Role of allopurinol in the treatment of hyperuricemic patients with non alcoholic fatty liver disease

Non Alcoholic Fatty Liver Disease [NAFLD] is the most common cause of chronic liver injury, recently elevated uric acid [UA] level was found to be an important factor in the development of NAFLD so lowering the level of UA by allopurinol might play an important role in the improvement of NAFLD. The objective of the study is to evaluate the effect of treating hyperuricemia by allopurinol on NAFLD patients assessed by ultrasonography [U/S] and liver enzymes. 3l hyperuricemic patients suffering from NAFLD were enrolled in the study. These patients were randomly assigned into two groups; Group A [14 patients]: Placebo group who received starch based placebo for 2-3 months and Group B [17 patients]: Treatment group who received allopurinol for 2-3 months. Fatty liver [FL] grade and size were assessed by U/S before and after treatment; also liver enzymes [GPT , GOT] and UA were measured before and after treatment. The present study showed significant difference between GPT and GOT before and after lowering UA level [P<0.001 and P=0.013, respectively] in the treatment group while U/S parameters showed no significant difference in the FL size and grade before and after treatment [P:0.208 and 0.325 respectively]. We concluded that Allopurinol can be used to improve patients with NAFLD associated with hyperuricemia as assessed by improved liver enzymes

Toxicokinetics versus pi-tarmacokinetics of oral anabolic steroids abused in doping practice

Despite the high prevalence of toxicological profile of oral anabolic steroids, laboratory investigations on toxicokinetic profile of anabolic steroids overdoses have been largely unknown and underestimated. In the present study toxicokinetics of methyltestosterone and testosterone undecanoate were studied in male adult rats after oral administration of single toxic dose to explore possible alteratiolls in their pharmacokinetic behavior in comparison to their corresponding parameters at therapeutic doses. The extraction methods adapted for plasma samples showed mean recoveries of 87.4+0.19% and 103.5 +/- 0.1% for methyltestosterone and testosterone undecanoate respectively. Inter- and intra-day precision were 2.4 -8.7% coefficient of variance [CV.], and 4.3 -2.8% [CV.] for methyltestosterone and testosterone undecanoate respectively. Plasma concentrations measured by high performance liquid chromatography method was applied for the analysis of both methyltestosterone and testosterone undecanoate with high sensitivity and low detection limit of 1ng/ml. The pharmacokinetic parameters were estimated using non-compartmental method. Both drugs showed non-linear pharmacokinetic behavior represented in disproportional increase in C[max], AUC[0-infinity] and increase in V, CI, t1/2 and lambda. The present data indicate accumulation of steroids in tissues leading to severe toxicological consequences

Comparative in vivo and in vitro hepato-toxicity studies for oral anabolic steroids abused in sports

Studies on hepatotoxicity of anabolic- androgenic steroids in experimental animals and in controlled clinical studies were based on the use of doses at substantially lower level than those practiced by the abusers. the aim of this study was to investigate acute hepatotoxic effects after administration of suprapharmacological doses to experimental animals as well as to isolated hepatocytes suspension to reflect any hepatic dysfunction caused by anabolic steroid abuse. Male adult albino rats were administered daily oral doses of methyltestosterone [175mg/Kg], testosterone-undecanoate [420 mg/Kg], and their combination for 7 days. In vivo results showed significant increase in serum aspartate aminotransferase [AST] and lactate dehydrognease [LDU]. While both steroids did not affect serum levels of alanine aminotransferase [ALT], thiobarbituric acid reactive substances [TBARS], reduced glutathione levels and total protein, when administered either individually or in combination. Leakage of ALT, AST and LDH was observed in any vitro studies in addition to increase in TBARS content. All treatments did not result in any significant difference in reduced glutathione content compared to the respective control. Histopathological examination of the liver revealed inflammatory and degenerative lesions in addition to focal necrosis. The histopathological findings confirm the biochemical studies [both in vivo and in vitro] and show clear toxic manifestations of suprapharmacological doses of theses anabolies on the liver

