Sex dependent effect of chronic ethanol consumption in rats on hepatic microsome mediated mutagenicity of benzo[a]pyrene

The effect of chronic ethanol consumption by rats on hepatic microsomal metabolism of the procarcinogen benzo[a]pyrene (B[a]P) was investigated both with respect to induction of microsomal arylhydrocarbon hydroxylase (AHH) activity and activation of B[a]P to a mutagen. In female rats, chronic ethanol ingestion produced a 42% increase in AHH activity (P < 0.01), as measured in isolated microsomes, and also resulted in a significantly enhanced capacity (P < 0.01) of these microsomes to activate B[a]P to a mutagen detectable in the Ames bacterial mutagenesis assay. Hepatic microsomes from male rats on the other hand did not exhibit any significant differences, either in AHH activity or in their capacity to activate B[a]P to a mutagen after chronic ethanol feeding.     

Alcoholism and Nutrition: A Seminar

M alnutrition and alcoholism are commonly associated. Thirty years ago, researchers considered the possibility that malnutrition promotes alcoholism, yet more recently, this theory has been abandoned. Indeed, it is now generally accepted that vitamin therapy does not reduce addiction to alcohol in man. Malnutrition is now considered a result of chronic alcohol consumption. The pathogenesis of malnutrition, however, is complex and may be related to nutritional intake, digestion and absorption, tissue transport, organ injury, nutrient catabolism, direct effects of ethanol, and genetic predisposition. Many of these complex interactions are illustrated by the articles presented in this seminar.     

Interaction of ethanol with acetaminophen metabolism in the baboon

To evaluate the effects of ethanol on acetaminophen metabolism and toxicity, twelve female baboons were studied using three experimental designs. In the first one, animals fed ethanol chronically and their pair-fed controls received acetaminophen intravenously (40 mg/kg), and drug metabolism was studied for 6hr in blood and urine. Elimination of acetaminophen from plasma was accelerated significantly in baboons fed alcohol chronically, urinary excretion of mercapturic acid conjugate was increased. In the second, the experiments were repeated with the addition of ethanol infusion (120–160 mg/kg/hr). During ethanol infusion, elimination of acetaminophen from plasma was still accelerated significantly in baboons fed alcohol chronically. In the third experimental design, four pairs of baboons fed an alcohol or an isocaloric control liquid diet received, in addition, acetaminophen (85 mg/kg/day) in their respective liquid diets for 2 weeks. Liver histology was studied before and after acetaminophen feeding; SGPT, SGOT, SGDH, acetaminophen blood levels and acetaminophen urinary metabolites were also assessed. No morphological or functional liver alterations were found after chronic acetaminophen treatment, and urinary excretion of mercapturic acid conjugate was not increased in baboons fed alcohol chronically. Thus, our results in primates confirm that chronic ethanol consumption increases, whereas acute ethanol administration decreases, the excretion of mercapturic acid conjugate. When acute and chronic ethanol administration were combined, the effects tended to cancel each other out. A dose of acetaminophen which maintained blood levels similar to those recommended for humans did not produce deletions effects in baboons drinking alcohol.     

In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O6-methylguanine transferase

Human and rat O⁶-methylguanine transferase (O⁶MeGT) are inhibitedin vitro by ethanol at concentrations of 10 to 50 mM and byacetaldehyde, the first metabolite of ethanol, at concentrationsas low as 0.01 µM. Several other enzymes, including glyceraldehyde-3-phosphatedehydrogenase and yeast alcohol dehydrogenase, which like O⁶MeGThave cysteines in their active sites, were not inhibited byacetaldehyde at the levels that inhibited O⁶MeGT. Disulfiram,an acetaldehyde dehydrogenase inhibitor, enhanced the inhibitoryeffect of ethanol in vivo. These results indicate that the inhibitoryeffect of ethanol on O⁶MeGT activity is mediated primarily viaits metabolite, acetaldehyde.     

替比夫定联合抗HBV特异性主动免疫疗法治疗慢性HBV携带者临床观察

目的:观察替比夫定联合抗HBV特异性主动免疫疗法治疗慢性HBV携带者的临床疗效。方法:68例慢性HBV携带者分为治疗组38例,对照组30例。治疗组,替比夫定600㎎/天,口服,同时抗HBV特异性主动免疫治疗,1次/4周,皮下注射,疗程48周;对照组,单用替比夫定600㎎/天,口服。比较治疗12周、24周、48周两组HBV-DNA阴转率及HBeAg阴转率和HBeAg血清转换率。结果:12周、24周及48周HBV-DNA阴转率治疗组为40.2%、68.3%和87.5%,均高于对照组20.3%、37.6%和28.9%(P<0.05);治疗组HBeAg阴转率39.4%,HBeAg血清转换率26.3%,均高于对照组(P<0.05)。结论:替比夫定联合抗HBV特异性主动免疫疗法治疗慢性HBV携带者优于单一替比夫定治疗。     

愈肝方联合熊去氧胆酸治疗原发性胆汁性肝硬化临床疗效分析

目的：观察中药愈肝方联合熊去氧胆酸（UDCA）治疗原发性胆汁性肝硬化（PBC）的临床疗效。方法：回顾性分析2007年1月-2010年12月在我院住院且符合纳入标准的PBC患者共66人,根据治疗方案不同,分为愈肝方与UDCA治疗组及UDCA治疗组,比较两组的临床疗效。结果：治疗4周后,愈肝方与UDCA组的好转率优于UDCA组,且在总胆红素、碱性磷酸酶两项主要生化指标方面均较UDCA组有显著下降。结论：愈肝方联合UDCA治疗原发性胆汁性肝硬化,较单用UDCA能更有效。     

肝移植术中不同时相供肝胆道上皮细胞的病理组织结构改变

目的研究肝移植术中胆管上皮细胞在不同时相的病理结构改变。方法选择无胆道疾病的肝移植病人50例,供体胆道灌洗液为HC-A肾保存液,器官保存液为UW液。术中不同时间段(供肝植入前、门静脉开放时、动脉开放时、动脉开放后30 min)留取胆道组织标本,行病理检查。结果不同时间段所取的胆道标本上皮所受损伤逐渐加重。观察到细胞的肿胀、炎细胞浸润、细胞核的皱缩、微绒毛断裂等。结论胆道缺血时间的延长可导致胆道上皮细胞损伤加重。但是当冷缺血时间小于12 h,胆道上皮损伤可修复,并不增加术后胆道并发症的发生几率。     

1例肝豆状核变性合并杜兴型肌营养不良症及其家系报道

YAN Jian-guo;CHEN Da-wei;DONG Yi;XU Zhi-qiang;WANG Li-min;GAN Yu;WANG Fu-chuan;ZHANG Min(Pediatric Liver Disease Treatment and Research Center,the Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China)     

以肝功能轻度异常为首发表现的高苯丙氨酸血症1例

高苯丙氨酸血症(hyperphenylalaninemia,HPA)是一种遗传代谢性疾病,以苯丙氨酸羟化酶(phenylalanine hydroxylase,PAH)活性缺乏,致血浆苯丙氨酸浓度升高为特征。该病早期无明显临床症状,随着病情加重会逐渐出现严重神经系统功能障碍,但首发症状为肝功能异常的着实罕见。本文现对1例以肝功能轻度异常为首发表现的HPA患者进行报道,并回顾相关文献,以进一步提高临床医生对此类疾病不典型表现的辨识能力,达到早诊断、早治疗的目的。