Dose-dependent localization of TCDD in isolated centrilobular and periportal hepatocytes

Dose-response relationships for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suggest a differential sensitivity of liver cell types to the induction of cytochrome P450 gene expression, and that the induction of hepatic protein CYP1A2 causes sequestration of TCDD. In addition, immunolocalization of hepatic CYP1A1/1B1/1A2 proteins is not uniform after exposure to TCDD. The mechanism for the regio-specific induction of hepatic P450s by TCDD is unknown, but may involve the differential distribution of participants in the AhR-mediated pathway and/or regional P450 isozymes, as well as, non-uniform distribution/sequestration of TCDD. Therefore, this study examined the effects of TCDD in unfractionated, centrilobular and periportal hepatocytes isolated from female Sprague-Dawley rats acutely exposed (3 days) to a single oral dose of 0.01-10.0 microg [3H]TCDD/kg. A dose- dependent increase in concentration of TCDD was accompanied by a dose- dependent increase in CYP1A1, CYP1A2, and CYP1B1 mRNA expression and associated enzymes in all liver-cell populations. Centrilobular hepatocytes showed a 2.7- to 4.5-fold higher concentration of TCDD as compared to the periportal hepatocytes at doses up to 0.3 microg TCDD/kg. Centrilobular hepatocytes also exhibited an elevated MROD activity as compared to the periportal hepatocytes at doses up to 0.3 microg TCDD/kg. Furthermore, centrilobular hepatocytes showed an elevated concentration of induced CYP1A2 and CYP1B1 mRNA as compared to periportal hepatocytes within the 0.01- and 0.3-microg TCDD/kg- treatment groups. This is the first study to demonstrate that a dose- dependent difference in distribution of TCDD exists between centrilobular and periportal cells that might be related to regional differences in P450 induction.      

Nebulized budesonide versus oral steroid in severe exacerbations of childhood asthma

The aim of this study was to assess whether nebulized budesonide may substitute for oral prednisolone in the management of children whose asthma is severe enough to warrant hospital admission, but who have no life threatening features. In a prospective, double-blind, randomized study nebulized budesonide (2 mg 8 hourly) was compared with oral prednisolone (2 mg/kg at entry and again at 24 h) in 46 children admitted to hospital with severe asthma exacerbations. Efficacy variables (including lung function measurements such as the primary outcome variable, Forced Expiratory Volume in 1 second (FEV₁) and symptoms) were measured 24 h after treatment initiation. FEV₁ improved significantly compared to baseline in patients who received nebulized budesonide compared to the prednislone group. The data show nebulized budesonide to be at least as effective as oral steroid in improving lung function and symptom severity in severe exacerbations of childhood asthma.     

Therapy for cessation of smoking

Tobacco dependence is a chronic relapsing medical illness. Unfortunately more than 1.1 billion people worldwide smoke tobacco. Tobacco consumption rate is very high in India. Providing three minutes counseling by physicians doubles the cessation rate as compared to no intervention. Nicotine replacement products (gums, transdermal patch, nasal spray, inhaler and lozenge), bupropion and varenicline used with counseling by physicians double the cessation rates at one year. There are drugs like buspirone, naltrexone, mecamylamine and silver acetate; some of which either alone or in combination with any of the above drugs may be routinely used in near future for smoking cessation in at least some specific groups of population. The most difficult problem for patients in smoking cessation is withdrawal symptoms. Counseling with continuous support from physician, family members, friends and overall from the society will help in achieving a higher rate of smoking cessation, with the final aim of making ours a tobacco smoke-free world for future generations.     

弯喙乌头的化学成分研究

从弯喙乌头(Aconitum campylorrhynchum)中分离出一个微量新生物碱,经光谱和化学方法证明为8-乙酰嘟啦碱-(8-acetytdolaconine,Ⅰ),同时分离得到2个已知生物碱;即嘟啦碱(Ⅱ)和aconosine,(Ⅲ),后者是该植物的主要生物碱成分,在非生物碱部分还分离得到β-谷甾醇,棕榈酸和香豆酸。     

昆明山海棠化学成分研究

从昆明山海棠(Tripterygium hypoglaucum (Lévl.)Hutch)根中分得三个单体,经光谱分析鉴定晶1为已知物雷藤二萜酸(triptoditerpenic acid),晶2和晶3为新二萜化合物,分别命名为雷藤二萜酸B(triptoditerpenic acid B)和山海棠二萜内酯A(hypodiolide A)。     

苦红菇化学成分的研究

从野生真菌苦红菇(Russula rosacea(Bull)Grrayem,Fr.)子实体酸性部分得到两个新的四环三萜酸化合物,经光谱(IR,¹HNMR,¹³CNMR,MS)、尤其是二维核磁共振(¹³C-¹HCOSY,COLOC,NOEDIFF)谱解析,确定其结构分别如Ⅰ和Ⅱ所示,Ⅰ命名为苦红菇酸A(rosaceaacidA),Ⅱ为苦红菇酸B(rosaceaacidB)。