Allopurinol
Zonal distribution of allopurinol-oxidizing enzymes in rat liver.

Moriwaki Y, Yamamoto T, Yamakita J, Takahashi S, Tsutsumi Z, Higashino K.

Third Department of Internal Medicine, Hyogo College of Medicine Mukogawa-cho 1-1, Japan.

We describe an enzymatic histochemical localization of two allopurinol-oxidizing enzymes, xanthine oxidase and aldehyde oxidase in rat hepatic tissues. This method is based on the tetrazolium salt procedures by use of a tissue protectant, polyvinyl alcohol, with tetra-nitro BT as the final electron acceptor. The present study demonstrated that both oxidases are present in the cytoplasm of hepatic cells. However, the distribution of the enzymes was uneven, being seen mainly in the pericentral rather than the periportal area. When allopurinol was used as a substrate, the specific staining by xanthine oxidase was more prominent than that of aldehyde oxidase. The results suggested that xanthine oxidase is more effective in oxidizing allopurinol than aldehyde oxidase.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9598029&dopt=Abstract allopurinol Zyloprim



Allopurinol
Effect of deferoxamine and allopurinol on non-protein-bound iron concentrations in plasma and cortical brain tissue of newborn lambs following hypoxia-ischemia.

Shadid M, Buonocore G, Groenendaal F, Moison R, Ferrali M, Berger HM, van Bel F.

Department of Pediatrics, Leiden University Medical Centre, The Netherlands.

Reduction of non-protein-bound iron (NPBI) using iron chelators may attenuate hypoxia-ischemia-induced reperfusion injury of the brain. This study investigated whether administration of low-dose deferoxamine and allopurinol, both having NPBI-chelating properties, reduced hypoxia-ischemia-induced NPBI formation in plasma effluent from the brain and in cerebral cortical tissue. Twenty-one newborn lambs underwent severe hypoxia-ischemia. Upon reperfusion and reoxygenation the lambs received either a placebo (n = 7), or deferoxamine 2.5 mg/kg (n = 7) or allopurinol 20 mg/kg (n = 7). The post-hypoxic-ischemic NPBI levels in plasma were significantly lower after deferoxamine but not after allopurinol as compared to placebo-treated lambs. Cortical NPBI levels in both deferoxamine and allopurinol-treated lambs were significantly lower than NPBI levels in placebo-treated lambs. We conclude that deferoxamine effectively lowers NPBI in plasma effluent from the brain, and that both, deferoxamine and allopurinol, lower NPBI in cortical brain tissue.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9665650&dopt=Abstract allopurinol Zyloprim



Allopurinol
Use of allopurinol for maintenance of remission in dogs with leishmaniasis.

Ginel PJ, Lucena R, Lopez R, Molleda JM.

Department of Veterinary Clinical Pathology, Faculty of Veterinary Medicine, Cordoba, Spain.

Current treatments for infected dogs with leishmaniasis do not always provide long-term control of the disease and clinical relapses are common. In this study, the usefulness of long-term allopurinol administration in the maintenance of clinical remission in canine leishmaniasis was evaluated. Fifteen dogs with natural leishmania infection were subjected to an initial treatment based on the simultaneous administration of meglumine antimoniate (100 mg/kg/day) and allopurinol (30 mg/kg/day). Once clinical remission was achieved, a maintenance treatment with allopurinol (20 mg/kg/day) administered for one week a month was instituted. Results were compared with those of a retrospective control group comprising 15 infected dogs which only followed the induction treatment. Relapses occurred in 86 per cent of control dogs within 14 months of discontinuing treatment. In contrast, those dogs on intermittent oral allopurinol administration were successfully maintained in clinical remission for a follow-up period of 10 to 44 months. In this latter group, specific antibody titres decreased or were unchanged, no side effects directly attributable to allopurinol were seen and treatment was well accepted by the owners. It is concluded that long-term intermittent administration of allopurinol is an effective way of maintaining clinical remission in dogs with leishmaniasis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9673902&dopt=Abstract allopurinol Zyloprim



Allopurinol
[Serologic evaluation of treatment of chronic Chagas disease with allopurinol and itraconazole]

[Article in Spanish]

Zulantay I, Apt W, Rodriguez J, Venegas J, Sanchez G.

