核因子κBp65特异性小干涉核糖核酸抑制肿瘤坏死因子α诱导大鼠关节滑膜细胞中一氧化氮合酶2和环氧合酶2的表达

目的:利用核因子κBp65特异性小干涉核糖核酸抑制肿瘤坏死因子α诱导的关节滑膜细胞中一氧化氮合酶2和环氧合酶2的表达,探讨基因治疗类风湿性关节炎的新方法。方法:实验于2005-03/2006-03在北京大学医学部中心实验室(国家级)完成。①实验材料:清洁级健康近交系SD大鼠10只;一氧化氮合酶2,环氧合酶2,3-磷酸甘油醛脱氢酶引物(由北京奥科生物公司合成);肿瘤坏死因子α(Sigma公司);核因子κBp65特异性小干涉核糖核酸和转染条件由北京大学运动医学研究所陈连旭博士提供。②实验干预:切取大鼠髋关节和膝关节的滑膜体外培养滑膜细胞。利用脂质体siPORTTMLipid将核因子κBp65特异性小干涉核糖核酸转染滑膜细胞,再加入肿瘤坏死因子α刺激。阴性对照为任意编码的小干涉核糖核酸,阳性对照为针对3-磷酸甘油醛脱氢酶的小干涉核糖核酸。③实验评估:提取滑膜细胞中的核蛋白,利用电泳迁移率试验检测核因子κB的活性;提取滑膜细胞的核糖核酸和总蛋白,利用反转录聚合酶链反应和蛋白质免疫印记法从信使核糖核酸和蛋白质两水平检测一氧化氮合酶2和环氧合酶2的表达。结果:①肿瘤坏死因子α和核因子κBp65特异性小干涉核糖核酸对核因子κB转录活性的影响:与正常滑膜细胞相比,肿瘤坏死因子α可以显著提高核因子κB的结合能力,而事先转染小干涉核糖核酸48h,再用肿瘤坏死因子α刺激,核因子κB的结合能力又显著降低。②核因子κBp65特异性小干涉核糖核酸对核因子κB下游因子的影响:在培养的滑膜细胞中,肿瘤坏死因子α可以显著增加一氧化氮合酶2和环氧合酶2的表达;在转染小干涉核糖核酸抑制核因子κBp65的表达后再用肿瘤坏死因子α刺激,一氧化氮合酶2和环氧合酶2的表达被抑制。结论:①核因子κBp65特异性小干涉核糖核酸可降低肿瘤坏死因子α诱导的滑膜细胞中核因子κB的转录活性,抑制其下游因子一氧化氮合酶2和环氧合酶2的表达。②核因子κBp65特异性小干涉核糖核酸可用于基因治疗类风湿性关节炎的试验研究。     

'Localized amyloidosis': 123I-labelled SAP component scintigraphy and labial salivary gland biopsy

In apparently localized amyloidosis, there is no appropriate test to determine whether systemic deposits exist. We studied the value of serum amyloid P component (SAP) scintigraphy and labial salivary gland (LSG) biopsy on patients with apparently localized amyloidosis in 12 patients who had neither clinical nor biological evidence of systemic amyloidosis. All patients had an LSG biopsy and echocardiography. Iodine-123-labelled serum amyloid P component (123I-SAP) scintigraphy was performed in all patients. Whole-body scintigraphy was done, and tissue retention was evaluated at 24 h and 48 h. Of these 12 patients, three had amyloidosis in their LSG and had abnormal 123I-SAP scintigraphy; these three had a secondary clinical history of systemic amyloidosis. Three other patients had abnormal 123I-SAP scintigraphy without detectable systemic amyloid deposits, but one had a previous history of bilateral carpal tunnel syndrome treated with infiltration. 123I-SAP scintigraphy in association with LSG biopsy may be helpful in determining the localized or systemic character of amyloid disease.      

鸡胚胎素对小鼠红细胞数量及免疫器官质量的影响

目的:建立血虚和免疫抑制动物模型,观察鸡胚胎低温提取物对其红细胞造血以及免疫器官质量的影响。方法:实验于2001-04/2002-09在新乡医学院药物研究室完成。①实验材料:健康昆明种小鼠50只,雌雄各半。鸡胚胎素[中国发明专利公开(公告)号:CN1748713],符合研究者申报专利时提出的质量检验标准。②鸡胚胎素对血虚模型小鼠红细胞数值及血红蛋白含量的影响:取20只小鼠,随机排列表法分为鸡胚胎素组、模型对照组,10只/组,建立失血性血虚动物模型。失血后24h当红细胞数<3.2×1012L-1、血红蛋白含量<84g/L,且小鼠外观出现皮色苍白、食欲不振等现象时,代表造模成功。次日,鸡胚胎素组给予鸡胚胎素5g/(kg·d)灌胃,模型对照组给予生理盐水20mL/(kg·d)灌胃,连续14d。分别于失血前、失血后24h、末次给鸡胚胎素后2h尾部采血测定两组红细胞数量及血红蛋白含量的变化。③鸡胚胎素对免疫抑制模型小鼠免疫器官质量的影响:取30只小鼠,随机排列表法分为鸡胚胎素组、模型对照组、正常对照组,10只/组。鸡胚胎素组给予鸡胚胎素5g/(kg·d)灌胃,模型对照组和正常对照组均灌服等量生理盐水,连续14d。在第11天上午鸡胚胎素灌胃2h后,鸡胚胎素组、模型对照组腹腔注射环磷酰胺60mg/(kg·d),连续4d,复制免疫抑制动物模型。末次给予环磷酰胺2h后颈椎脱位法处死小鼠,计算胸腺、脾脏质量指数。结果:50只小鼠均进入结果分析。①失血前及失血后24h鸡胚胎素组与模型对照组的红细胞数值、血红蛋白含量基本相似(P>0.05)。末次给鸡胚胎素后2h与模型对照组比较,鸡胚胎素组红细胞数值、血红蛋白含量均明显升高(t=3.39,P<0.01;t=2.52,P<0.05)。②末次给环磷酰胺2h后与模型对照组比较,鸡胚胎素组、正常对照组的胸腺质量指数和脾脏质量指数均明显升高(t=6.62,P<0.01;t=2.47,P<0.05)。结论:鸡胚胎素灌胃对血虚小鼠具有较好的促红细胞造血功能,同时对环磷酰胺造成的免疫器官质量下降具有明显的增重作用。     

On the best strategies on the best results for surgery of frontal epilepsy

Frontal lobe epilepsy surgery is the second most common surgery performed for drug-resistant partial epilepsy. We investigated the longitudinal outcome in a cohort of patients investigated since 1990 with SEEG and modern diagnostic techniques. We reviewed 105 patients who underwent surgery between 1990 and 2005 (mean follow-up, six years; range: one to17 years) and analyzed the year-per-year follow-up according to Engel's classification. Favorable outcome (Class I) was observed for 70% and this result was stable at least five years after surgery. More than 90% of patients with lesion-related epilepsies (focal cortical dysplasia and dysembryoplastic neuroepithelial tumors) became seizure-free. Less than 50% of patients classified as having cryptogenic epilepsy (defined as normal imaging and neuropathology on surgical specimen) had a favorable outcome.Permanent neurological sequelae were subtle and rare, especially after surgery for dysplasia in eloquent cortex (primary motor cortex).Our data indicate that frontal surgery is a successful treatment in patients when electrophysiological and morphological investigations demonstrate a well-defined epileptogenic zone or lesion to be surgically resected. Progress in electrophysiological and brain-imaging techniques will further improve the selection of frontal lobe epilepsy surgery candidates.     

La vérification ultime au lit du malade: résultats d''une enquête nationale sur les réactifs et dispositifs utilisés en France

The national reference Center for blood groups checked samples of reagents and devices used in France for a definitive verification of pretransfusion ABO tests performed at the patient's bedside, as defined by French health authority regulations. The results of an initial inquiry was published in 1991. The new study shows no significant improvement of the quality of reagents and devices. This is a major concern considering the importance of ABO incompatibility in severe hemolytic transfusion reactions.     

A randomized prospective comparison of oral versus intraperitoneal ofloxacin as the primary treatment of CAPD peritonitis

Summary: Oral ofloxacin has been successfully used in our centres for the primary treatment of peritonitis complicating continous ambulatory peritoneal dialysis (CAPD). In view of the progressive rise in the resistance rate to ofloxacin among peritoneal bacterial isolates, a study was conducted to determine if oral ofloxacin remains a viable first line treatment for CAPD peritonitis in our centres and if the result can be improved by changing from an oral to an intraperitoneal (i.p.) route. In patients on three 2 L daily CAPD exchanges, ofloxacin given at the i.p. dosage of 200 mg loading followed by 25 mg/L of peritoneal dialysate achieved overnight trough peritoneal levels which are at least four times the minimal 90% inhibitory concentration (MIC90) of most bacterial pathogens without significant accumulation in the systemic circulation. This i.p. dosage was therefore chosen for the clinical study and the result was compared to that using ofloxacin given in the oral dosage of 400 mg loading followed by 300 mg once daily as maintenance. of all the recruited episodes, 35 were eligible for analysis. the overall primary cure rate including primary failures and relapses was 55.6% (10/18) in the oral treatment group and 70.6% (12/17) in the i.p. treatment group. the corresponding figures for gram positive bacterial (g +) infections were 36.4% and 50%, for gram negative bacterial (g -) infections were 66.7 and 80% and for culture negative infections were 75 and 80%. In culture positive cases, all treatment failures were due to resistant infections which were observed in 42.3% of all bacterial isolates, 47.1% of g + isolates and 33.3% of g - isolates. Due to the high background level of bacterial resistance among our CAPD population, ofloxacin monotherapy given either by the oral or the i.p. route can no longer be recommended for the primary treatment of CAPD peritonitis.     

A STUDY OF THE APPROPRIATENESS OF ANTIBIOTIC USE IN THE MEDICAL WARDS OF A TERTIARY TEACHING HOSPITAL IN MALAYSIA

A prospective study was conducted to determine the proportion of patients who received an antibiotic within 12 hours of admission to the medical wards. During the four-week study, 234 patients were admitted to medical wards from casualty; 68 patients (29%) received an antibiotic. The survey indicated that antibiotics were inappropriate in 22–65% of those treated. This study also shows that as many as 67% of patients who received intravenous antibiotics could have been equally well treated with oral preparations.     

Safety of Fixed Dose of Antihypertensive Drug Combinations Compared to (Single Pill) Free-Combinations: A Nested Matched Case–Control Analysis

To compare serious adverse events of fixed-dose dual antihypertensive drug combination (FIXED) to component-based free-combination (FREE).A population-based nationwide cohort from the French Health Insurance System included subjects over 50 years with first time claims (new user) in the second half of 2009 for a calcium-channel blocker or a thiazide-like diuretic in combination with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker as FREE or FIXED. We designed a nested matched case–control analysis with 304 cases, hospitalized for hypotension, syncope, or collapse (n = 224), renal failure (n = 19), hyponatremia, hyper- or hypokalemia (n = 61) and 1394 controls matched for gender, age, date of inclusion in the cohort, and administrative county. Subjects with a medical history of cardiovascular disease, chronic renal failure, or cancer were excluded.The mean age ± SD was 73 ± 10 years and 70% were women. Based on the last delivery preceding the index date, 1414 patients (83%) were exposed to FIXED. Homogeneity of FIXED effect compared to FREE across components of the main composite outcome was rejected (P = 0.0099). FIXED formulation significantly increased the odd of the most frequent component (ie, hypotension, syncope, or collapse): OR = 1.88 (95% CI: 1.15–3.05) compared to FREE after adjusting for confounding factors including dose.Serious adverse event occurring in the early phase of treatment deserves attention of physicians because it could alter the benefit/risk ratio of antihypertensive drug combination.     

升麻酰胺及其类似物的合成

升麻酰胺是从兴安升麻(Cimicifuga dahurica)根茎中分到的新天然产物,本文经7步反应完成了该化合物的全合成,总收率为31%,三氟乙酰氧基用作C-1的离去基团,其结构经光谱分析和元素分析证实与天然物相一致。此外,还报道其7个类似物的合成及初步的抗肿瘤活性实验结果。