均相催化合成丙二醇甲醚的研究

研究了甲醇与五氧丙烷在碱性催化剂ＴＡ存在下均相合成丙二醇甲醚的过程。在甲醇与环氧丙烷的配比为３：１－５：１，催化剂使用量为０．５％－１．０％，反应温度６０－１２０℃条件下，环氧丙烷转化率在９９％以上，丙二醇甲醚的选择性在９５％以上。     

输卵管注药绝育术副反应和并发症的近远期观察

采用多中心随机化临床试验,共接纳1705例合格受术对象,其中871例使用复方苯酚糊剂(PAP),834例使用显影苯酚胶浆(PM)。观察结果表明,术后发热率两组分别为8.0％和4.4％,组间差别有统计学意义。发热主要因药物反应所致。两组附件感染率分别为2.3‰和1.2‰。盆腔化学性腹膜炎发生率分别为1.1‰和2.4‰。未见子宫穿孔、盆腔脓肿和宫外孕。术后伴有轻度腹痛者分别占33.6％和30.8％,偶见重度者。腹痛与药物在卵管内充盈的长度和引起的组织反应范围明显有关。腰痛情况与腹痛相似。术后有症状者,多数在短时间内缓解,少数需对症治疗。术后,轻度子宫出血者两组分别为23.2％和18.0％。出血与术时取出节育器明显有关。本术对受术妇女月经无明显影响。五年随访做妇科检查和宫颈细胞学检查无阳性发现,也未查见与绝育药物主要成份有关的潜在疾患。研究表明,本术安全可靠。为进一步降低副反应和并发症的发生,研究机构应着重于现有药物配方的改进,并在保证效果的基础上,尽量减少阿的平含量。主管部门应重新估价这一技术,并加强施术管理和施术者培训,制定全国统一的操作规范,确保服务质量。本术现已得到广泛使用,有很大的发展前景,各界应予更大的关注。     

Longitudinal and topographical organization of the olivary projection to the cat ansiform lobule

This study on the organization of the olivary projections to the ansiform lobule in the cat was aimed at defining the longitudinal zonal pattern and the internal topography within the zones.The horseradish peroxidase method was used. Two types of injections were made: large injections covering the full extent of small groups of folia, and small injections aimed to be restricted to the single zones proposed by Voogd.It was shown that olivary projections to these parts of the cerebellum originate from the dorsal and medial accessory nuclei and from the principal nucleus, in agreement with previous studies. Moreover it was found that the ventral lamella and the dorsal lamella (and bend) of the principal nucleus give rise to two distinct, non-overlapping, cerebellar projections to D1 and D2 zones, respectively. It is thus concluded that in the cat four separate olivo-cerebellar strips, corresponnding to the C2, C3, D1 and D2 zones of Voogd, are present in the ansiform lobule.In addition a transverse rostro-caudal organization was found, in which discrete regions of each olivary subdivision are connected to discrete areas of the crural cortex, within each olivo-cerebellar strip. The old idea of a point-to-point topography in the olivo-cerebellar system is consequently still valid, being compatible with the now proven longitudinal zonal pattern of the olivo-ansiform projection.The fact that the two subdivisions of the principal olive, here shown to project to separate D1 and D2 zones of the ansiform lobule, receive specific sets of afferents suggests that the two cortical zones are part of two different cerebellar operational units.     

Chronic bronchitis and urban air pollution in an international study

Objectives

The chronic effects of urban air pollution are not well known. The authors'' aim was to investigate the association between the prevalence and new onset of chronic bronchitis and urban air pollution.

Methods

Subjects from the general population randomly selected for the European Community Respiratory Health Survey (ECRHS I) during 1991–93 in 21 centres in 10 countries were followed up from the years 2000 to 2002 (n = 3232 males and 3592 females; average response rate = 65.3%). PM_2.5 and elements, with the same equipment at centre level, and home outdoor NO₂ in 1634 individuals were measured. Hierarchical models were used.

Results

The prevalence and new onset of chronic phlegm during follow up were 6.9% and 4.5%, respectively, 5.3% in males and 3.5% in females. Smoking, rhinitis, poor education, and low social class were associated with (prevalence and new onset of) chronic phlegm in both genders, and occupational exposures in males and traffic intensity (adjusted odds ratio for constant traffic, OR = 1.86; 95% CI 1.24 to 2.77) as well as home outdoor NO₂ (OR > 50 μg/m³v < 20μg³  =  2.71; 95% CI 1.03 to 7.16) among females. PM_2.5 and S content at centre level did not show any association with prevalence or new onset of chronic phlegm. Similar results were obtained with chronic productive cough.

Conclusion

Individual markers of traffic at household level such as reported intensity and outdoor NO₂ were risk factors for chronic bronchitis among females.     

