Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence suggests an important role for kinins in the generation of pain, swelling and the cellular damage associated with inflammatory joint disease. Kinins are considered to be pro-inflammatory peptides for a variety of reasons. They stimulate c fibres in the synovium to cause pain and increase extravasation of fluid to produce swelling. Kinins possess the capacity to release neurotransmitters (substance P, acetylcholine) and a second wave of mediators (interleukin-1, tumour necrosis factor, interleukin-8, prostaglandins, leukotrienes). The steady levels and turnover of kinins is regulated by formation (enzymic action of kininogenases on endogenous substrates called kininogens) and by metabolism (kininases, peptidases that hydrolyse kinins). These components of the kinin system can enter the synovial joint space either by transudation from the plasma or from degranulating neutrophils chemotactically attracted into the synovium from which they migrate into the synovial fluid. If kinins are involved, one would expect neutrophil derived mediators of the system to dominate in rheumatoid arthritis and psoriatic arthritis and plasma derived products to be more important in osteoarthritis and gout. But, the question whether any of the functions attributed to each component of the system can be considered to be a primary factor in the cellular pathology of inflamed joints remains to be established. Future investigations, including therapeutic trials with kinin antagonists and kallikrein inhibitors, will need to address the differential role of the kallikreins and kinins in the different types of synovitis, on symptoms of inflammation and on any remedial effects on the progression of tissue damage within the joint.
 ...
PMID:Kinins--key mediators in inflammatory arthritis? 164 49

The third and the fourth fraction of the complement (C3 and C4), haptoglobin, fibrinogen, alpha 1-glycoprotein, alpha 2-macroglobulin and transferrin were examined in 692 patients with inflammatory joint disease--rheumatism, rheumatoid arthritis, ankylosing spondylarthritis, psoriatic arthritis, Reiter's syndrome, sacroiliitis [correction of sacroileitis], reactive arthritis, gout, osteoarthrosis and nosologically undefined arthritis in active or nonactive phase and in 60 healthy controls. The complement fractions studied show an increase of various degree and importance in almost all groups of patients in both phases studied. The relations between the complement fractions and the other acute phase indices show significant correlations between them and the other acute phase indices. C3 and to a certain degree C4 could be added to the acute phase reacting indices. Their place in the downgrade scale is as follows: fibrinogen, haptoglobin, alpha 1-glycoprotein, C3, C4, alpha 2-macroglobulin, transferrin.
 ...
PMID:[A comparative study of serum complement (C3 and C4) in inflammatory joint diseases]. 170 1

Gout is an inflammatory joint disease that primarily affects middle-aged men and postmenopausal women. It is characterized by severe pain and erythema in the big toe and other affected joints. Acute gout may be triggered by diuretics, aspirin, minor trauma, or acute illness. The presence of monosodium urate crystals within phagocytes from synovial fluid aspirates is almost always diagnostic. Calcium pyrophosphate deposition disease ("pseudogout") usually affects larger joints and often follows trauma, surgery, or ischemic heart disease. Microscopic examination of crystals under compensated polarized light is used to differentiate gout and pseudogout. Disorders involving basic calcium phosphate are often more difficult to diagnose and treat but are also less likely to be disabling.
 ...
PMID:Gout or 'pseudogout': how to differentiate crystal-induced arthropathies. 772 Nov 12

