Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.     

从临床标本分离出510株病原菌的初步报告

报告１９９４年我院临床标本检出的常见菌及其对抗生素的敏感性变化。结果表明，革兰氏阴性杆菌占检出菌的第一位６３．７２％，革 兰氏阳性菌居第二位２９．４１％。在革兰氏阴性杆菌中铜绿假单胞菌居首位，并占革兰氏阴性杆菌的２９．２３％；大肠艾希氏菌占第二位２２．７７％，不动杆菌占第三位１２．３０％。在革兰氏阳性球菌中，凝固酶阴性葡萄球菌居检出菌的第一位，并占革兰氏阳性球菌的３７．３３％；金黄色葡萄球菌占第二     

泌尿系感染者病原菌及耐药性分析

目的：了解近年来泌尿系细菌感染致病菌及耐药性，为合理应用抗生素，提供临床根据。方法：对泌尿系感染患者298株病原菌进行药物敏感试验。结果：大肠埃希菌仍是引发泌尿系感染的主要病原菌，占53％，其次是葡萄球菌属，占19．40％，肠杆菌属占10．06％，肠球菌属占4．70％等，各类菌属耐药情况。结论：临床医师必须关注本地病原菌分布及耐药情况，合理应用抗生素，减少耐药性播散。     

Oral self-administration of etonitazene in rhesus monkeys: Use of a fading procedure to establish etonitazene as a reinforcer

The establishment of orally delivered etonitazene (a potent opioid) as a reinforcer, was studied in eight rhesus monkeys. Initially, when given concurrent access to 2.5 μg/ml etonitazene and the water vehicle, five of the monkeys rejected the drug, whereas the other three monkeys consumed more drug solution than water. The five monkeys that rejected the drug solution underwent an acquisition phase to establish the drug as a reinforcer. A fading procedure was used to transfer control of responding from a 2% (wt/vol) ethanol solution to a 2.5 μg/ml etonitazene solution. Initially, responding was maintained by contingent deliveries of 2% ethanol. Next, across blocks of six or more sessions, increasing amounts of etonitazene were added in steps to the 2% ethanol solution. Subsequently, the 2% ethanol solution was decreased in steps to zero, leaving only the 2.5 μg/ml etonitazene present. When the fading procedure was completed, dose of etonitazene was varied by increasing the volume delivered, first under fixed ratio (FR 4) and then under an FR 8 reinforcement schedule. The same dose manipulations were made with the three monkeys who did not undergo the fading procedure because they preferred etonitazene over water when first tested. Etonitazene was established as a reinforcer for six of the eight monkeys because drug deliveries exceeded vehicle deliveries across a range of drug doses.     

A preliminary study of the relationship between antibiotic administration and changes in bacteriological profile of wound infection in a burn unit

Objective:To investigate the relationship between antibiotic administration and the changes in bacteriological profile in a burn unit. Methods: The data of consumption of different kinds of antibiotics, including total antibiotic consumption [expressed as the number of defined daily doses (DDD)] as well as pathogen identification, were collected in a 8-year period. The constituent ratios of different kinds of antibiotics in total antibiotic consumption to isolation rates of various species of bacteria were calculated, and their correlation was analyzed. Results: Within this period, it was found that the aminoglycosides and first generation cephalosporins were used less frequently, while the polypeptides, carbopenem and macrolides were used proportionally more. At the same time, the isolation rates of Staphylococcus aureus, Acinetobacter sp, Enterobacter cloacae, Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus were gradually increased. The constituent ratios of predominant pathogens were correlated to the different kinds of antibiotics consumption in the burn unit. Conclusion: The results suggested that the consumption of different antibiotics was closely related to the trends of emergence of bacterial isolates from infected burn wounds. The result might imply that to regulate the administration of certain antibiotics might help decrease the emergence of certain pathogenic bacteria in burn infections.     

