Plasma concentrations and bioavailability of propranolol by oral, rectal, and intravenous administration in man

Eight normal male volunteers received 80 mg doses of propranolol by the oral and rectal routes and 2.2 mg by intravenous administration in a crossover fashion. Plasma concentrations of propranolol were measured by a gas chromatographic method using an electron capture detector. Individual subject concentration-time data were analysed and results indicated that the data fit a two compartment model with first order absorption. An approximately two-fold higher plasma propranolol concentration was observed after rectal administration as compared with oral dosing. Statistical analysis of the difference in the total AUCs indicates a significantly higher bioavailability of propranolol administered by the rectal route. The reduced bioavailability after oral administration indicates a substantial first pass effect but that it is possible to bypass the liver, at least partially, by giving the drug rectally to man.     

Cough and converting enzyme inhibitors

Persisting cough developed in three children treated with converting enzyme inhibitors. The symptoms disappeared within 3–7 days after withdrawing medication. These observations in children complement previous reports in adults and indicate that cough may be induced by treatment with these agents.     

Effects of Carbamazepine on Murine Humoral and Cellular Immune Responses

Summary: Oral administration of carbamazepine (CBZ)(15, 10, or 5 mg/kg) to mice significantly decreased both humoral and cellular immune responses evaluated by enumeration of direct and indirect plaque-forming spleen cells (PFC) and delayed–type hypersensitivity reaction (DTH) against sheep red blood cells (SRBC) as compared with those observed in normal control animals. Moreover, spleen T cells obtained from CBZ–treated donor mice were capable of decreasing both PFC and DTH responses of normal spleen cells transferred into lethally irradiated recipient animals. The immunodepressor effect of CBZ was observed even though administration of CBZ induced augmentation of spleen cellularity.     

Anticonvulsant Activities of 4–Bromobenzaldehyde Semicarbazone

Summary: Some of the properties of 4–bromobenzalde-hyde semicarbazone (compound IV), a prototype molecule of a new class of anticonvulsants, aryl semicarbazones, are described. Compound IV demonstrated activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests in mice, with low neurotoxicity. When given orally to rats, it displayed high potency in the MES test and very low neurotoxicity, resulting in a high protective index (PI). Compound IV displayed no proconvulsant properties, and development of rapid tolerance was not noted. When administered intraperitoneally (i.p.) at doses of 100, 300, or 600 mg/kg to rats, compound IV had no effect on levels of γ-aminobu-tyric acid (GABA) or on GABA-T activity in whole brain. When tested in vitro, compound IV had no effect on rat brain GABA-T at a drug concentration of 100 μM. Although the activities of certain drug-metabolizing enzymes were increased after oral administration of compound IV to rats, these effects were less prominent than those of phenytoin (PHT) and carbamazepine (CBZ). The principal mode of action of compound IV does not appear to be an interaction with the GABA_A receptor complex, and other mechanisms, involving excitatory amino acid neurotransmission, will have to be considered in future investigations of the anticonvulsant activity of this compound.     

老年患者尿路感染菌群分布及其耐药性分析

目的 :了解老年患者尿路感染致病菌的菌群分布及其对抗生素的耐药情况 ,为临床合理使用抗生素提供依据。方法 :收集湖北省 15所三级甲等医院 2 0 0 2年尿路感染老年患者清洁中段尿细菌培养分离的 5 34株致病菌 ,对其进行耐药性监测。药敏采用K B法 ,用WHONET 5软件进行数据分析。结果 :共收集致病菌 5 34株 ,其中革兰阴性菌 4 0 9株 (76 .6 % ) ,革兰阳性菌 12 5株(2 3.4 % )。革兰阴性菌中大肠埃希菌检出率最高 (2 6 4株 ,4 9.4 % ) ,其次为克雷白杆菌 (44株 ,8.2 % )。 16 .7%的大肠埃希菌和 2 2 .7%的克雷白杆菌产超广谱 β 内酰胺酶。亚胺培南、阿米卡星、头孢他啶对革兰阴性菌的抗菌活性最强 ,而革兰阴性菌对环丙沙星、庆大霉素、哌拉西林的耐药率均在 5 0 %以上。革兰阳性菌以肠球菌最多见 (6 4株 ,12 % ) ,其次为葡萄球菌属 (43株 ,8.1% )。革兰阳性菌对SMZco、红霉素等的耐药率均在 4 0 %以上 ,但对万古霉素均敏感。结论 :老年患者尿路感染以革兰阴性菌为优势菌株 ,且耐药性日益严重 ,对亚胺培南、阿米卡星、头孢他啶最为敏感。革兰阳性菌宜以万古霉素为首选。     

