De Novo Non-Alcoholic Fatty Liver Disease Following Orthotopic Liver Transplantation

Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized clinico-pathologic entity typically associated with obesity, type II diabetes and hyperlipidemia. It has been noted to recur after orthotopic liver transplantation (OLT). We report four patients who developed de novo NAFLD within 3 months of OLT without the typical predisposing factors of diabetes mellitus or obesity. Three of the four patients underwent OLT for hepatitis C-related cirrhosis, and the other for alcoholic cirrhosis. Examination of the liver explants revealed no evidence of steatosis. No surreptitious alcohol use or a drug-induced process could be identified in these patients. Treatment of recurrent hepatitis C infection in one patient with interferon and ribavirin led to sustained suppression of the viral RNA to undetectable levels, but no improvement in histology or liver enzymes. All four patients had histologic evidence of preservation injury on the initial post-OLT biopsies, but the significance of this finding in relationship to the development of NAFLD is unknown. NAFLD can develop without any of the known predisposing conditions after transplantation, and this raises further questions about the pathogenesis of this condition .     

化痰方、肝脾方抗大鼠脂肪肝模型作用机制的比较研究

目的 :探讨和比较化痰方、肝脾方抗大鼠脂肪肝模型作用机制。方法 :用高脂饮食联合四环素腹腔注射致大鼠脂肪肝模型 ,观察肝组织病理变化 ,检测肝功能 (ALT、AST)、血甘油三酯 (TG)、肝匀浆TG、游离脂肪酸 (FFA)、丙二醛 (MDA)的含量。并与正常组、东宝肝泰组对照。结果 :三个用药组的血清ALT、AST及肝匀浆FFA、TG、MDA均显著低于模型组 (P <0 .0 1 ) ,并显示抗脂肪肝的作用强弱依次为 :肝脾组优于化痰组优于东宝组 (P <0 .0 5或P <0 .0 1 )。结论 :促进脂质代谢、抗脂质过氧化可能是化痰祛浊、疏肝健脾法治疗脂肪肝作用的主要机制     

Increase in levels of total free fatty acids in rat brain regions following 3-nitropropionic acid administration

Acute exposure to a neurotoxin, 3-nitropropionic acid (3-NPA), in rats results in an increase in total free fatty acid (FFA) concentration in selective brain regions. We investigated the effect of 3-NPA administration on the cerebral concentrations of FFA used as a marker of oxidative stress. Rats (n=3/group) were dosed subcutaneously (s.c.) either with a vehicle (phosphate buffer) or 3-NPA in phosphate buffer at 30 mg/kg body weight. Animals were sacrificed after 1, 2, 3, and 6 h of injection. Brains were then dissected into frontal cortex (FC), caudate nucleus (CN), and hippocampus (HIP). The concentration of total FFA increased from 130 to 300% within 1–2 h after 3-NPA injection in all brain regions when compared with the baseline level obtained from the control rats and taken as 100%. In CN, FFA returned to the baseline level within 3 h of treatment. However, in FC and HIP the concentration of FFA remained significantly elevated above the baseline until 6 h. The released FFA provide a substrate for free radicals formation. The results of this study suggest a role of oxidative stress in the mechanism of 3-NPA toxicity.     

农药唑呀威毒理及中毒治疗的实验研究

唑呀威（Ｔｒｉａｚｕｒｏｎ）系新型的高效杀蚜虫剂。目前，对其抑制胆碱酯酶活性的毒理尚报道不一。作者在进行毒性测试和发现１６名包装工夏季作业时８名出现明显症状的基础上，开展动物实验研究。结果发现，唑呀威有较有机磷农药更为快速的胆碱酯酶抑制作用，大鼠经口染毒１１２．５ｍｇ／ｋｇ仅３０ｍｉｎ内即见全血胆碱酯酶活性显著下降，Ｐ＜０．０１；且存在明显剂量－反应关系。高剂量（２００ｍｇ／ｋｇ）还可引起心血管系统的损害。注射阿托品有显著解救效果，染毒同时给药的解救效果明显优于染毒后５分钟给药，提示愈早给药解救效果愈好。作者由此提出了临床中毒急救措施的建议     

N-3 fatty acids only delay early relapse of ulcerative colitis in remission

Relapse prevention by dietary n-3 fatty acids (5.1 g/day) was studied in a double-blind, placebo-controlled trial of 64 patients with ulcerative colitis in remission and off steroids. 5-ASA compounds were stopped three months after randomization and clinical disease activity monitored for two years. Macroscopic and histologic activity and extension was assessed by colonoscopy at entry and at exit. Both treatment groups were well matched at start. Nine patients on placebo and eight on n-3 fatty acids stopped taking their medication prematurely. Actuarial relapse-free survival was improved by n-3 fatty acids only during months 2 and 3 (2P<0.05–0.01), but cumulative relapse rate at two years was similar for those taking placebo (18/33=55%) and n-3 fatty acids (18/31=58%). There was also no consistent difference in clinical, macroscopic, and histologic disease activity between treatment groups. The n-3 fatty acids temporarily retard, but do not prevent, relapse of ulcerative colitis.     

Inhibition of warm ischemic injury to rat liver, pancreas, and heart grafts by controlling the nutritional status of both donor and recipient

In this study, we tested the effect of donor fasting with or without the use of an essential fatty acids deficiency (EFAD) diet in the recipient using rat heart, pancreas, and liver transplant models. We then compared the survivals, tumor necrosis factor alpha (TNF-α) response, and white cell accumulation in rats in order to clarify the mechanisms of the beneficial effect of donor fasting and recipient EFAD. It was found that when the grafts were obtained from fasted donors and then transplanted into fed recipients, the survival rate was significantly higher for all three grafts than for those obtained from fed rats and transplanted into fed rats. The best survival was seen for pancreas grafts obtained from fasted donors and then transplanted into EFAD recipients. TNF-α secretion was significantly suppressed in both fasted and EFAD rats, and both the total cell count and neutrophil count were suppressed in EFAD rats. These results clearly indicate that in addition to liver grafts, both heart and pancreas grafts obtained from fasted animals are more tolerant to warm ischemic injury. Furthermore, the combination of donor fasting and recipient EFAD acts synergistically to inhibit the post-transplantation inflammatory reaction (through decreased TNF-α secretion and white cell accumulation), thus resulting in an improved survival.     

Interactions between epidermal growth factor-mediated autocrine regulation and linoleic acid-stimulated growth of a human prostate cancer cell line.

Human prostate cancer (PC) cell lines possess epidermal growth factor (EGF) receptors and secrete EGF-related polypeptides. We used an EGF receptor-blocking antibody (anti-EGF.R) to demonstrate a functional autocrine loop, as well as the interaction between this and the effects of linoleic acid (LA), an omega-6 fatty acid, on PC cell growth. The anti-EGF.R competed effectively with [125I]EGF for receptors on DU145 PC cells, and on a high-passage DU145 variant (DU145M); when added to the culture medium, it suppressed both DU145 and DU145M cell growth in a dose-dependent manner. LA, a precursor for eicosanoid synthesis, had little effect on DU145 cell growth rate but stimulated DU145M growth in a concentration-related manner over a range of 0.25-2.0 micrograms/ml. anti-EGF.R (10(-9) M) caused suppression of LA-stimulated growth of DU145M cells in serum-free medium, which was prevented by the addition of 2 nM EGF. We conclude that an EGF.R-mediated autocrine loop is involved in PC cell growth regulation and that at least one site of action may be the synthesis of eicosanoids from their LA precursor.     

环孢素A体外抗曼氏血吸虫作用的观察

ＭＦ１小鼠实验感染曼氏血吸虫尾蚴１周、３周和６周后，分别经肺静脉和门静脉灌注取虫。实验显示，药物体外抗曼氏血吸虫的作用呈时间、剂量和虫龄依赖方式，童虫和雄虫对药物更敏感。     

易善复加丹参治疗病毒性肝炎合并脂肪肝疗效观察

目的　评价易善复加丹参在病毒性肝炎合并脂肪肝的临床疗效。方法　选择病毒性肝炎合并脂肪肝 98例 ,随机分成治疗组和对照组 ,治疗组 68例 ,应用易善复加丹参治疗 ,疗程 3个月。结果　治疗组血脂 (TC、TG)、肝功能 (ALT、γ -GT)、B超脂肪肝图象及临床症状等项目的改善均明显优于对照组 (P <0 .0 1～ 0 .0 5) ,且无明显副作用。结论　易善复加丹参治疗病毒性肝炎合并脂肪肝对促进肝脏脂肪代谢、降低血脂、修复损伤的肝细胞 ,且阻止或改善肝纤维化均有明显的功效     

氯丙醇对大鼠的毒性研究

进行氯丙醇对大鼠毒作用研究 ,并进行氯丙醇暴露对健康影响评价的生物效应标志物探讨 ,为进行人群氯丙醇暴露对健康的影响评价提供科学依据。选用健康雄性断乳SD大鼠 1 76只 ,随机分为 8组 ,经口灌胃给予 0、0 2 5、0 5、1 0、2 0、4 0、8 0、1 6 0mg kg的 3 氯 1 ,2 丙二醇 (3 MCDP) 90天 ,进行体重、食物利用率、血液学指标、血生化指标、尿液中N 乙酰 β D 氨基葡萄糖苷酶 (NAG)、γ 谷胺酰转肽酶 (GGT)和总蛋白、精子数目、精子存活率和畸形率、睾丸组织中乳酸脱氢酶 (LDH)和乳酸脱氢酶同工酶 X(LDH X)、脏体比及其病理组织学测定和分析。结果表明 ,不同暴露剂量的氯丙醇对动物体重、食物利用率、血红蛋白、红细胞、白细胞、血丙氨酸氨基转移酶 (AST)、天冬氨酸氨基转移酶 (ALT)、肌酐、尿素氮、血清碱性磷酸酶 (ALP)、乳酸脱氢酶 (LDH)、总蛋白、白蛋白、尿GGT酶和总蛋白及睾丸LDH酶均未见显著影响。在 4 0、8 0和 1 6 0mg kg剂量组 ,动物尿N 乙酰 β D 氨基葡萄糖苷酶 (NAG)活性显著增加 ,肾体比增大 ,并出现肾毒性病理改变 ,精子数目也降低。在 8 0和 1 6 0mg kg剂量组 ,精子存活率和睾丸LDH X显著降低 ,睾丸和附睾出现病理改变 ,3 MCDP无致精子畸变作用。由此可见尿液中NAG酶活性和精子