Influence of ondansetron on the antitumor activity and lung toxicity of bleomycin

Bleomycin [BLM] is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Moderate nausea and vomiting occur in virtually all patients taken BLM. Ondansetron [OND] is a highly selective 5-HT3 receptor antagonist with significant antiemetic activity. This study was conducted to investigate the effect of OND administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma [EAC] cells. Ondansetron did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5-HT and increase in the contractility of tracheal smooth muscles induced by ACh. The toxicity was also confirmed biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in GSH level. Pretreatment with ondansetron decreased lipid peroxidation and normalized GSH level and hence enhanced the percent survival of rats. The results of the present study indicate that OND did not modify the antitumor effect of BLM but ameliorated the increase in some biochemical markers associated with BLM-induced lung toxicity

Neuroprotective effect of melatonin against ethanol-induced damage in rat brain stem

Chronic ethanol administration has been found to have neuronal damaging effect through free radical generation. The aim of this study is to determine the possible neuroprotective effect of melatonin [MLT] against ethanol induced neuronal damage in the brain stem of male albino rats. Rats were randomly divided into 3 groups: control group, 35% ethanol-treated group and melatonin [l0mg/kg I. P. for 7 consecutive days] pre-treated ethanol group. Administration of ethanol [35%] orally in drinking water for 30 consecutive days decreased glutathione [GSH], dopamine [DA], norepinephrine [NE] and serotonin [5-HT] contents and superoxide dismutase [SOD] activity. The maximal percentage of decrease was 44%, 34%, 41%, 29% and 40%, respectively. On the other hand; there was a progressive increase in malondialdehyde [MDA] level and DNA fragmentation by 128% and 53%, respectively. Melatonin administration prior to ethanol significantly increased. GSH, DA, 5-HT, and NE contents in brain stem by 53%, 30%, 33%, 33% respectively and SOD activity by 35%. MDA level and DNA fragmentation were markedly reduced by 36% and 30%, respectively. Our data suggest that melatonin is capable of at least partially preventing ethanol -induced neurodegeneration in the brain stem of rats. This effect might be attributed to direct free radical scavenging properties and regulation of antioxidative enzyme activity of melatonin

Prospects for drug treatment of aids

The first recognized cases of the acquired immune deficiency syndrome [AIDS] occurred in the summer of 1981 in America. Human immunodeficiency virus [HIV] was discovered by Barre-Sinoussi, Montgnier and colleagues at the institute Pasteur Paris 1983. HIV-1 and HIV-2, the major and minor human AIDS viruses, are transmitted in ways that are typical for all retroviruses- "vertically", that is from mother to infant, and "horizontally" through sexual intercourse and through infected blood. Infection with HIV causes a spectrum of" clinical problems beginning at the time of serconversion and terminating with AIDS and death. Various potential targets for antiviral treatment have been identified since we have gained a better understanding of the replicative cycle and molecular biology of HIV. The first drugs made available for clinical use were inhibitors of the reverse transcriptase enzyme [RT]. RT inhibitors include nucleoside analogues that inhibit by chain termination and competitive inhibition of the enzyme and non-nucleoside agents which bind directly to RT and are non-competitive inhibitors. More recently, specific inhibitors of the HIV protease and integrase enzymes have been evaluated and introduced into clinical use. HIV replication from its integrated site is controlled by a number of regulatory genes. The tat [transactivating transcription] gene codes for a protein that transactivates the promoter in the HIV long terminal repeat [LTR] region which amplifies viral transcription. Tat inhibitors are under clinical investigation. Regarding HIV vaccines, novel approaches are being tried. Chemoprophylaxis against pneumocystis carinii pneumonia, which remains the most serious opportunistic infection, continues to be recommended as the standard care for HIV-infected person with CD [4]. counts of less than 200/[micro]l. Guidelines for managing HIV infection include regular monitoring of IIIV-1 plasma RNA [viral load] and the use of triple antiretroviral drug combination. Development of antiviral therapy aimed at other parts of the viral replication cycle is urgently needed