Flunarizine in Migraine Prophylaxis: An Indian Trial

Flunarizine, a calcium channel blocker is considered useful in migraine prophylaxis. We report the first Indian trial with this drug. Fifteen patients with migraine were studied in a 6 months double-blind, placebo-controlled crossover trial. Flunarizine was superior to placebo in reducing the severity and duration of the individual attacks though there was no statistically significant effect on frequency of migraine attacks. The side effects most frequently caused by flunarizine were weight gain and daytime sleepiness.     

Epidemiology of beta-lactamases in Africa: correlation with resistance to beta-lactam antibiotics

In 45 centers from eight African countries, 2,888 bacterial isolates were collected from patients with community-acquired infections. Isolated pathogens included Staphylococcus aureus (29%), Escherichia coli (20%), Neisseria gonorrhoeae (6%), Proteus species (6%), Klebsiella species (6%), Klebsiella pneumoniae (4%), and Staphylococcus epidermidis (4%). An overall sensitivity of 16.2% was shown to penicillin G (number of isolates tested = 2,467), 31.8% to ampicillin (2,687), 45% to amoxicillin (1,959), and 84.9% to cefuroxime (2,888). Beta-lactamase presence was measured by a chromogenic method. Beta-lactamase was found in 75% of all pathogens tested, including 69.5% of gram-negative and 83.3% of gram-positive pathogens; 73% of E coli isolates, 76% of N gonorrhoeae, 75% of Klebsiella species, and 84% of S aureus were beta-lactamase positive. Beta-lactamase presence was associated with bacterial resistance for penicillin G, ampicillin, and amoxicillin, but not cefuroxime, whose sensitivity remained high. The higher resistance rates and beta-lactamase prevalence in Africa suggest the need for national antibiotic prescribing policies and surveillance schemes and replacement of relatively ineffective penicillins with newer agents such as cefuroxime.     

Carrier-directed anti-hapten responses by b-cell subsets

The capacity of the trinitrophenyl (TNP) haptenic group, coupled to a series of chemically dissimilar carriers, to cross-stimulate putative T- dependent and T-independent murine B-cell subpepulations was determined by using an in vitro limiting dilution technique to generate primary IgM responses. It was found that TNP-Ficoll and TNP-dextran, two T- independent antigens with little or no polyclonal mitogenicity, stimulate the same population of anti-TNP precursors, which is distinct from the precursor population activated by TNP-bacterial lipopolysaccharide (LPS), a T-independent polyclonal mitogen, or TNP-horse erythrocytes (HRBC), a T-dependent antigen. On the other hand, TNP-LPS and TNP-HRBC activate the same precursor population, indicating that LPS can substitute for the T- cell signal in T-dependent B-cell responses, whereas nonmitogenic T- independent antigens cannot. However, the cumulative evidence from this and other laboratories strongly indicates that LPS and T-dependent antigens activate B cells by different mechanisms. Of particular interest, LPS is incapable of activating B cells responsive to weakly- or nonmitogenic T-independent antigens. Based on clonal burst size, T-dependent antigens are capable of inducing greater antigen-specific B-cell proliferation than T-independent antigens. However, TNP conjugates of Ficoll and dextran, which are relatively poor inducers of polyclonal B-cell activation, induced larger anti-TNP clones than did TNP-LPS, a strong polyclonal mitogen. The findings reinforce the evidence favoring existence of multiple B- cell subpopulations with distinctive activation pathways. They also strengthen the proposition that a given B-cell subset can be activated by more than one mechanism.     

血管内皮细胞生长因子受体KDR基因靶向RNA干扰质粒的构建

目的:应用RNA干扰技术设计构建针对血管内皮细胞生长因子受体KDR的小干扰RNA,并观察脂质体转染肺癌细胞A549后的干扰效果。方法:实验于2005-03/2006-01在沈阳医学院生物化学及分子生物学教研室完成。①设计针对KDR编码区有短发夹结构的3条mRNA序列,经退火成互补双链,克隆到pGCsi.H1/neo/GFP载体中构建3个重组质粒,分别命名为KDR-siRNA1、KDR-siRNA2和KDR-siRNA3。②设立5组:小干扰RNA组,分别转染KDR-siRNA1、KDR-siRNA2和KDR-siRNA3;阳性对照组,转染pGCsi.H1/neo/siGFP,该质粒载体中的插入序列为针对绿色荧光蛋白的小干扰RNA,不干扰待研究的内源性基因;阴性对照组,转染pGCsi.H1/neo/GFP/NON,该载体为不干扰任何内源性基因的小干扰RNA;空白对照组,转染pGCsi.H1/neo/GFP空载体;正常对照组,不进行任何转染。③对重组质粒进行酶切鉴定、DNA测序分析;脂质体法转染质粒至肺癌A549细胞株后,实时定量PCR检测KDRmRNA的水平变化;细胞计数法绘制细胞生长曲线。结果:①小干扰RNA表达载体的鉴定:KDR-siRNA1、KDR-siRNA2和KDR-siRNA3表达载体用限制性内切酶NdeⅠ和SmaⅠ进行单酶切后,均产生约713bp、5480bp和2403bp、3790bp两个片段,与预期结果相同。测序结果与设计的编码相应短发夹状KDR-小干扰RNA的寡核苷酸序列一致,证明KDR-小干扰RNA真核表达载体构建成功。②KDR-小干扰RNA对A549细胞中KDRmRNA水平的影响:与阳性对照组、阴性对照组、空白对照组和正常对照组的A549细胞相比,KDR-siRNA1,2,3表达载体转染后的A549细胞KDR基因表达水平均明显受到抑制,抑制率分别为64%、81%和72%,其中以KDR-siRNA2抑制作用最为明显。③KDR-小干扰RNA对A549细胞生长的影响:阳性对照组、阴性对照组、空白对照组、正常对照组的A549细胞生长趋势较为一致,且生长速度均明显高于转染3种KDR-小干扰RNA表达载体的A549细胞,从接种第2天开始差异有显著性意义(t=15.29～17.65,P均<0.01)。结论:血管内皮细胞生长因子受体KDR靶向RNA干扰重组质粒构建成功,该载体能有效抑制肺癌A549细胞KDR基因表达与细胞增殖。     

Surgical considerations for ‘intrinsic＇ brainstem gliomas： proposal of a modification in classification

BACKGROUND： Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unelear. OBJECTIVE： To evaluate the clinical, radiological and surgical outcome of 40 focal ＂intrinsic＂ brainstem gliomas and propose a surgical strategyoriented classification. MATERIALS AND METHODS： A total of 40 focal ‘intrinsie’ （＂expanding variety＂） tumors have been operated over a period of 8.5-years （January 1998-June 2007）. Our criteria included patients with （1） well-defined gadolinium enhancing tumor, （2） relatively long duration of symptoms （〉 six months） and （3） good neurological functional status and independent for all activities of davy living. The cutoff size of 2 cm was not rigidly adhered to. RESULTS： The ＂intrinsic＂ brainstem tumors were classified into three types： Expanding, diffuse infiltrative and pure ventral varieties.