Programa de Parasitologia, Facultad de Medicina, Universidad de Chile.

BACKGROUND: Chagas disease is endemic in Chile. Allopurinol and itraconazole have activity against Trypanosoma cruzi and are recommended for the treatment of chronic disease in adults. AIM: To evaluate the chemotherapeutic effects of allopurinol and itraconazole using conventional and non conventional serologic tests. PATIENTS AND METHODS: Sera of 90 patients with chronic Chagas disease were studied before and after 9 to 11 months of treatment with allopurinol or itraconazole and after two months of treatment with placebo. Indirect immunofluorescence, ELISA and Western Blot analysis were the conventional serologic tests used and antibody dependent complement mediated lysis (CoML) the non conventional test. RESULTS: There were no differences in ELISA and indirect immunofluorescence tests before and after therapy. Antigenic recognition profiles by Western Blot showed qualitative and quantitative differences in a small number of cases. CoML showed that the greater negativity was achieved in the Chagasic group treated with allopurinol or itraconazole that had a negative xenodiagnosis before drug treatment (35.8 and 61.6%, respectively). CONCLUSIONS: There is a reversion of lytic activity in sera of patients with negative xenodiagnosis before treatment, suggesting the parasitemia could be an important parameter to be considered in the chemotherapy of Chagas disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9674295&dopt=Abstract allopurinol Zyloprim



Allopurinol
Immunological effects of allopurinol in the treatment of experimental autoimmune uveitis (EAU) after onset of the disease.

Grus FH, Augustin AJ, Loeffler K, Lutz J, Pfeiffer N.

Department of Ophthalmology, University of Mainz, Germany. f grus.de

PURPOSE: Allopurinol reduces oxidative tissue damage and exerts immunomodulating effects in the treatment of experimental autoimmune uveitis (EAU). However, the mechanism of the immunologic pathway remains unclear. In previous studies, treatment was started at the time of immunization. Therefore, whether allopurinol prevents the onset of the disease (i.e., acts in a protective manner) is not known. METHODS: Sixteen male Lewis rats were used: 6 EAU without therapy [control]; 4 EAU with allopurinol treatment starting 7 days after immunization [AL7]; and 6 EAU with allopurinol treatment starting 11 days after immunization [AL11]. Their sera were tested against Western blots of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of retinal proteins. Based on digital image analysis, analysis of discriminance was done. RESULTS: There were significant immunomodulating effects in both therapy groups (Wilks' lambda 0.001, P < 0.008) compared to controls. However, the effects were more pronounced in the AL7 group, where peak intensities and the number of peaks were markedly more reduced. CONCLUSIONS: Immunomodulating effects of allopurinol can be detected even if the therapy starts after the onset of the disease. Thus allopurinol strongly influences the immunologic mechanism in this model of autoimmune disease. In view of its minimal side effects, the drug could be a promising alternative for the therapy and prophylaxis of uveitis and other autoimmune diseases.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12696638&dopt=Abstract allopurinol Zyloprim



Allopurinol
Allopurinol-induced pyrimidinuria in cancer patients.

Carducci MA, Choti M, Maestri NE, Brusilow SW.

Department of Oncology, Johns Hopkins University School of Medicine, Baltimore 21205, USA.

Allopurinol induced pyrimidinuria is a sensitive and specific test that identifies the increased de novo pyrimidine mononucleotide biosynthesis accompanying ornithine trans carbamylase deficiency. We hypothesize that the increased de novo DNA synthesis characteristic of malignant tumors can be detected using this method. Eleven cancer patients and a 30 subject control group were studied. The allopurinol test protocol consists of five urine collection periods--a baseline collection after which time a 300 mg dose of allopurinol is taken, followed by collection of four 6 hour fractional urine collections. Orotate, orotidine and creatinine were measured on the samples. Eight of 11 patients had significantly elevated urine levels of either orotate or orotidine either prior to challenge with allopurinol or during one of the time periods. The allopurinol test for this unstratified group has a sensitivity of 0.73 and a specificity of 1.0. This observational and preliminary report suggest that further study of the potential significance and usefulness of the allopurinol test in patients at risk for or with malignancy is warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9706470&dopt=Abstract allopurinol Zyloprim