CYP2E1 inhibition enhances mallory body formation

Mallory body (MB) formation is a complex phenomenon seen in chronic liver disease. CYP2E1 may play a role in preventing MB formation since it is involved in the elimination of toxic drugs and chemicals. When mice were fed with diethyl-1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) for 10 weeks, Mallory bodies (MBs) developed in the liver at the end of this period. When DDC feeding was combined with CMZ (an efficient in vivo CYP2E1 inhibitor), more MBs formed compared to DDC feeding alone. DDC was shown to be a suicide inhibitor of CYP2E1. The level of CYP2E1 protein in the liver was further reduced by the DDC and CMZ treatment when measured by Western blot. To test whether CYP2E1 reduced MB formation, CYP2E1 knockout mice and CYP2E1 overexpressed mice were fed with DDC or DDC and CMZ for 10 weeks. MB formation increased markedly in the liver of CYP2E1 knockout mice when fed with DDC only. CYP2E1 overexpressed mice showed an increase in MB formation when the mice were fed with the combination of DDC and CMZ where the amount of CYP2E1 was reduced to levels seen in wild type mice. It was concluded that CYP2E1 inhibits MB formation by increasing the rate of elimination of DDC and/or its toxic intermediates.     

美沙酮合并丁丙诺啡和东莨菪碱脱毒治疗

目的：比较美沙酮脱毒疗程早期改用丁丙诺啡合并东莨若碱替代治疗与单用美沙酮替代治疗方法之优劣。方法：108例符合DSM—IV阿片类依赖的戒毒者随机分为试验组和对照组，试验组于美沙酮脱毒疗程早期(第四天)改用丁丙诺啡合并东莨若碱替代治疗，对照组则单用美沙酮替代治疗。采用《阿片类药物戒断症状量表》(owS)评定疗效。结果：试验组和对照组的脱毒率分别为94．4％和74％，有显著性差异(P＜0．01＝。owS量表总分在治疗d1—4无显著性差异(P＞0．05)；在治疗d5—8，试验组总分平稳下降，与对照组逐日比较有显著性差异(P＜0．05或P＜0．01＝；治疗药物停用48h后试验组症状未见波动，而对照组症状波动，owS总分两组间有显著性差异(P＜0．01＝。结论：美沙酮脱毒疗程早期改用丁丙诺啡合并东莨若碱替代治疗优于单用美沙酮，是快速脱毒、提高脱毒成功率的较好方法。     

血液透析治疗海洛因依赖80例分析

目的:总结、分析血液透析治疗海洛因依赖的效果及原理。方法:对80例海洛因依赖者进行血液透析治疗1周。1周内透析2～3次,每次4 h;同时辅以抗焦虑、抗抑郁剂治疗;用美沙酮治疗80例作为对照组。结果:血液透析组80例患者均脱毒成功,未出现明显的戒断症状,效果优于美沙酮组(P<0.01)。结论:血液透析可能是较好的脱毒方法,脱毒快,成功率高,副作用小。     

美沙酮口服脱毒治疗的给药管理及对策

目的：为加强美沙酮的管理，提高美沙酮脱毒治疗及护理质量。方法：提高美沙酮的认识，给药时按照制度坚持原则，根据戒毒病人的心理及行为反应进行相应的对策。结果：2000年1月至2001年12月共收治戒毒病人115人次，用美沙酮口服液5683支，计41615mg。在用药过程中未造成美沙酮外流。结论：在美沙酮脱毒治疗中给药是一个重要环节，坚持原则和相应的对策是不可缺少的一项。     

海洛因依赖者心电图改变及相关因素分析

目的:探讨海洛因依赖者的心电图(ECG)变化及其危险因素.方法:对122例海洛因依赖者的心电图进行分析,并调查患者的海洛因滥用情况、肝功能及心肌酶等资料.结果:36例(29.5%)患者有ECG异常,且ST-T改变最为常见.海洛因滥用时间、滥用量、多药滥用情况以及血清丙氨酸氨基转移酶(ALT)和血清肌酸激酶(CK)等在ECG异常与正常组间有显著差异.Logistic回归分析,海洛因滥用时间、滥用量和CK 3个变量进入回归方程.结论:海洛因依赖者ECG异常较多见,患者滥用时间和滥用量、CK异常为危险因素.脱毒治疗时应注意躯体情况.     

Optimization of process parameters for reduction of gossypol levels in cottonseed meal by Candida tropicalis ZD-3 during solid substrate fermentation.

The objective of this work is to optimize the process parameters for detoxification of gossypol in cottonseed meal (CSM) by Candida tropicalis ZD-3 during solid substrate fermentation (SSF). The maximum detoxification efficiency of gossypol was achieved by employing the substrate, which consists of 70% of CSM, 20% of corn flour and 10% of wheat bran. The optimum fermentation conditions for gossypol detoxification are incubation period of 48h, incubation temperature at 30 degrees Celsius, inoculum level 5% v/w, moisture content of solid substrate 50% and pH in nature. Adding minerals solution to CSM substrate benefit fermentation detoxification.     

Effect of different detoxification procedures on the residual pertussis toxin activities in vaccines

Pertussis toxin (PTx) is a major virulence factor produced by Bordetella pertussis and its detoxified form is one of the major protective antigens in vaccines against whooping cough. Ideally, PTx in the vaccine should be completely detoxified while still preserving immunogenicity. However, this may not always be the case. Due to multilevel reaction mechanisms of chemical detoxification that act on different molecular sites and with different production processes, it is difficult to define a molecular characteristic of a pertussis toxoid. PTx has two functional distinctive domains: the ADP-ribosyltransferase enzymatic subunit S1 (A-protomer) and the host cell binding carbohydrate-binding subunits S2–5 (B-oligomer); and in this study, we investigated the effect of different detoxification processes on these two functional activities of the residual PTx in toxoids and vaccines currently marketed worldwide using a recently developed in vitro biochemical assay system. The patho-physiological activities in these samples were also estimated using the in vivo official histamine sensitisation tests. Different types of vaccines, detoxified by formaldehyde, glutaraldehyde or by both, have different residual functional and individual baseline activities. Of the vaccines tested, PT toxoid detoxified by formaldehyde had the lowest residual PTx ADP-ribosyltransferase activity. The carbohydrate binding results detected by anti-PTx polyclonal (pAb) and anti-PTx subunits monoclonal antibodies (mAb) showed specific binding profiles for toxoids and vaccines produced from different detoxification methods. In addition, we also demonstrated that using pAb or mAb S2/3 as detection antibodies would give a better differential difference between these vaccine lots than using mAbs S1 or S4. In summary, we showed for the first time that by measuring the activities of the two functional domains of PTx, we could characterise pertussis toxoids prepared from different chemical detoxification methods and this study also highlights the potential use of this in vitro biochemical assay system for in-process control.     

杨志宏教授治疗帕金森病经验

帕金森病是一种多发于中老年的神节系统变性疾病.杨志宏教授治疗帕金森病独具特色,注重滋补肝肾以固本;在化痰祛瘀的同时,注重益气;倡导清热除湿、解毒排毒以护脑;常用解表除湿的方法治疗汗出,疗效显著.     

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

The aldo-keto reductase (AKR) superfamily comprises enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification. Substrates of AKRs include glucose, steroids, glycosylation end-products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (β /α )₈ barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics.