预防治疗2型糖尿病药物分子作用靶点的相关研究与进展

目的:综合分析2型糖尿病新药研究的分子靶点。资料来源:应用计算机检索Springer1990-01/2005-02和Pubmed2000-01/2005-08有关预防和治疗2型糖尿病药物的文献,检索词“diabetes,drug,target”,并限定文献语言种类为English。资料选择:对检索到的有关预防和治疗2型糖尿病药物的相关信息进行整理,筛选针对性强、影响因子较大、最近几年发表的论文。资料提炼:共检索到相关文献49篇,其中15篇符合要求,排除34篇。排除的文章中6篇是关于2型糖尿病的病理生理及生化方面的基础研究,其余为2型糖尿病预防和治疗效果方面的文献。资料综合:综合文献资料发现,以往研制的治疗糖尿病的药物或者因缺乏明确的分子靶点,或者因对疾病本身的病理反应不清楚,因而存在各种弊端。有关预防和治疗2型糖尿病和代谢综合征的分子靶点为抗糖尿病药物的研发展示了光明的前景,涉及的药物包括经典受体的小分子调节剂、酶作用靶点、蛋白质制剂和反义寡核苷酸等。结论:根据2型糖尿病和代谢综合征特异的病理反应机制作为筛选药物的分子基础是未来抗糖尿病药物研发的主攻方向。     

Absinthe - history of dependence to thujone or to alcohol?

The etiopathology of absinthe dependence was previously attributed to the effects of the wormwood constituent thujone. Current research proves otherwise. Foremost, it must be considered that the wormwood plant shows a very large variance in quantity of thujone (0 - 70 % in essential oil) dependent on chemo type and cultivation area. Thus, absinthe does not contain thujone in general. Experimental production of absinthes and analyses of vintage absinthes (1900 - 1930) consistently showed that they contained only relatively low concentrations of thujone below today's maximum limits. Scientific literature contains no proof that historic absinthes may have contained thujone in concentrations able to produce toxic effects. The current state of research considers absinthism to be a type of alcoholism with thujone playing none or only a secondary role.     

Alcohol in Mayan Guatemala: consumption, distribution, production and composition of cuxa

Aims   To describe the consumption, distribution, production and chemical composition of alcohol, including cuxa (pronounced 'coo sha'), in Nahualá, a highland Mayan municipality in Guatemala. Cuxa is a sugarcane-derived spirit, in part produced clandestinely, that has been distributed in the community for several decades.
Methods   Key informant interviews with alcohol distributors and consumers, cuxa producers and health professionals, as well as analyses of questionnaires from a sample of 47 spouses who came to the local health centre for problems related to their husband's drinking. Sampling and chemical analysis of cuxa from 12 of 13 identified sales points in the head-town of Nahualá and its nearby settlements (10 km radius). Fieldwork was conducted between November 2007 and March 2008.
Results   Alcohol consumption was found to be integrated culturally in this community. The overall drinking culture was marked by irregular heavy drinking occasions, especially around market days, with substantial inebriation and health problems, especially among street inhabiting drinkers. Cuxa contributed to these problems, and cuxa drinking was socially stigmatized. Cuxa was produced both clandestinely and industrially, and sold legally by taverns and illegally by clandestine distributors. The alcoholic strength of the samples was typically between 17 and 19% vol.; clandestinely produced cuxa samples showed acetaldehyde contamination.
Conclusions   Measures should be taken to reduce the harm associated with alcohol in this community, including efforts to reduce acetaldehyde levels in cuxa.     

Dose-concentration relationships of methadone and EDDP in hair of patients on a methadone-maintenance program

After controlled oral administration of d,l-methadone solution (15–260 mg/day) in the context of a methadone-maintenance program, concentrations of methadone and 2-ethylidine-1,5-dimethyl-3,3-diphenyl-l-pyrrolidine (EDDP), in head hair were determined (N=41), using a fully automated headspace solid-phase microextraction procedure in combination with gas chromatography and mass spectrometry (HS-SPME/GC/MS). Methadone was present in all samples in concentrations ranging from 0.25 to 13.29 ng/mg (mean 2.69±0.45 ng/mg). EDDP was also present in every sample in concentrations ranging from 0.05 to 2.17 ng/mg (mean 0.43±0.08). The concentration ratio methadone/EDDP was 7.5±5.7 in the proximal segments, but decreased to 4.8±1.4 in the distal segments. A statistically significant correlation between the intake dose and the methadone and EDDP concentrations in the subjects’ hair could be established only in the proximal segments (r=0.913 for methadone and r=0.901 for EDDP), but not in the distal segments. In all, 131 segments analyzed, the correlation coefficient was r=0.760 for methadone and r=0.738 for EDDP. In comparison to the dose-concentration relationship reported in the literature, we found a better correlation with higher correlation coefficients especially in the proximal segments. However, owing to a broad distribution in the correlation between dosage and concentration, the determination of methadone and EDDP in hair holds only limited information about prior methadone administration.     

Adherence of L1210 murine leukemia cells to sephacryl- aminopropylcobalamin beads treated with transcobalamin-II

Sephacryl beads containing an immobilized aminopropylcobalamin- transcobalamin-II complex serve as foci for the adherence of L1210 murine leukemia cells. Bead-cell interaction does not occur when (A) nonderivatized beads are used; (B) transcobalamin-II is omitted or presaturated with cyanocobalamin in the preparation of the bead complex; (C) intrinsic factor replaces transcobalamin-II; and (D) the complex is removed from beads by photolysis. These observations suggest that adherence results from the ability of transcobalamin-II to form a bridge between immobilized cobalamin on the bead and receptors in the plasma membrane of the cell.