheumatoid arthritis.”
Susceptibility to develop Rheumatoid arthritis (RA) maps to a highly conserved amino acid motif (“the shared epitope”) expressed in the third hypervariable region of different HLA-DRB1 alleles. This motif, namely QKRAA, QRRAA or RRRAA helps the development of RA by an unknown mechanism.
However, it is now established that the shared epitope can 1/ Shape the T cell repertoire 2/ Interact with 70 kD heat shock proteins
Studies of the descriptive epidemiology of RA indicate a population prevalence of 0.5% to 1% and a highly variable annual incidence (12-1200 per 100,000 population) depending on gender, race/ethnicity, and calendar year. Secular trends in RA incidence over time have been shown in several studies, supporting the hypothesis of a host-environment interaction. People with RA have a significantly increased risk of death compared with age- and sex-matched controls without RA from the same community. The determinants of this excess mortality remain unclear; however, reports suggest increased risk from gastrointestinal, respiratory, cardiovascular, infectious, and hematologic diseases among RA patients compared with controls. Despite extensive epidemiologic research, the etiology of RA is unknown. Several risk factors have been suggested as important in the development or progression of RA. These include genetics, infectious agents, oral contraceptives, smoking, and formal education. Epidemiologic research is an essential contributor to our understanding of RA.
Objective. To determine the point prevalence of musculoskeletal complaints and rheumatic diseases in a Filipino urban community. Methods. A descriptive cross-sectional 2 phase survey was conducted in an urban community in Metropolitan Manila. Phase I (screening) used face-to-face interviews, while phase II (examination) involved case identification of the rheumatic diseases. We sampled 670 households (3065 adults) using a multistage cluster sampling method. A pilot study was conducted to pretest the questionnaire for cross-cultural adaptation and validation, field procedures, sampling design, and data management plan. Standardized translated COPCORD questionnaires (blind translation and blind back- translation) were administered by trained interviewers. Two weeks after Phase I, Phase II was conducted at local health centers. The COPCORD questionnaire screened the number of cases with musculoskeletal complaints. Identification of cases with rheumatic disease was based on American College of Rheumatology (ACR) criteria. Results. Respondents completed 3006 questionnaires (phase I response rate 98%). Of these 489 respondents had musculoskeletal complaints. Functional disability was reported in 25% among these respondents. We examined 353 (phase II response rate 72%), revealing 294 with rheumatic conditions. In 26 persons there were no abnormalities, while 32 had nonrheumatic conditions at examination. The most common rheumatic diseases were osteoarthritis (OA) (n = 124) and soft tissue rheumatism (n = 115). Conclusion. The prevalence of musculoskeletal complaints was 16.3% (95% CI 8.6-24.0) of the adult population in a Filipino urban community. The total prevalence of rheumatic disease is 9.8% (95% CI 8.2-11.4). The prevalence of OA was 4.1% (95% CI 3.3-4.9) and soft tissue rheumatism 3.8% (95% CI 2.9- 4.8). The prevalence of rheumatoid arthritis; 0. 17% (95% CI 0-0.36), was notably low compared to the prevalence in other developing countries.
PURPOSE OF REVIEW: Alkaline phosphatase is an important component in hard tissue formation, highly expressed in mineralized tissue cells. It is appropriate to review the current status of this important enzyme. RECENT FINDINGS: The mechanism with which this enzyme carries out its function is not completely understood, but it appears to act both to increase the local concentration of inorganic phosphate, a mineralization promoter, and to decrease the concentration of extracellular pyrophosphate, an inhibitor of mineral formation. The enzyme is localized to the outside of the plasma membrane of cells, and of the membrane of matrix vesicles. It is attached to the membrane by a glycophosphatidylinositol anchor, and is found in membrane microdomains known as rafts. Alkaline phosphatase has also been implicated in cardiovascular calcification which appears to proceed by an osteogenic mechanism. Significant interest in alkaline phosphatase expression has also come from tissue engineering experiments, where enzyme expression is a good predictor of neotissue mineralization. SUMMARY: The high level of activity in this field is sure to provide new and important information into the fundamental mechanisms of hard tissue formation, provide therapeutic opportunities for treatment of bone diseases, and enhance our ability to create useful bone biomaterials.
Regulation of important biological processes such as proliferation and differentiation of articular chondrocytes is known to be mediated by prostaglandin E(2) (PGE(2)) in both normal and pathological states. Articular chondrocytes also undergo apoptosis, a biological phenomenon implicated in many physiological processes. Whether or not PGE(2) induces apoptosis in articular chondrocytes, however, is not known.
Bovine articular chondrocytes were cultured with or without PGE(2) for 24 h and amounts of fragmented DNA, which is a distinct characteristic of apoptosis, were measured by enzyme-linked immunosorbent assay. Also effect of cyclic AMP (cAMP), which is one of the intracellular downstream mediator of PGE(2), on chondrocyte apoptosis was investigated.
Administration of exogenous PGE(2) on bovine articular cartilage grown as a monolayer culture resulted in the induction of DNA fragmentation. This DNA fragmentation was accompanied with a marked dose-dependent increase in intracellular cAMP. Also cultured cells were treated with cAMP analogue, dibutyryl-cAMP or forskolin, a direct activator of adenylate cyclase, and the incidence of apoptosis in the chondrocytes was determined. As well as PGE(2), dibutyryl-cAMP and forskolin stimulated chondrocyte DNA fragmentation.
It is the first report that PGE(2) can induce articular chondrocyte apoptosis in vitro. It is also suggest that apoptosis of chondrocytes by PGE(2) is linked with cAMP-dependent pathway.