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

The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and then to uric acid, which plays a crucial role in gout. A total of 122 traditional Chinese medicinal plants, selected according to the clinical efficacy and prescription frequency for the treatment of gout and other hyperuricemia-related disorders, have been evaluated for the enzyme inhibitory activity. Among the 122 methanol extracts derived from these species, 69 were shown to be inhibitory at 100 microg/ml, with 29 having greater than 50% inhibition. As to the equal amount of water extracts, 40 were disclosed to be active at 100 microg/ml, with 13 possessing more than 50% inhibition. At 50 microg/ml, 58 methanol and 24 water extracts exhibited inhibitory activity, with 15 of the former and two of the latter showing greater than 50% inhibition. The most active was the methanol extract of the twig of Cinnamomum cassia (Lauraceae) (IC(50), 18 microg/ml), which was followed immediately by those of the flower of Chrysanthemum indicum (Asteraceae) (IC(50), 22 microg/ml) and the leaves of Lycopus europaeus (Lamiatae) (IC(50), 26 microg/ml). Among the water extracts, the strongest inhibition of the enzyme was observed with that of the rhizome of Polygonum cuspidatum (Polygonaceae) (IC(50), 38 microg/ml). The IC(50) value of allopurinol used as a positive control was 1.06 microg/ml. The study demonstrated that the effects for these medicinal plants used for the gout treatment were based, at least in part, on the xanthine oxidase inhibitory action.
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PMID:Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat gout. 1102 57

Uricase-deficient mice develop uric acid nephropathy, with high mortality rates before weaning. Urate excretion was quantitated and renal function was better defined in this study, to facilitate the use of these mice as a model for evaluating poly(ethylene glycol)-modified recombinant mammalian uricases (PEG-uricase) as a potential therapy for gout and uric acid nephropathy. The uric acid/creatinine ratio in the urine of uricase-deficient mice ranges from 10 to >30; on a weight basis, these mice excrete 20- to 40-fold more urate than do human subjects. These mice consistently develop a severe defect in renal concentrating ability, resulting in an approximately sixfold greater urine volume and a fivefold greater fluid requirement, compared with normal mice. This nephrogenic diabetes insipidus leads to dehydration and death of nursing mice but, with adequate water replacement, high urine flow protects adults from progressive renal damage. Treatment of uricase-deficient mice with PEG-uricase markedly reduced urate levels and, when initiated before weaning, preserved the renal architecture (as evaluated by magnetic resonance micros-copy) and prevented the loss of renal concentrating function. PEG-uricase was far more effective and less immunogenic than unmodified uricase. Retention of uricase in most mammals and its loss in humans and some other primates may reflect the evolution of renal function under different environmental conditions. PEG-uricase could provide an effective therapy for uric acid nephropathy and refractory gout in human patients.
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PMID:Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase. 1131 59

After describing some of the symptoms of gout and considering some causes, such as an excess of ethanol, the source of the pain in the infected joint is discussed. This is known to be from urate crystals formed in the synovial fluid inside the joint. It is suggested herein that the pain is due to grinding from the crystals through the surface film of the joint, and possibly into the bone itself, which is relatively soft. The pain then stems in part from the resulting inflammation. The key hypothesis is that these urate crystals dissolve on warming. Hence, by warming the joint concerned in hot water, and moving the joint around to encourage diffusion, the urate concentration is reduced and crystals no longer form, provided the treatment is continued.
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PMID:Self-treatment for gout. 1146 Nov 81