Absorption of chemicals through compromised skin

Skin is an important route of entry for many chemicals in the work place. To assess systemic uptake of a chemical in contact with the skin, quantitative information on dermal absorption rates of chemicals is needed. Absorption rates are mainly obtained from studies performed with intact, healthy skin. At the work place, however, a compromised skin barrier, although not necessarily visible is common, e.g. due to physical and chemical damage. As reviewed in this article, there are several lines of evidence that reduced integrity of the skin barrier may increase dermal absorption of chemicals in the occupational setting. An impaired skin barrier might lead not only to enhanced absorption of a specific chemical, but also to entrance of larger molecules such as proteins and nanoparticles which normally are not able to penetrate intact skin. In addition to environmental influences, there is increasing evidence that some individuals have an intrinsically affected skin barrier which will facilitate entrance of chemicals into and through the skin making these persons more susceptible for local as well for systemic toxicity. This review addresses mechanisms of barrier alteration caused by the most common skin-damaging factors in the occupational settings and the consequences for dermal absorption of chemicals. Furthermore, this review emphasizes the importance of maintained barrier properties of the skin.     

Introduction of “international syringe labelling” in the Republic of Ireland

Introduction  Medication errors are a preventable cause of patient injury. In May 2003, as a result of a joint initiative by the Royal College of Anaesthetists, the Association of Anaesthetists of Great Britain and Ireland, the Intercollegiate Faculty of Accident and Emergency Medicine and the Intensive Care Society, a new colour code chart for syringe labelling was introduced. The introduction of the new system has not been uniform in the Irish Republic with no national guidelines or time scale in place. Methods  A questionnaire was administered to doctors working in Anaesthesia in two Dublin teaching hospitals. Results  As much as 23% had administered an incorrect medication and 53% admitted to a near miss as a result of the introduction of the new label. Discussion  Future action should focus on practical, common sense interventions including techniques such as those that reduce reliance on memory, standardization, the use of protocols and checklists, and the elimination of look-alike products.     

The resurgence of tuberculosis in the Republic of Ireland: Perceptions and reality

Tuberculosis remained a very significant cause of death in Ireland until the mid-20th century and still occupies a prominent position in the folk memory. As I show with reference to recent Irish media coverage, the global resurgence of tuberculosis is therefore viewed with concern in Ireland. Using data collated by the Health Protection Surveillance Centre between 1998 and 2005 however, I show that the recent increase in tuberculosis incidence in Ireland is less than is popularly perceived. This increase is largely associated with economic immigrants attracted to Ireland by the ‘Celtic Tiger’ economic boom, but there is little evidence to suggest that this has had a negative impact on the Irish-born population. Drug resistance is still a small but growing problem. Whilst vigilance is required, it is argued that the recent increase does not at present indicate a likely return to the situation in the mid-20th century.     

Vascular PET Prostheses Surface Modification with Cyclodextrin Coating: Development of a New Drug Delivery System

PURPOSE: Cyclodextrins (CDs) are torus shaped cyclic oligosaccharides with a hydrophobic internal cavity and a hydrophilic external surface. We performed and analysed an antibiotic binding on Dacron (polyethyleneterephtalate, PET) vascular grafts, previously coated with CDs based polymers. METHODS: The CDs coating process was based on the pad-dry-cure method patented in our laboratory. The Dacron prostheses were immersed into a solution containing a polycarboxylic acid, a cyclodextrin and a catalyst, and placed into a thermofixation oven before impregnation with an antibiotic solution (Vancomycin). Biocompatibility tests were performed with L132 human epithelial cells. The antibiotic release in an aqueous medium was assessed by batch type experiments using UV spectroscopy. RESULTS: Viability tests confirmed that the CDs polymers coating the Dacron fibers were not toxic towards L132 cell. Cell proliferation was similar on coated and uncoated grafts. A linear release of Vancomycin was observed over 50 days. CONCLUSION: Our results demonstrate the feasibility of coating CDs onto vascular Dacron grafts. Biological tests show no toxicity of the different cyclodextrins coated. A linear release of antibiotics was depicted over 50 days, demonstrating that cyclodextrin grafting was an efficient drug delivery system.     

小肠吸收胆固醇的分子生物学研究进展

胆固醇通过分布于十二指肠和近段空肠黏膜上皮细胞刷状缘膜的Niemann—Pick C1样蛋白1摄取，ATP结合盒G5、G8抑制小肠对胆固醇的摄取过程。进入上皮细胞的胆固醇大多数被乙酰辅酶A，胆固醇转乙酰基酶2酯化，随后通过组装形成乳糜微粒，经淋巴管进入血循环；另一部分胆固醇则以未酯化形式直接进入血循环形成高密度脂蛋白颗粒。这些过程受核受体——肝脏X受体的调控。年龄、性别、黏膜屏障和小肠传输速度也影响胆固醇的吸收。