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Xanthine

About: Xanthine is a research topic. Over the lifetime, 4046 publications have been published within this topic receiving 129820 citations. The topic is also known as: Xanthine.


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Journal ArticleDOI
TL;DR: The heterozygous mutation, the chemical findings, and the positive allopurinol test altogether prove xanthinuria type I, which may present wide clinical intrafamilial variation.
Abstract: Xanthinuria type I is a rare disorder of purine metabolism caused by xanthine oxidoreductase or dehydrogenase (XDH) deficiency. We report a family with two affected children out of 335 pediatric stone patients studied since 1991 in Armenia. The propositus, a 13-month-old boy, presented with abdominal pain and urinary retention followed by stone passage (0.9×0.6 cm). Infrared spectroscopy in Yerevan revealed a pure xanthine stone. Family examination in the parents and brother was normal, but the propositus and his 8-year-old asymptomatic sister had hypouricemia, hypouricosuria, and high urinary excretion of hypoxanthine and xanthine. Ultrasonography in the index patient showed bilateral stones requiring pyelolithotomy. High fluid intake and purine restriction did not prevent further stone passages. The affected asymptomatic sister had a small pelvic stone (4 mm). Mutation analysis revealed a heterozygous novel base pair substitution in exon 25 of the XDH gene (c.2810C>T), resulting in an amino acid substitution (p.Thr910Met). The second mutation could not be detected. Despite this, the heterozygous mutation, the chemical findings, and the positive allopurinol test altogether prove xanthinuria type I, which may present wide clinical intrafamilial variation. Diagnosis is suspected usually from low serum uric acid. No specific therapy is available.

50 citations

Journal ArticleDOI
TL;DR: Direct inhibition of PMN activation as well as potentiation of catecholamine activity may be important therapeutic effects of theophylline and enprofylline.
Abstract: Methylxanthines are primary agents used in treatment of hypersensitivity disease. Because polymorphonuclear leukocyte (PMN) activation is associated with generation of potent inflammatory mediators, xanthine effects on the PMN respiratory burst were studied. Enprofylline, a xanthine with important therapeutic potential, does not antagonize adenosine and was contrasted with theophylline. Although enprofylline was more potent at low concentrations, both drugs exhibited dose-dependent inhibition of PMN activation at concentrations >10 μmol/L (1.8 μg/ml). Oxygen metabolite generation was decreased by 30% to 40% at therapeutic drug concentrations and by 85% at 1 mmol/L of theophylline. Inhibition by isoproterenol or prostaglandin E 2 but not dibutyryl cAMP was potentiated by either xanthine. Isoproterenol effects were also increased when isoproterenol was evaluated in whole blood specimens obtained from subjects after a loading dose of aminophylline. Although these results were most compatible with cAMP phosphodiesterase inhibition, other commonly proposed mechanisms of methlxanthine activity were also studied. Theophylline but not enprofylline blocked adenosine inhibition of PMN activation. Neither xanthine shifted the calcium dose-response when PMNs were activated with calcium ionophore. Because oxygen metabolites generated by the PMN are mediators of inflammation and hypersensitivity, direct inhibition of PMN activation as well as potentiation of catecholamine activity may be important therapeutic effects of theophylline and enprofylline.

49 citations

Journal ArticleDOI
TL;DR: In considering mercurial diuretics, it is proposed to summarize the well-established concepts quite briefly and to devote most of the authors' space to some of the more controversial problems that have recently arisen.
Abstract: Possibly the most remarkable thing about the xanthine diuretics is that so few facts have been established on the mechanism of their action. An increase in glomerular filtration rate undoubtedly occurs in some instances and probably accounts for a part of the diuretic action. However, an action on tubular reabsorption can also be implicated, since there are a number of circumstances in which diuresis occurs in the absence of any increase in filtered load.’ When xanthines are administered during a water diuresis there is a rapid rise in the urinary concentration of both sodium and chloride, with a concomitant increase in their rates of excretion. This effect, similar to that seen with mercurials, strongly suggests an action on the reabsorptive transport of sodium and/or chloride. Preliminary observations suggest the possibility that xanthines may increase the permeability of the renal tubule to water, but the data are not conclusive, and the possibility has not been ruled out that these effects may result from central stimulation with release of antidiuretic hormone (ADH). However, it is clear that there is an increase in solute excretion; hence we are not dealing with a type of “water diuresis” that might result from decreased secretion of ADH or from inhibition of its action. Other tubular transport systems seem not to be affected? In the hydrated dog there is an increase in potassium excretion, but this is probably not specific, since a similar increase occurs under other conditions leading to a rise in solute excretion. In contrast to the mercurials, however, xanthines do not inhibit the tubular secretion of potassium? Although acidification mechanisms have not been studied systematically, on the basis of available data it is unlikely that these are affected. Virtually nothing is known about the influence of plasma composition on xanthine diuresis. Is f H important? What of the plasma levels of bicarbonate, of chloride, or of sodium? The only pertinent study that has come to our attention is an incidental observation of Chakravarty et al.4 These investigators studied osmotic loading in the rhesus monkey and obtained a normal chloruretic response when mannitol had been given with saline. However, when mannitol was administered with water there was a fall in plasma chloride to about 15 mEq./l. below control levels, and this was associated with the absence of a diuretic response to xanthines. Certainly, this is a field that warrants a more systematic type of study. In considering mercurial diuretics, we propose to summarize the well-established concepts quite briefly and to devote most of our space to some of the more controversial problems that have recently arisen.

49 citations

Journal ArticleDOI
TL;DR: It is suggested that hydrogen peroxide could represent a specific inducer of the observed phenomenon and it may therefore be considered as an intracellular messenger involved in the regulation of some aspects of astroglial oxidative metabolism, particularly the defence against ROS.
Abstract: Cytosolic and mitochondrial alterations induced by exposure of rat astroglial primary cultures to reactive oxygen species (ROS) generated by a xanthine/ xanthine oxidase (X/XO) mixture or by lipopolysaccharide (LPS) have been investigated biochemically and irnmunochemically. In the presence of ROS generated by X/XO, a significant decrease in Cu,Zn superoxide dismutase (Cu,Zn-SOD) and in glutamine synthetase (GS) activity was observed whereas mitochondrial Mn-SOD activity and enzyme protein levels were significantly enhanced. Similar effects on GS, Cu,Zn- and Mn-SOD activities were observed by glucose/glucose oxidase treatment of the cells. Addition of LPS to the cell growth medium also specifically induces Mn-SOD synthesis but was without effect on Cu,Zn-SOD. It is suggested that in all these tested situations, hydrogen peroxide could represent a specific inducer of the observed phenomenon and it may therefore be considered as an intracellular messenger involved in the regulation of some aspects of astroglial oxidative metabolism, particularly the defence against ROS.

49 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202361
2022108
202157
202060
201961
201869