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Eur Surg Res. 1995;27(5):285-91.
Allopurinol effects in rat liver transplantation on recovery of energy metabolism and free radical-induced damage.

Kusumoto K, Morimoto T, Minor T, Uchino J, Isselhard W.

Institute for Experimental Medicine, University of Cologne, Germany.

Rat livers were orthotopically transplanted after 90-min cold ischemia (group 1) or after 20-min warm and 70-min cold ischemia without (group 2) or with (group 3) allopurinol treatment (AT) (50 mg/kg i.v. 10 min prior to warm ischemia into the donor, flush perfusates with 1 mmol/l). Recovery processes were followed up for 60 min of reperfusion. Liver tissue levels of ATP and total adenine nucleotides were restored in group 1 to almost preischemic ranges within 15-30 min, remained significantly reduced by 30 and 20%, respectively, in group 2, and recovered with AT within 60 min in group 3 to almost the same extent as in group 1. A massive increase in the tissue malondialdehyde concentration, indicative of lipid peroxidation, occurred in the beginning of reperfusion of warm-ischemically damaged donor livers, which in group 3 with AT tended to be less pronounced than in group 2 without AT. The GSSG/GSH ratio reflecting intracellular oxidant stress averaged 3.3 x 10(-3) in group 1 between 15 and 60 min reperfusion. In group 3 AT resulted in comparably low values averaging 3.8 x 10(-3), while in warm-ischemically damaged livers without AT of group 2 this ratio was significantly and continuously elevated averaging 5.8 x 10(-3).(ABSTRACT TRUNCATED AT 250 WORDS)

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Cell Biochem Funct. 1994 Dec;12(4):237-45.
Uric acid synthesis by rat liver supernatants from purine bases, nucleosides and nucleotides. Effect of allopurinol.

Bleisch S, Sillero MA, Torrecilla A, Sillero A.

Departamento de Bioquimica, Facultad de Medicina, Universidad Autonoma de Madrid, Spain.

The synthesis of uric acid from purine bases, nucleosides and nucleotides has been measured in reaction mixtures containing rat liver supernatant and each one of the following compounds at 1 mM concentration (except xanthine, 0.5 mM and guanosine and guanine, 0.1 mM). The rates of the reaction, expressed as nanomoles of uric acid synthesized g-1 of wet liver min-1 were: ATP, 10; ADP, 37; AMP, 62; adenosine, 108; adenine 6; adenylosuccinate, 9; IMP 32; inosine, 112; hypoxanthine, 50; GTP, 19; GDP, 19; GMP, 27; guanosine, 34; guanine, 72; XMP, 10; xanthosine, 24; xanthine, 144. These figures divided by 55 correspond to nanomoles of uric acid synthesized min-1 per mg-1 of protein. The rate of synthesis of uric acid obtained with each one of those compounds at 0.1 and 0.05 mM concentrations was also determined. ATP (1 mM) strongly inhibited uric acid synthesis from 0.05 mM AMP (91 per cent) and from 0.05 mM ADP (88 per cent), but not from adenosine. CTP or UTP (1 mM) also inhibited (by more than 90 per cent) the synthesis of uric acid from 0.05 mM AMP. Xanthine oxidase was inhibited by concentrations of hypoxanthine higher than 0.012 mM. The results favour the view that the level of uric acid in plasma may be an index of the energetic state of the organism. Allopurinol, besides inhibiting uric acid synthesis, reduced the rate of degradation of AMP. The ability of crude extracts to catabolize purine nucleotides to uric acid is an important factor to be considered when some enzymes related to purine nucleotide metabolism, particularly CTP synthase, are measured in crude liver extracts.

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Circ Shock. 1982;9(4):369-74.
Changes in hepatic lipoperoxide concentration in endotoxemic rats.

Ogawa R, Morita T, Kunimoto F, Fujita T.

Wistar strain rats were treated with E. coli endotoxin by intraperitoneal injection (1 mg/100g body weight). Three hours after injection, the livers were excised to determine lipoperoxide concentration and superoxide dismutase activity. A significant elevation of lipoperoxide concentration and a marked reduction of superoxide dismutase activity were observed. Treatment with xanthine oxidase inhibitor were observed. Treatment with xanthine oxidase inhibitor allopurinol (10 mg/100g) 20 minutes prior the injection of endotoxin inhibited the elevation of lipoperoxide and the reduction of superoxide dismutase induced by endotoxin. Pretreatment of free radical scavengers such as reduced glutathione and alpha-tocopherol prevented the accumulation of lipoperoxide in the liver. Reduced glutathione protected the hepatic superoxide dismutase from decrease by endotoxin treatment. However, alpha-tocopherol did not maintain liver superoxide dismutase activity following the injection of endotoxin. These results indicate that endotoxemia gives rise to the accumulation of hepatic lipoperoxide by the activation of a production system and impairment of an elimination system of superoxide radicals.

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