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)

We demonstrated the simultaneous occurrence of psoriatic arthropathy and the 2 major types of crystalline arthritis--pseudogout and gout. The crystals found within aspirated synovial fluid and exudative leukocytes were unequivocally identified using the compensating polarizing microscope as calcium pyrophosphate dihydrate in one case and sodium monourate in the other. The surface topography of the intracellular sodium monourate crystals were also displayed.
 ...
PMID:Psoriatic arthropathy and crystal-induced synovitis. 737 24

Human neutrophils at inflammatory sites may be an important source of the chemotactic cytokines macrophage inflammatory protein 1 alpha (M1P-1 alpha; a C-C chemokine) and interleukin 8 (IL-8; a C-X-C chemokine). In this study, we show that the inflammatory microcrystals monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD), the major mediators of gout and pseudogout, differentially regulate the production of these two chemokines by human neutrophils. Both MSU and CPPD increased the secretion of IL-8 by neutrophils in a dose- and time-dependent manner, but had no effect on that of MIP-1 alpha. Since inflammatory cytokines are likely to be present in the synovium during crystal-induced inflammation, we examined the interaction between TNF-alpha and GM-CSF and the crystals. Both TNF-alpha and GM-CSF stimulated IL-8 production; however, only TNF-alpha exerted a significant effect on MIP-1 alpha secretion in neutrophils. IL-8 production induced by TNF-alpha and GM-CSF was synergistically enhanced in the presence of MSU or CPPD, whereas MIP-1 alpha secretion induced by TNF was completely inhibited in the presence of either MSU or CPPD. Interestingly, no interaction between the crystals and the inflammatory cytokines was observed with respect to synthesis of the C-X-C chemokine MGSA in neutrophils. These results suggest that the combination of TNF-alpha and GM-CSF with MSU or CPPD will lead to the production of IL-8 by neutrophils and abolish the release of MIP-1 alpha, an event that will theoretically lead to recruitment of neutrophils but not mononuclear cells. These results are in accordance with the pathological state of gout and pseudogout, where the predominant inflammatory cell is the neutrophil.
 ...
PMID:Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein 1 and interleukin 8 by human neutrophils: a possible mechanism of neutrophil recruitment to sites of inflammation in synovitis. 750 47

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

Crystal-associated arthritis includes gout, calcium pyrophosphate deposition (CPPD) disease, and the basic calcium phosphate (BCP)-related syndromes. In this article, the authors discuss the use of drug combinations and steroids for refractory gout patients and recommend management strategies for gout in the organ transplant recipient. Difficult cases of CPPD disease can be treated with colchicine and intra-articular steroids. The BCP-associated syndromes are best managed with NSAIDs and intraarticular measures. Experimental therapies for all forms of crystal-related arthritis are also discussed.
 ...
PMID:Treatment of refractory crystal-associated arthritis. 773 65

Findings on the efficacy of nutritional supplements used by athletes are reviewed. Many athletes have turned away from anabolic steroids and toward nutritional supplements in the hope of gaining a competitive edge without threatening their health. Athletes may require slightly more protein than sedentary people do to maintain positive nitrogen balance, but it is dubious whether extra dietary protein will help someone to achieve athletic goals. Purified amino acids have become a popular if expensive form of protein supplementation; there is no scientific evidence, however, to support their use. Excessive protein supplementation can lead to dehydration, gout, liver and kidney damage, calcium loss, and gastrointestinal effects. Supplementation with vitamins and minerals in excess of recommended daily allowances appears to have no effect on muscle mass or athletic performance. Other substances touted as having ergogenic properties are carnitine, cobamamide, growth hormone releasers, octacosanol, and ginseng; again, there is no reliable scientific evidence to support claims that products containing these compounds have ergogenic potential, and heavy supplementation may lead to adverse effects. Nutritional supplements are promoted through unsubstantiated claims by magazine advertisements, health food stores, coaches, and other sources. The FDA considers nutritional supplements to be foodstuffs, not drugs, and therefore has not required that they be proved safe and effective. Dosage guidelines are inadequate, and quality control is poor. The FDA has begun to revise regulations governing labeling and health claims for these products. There is little if any evidence that nutritional supplements have ergogenic effects in athletes consuming a balanced diet, and some products have the potential for harm.
 ...
PMID:Efficacy of nutritional supplements used by athletes. 813 7

