Drugs online research references
Eur J Biochem. 1997 May 1;245(3):541-8.
NADH oxidase activity of human xanthine oxidoreductase--generation of superoxide anion.
Sanders SA, Eisenthal R, Harrison R.
School of Biology and Biochemistry, University of Bath, UK.
Human xanthine oxidase was purified from breast milk. The dehydrogenase form of the enzyme, which predominates in most mammalian tissues, catalyses the oxidation of NADH by oxygen, generating superoxide anion significantly faster than does the oxidase form. The corresponding forms of bovine enzyme behave very similarly. The steady-state kinetics of NADH oxidation and superoxide production, including inhibition by NAD, by the dehydrogenase forms of both enzymes, are analysed in terms of a model involving two-stage recycling of oxidised enzyme. Established inhibitors of xanthine oxidoreductases (allopurinol oxypurinol, amflutizole and BOF 4272), which block all other reducing substrates, were ineffective in the case of NADH. Diphenyleneiodonium, on the other hand, was a powerful inhibitor of NADH oxidation. The potential involvement of reactive oxygen species arising from NADH oxidation by xanthine oxidoreductase in ischaemia-reperfusion injury and other disease states, as well as in normal signal transduction, is discusssed.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9182988&dopt=Abstract
Clin Sci (Lond). 1991 Mar;80(3):191-7.
Orotidine accumulation in human erythrocytes during allopurinol therapy: association with high urinary oxypurinol-7-riboside concentrations in renal failure and in the Lesch-Nyhan syndrome.
Simmonds HA, Reiter S, Davies PM, Cameron JS.
Purine Research Laboratory, Clinical Science Laboratories, UMDS, Guy's Hospital Medical School, London.
1. A compound identified as orotidine has been found in the erythrocytes of all subjects on allopurinol. 2. The erythrocyte orotidine concentrations were much higher in patients with renal failure or with the Lesch-Nyhan syndrome. 3. In addition, increased amounts of oxypurinol-7-riboside were excreted in the urine by both of these groups compared with control subjects or with patients with normal renal function on allopurinol. 4. A good correlation was found between urinary oxypurinol-7-riboside excretion and erythrocyte orotidine concentrations. 5. Increased erythrocyte levels of the pyrimidine-sugar UDP-glucose were also found in patients with the highest orotidine levels. 6. The combined results suggest a derangement of pyrimidine nucleotide metabolism during allopurinol therapy. We propose that erythrocyte orotidine formation results primarily from inhibition of orotidine-5'-monophosphate decarboxylase by oxypurinol-7-ribotide.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1850677&dopt=Abstract
J Heart Transplant. 1990 May-Jun;9(3 Pt 1):220-9.
Acute physiologic changes after extended pulmonary preservation.
Bonser RS, Fragomeni LS, Harris K, Edwards BJ, Fischel RJ, Rotenberg D, Jamieson SW, Kaye MP.
London Chest Hospital, U.K.
The physiologic effects of 12-hour lung preservation were assessed in six mongrel dogs studied for 20 hours after double-lung allograft implantation. Donor animals were pretreated with allopurinol (30 mg/kg) and methylprednisolone (500 mg) intravenously at anesthesia induction. Heart-lung blocks were harvested after cardioplegic arrest, and a simple pulmonary artery flush of 4 degrees C modified Collins' solution was administered at 15 ml/kg/min. The lungs were ventilated with 100% nitrogen during flushing and inflation. Recipient animals received an infusion of deferoxamine (20 mg/kg) during implantation and were pretreated with methylprednisolone (500 mg) intravenously. All six implantations were technically successful. Two animals died of cardiac standstill 12 and 24 hours postoperatively. Gas exchange deteriorated after implantation compared with donor levels but remained in a range compatible with survival, and at 20 hours arterial oxygen tension (FiO2 0.4) was 138 +/- 91 mm Hg. Similar changes were seen in alveolar-arterial oxygen gradients and arterial-alveolar oxygen tension fraction. Elimination of carbon dioxide was satisfactory. Pulmonary venous shunt fraction rose significantly at the end of the study. Hemodynamic changes consisted of a gradual increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also deteriorated, with a gradual rise in airway resistance and a fall in compliance. The double-lung model allows detailed assessment of the early effects of preservation and may have certain advantages over heart-lung models of preservation. The preservation technique warrants further study.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2355275&dopt=Abstract
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