Chronic lead poisoning may cause hypertension, gout, and renal insufficiency. Most experimental poisoning studies have involved the use of high doses over short periods (ie, acute poisoning). Although chelating treatment leads to remission of acute lead nephropathy, its effects in the treatment of chronic poisoning are unclear. The aims of this study were to evaluate renal alterations produced during chronic lead poisoning and their progression when poisoning was over and to determine the efficiency of chelating treatment with calcium disodium ethylenediaminetetraacetate (EDTA). In this study, 56 male Wistar rats were administered lead in drinking water (500 ppm lead acetate) over 90 days. The control group consisted of 21 nonexposed rats. Seven rats from each group were killed on days 60 and 90. At the end of the 90-day period, 21 of the lead-exposed rats were treated with disodium monocalcium EDTA (50 mg/kg/d x 5 days) intraperitoneally, and 21 were administered serum saline by the same route. Three treatment courses were given separated by 9 days free of treatment. Seven rats from each subgroup were sacrificed at the end of each treatment course. Main findings related to poisoning were hypertrophy and vacuolization of medium and small arteries; mucoid edema and muscular hypertrophy in arterioles; loss of cell brush borders, cell loss, and intranuclear inclusion bodies in the proximal tubule; and fibrosis and the presence of infiltrates in the interstitial component. Treatment with EDTA slowed the progression of most alterations. No damage associated with the use of the chelating agent was observed. Longer term studies of the effects of this drug are required to establish whether the damage caused by lead poisoning may be reversed.
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PMID:Experimental lead nephropathy: treatment with calcium disodium ethylenediaminetetraacetate. 1208 80

About one-half million adults in the United States experience a renal stone each year, about two hundred thousand of whom are hospitalized; the lifetime incidence of renal stones in men is about ten percent. Risk factors for stone formation include a positive family history, nutritional factors (excessive intake of animal protein, fat, sugar, oxalates, colas, alcohol, caffeine, salt, and vitamin D), nutritional deficiencies (water, magnesium, calcium, potassium, and vitamin B6), lifestyle factors (physical inactivity and problematic pharmaceuticals), and associated disease states (osteoporosis, parathyroid problems, osteoporosis, gout and recurrent urinary tract infections). The chemical makeup of the stone is important since prevention of recurrences varies somewhat depending on the type of stone involved. The outline of preventive steps holds the potential for preventing recurrence in the vast majority of cases.
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PMID:A complementary approach to urolithiasis prevention. 1252 85

Snakes from temperate climates are often made to hibernate in zoos to stimulate reproduction. Unfortunately, deaths have occurred during and after hibernation. This study evaluated the health status, pre- and posthibernation, of 31 adult viperid snakes. It included morphometric measurements, hematology, and blood chemistry. No differences were seen in body weights and weight to length ratios between pre- and posthibernation examinations, suggesting that the overall condition of the snakes did not change. No differences were seen in hematologic and blood chemistry parameters, except that bile acids (3alpha-hydroxybile acids) decreased, the implications of which are unknown. Three individuals had markedly high plasma uric acid levels posthibernation; of these, two individuals died from extensive visceral gout and one recovered with fluid therapy. Viperid snakes should be clinically healthy, well hydrated, and in good body condition when they are put into hibernation. They should be maintained in an environment with sufficient humidity and should have access to water. Blood samples should be collected on arousal for measuring plasma uric acid levels. Changes in morphometry, hematology, and blood chemistry appear to be abnormal and should be investigated thoroughly.
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PMID:A comparison between pre- and posthibernation morphometry, hematology, and blood chemistry in viperid snakes. 1272

Ermiao wan, which is composed of phellodendri cortex and atractylodis rhizome, is described as eliminating heat, excreting dampness and anti-edema prescription in traditional Chinese medical literatures including Danxi's Experiences in Medicine and State Pharmacopoeia of People's Republic of China. So it is being used clinically in the treatment of gout and hyperuricemia in China. In the present study, the water extracts of Ermiao wan and phellodendri cortex at 840 and 480 mg/kg/day orally for 7 days were demonstrated to possess in vivo potent hypouricemic effects both in hyperuricemic mice pretreated with oxonate and in normal mice, respectively. In the hyperuricemic animals, the effect of Ermiao wan was equal to that of the reference drug allopurinol (at 10 mg/kg/day orally for 7 days), but in the normal mice, the former was weaker than latter. In addition, both Ermiao wan and phellodendri cortex were found to have in vivo relatively inhibitory effects on mouse liver xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activities at the same dose described above. These inhibitory effects were weaker than that observed for allopurinol. Atractylodis rhizome at 340 mg/kg/day orally for 7 days did not show any effects on the above experiments. These results suggested that atractylodis rhizomes assisted and enhanced the effect of phellodendri cortex on reduction of serum uric acid level in hyperuricemic mice, and hypouricemic effects of Ermiao wan and phellodendri cortex may be achieved by other mechanism partly instead of the XDH and XO inhibition.
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PMID:A Chinese herbal medicine Ermiao wan reduces serum uric acid level and inhibits liver xanthine dehydrogenase and xanthine oxidase in mice. 1523 72