The mechanism of crystal deposition in joints varies with the chemical nature of the crystal. Crystallisation of monosodium urate, characteristic of gout, requires a neutral pH and supersatured tissues, which is the basis for the clinical definition of the upper limit of normal blood uric acid level. The appearance of crystals also is dependent on time since crystallisation of monosodium urate is very slow. Inhibitory or promoting factors could intervene and explain rare cases of gout without hyperuricemia or the rapid crystallisation which seems to characterise some types of drug-induced gout. Crystal deposits of calcium pyrophosphate dihydrate form mainly in the cartilage where they seem favoured by ageing or by trauma, which could deplete cartilage of crystallisation inhibitors, notably proteoglycans. High pyrophosphate levels within cartilage also play an important role. The appearance of these pyrophosphates in the interstitial cartilagenous medium would be in large part due to the activity of an ectoenzyme, nucleoside triphosphate pyrophosphatase; increased activity of this ectoenzyme could be responsible for some chondrocalcinosis. Chronic hypercalcaemia can also be involved in the pathogenesis of cartilage deposition of calcium pyrophosphate dihydrate by raising the calcium-pyrophosphate product, or by decreasing the activity of alkaline phosphatase, an enzyme responsible for breakdown of extracellular pyrophosphates. The pathophysiology of calcium phosphate deposits is poorly understood. For some authors, these deposits occur within matrix vesicles, but for others, within collagen fibres. Increase in the calcium-phosphate product can also be a cause, for example, during renal osteodystrophy or vitamin D intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Mechanism of crystal deposition in the joints]. 817 67

Articular chondrocalcinosis is identified by radiological opacity of articular cartilage and fibrocartilage with calcium intensity. This disease is often asymptomatic. The most significant clinical pattern is an acute arthritis, caused by microcrystals of calcium pyrophosphate dihydrate, the so-called pseudo-gout syndrome. Chronic pyrophosphate arthropathy can blend mechanical illness and inflammatory flares. When the X-rays are normal or display ordinary osteoarthritis, arthrocentesis makes the diagnosis thanks to the identification of calcium pyrophosphate crystals by polarizing microscope. Large joints are usually involved but the disease can impair the spine, small joints, tendon sheaths or synovial bursae. Though unpredictable the evolution can be worse than that of common osteoarthritis and strike joints that are usually spared by primary arthrosis. One can even see articular destruction. Thus certain patients may resemble rheumatoid arthritis, others a Charcot joint. The disease does not exist in children. Its outcome before the age of fifty implies the search for familial occurrence or a secondary form (hyperparathyroidism, hypophosphatasia, hemochromatosis, hypomagnesemia). The sporadic, primary chondrocalcinosis is very frequent in old age.
 ...
PMID:[Clinical manifestations of joint chondrocalcinosis]. 817 72

Monosodium urate, calcium pyrophosphate dihydrate, and basic calcium phosphate (carbonate-substituted hydroxyapatite and octacalcium phosphate) crystal aggregates are associated with gout, pseudogout, and cartilage degeneration (osteoarthritis, Milwaukee Shoulder/Knee Syndrome), respectively. Hyperuricemia is a frequent but nonspecific and inconstant feature of gout just as an elevated synovial fluid inorganic pyrophosphate level is an inconstant feature of pseudogout. Monosodium urate, calcium pyrophosphate dihydrate, or basic calcium phosphate crystals can cause acute inflammation associated with phagocytosis by neutrophilic leukocytes. Each induces neutral protease synthesis and secretion and arachidonic acid metabolism by synoviocytes and macrophages in a dose-dependent fashion, postulated to produce the damage to bone, cartilage, and other joint tissues that is perceived clinically as tophaceous destruction or degenerative joint disease. Crystals containing calcium are potent mitogens. All three types of crystals are more common in older persons and will attract additional attention as the mean age of our population increases. Gout is perhaps the most treatable disease in medicine, although mistakes in diagnosis and in choice of appropriate therapy are very common. Acute pseudogout and acute calcific periarthritis are readily treated medically, but the chronic effects of crystals containing calcium are not. New approaches using drugs derived from scientific study of the biologic effects of these crystals may become useful therapeutically.
 ...
PMID:Crystals and arthritis. 819 28