There have been few epidemiological studies of bone and joint diseases in black Africa. Available data were generated by hospital studies which were inevitably flawed by selection bias. They found that the incidence and/or severity of rheumatoid arthritis were reduced in West Africa but not in urban areas of Southern and East Africa, as compared with industrialized countries. Ankylosing spondylitis was infrequent. The human immunodeficiency virus epidemic can be expected to increase the prevalence of spondyloarthropathies despite the fact that few black Africans are HLA B27-positive. Gout was the most common inflammatory joint disease seen in inpatients in West Africa and Equatorial Africa. Osteoarthritis of the fingers or hip and dysplasia of the hip were infrequent. The main causes of hip symptoms were sickle cell anemia and hemoglobin C disease whose manifestations include bone necrosis, osteomyelitis, and attacks of bone and joint pain. Osteoarthritis of the knee was common in West and Southern Africa, especially in obese women. Low back pain and sciatica due to disc herniation were as common as in Europe. Lumbar canal stenosis appeared more common in West Africa than in Southern Africa, with a predominance in females. Postmenopausal osteoporosis was exceedingly rare. Infectious diseases were prevalent as a result of underindustrialization and defective hygiene. The paucity of rheumatologists, young mean age of the population, and scarcity of population-based studies are sources of bias which should be taken into account when interpreting the available data on rheumatological diseases in black Africa. In the future, more rigorous studies made possible by increased access to health care will provide improved insight into the semiology and epidemiology of bone and joint diseases in this area.
 ...
PMID:[Rheumatic diseases in black Africa]. 812 80

Macrophages infiltrated into synovium play an important role in joint destruction in inflammatory joint diseases. In this study we focused on the production of monocyte chemoattractant protein-1 (MCP-1), a recently identified monocyte chemotactic protein, by inflammatory synovium. Synovial fluid (SF) from rheumatoid arthritis (RA), osteoarthritis, gout, and traumatic arthritis contained MCP-1. MCP-1 was produced in the synovium of patients with RA and other inflammatory joint disease in in vitro culture systems; differences in the amounts produced were not significant. Synovial MCP-1 production in RA was further investigated. Levels of MCP-1 were significantly correlated with levels of IL-1 beta, IL-6, and IL-8 in the culture supernatants of synovia from RA. Using immunohistochemical techniques, MCP-1 was detected in the lining and sublining cells and in the vascular endothelial cells of rheumatoid synovia. Rheumatoid synovia with active inflammation were stained more intensely by anti-MCP-1 antibody than were those with weak or inactive inflammation. IL-1 beta and TNF-alpha stimulated the expression of MCP-1 mRNA and de novo MCP-1 synthesis by cultured synovial cells. These results suggest the production of MCP-1 by synovium of various inflammatory joint diseases. In rheumatoid synovium, a cytokine network involving MCP-1 and other proinflammatory cytokines (IL-1 beta, IL-6, IL-8, and TNF-alpha) contributes to the immunopathogenesis of RA.
 ...
PMID:Monocyte chemoattractant protein-1 (MCP-1) in inflammatory joint diseases and its involvement in the cytokine network of rheumatoid synovium. 840 45

Synovial fluids from the knees of patients with degenerative joint disease (n = 29), osteoarthritis (n = 16), diabetic arthropathy (n = 12), gout (n = 7) and acute inflammatory joint disease (n = 7) were investigated by high-performance size-exclusion chromatography combined with multiangle laser light scattering detection and differential refractometry. These data were compared with the viscosities of the same samples measured by rotation viscometry with one low shear rate, as well as with C reactive protein. The median value of the weight-average molecular weight of hyaluronan in synovial fluids, which differed less than the viscosity of these groups, varied between 1.09 x 10(6) g/mol (range 0.849-1.63 x 10(6) g/mol) (acute-inflammatory joint disease) and 1.91 x 10(6) g/mol (range 1.06-3.48 x 10(6) g/mol) (degenerative joint disease). The correlation between viscosity and hyaluronan concentration was much better than between viscosity and weight-average molecular weight. Changes in C reactive protein concentration were correlated with the disease activity. The concentration of hyaluronan was significantly higher in the cases of degenerative joint disease and diabetic arthropathy. These results suggest that synovial fluid concentration of hyaluronan is appropriate as a prognostic value in the evaluation of different kinds of joint diseases.
 ...
PMID:Assay of synovial fluid parameters: hyaluronan concentration as a potential marker for joint diseases. 943 40