Rasburicase (Fasturtec) is an enzyme that transforms uric acid to the more water soluble allantoin to be excreted by the kidneys. Rasburicase fulfills an unmet clinical need in the treatment of hyperuricemia in that it produces a more rapid action of controlling serum uric acid compared with allopurinol. Tumours with high proliferative rate and sensitive to chemotherapy such as hematological malignancies (mainly) solid tumours (occasionally) may lead to a tumor lysis syndrome. In this situation rasburicase can effectively lower serum uric acid concentrations with a secondary improvement in renal function. Hyperuricemia is the hallmark of severe gout with tophi formation. Rasburicase represents an interesting new option in controlling serum uric acid in patients with severe tophaceous gout.
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PMID:[Rasburicase (Fasturtec)]. 1549 20

The health status of Tibetan herders in the Sanjiangyuan region of the Tibetan Plateau, in southwest Qinghai Province, is assessed in this paper. The field study was conducted in 2002 in the context of a broader community development and research framework, the ultimate goal of which is to achieve an effective region-specific programme of preventative health care and training for Tibetan pastoralists. Specifically, the authors analysed the impact of a number of potentially health-related environmental and lifestyle risk factors on self-reported health indicators, with a special emphasis on mother and child health. Several health status indicators were used, including a general morbidity index and a measurement of functional incapacity due to illness in the sample households. Maternal and child health findings were alarming with high rates of miscarriage and infant loss, with no traditional midwives to assist in pregnancy and delivery. Preventable childhood illnesses were also common. Other debilitating diseases included hepatitis, tuberculosis, arthritis (gout), gall bladder disease, peptic ulcers and back pain. Finally, binary logistic regression analysis showed a significant link between general morbidity and the time it takes to obtain water. The survey findings, validated by the focus groups, indicate a real need for increased accessibility and quality of health service provision to women and men and effective preventative health strategies.
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PMID:Assessment of the health status and risk factors of Kham Tibetan pastoralists in the alpine grasslands of the Tibetan plateau. 1689 Oct 47

Xanthine oxidase inhibitory activity was assayed from six species belonging to different families traditionally used for the treatment of gout and related symptoms by indigenous people of India. The aqueous, methanol-water mixture and methanolic extract of these plants were used for the experiment. Of the 18 extracts assayed, 14 extracts demonstrated xanthine oxidase inhibitory activity at 100 microg/ml, among which 10 extracts showed an inhibition greater than 50% and IC(50) values below 100 microg/ml. The methanolic extracts of Coccinia grandis, Datura metel, Strychnos nux-vomica and Vitex negundo showed more than 50% inhibition, hence, they were screened for their in vivo hypouricaemic activity against potassium oxonate-induced hyperuricaemia in mice. Methanolic extracts of Coccinia grandis and Vitex negundo showed a significant decrease in the serum urate level (3.90+/-0.07 mg/dl, P<0.001) and (6.26+/-0.06 mg/dl, P<0.01), respectively, when compared to hyperuricaemic control (11.42+/-0.14 mg/dl). This effect is almost similar to the serum urate level of allopurinol (3.89+/-0.07 mg/dl).
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PMID:Xanthine oxidase inhibitory activity of some Indian medical plants. 1701 77


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