Chondrocalcinosis is a really frequent clinicopathologic entity, which is caused by the penetration of calcium pyrophosphate dihydrate microcrystals into the structures of the joint, including hyaline cartilages and fibrocartilages--hense its name--as well as the synovial fluid and membrane. Calcium gout, which preferentially appears in the knees, is the most spectacular and characteristic symptom of chondrocalcinosis, expressing a crisis of acute microcrystal synovitis, of which it has all the usual clinical features, and thus simulating uratic gout. The positive diagnosis is based on: a) the radiologic demonstration of articular calcifications in the lining cartilages, forming a continuous or fragmented opaque border on the subchondral bone, from which it is separated by a light space, and/or in the fibrocartilaginous structures (most often the menisci, the symphysis pubis, the disk of the inferior radioulnar joint) where they appear as small, irregular clusters with blurred or cloudy margins. The knee is the most frequent site of calcium impregnation images, both in hyaline cartilages and in fibrocartilages. b) the presence of calcium pyrophosphate microcrystals in the synovial fluid; their nature is usually demonstrated convincingly enough with a conventional light microscope; c) needle biopsy findings of microcrystalline clusters embedded in the synovial membrane, that can be easily identified with routine staining. In practice, demonstrating radiologic signs, when these are characteristic and can be detected in their preferred sites, allows recognizing diffuse chondrocalcinosis in satisfactory safety conditions after a calcium gout crisis, as well as in the presence of the many atypical or misleading symptomatic aspects of this microcystal arthropathy, that will be the subject of a further paper.
 ...
PMID:[Role of radiology in the diagnosis of joint chondrocalcinosis. Calcium pseudogout]. 828 7

The activation of human neutrophils by monosodium urate and calcium pyrophosphate dihydrate crystals is believed to play a critical role in the pathogenesis of arthritides such as acute gout and pseudogout, respectively. In this study, we investigated the potential involvement of tyrosine phosphorylation in microcrystal-mediated activation of human neutrophils. Immunoblot analysis with antiphosphotyrosine antibodies demonstrated that triclinic monosodium urate and calcium pyrophosphate dihydrate crystals stimulated a time- and concentration-dependent tyrosine phosphorylation of at least five proteins (pp130, 118, 80, 70, and 60). While phosphoprotein (pp) 118 and pp70 were the major phosphorylated substrates, pp70 was the dominant one in reactivity with antiphosphotyrosine antibodies. When the temporal patterns, as well as the levels of tyrosine phosphorylation for both types of crystals were compared, monosodium urate crystals were found to be more potent activators than calcium pyrophosphate dihydrate crystals. The tyrosine phosphorylation patterns induced by microcrystals differed from those stimulated by other soluble (FMLP, C5a, or leukotriene B4) or particulate (unopsonized latex beads or zymosan) agonists which stimulated preferentially the tyrosine phosphorylation of pp118. The ratio of the intensities of pp118 and pp70 were specific of the stimulation with microcrystals when compared to those observed with the other soluble or particulate agonists. Colchicine, a drug used specifically in the treatment of gout and pseudogout, inhibited microcrystal-induced tyrosine phosphorylation, while beta- and gamma-lumicolchicine were without effect. On the other hand, colchicine failed to inhibit FMLP-induced tyrosine phosphorylation. Furthermore, while colchicine inhibited the activation of the NADPH oxidase by microcrystals, it, on the other hand, enhanced the production of superoxide anions by FMLP. Taken together, these results (a) demonstrate that tyrosine phosphorylation is involved in the mechanism of activation of human neutrophils induced by microcrystals; and (b) suggest, on the basis of the characteristics of the observed patterns of tyrosine phosphorylation, that this response may be specific to the microcrystals and relevant to their phlogistic properties.
 ...
PMID:Crystal-induced neutrophil activation. III. Inflammatory microcrystals induce a distinct pattern of tyrosine phosphorylation in human neutrophils. 838 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>