Environmental Health Research in the Post-Genome Era: New Fields,New Challenges,and New Opportunities

The human genome sequence provides researchers with a genetic framework to eventually understand the relationships of gene–environment interactions. This wealth of information has led to the birth of several related areas of research, including proteomics, functional genomics, pharmacogenomics, and toxicogenomics. Developing techniques such as DNA/protein microarrays, small-interfering RNA (siRNA) applications, two-dimensional gel electrophoresis, and mass spectrometry in conjunction with advanced analysis software and the availability of Internet databases offers a powerful set of tools to investigate an individual’s response to specific stimuli. This review summarizes these emerging scientific fields and techniques focusing specifically on their applications to the complexities of gene–environment interactions and their potential role in environmental biosecurity.     

抗感染新药仑氨西林

仑氨西林是氨苄西林的前体药物，口服后水解成氨苄西林而在体内发挥抗菌作用，其口服吸收优于氨苄西林。本文对仑氨西林的药理、药代、临床研究情况做一综述，为临床应用提供参考。     

新碳青霉烯类抗生素比阿培南

比阿培南是碳青霉烯类抗生素，对革兰阴性和阳性菌的需氧菌和厌氧菌等均具有超广谱强敏抗菌作用，并有良好的组织渗透性；药代动力学特性优良；用于治疗下呼吸道感染和泌尿道感染；临床有效率为89．5％～100％；药物不良反应轻微。     

老药新靶标

在已上市的老药中发掘新的用法，其成本及不良反应的风险会大大降低。一个关于药物作用靶标的预测方法的研究为这个研发思路导入分子机制提供了新方法。     

Sirolimus,a New,Potent Immunosuppressive Agent

Sirolimus (SRL), a potent immunosuppressant, is currently being investigated in phase III trials for prophylaxis of renal transplant rejection. The mechanism of action of SRL is a blockade of the response of T and B cells to cytokines, thereby preventing cell cycle progression in G1 and consequently cell proliferation. There seems to be a good correlation between SRL concentrations, estimated as exposure by the area under the concentration versus time curve, and trough whole blood concentration, so that therapeutic monitoring may be done by trough levels only. Because of the low frequency of allograft rejection, there has been no documented correlation between trough concentrations and efficacy. Trough SRL concentrations of 15 ng/ml or higher seem to be associated with an increased frequency of adverse effects. Drug-associated toxicities include thrombocytopenia, leukopenia, and increases in cholesterol and triglyceride levels. The drug has synergy with cyclosporine (CsA) in vitro as well as in animal and clinical studies. In phase II trials the combination of SRL-CsA therapy reduced the frequency of acute rejection episodes, permit withdrawal of concomitant corticosteroid therapy, and allowed reduction of CsA dosages in nonblack patients.     

New, long-acting, potent bradykinin antagonists.

1. Three new bradykinin (BK) antagonists, D-Arg0-Hyp3-Thi5-D-Tic7-Oic8-BK (compound I), D-Arg0-Hyp3-D-Tic7-Oic8-BK (compound II), and Arg(Tos)1-Hyp3-Thi5-D-Tic7-Oic8-BK (compound III), were tested against the effects of BK in 9 bioassay preparations including visceral smooth muscles, vasoconstriction, plasma protein extravasation, release of prostaglandin E2, bronchoconstriction, and stimulation of afferent C-fibre nociceptors. In some of these tests the effects of the new compounds were compared with those of the antagonist D-Arg0-Hyp2-Thi5,8-D-Phe7-BK (compound IV), described by Stewart & Vavrek (1987). 2. For all bioassays the general rank order of potency of the compounds was found to be I greater than II greater than III much greater than IV. The new antagonists were long-acting; in some bioassays their effects outlasted the duration of the experiment. 3. The inhibitory effects of the new BK antagonists were specific for BK; actions of noradrenaline, angiotensin II, acetylcholine or histamine were unaffected by the antagonists. They did not stimulate the release of histamine or prostaglandins. An agonistic effect was observed only with very high concentrations of compounds I and II in the plasma protein extravasation test. 4. The long duration of action of the new BK antagonists is probably due to a high and long-lasting affinity to the BK receptors. A high resistance of the antagonists to enzymatic destruction may be another reason. 5. The new BK antagonists will be valuable tools for the investigation of the pathophysiological role of BK. In addition they may offer a potential for therapeutic applications.     

Meropenem,a New Carbapenem Antibiotic

Meropenem is the second carbapenem antibiotic available in the United States. It has a broad spectrum of activity that includes moderate activity against gram-positive bacteria and excellent gram-negative aerobic and anaerobic activity. Meropenem has enhanced gram-negative activity relative to imipenem-cilastatin and often retains activity against strains resistant to third-generation cephalosporins and imipenem-cilastatin. The drug penetrates well into most body fluids and tissues, including cerebrospinal fluid. It is also stable against renal dehydropeptidase hydrolysis and does not require coadministration of a dehydropeptidase inhibitor. Meropenem showed excellent efficacy in clinical studies involving seriously ill patients with intraabdominal, central nervous system, lower respiratory tract, skin and soft tissue, urinary tract, and febrile neutropenic infections. It appears well tolerated and, relative to imipenem-cilastatin, may have reduced potential for causing seizures and other central nervous system toxicities. Although it has many favorable qualities and some potential advantages relative to other broad-spectrum agents, additional trials and clinical experience are necessary to define its optimal place in clinical practice.     

一种新型抗癫痫药物普瑞巴林

普瑞巴林是3-氨甲基-5-甲基己酸的具有药理活性的S型异构体,被用于部分性癫痫的加用治疗、神经痛及广泛性焦虑症.本文介绍普瑞巴林在部分性癫痫方面的应用.     

New Furanoeremophilanes, Cacalohastin Derivatives, from Senecio linifolius

Investigation of the aerial parts of SENECIO LINIFOLIUS afforded the furanoeremophilanes maturinone and seven cacalohastin derivatives, five of them being isolated for the first time as natural compounds. Structures were elucidated by spectroscopics methods.