It has been suggested that rheumatological disorders are underdiagnosed in patients with medical problems and that this might be rectified by incorporating a standard brief screening examination as part of the routine assessment of all patients admitted to hospital with medical conditions. Therefore the GALS screening examination was used to assess the prevalence of rheumatic disease in 100 patients admitted with acute medical problems and in a further 100 in the rehabilitative phase of their disease. The nature of locomotor dysfunction in all patients with a positive result was defined by an independent review and then sensitivity and specificity of the screening test was calculated for rheumatic disease in both populations. The median age of the two populations were 63 and 78 years respectively, with more females in the rehabilitation group. The overall prevalence of a positive screening test was 53% in the acute and 94% in the chronic disease groups, although the false positive rate in the rehabilitation patients was 30% due to factors other than rheumatic disorders limiting locomotor function (mainly orthopaedic and neurological conditions). The diagnosis of a rheumatological disorder was made de novo in a significant minority (10%) of patients and was usually amenable to treatment. The commonest rheumatic disorder was osteoarthritis which accounted for 55% of all rheumatic disease, followed by inflammatory joint disease (16%), and osteoporosis (12%). In addition to osteoporosis, Paget's disease of bone and polymyalgia rheumatica were found more frequently in those patients undergoing rehabilitation than in those admitted with an acute medical problem. A number of clinically important associations between medical and rheumatic disorders were found, such as stroke disease with shoulder capsulitis and heart failure with gout. The sensitivity of the GALS screening test was extremely high (92% and 100%), while its specificity fell in the rehabilitation group from 83% to 17%. None the less, it is felt that this study indicates that the routine use of this test should be considered as part of the assessment of all hospitalised patients with medical problems, whether acute or chronic.
 ...
PMID:What is the prevalence of rheumatic disorders in general medical inpatients? 1172 16

Angiogenesis is a key process in the pathogenesis of inflammatory arthritis. Angiogenin is one of the most potent inducers of neovascularization in experimental models in vivo. To look for evidence that angiogenin is involved in inflammatory joint disease, we examined plasma and synovial fluid (SF) samples from rheumatology patients and synovial fibroblast cell culture supernatants. Angiogenin levels were determined by radioimmunoassay and ELISA. Plasma angiogenin concentrations ranged from 96 to 478 ng/ml, with no significant difference between patients and normal controls. In SF, angiogenin concentrations were significantly higher in patients with acute or chronic synovitis (rheumatoid arthritis (RA): median, 104 ng/ml; range 13-748, n = 14; crystal-induced arthritis (CIA): median, 149 ng/ml; range, 37-616, n = 14, and other chronic inflammatory arthritis: median, 42 ng/ml; range, 15-205; n = 9) than in the 18 patients with osteoarthritis (OA) (median, 20 ng/ml; range 8-116) (P < 0.0001, anova). Angiogenin levels in SF from RA patients in remission with secondary OA were similar to those achieved in primary OA, and decreased in parallel with the resolution of acute gout. Angiogenin protein was released by cultured synovial fibroblasts from OA and RA patients, and reached 1.18 ng/106 cells/day. These data suggest that angiogenin may mediate local inflammation in arthritis via effects on angiogenesis and leucocyte regulation.
 ...
PMID:Elevated angiogenin levels in synovial fluid from patients with inflammatory arthritis and secretion of angiogenin by cultured synovial fibroblasts. 1265 52

Gout and calcium pyrophosphate deposition disease are two common causes of inflammatory joint disease. Despite differences underlying their pathogenesis, their clinical presentation and treatment share some common features. Optimal treatment for both requires prompt resolution of acute synovitis, reduction of chronic joint damage and management of associated conditions. Available therapeutic interventions and future strategies are reviewed in this article.
 ...
PMID:An update on the treatment options for gout and calcium pyrophosphate deposition. 1625 76

The past 10 years have seen the description of families of receptors that drive proinflammatory cytokine production in infection and tissue injury. Two major classes have been examined in the context of inflammatory joint disease--the Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLRs such as TLR2 and TLR4 are being implicated in the pathology of rheumatoid arthritis, ankylosing spondylitis, lyme arthritis and osteoarthritis. Nalp3 has been identified as a key NLR for IL-1beta production and has been shown to have a particular role in gout. These findings present new therapeutic opportunities, possibly allowing for the replacement of biologics with small molecule inhibitors.
 ...
PMID:Toll-like receptors and NOD-like receptors in rheumatic diseases. 1983 40


1 2 Next >>