丙型肝炎传播途径的病例对照研究

本文按１１病例对照设计研究了丙型肝炎的传播途径。结果显示：无论单因素还是多因素条件Ｌｏｇｉｓｔｉｃ回归分析，输血及血制品都是丙型肝炎传播的一条重要途径。多因素条件Ｌｏｇｉｓ－ｔｉｃ回归分析的ＯＲ＝４．４８０，Ｐ＝０．００１。另外，肝炎家族史和外科手术史也可能与丙型肝炎的感染有关。本研究未发现注射、有创性检查以及外出饮食习惯与ＨＣＶ感染的关系     

外源性凝血途径和内皮细胞损伤与动脉粥样硬化之间的关系研究

目的探讨外源性凝血途径在动脉粥样硬化(AS)发病中的作用。方法均采用ELISA法测定心肌梗死、脑梗死、脑出血病人及正常对照组血浆TF、FⅦa的含量及不同时期这些物质浓度的变化、同时通过测定内皮细胞损伤的分子标记物vWF、内皮素 -1(ET -1)、总组织因子途径抑制物(TFPI)、组织因子(TF)探讨外源性凝血途径的活化与水平状况及内皮细胞损伤之间的关系。结果心肌梗死、脑梗死、脑出血病人TF、TFPT、ET -1、vWF、FⅦa,血中的浓度较正常对照组高 (P<0.01) ,有非常显著意义。结论外源性凝血途径与内皮细胞损伤和AS有密切相关。     

Vagal mediation of the cholecystokinin satiety effect in rats

Central (intracerebroventricular) and peripheral (intraperitoneal) injections of the octapeptide of cholecystokinin (CCK-8) were compared to determine the most effective route of administration to elicit satiety for food intake in the rat. Subdiaphragmatic bilateral vagotomy and spinal cordotomy (T2-T3) were also performed to investigate the importance of visceral nerves for the satiety effect. CCK-8 suppressed feeding and elicited satiety resting behavior when injected peripherally but it was less effective when injected centrally. The satiety effect of CCK-8 or CCK-33 following peripheral injections was blocked by vagotomy whereas spinal cordotomy had no effect. The results indicate that some component of the vagus is required to mediate the peripherally induced cholecystokinin satiety effect, but the splanchnic nerves are not necessary. The weak effect of CCK-8 following ventricular administration is additional evidence suggesting that cholecystokinin of intestinal origin acts in the periphery rather than directly on the brain to elicit its typically rapid satiety effect in rats.     

齿龈内阿米巴的致病作用与致病机制的研究

在注射免疫抑制剂 1周后的大白鼠龈缘涂抹齿龈内阿米巴 (Emtamoebagingivalis ,E .g .) ,5天后 ,牙龈组织出现溃疡、牙周脓肿形成、脓液查见活E .g .、牙槽骨吸收等牙周炎病症。电镜术与生化分析发现 :E .g .伪足活跃、有丰富的溶酶体 ,所含水解酶与ACP显著较健康组高 (P <0 0 1) ,可使牙周组织溶解与受损。SOD较健康组显著性低 (P <0 0 1) ,MDA显著性增高 (P <0 0 1) ,说明E .g .感染产生较多氧自由基可使细胞膜受损 ,加上口腔共生菌的协同作用使免疫力低下的宿主发生牙周炎。     

基因芯片技术检测环境中常见致病菌的初步研究

目的：为了快速，准确地检测环境中存在的致病菌，建立一种采用基因芯片技术对环境中常见致病检测和鉴定的实验方法。方法：采用合成后点样的方法把自行设计合成的一系列寡核苷酸探针固定在经过醛基化修饰的显微镜载玻片上，制成用于致病菌检测的基因芯片。结果：在相同的条件下，扩增了涉及12个菌属的151株细菌的165rDNA基因片段并与基因芯片杂交，经Scan-Array3000芯片阅读仪扫描得到特异性的交杂图，归纳这些杂交图，得到一套属（种）特异的典型杂交图谱。待检的样品菌与基因芯片进行杂交，得到的杂交结果与典型图谱比对即可判断出样品的种类。用这样的方法对从实际样品中分离的细菌进行检测，准确率表达了96．2％（25／26）。结论：该项技术的建立为今后更大规模的检测研究奠定了基础，可以推广应用于感染性疾病诊断，环境监测，食品卫生监督，商品检验检疫等领域。