Oxidative damage of dust storm fine particles instillation on lungs, hearts and livers of rats

The purpose of this study was to investigate the effects of dust storm fine particles (PM_2.5) on oxidative damage in lungs, hearts and livers of rats. Wistar rats were randomly divided into treated groups using PM_2.5 at different concentration (1.5, 7.5, 37.5 mg/kg) and control groups using saline. After a single intratracheal instillation 24 h, rats were sacrificed and activities of Cu,Zn-superoxide dismutase (SOD), levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were investigated in these three organs of rats. Results show that dust storm PM_2.5 and normal weather PM_2.5 from both Baotou city and Wuwei city caused a dose-dependent decrease of SOD activities and GSH contents in lungs and livers, and a dose-dependent increase of TBARS levels in lungs, hearts and livers of rats as compared to their respective controls. Though the effects induced by normal weather PM_2.5 slightly heavier than dust storm PM_2.5 in both Baotou city and Wuwei city on each examined index, no significant difference was found. Furthermore, no significant difference was observed between the effects induced by dust storm PM_2.5 from Baotou city and that from Wuwei city, or between the effects induced by normal weather PM_2.5 from Baotou city and that from Wuwei city. These results lead to conclusions that both dust storm PM_2.5 and normal weather PM_2.5 could lead to oxidative damage of different disagrees in lungs, hearts and livers, suggesting that the dust storm PM_2.5 whose airborne mass concentrations were much higher should be more harmful. Its toxic effects might be attributed to oxidative damage mediated by pro-oxidant/antioxidant imbalance or excess free radicals. Further work is required to understand the toxicological role of dust storm PM_2.5 on multiple or even all organs in mammals.     

Regulation of lipid raft proteins by glimepiride- and insulin-induced glycosylphosphatidylinositol-specific phospholipase C in rat adipocytes

The insulin receptor-independent insulin-mimetic signalling provoked by the antidiabetic sulfonylurea drug, glimepiride, is accompanied by the redistribution and concomitant activation of lipid raft-associated signalling components, such as the acylated tyrosine kinase, pp59(Lyn), and some glycosylphosphatidylinositol-anchored proteins (GPI-proteins). We now found that impairment of glimepiride-induced lipolytic cleavage of GPI-proteins in rat adipocytes by the novel inhibitor of glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), GPI-2350, caused almost complete blockade of (i) dissociation from caveolin-1 of pp59(Lyn) and GPI-proteins, (ii) their redistribution from high cholesterol- (hcDIGs) to low cholesterol-containing (lcDIGs) lipid rafts, (iii) tyrosine phosphorylation of pp59(Lyn) and insulin receptor substrate-1 protein (IRS-1) and (iv) stimulation of glucose transport as well as (v) inhibition of isoproterenol-induced lipolysis in response to glimepiride. In contrast, blockade of the moderate insulin activation of the GPI-PLC and of lipid raft protein redistribution by GPI-2350 slightly reduced insulin signalling and metabolic action, only. Importantly, in response to both insulin and glimepiride, lipolytically cleaved hydrophilic GPI-proteins remain associated with hcDIGs rather than redistribute to lcDIGs as do their uncleaved amphiphilic versions. In conclusion, GPI-PLC controls the localization within lipid rafts and thereby the activity of certain GPI-anchored and acylated signalling proteins. Its stimulation is required and may even be sufficient for insulin-mimetic cross-talking to IRS-1 in response to glimepiride via redistributed and activated pp59(Lyn).     

Polymorphisms of human cytochrome P450 2C9 and the functional relevance

Human cytochrome P450 2C9 (CYP2C9) accounts for ∼20% of hepatic total CYP content and metabolizes ∼15% clinical drugs such as phenytoin, S-warfarin, tolbutamide, losartan, and many nonsteroidal anti-inflammatory agents (NSAIDs). CYP2C9 is highly polymorphic, with at least 33 variants of CYP2C9 (*1B through *34) being identified so far. CYP2C9*2 is frequent among Caucasians with ∼1% of the population being homozygous carriers and 22% are heterozygous. The corresponding figures for the CYP2C9*3 allele are 0.4% and 15%, respectively. There are a number of clinical studies addressing the impact of CYP2C9 polymorphisms on the clearance and/or therapeutic response of therapeutic drugs. These studies have highlighted the importance of the CYP2C9*2 and *3 alleles as a determining factor for drug clearance and drug response. The CYP2C9 polymorphisms are relevant for the efficacy and adverse effects of numerous NSAIDs, sulfonylurea antidiabetic drugs and, most critically, oral anticoagulants belonging to the class of vitamin K epoxide reductase inhibitors. Warfarin has served as a practical example of how pharmacogenetics can be utilized to achieve maximum efficacy and minimum toxicity. For many of these drugs, a clear gene–dose and gene–effect relationship has been observed in patients. In this regard, CYP2C9 alleles can be considered as a useful biomarker in monitoring drug response and adverse effects. Genetic testing of CYP2C9 is expected to play a role in predicting drug clearance and conducting individualized pharmacotherapy. However, prospective clinical studies with large samples are warranted to establish gene–dose and gene–effect relationships for CYP2C9 and its substrate drugs.