Showing papers on "Xanthine published in 1971"

Microscopic studies on skeletal muscle in gout patients treated with allopurinol.

Abstract: Crystals of hypoxanthine and xanthine and of oxipurinol (a metabolite of allopurinol) have been found in skeletal muscle biopsies from gout patients who are being treated with the xanthine oxidase inhibitor, allopurinol. These patients have no clinical manifestations of muscle disease. Biopsies from normal control subjects contained no more than two hypoxanthine crystals per standard size section, and no other crystals. Untreated gout patients' biopsies usually contained crystals of one or more of the following: anhydrous uric acid, uric acid dihydrate, sodium urate monohydrate, and no other crystals. The crystals were identified by: their size and shape, their extinction angle, their sign of birefringence, their refractive index, and the degree of asymmetry of the birefringence which was measured by positive and negative compensation in media of different refractive index. The latter method is described in the Appendix to this paper. The implications of these results for the treatment of gout, their relationship to the findings in congenital xanthine oxidase deficiency (xanthinuria) and the possible metabolic origin of the crystals are discussed.

Interactions of xanthine derivatives, catecholamines and glucose-6-phosphate on the isolated phrenic nerve diaphragm preparation of the rat.

Abstract: Aminophylline and caffeine produced an aug mentation of the twitch response of the isolated phrenic nerve diaphragm preparation caused either by direct or indirect stimulation. Both catecholamine and neostigmine potentiated the effect of xanthine derivatives. The effects of amino phylline and caffeine, both during indirect and direct stimulation, were equally depressed or abolished by nicotinic acid. Cyclic-3’,5’-AMP itself did not affect either the response of diaphragm to indirect or direct stimulation. Both xanthines exhibited an anti-curare effect. The effects of xanthine derivatives and catecholamines were well correlated with the action of glucose-6-phosphate, which by itself produced the same effects as did aminophylline, caffeine and catecholamines.

A quantitative study of skeletal-muscle purines and pyrazolo(3,4-d)pyrimidines in gout patients treated with allopurinol.

Abstract: SUMMARY 1. Hypoxanthine, xanthine, uric acid, allopurinol and oxipurinol have been deter­ mined in skeletal-muscle biopsies by quantitative high-resolution mass spectrometry. 2. The results obtained in six untreated gout patients and in seven gout patients who had been treated with the xanthine oxidase inhibitor allopurinol for periods of about 2 years, have been compared with those obtained on muscle tissue from non­ gouty subjects and with the results of previous microscopical studies of the same biopsies. 3. Measurable amounts of xanthine were detected more frequently in the allopuri­ nol-treated gout patients than in the untreated patients. The concentration of uric acid was generallylower in the allopurinol-treated than in the untreated gout patients' muscle; and all except one of the allopurinol-treated subjects' tissue contained a measurable amount of oxipurinoI. Allopurinol was detected less frequently than oxi­ purinoI. 4. The concentrations of hypoxanthine and xanthine in the allopurinol-treated patients' muscle tissue are very much less than those which have been reported in congenital xanthine oxidase deficiency. 5. It is concluded that allopurinol can still be recommended as a useful drug in the treatment of gout but that longer studies during the clinical use of the drug would be of value. The xanthine oxidase inhibitor allopurinol has been used extensively for the long-term treat­ ment of gout since its introduction into clinical practice in 1963 (Rundles, Wyngaarden, Hitchings, Elion & Silberman, 1963). The drug gives rise to few untoward side effectsin spite of the profound biochemical changes which it induces. The latter include: reduced oxidation of hypoxanthine and xanthine to uric acid, suppression of purine biosynthesis de novo (Kelley, Rosenbloom, Miller & Seegmiller, 1968; Kelley & Wyngaarden, 1970),increased utilization of

Structural Studies on Complexes. VI. X-Ray Investigation of A 2 : 1 5-Chlorosalicylic Acid : Theobromine Complex

Abstract: The dominant force of attraction in the 2 : 1 5-chlorosalicylic acid : theobromine crystalline complex is hydrogen bonding. There are three relatively strong hydrogen bonds, all involving a carboxyl group of the salicylate. A substantial degree of π overlap exists between the phenyl ring of the acid and the xanthine nucleus.

[128] Rabbit liver N1-methylnicotinamide oxidase (Aldehyde:Oxygen oxidoreductase, EC 1.2.3.1)

Abstract: Publisher Summary This chapter discusses the spectral and radioactive assay method used for the isolation of rabbit liver N-methylnicotinamide oxidase The spectral assay is based on the increase in optical density measured at 300 mμ due to the oxidation of N-methylnicotinamide to N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone- 3-carboxamide At the pH of the assay mixtures, the two pyridones have identical spectra This assay is used in monitoring the course of the isolation of rabbit liver N-methylnicotinamide oxidase due to its simplicity However, it has the liability that in crude homogenates it does not have the sensitivity necessary to distinguish between the oxidation of N-methylnicotinamide by xanthine oxidase and that by N-methylnicotinamide oxidase The procedures adopted to assure the validity of the isolation procedure are also discussed Two approaches are used to evaluate the extent of the contamination of N-methylnicotinamide oxidase with xanthine oxidase These are the direct assay using xanthine as substrate and the inclusion of allopurinol, an inhibitor of xanthine oxidase, in spectrophotometric assays for N-methylnicotinamide oxidase Optimal enzyme activity is dependent on the use of healthy, well-fed, and mature animals

Effect of riboflavin deficiency on the metabolism of oxypurines in chicks.

Abstract: Day-old broiler chicks of both sexes were used in three experiments to determine the effect of riboflavin deficiency on oxypurine metabolism catalyzed by xanthine dehydrogenase, a riboflavin-containing enzyme. Chicks fed a riboflavin-deficient diet (1.38 mg/kg) for 3 weeks exhibited depressed growth and a high incidence of curled-toe paralysis (higher than 80%) as compared to control chicks (15.1 mg riboflavin per kilogram diet; no incidence of curled-toe paralysis). In addition, the precursors of uric acid, hypoxanthine and/or xanthine, accumulated in the liver and kidney of deficient chicks showing curled-toe paralysis. These observations show that dietary riboflavin being incorporated into xanthine dehydrogenase is essential for oxypurine metabolism. Moreover in the chick, the liver and the kidney may be important sites of uric acid synthesis. The low uric acid concentration in the plasma of the deficient chicks appeared to be indicative of a disturbance in uric acid synthesis in the liver and kidney.

Cardioactive xanthinyl-guanylhydrazones

Abstract: Cardioactive xanthinyl-guanylhydrazones Title cpds. of formula (I) (where X is a xanthine ring such as theophylline or theobromine, R is H, alkyl, opt. substd. aryl or a heterocyclic ring, and n is 1-6) are prepd by conventional methods, pref. by condensing X(CH2)nCR=O with aminoguanidine or its salts. The products have superior cardiac activity to that of the present xanthines and their toxicity is low.

Effects of glutamine on purine metabolism in the lesch-Nyhan syndrome

Abstract: Glutamine (GLN) is the amino donor in two reactions of de novo purine synthesis and in the formation of guanylic from xanthylic acid (XMP). When confluent cultures of fibroblasts from normal individuals or from patients with the Lesch-Nyhan syndrome (LN) are maintained in GLN-free medium for 24 hours, their rate of de novo synthesis decreases to one-tenth of control cultures. Addition of GLN causes a 5–15-fold stimulation in both types of cells, but at comparable levels of GLN the rate in LN fibroblasts remains 2–5 times higher than normal. In GLN-free medium, LN cells convert 50% more adenine-14C to nucleotides than do normal cells. Of the radioactivity taken up, 1.1% is diverted to guanine nucleotide synthesis in the normals, and 2.8% in LN fibroblasts (sum of radioactivity in guanine nucleotides, XMP, the corresponding nucleosides and bases). In GLN-free medium, XMP, xanthosine, and xanthine contain 67% of this total in the mutants and 43% in the normals. Addition of GLN brings about a decrease in the total incorporation into the componets of the pathway, but a net increase in guanine nucleotide synthesis, as only 4% of the radioactivity is now found in the xanthine compounds in the mutants and 8.8% in the normals. The results show that the availability of GLN can be rate-limiting not only to de novo purine synthesis, but also to guanine nucleotide formation at the XMP aminase reaction. LN cells appear to be more sensitive to GLN deprivation in this reaction, and yet are solely dependent on it for guanine nucleotide synthesis, as they are grossly deficient in hypoxanthine guanine phosphoribosyltransferase activity.

[168] Determination of the xanthine oxidase

Abstract: Publisher Summary Xanthine—oxygen oxidoreductase is an enzyme that contains riboflavin in its molecule in the form of flavine-adenine dinucleotide (FAD). This chapter focuses on the determination of the xanthine oxidase. It is determined aerobically by Warburg manometry and anaerobically by using triphenyltetrazolium chloride (TTC). The TTC method is colorimetric and more readily adapted for measuring very low titers of the enzyme. It can be made more sensitive by using a longer time of incubation. Titers of xanthine oxidase in human milk or in the milk of animals thatis given tungstate are very low but is measured by the TTC method. Xanthine is omitted to obtain blanks. These blanks are easily measureable in cows' milk but are often negligible in goats' milk. Blanks on boiled cows' milk show color because the enzyme is not completely destroyed by boiling. Large blanks can be encountered in internal organs such as liver, because of the well-known nonspecific reduction due to endogenous respiration. The enzyme, in this type of assay is referred to as xanthine dehydrogenase, is measured by the amount of formazan it produces in a given time.

The antinociceptive and anti-exudative action of a xanthine oxidase inhibitor (allopurinol) and of xanthine.

Abstract: Using two different writhing syndromes(arachidonic acid peroxide- and phenyl-p-benzoquinoneinduced writhing in the mouse), it was shown that allopurinol displays an antinociceptive action This ‘milda

Studies in the imidazole series: LV. Synthesis of imidazo[1,2-f]xanthine derivatives based on 8-methylmercaptotheophylline

Abstract: Imidazo[1,2-f]xanthine derivatives were synthesized by the reaction of 8-methylmercaptotheophylline withα-haloketones and subsequent heating of the 7-acylalkyl-8-methylmercaptotheophyllines with ammonia and primary amines.

Genetic control of enzyme structure in hyperuricemia

Abstract: 1. 1. A correlation has been made between the hyperuricemic condition in one of the polymorphic forms of Aedes aegypti larvae (yellow) and a structural modification in the molecular organization of the enzyme xanthine dehydrogenase. 2. 2. There is differential accumulation of xanthine and hypoxanthine in the wild type and uric acid in the mutant yellow; these purines were partial inhibitors of XDH. 3. 3. The nutritional conditions of rearing determined the degree of hyperuricemia; the hybrid produced more uric acid than either homozygotes when reared with high concentrations of food suggesting polygenic regulation. 4. 4. Application of these results to the explanation of human hyperuricemia is discussed.

pH/R f diagrams of nucleotide bases

Abstract: The chromatographic mobilities of uracil, cytosine, thymine, orotic acid, adenine, guanine, hypoxanthine, and xanthine as functions of the pH of buffer systems in the pH range from 0 to 12 have been studied by absorption chromatography on paper. Changes in R f are observed comparatively rarely in the regions of the pKa values.