超临界流体萃取法及高效液相色谱法分析延胡索中延胡索乙素的含量

采用超临界流体萃取法提取延胡索及其成方制剂中的延胡索乙素,以苯作改性剂,于40℃,42 MPa压力下,二氧化碳静态萃取5 min,动态萃取3 ml。该法操作简便快速,提取完全,也为其它中药及其制剂中有效成分的定量分析建立了一种简便、快速、有效的提取方法。应用硅胶柱─反相洗脱系统的高效液相色谱法测定延胡索及其成方制剂中延胡索乙素的含量,方法简便、快速、精密度高。此色谱系统同样适于其它中药及其制剂中生物碱的定量分析。     

Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline-DNA adducts by indole-3-carbinol: dose-response studies in the rat colon

Indole-3-carbinol (I3C) inhibits the formation of colonic aberrant crypt foci and DNA adducts in rats given heterocyclic amine colon carcinogens, such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Mechanism studies indicate that I3C induces cytochromes P4501A1 and 1A2 (CYP1A1 and CYP1A2), isozymes that respectively metabolize IQ via ring hydroxylation or activate the carcinogen by N-hydroxylation. The present study examined the dose-response for induction of CYP1A1 versus CYP1A2 by I3C, and compared the profiles of induction with the dose- response for inhibition of IQ-DNA adducts in the colon of the F344 rat. Dietary equivalent doses of I3C in the range 100-1000 p.p.m. increased in a dose-related manner both ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities in the liver and colonic mucosa, and Western blots showed a corresponding induction of CYP1A1 and CYP1A2 proteins. However, dietary equivalent doses of I3C in the range 10-25 p.p.m. (i) reduced hepatic EROD and MROD activities and CYP1A protein levels compared with controls, (ii) increased the ratio of CYP1A2 versus CYP1A1, and (iii) activated IQ to a more potent mutagen when liver microsomes from rats given I3C were used for metabolic activation in the Salmonella assay. Rats given a single oral dose of I3C shortly before administering IQ (5 mg/kg body wt, p.o.) exhibited dose-related inhibition of colonic IQ-DNA adducts in the range 25-100 p.p.m. I3C, reaching 95% inhibition at doses > or = 100 p.p.m. I3C, but IQ-DNA adducts were elevated slightly at the lowest I3C dose as compared with the controls. The possible significance of the low versus high dose effects of I3C are discussed in the context of human dietary exposures to I3C and the reported chemopreventive mechanisms of I3C in vivo.      

Disseminated bacille Calmette�CGu��rin disease in HIV-infected South African infants

Objective

To determine the population-based incidence of disseminated bacille Calmette–Guérin (BCG) disease in HIV-infected infants (aged ≤ 1 year) in a setting with a high burden of tuberculosis and HIV infection coupled with a well-functioning programme for the prevention of HIV infection in infants.

Methods

The numerator, or number of new cases of disseminated BCG disease, was derived from multicentre surveillance data collected prospectively on infants with a confirmed HIV infection during 2004–2006. The denominator, or total number of HIV-infected infants who were BCG-vaccinated, was derived from population-based estimates of the number of live infants and from reported maternal HIV infection prevalence, vertical HIV transmission rates and BCG vaccination rates.

Findings

The estimated incidences of disseminated BCG disease per 100 000 BCG-vaccinated, HIV-infected infants were as follows: 778 (95% confidence interval, CI: 361–1319) in 2004 (vertical HIV transmission rate: 10.4%); 1300 (95% CI: 587–2290) in 2005 (transmission rate: 6.1%); and 1013 (95% CI: 377–1895) in 2006 (transmission rate: 5.4%). The pooled incidence over the study period was 992 (95% CI: 567–1495) per 100 000.

Conclusion

Multicentre surveillance data showed that the risk of disseminated BCG disease in HIV-infected infants is considerably higher than previously estimated, although likely to be under-estimated. There is an urgent need for data on the risk–benefit ratio of BCG vaccination in HIV-infected infants to inform decision-making in settings where HIV infection and tuberculosis burdens are high. Safe and effective tuberculosis prevention strategies are needed for HIV-infected infants.     

Long-distance Axonal Transport of AAV9 Is Driven by Dynein and Kinesin-2 and Is Trafficked in a Highly Motile Rab7-positive Compartment

Adeno-associated virus (AAV) vectors can move along axonal pathways after brain injection, resulting in transduction of distal brain regions. This can enhance the spread of therapeutic gene transfer and improve treatment of neurogenetic disorders that require global correction. To better understand the underlying cellular mechanisms that drive AAV trafficking in neurons, we investigated the axonal transport of dye-conjugated AAV9, utilizing microfluidic primary neuron cultures that isolate cell bodies from axon termini and permit independent analysis of retrograde and anterograde axonal transport. After entry, AAV was trafficked into nonmotile early and recycling endosomes, exocytic vesicles, and a retrograde-directed late endosome/lysosome compartment. Rab7-positive late endosomes/lysosomes that contained AAV were highly motile, exhibiting faster retrograde velocities and less pausing than Rab7-positive endosomes without virus. Inhibitor experiments indicated that the retrograde transport of AAV within these endosomes is driven by cytoplasmic dynein and requires Rab7 function, whereas anterograde transport of AAV is driven by kinesin-2 and exhibits unusually rapid velocities. Furthermore, increasing AAV9 uptake by neuraminidase treatment significantly enhanced virus transport in both directions. These findings provide novel insights into AAV trafficking within neurons, which should enhance progress toward the utilization of AAV for improved distribution of transgene delivery within the brain.     

硝普钠的光解分析法及其在透皮吸收研究中的应用

依据已报告的光解分析法原理,建立了定量分析硝普钠的方法。在光源照射下,硝普钠溶液在394nm处吸收度增加属非线性动力学,但对一定浓度溶液,吸收度增量对浓度呈直线关系;无论光照30min或60min,依据△A₃₉₄都能准确地定量。本文方法线性范围50～1000mg/L,日内变异系数<1.9%;日间变异系数<2.6%,回收率99.0～100.1%。共存的少量血清蛋白、十八醇、维生素B₁₂、丙二醇、氮酮以及间硝苯啶、尼群地平、维拉帕米等均不干扰测定。方法已成功地用于透皮吸收剂的研究。     

A Prospective Randomized Study to Assess the Efficacy of Rate and Site of Atrial Pacing on Long-Term Development of Atrial Fibrillation

The Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) study is a single-blinded, parallel randomized designed multicenter study in pacemaker indicated patients with paroxysmal atrial fibrillation (AF). The objective is to evaluate whether the site of atrial pacing–-conventional right atrial appendage versus low atrial septal—with or without atrial overdrive pacing will influence the development of persistent AF. The study will provide a definitive answer to whether a different atrial pacing site or the use of AF suppression pacing or both can give incremental antiarrhythmic benefit when one is implanting a device for a patient with a history of paroxysmal AF.