天津市汉沽区媒介生物调查初报

本文报道了天津市汉沽区域媒介生物的调查结果:本地区有蚊类6种;鼠类5种;蝇类31种;蜚蠊类3种;蚤类2种;螨类1种。     

I269S Mutation in horse liver alcohol dehydrogenase S isoenzyme and its reactivity for steroids and retinoids

Ile-269 in horse liver alcohol dehydrogenase isoenzyme S(HLADH-S) was mutated to serine by phosphorothioate-based site-directed mutagenesis in order to study the role of the residue in coenzyme binding. The specific activity of the mutant(I269S) enzyme to ethanol was increased 49-fold. All turnover numbers of I269S enzyme toward 9 primary alcohols were increased. The mutant enzyme showed 3.6, 4.6, 11.6-fold higher catalytic efficiency for 5β-androstane-3,17-dione, 5β-cholanic acid-3-one and retinal than wild-type, respectively. The reaction mechanism of I269S enzyme was ordered bi bi as wild-type's. These results indicate that the hydrophobic interaction of Ile-269 residue with coenzyme plays an important role in dissociation of coenzyme from enzyme-coenzyme complex, which has been known as the rate limiting step of ADH reaction.     

Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type II diabetes. 2. Syntheses and biological activities of 1,4-dialkyl-, 1,4-dibenzyl, and 1-benzyl-4-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines and isosteric analogues of imidazoline

Piperazine derivatives have been identified as new antidiabetic compounds. Structure-activity relationship studies in a series of 1-benzyl-4-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines resulted in the identification of 1-methyl-4-(2', 4'-dichlorobenzyl)-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazine, PMS 812 (S-21663), as a highly potent antidiabetic agent on a rat model of diabetes, mediated by an important increase of insulin secretion independently of alpha2 adrenoceptor blockage. These studies were extended to find additional compounds in these series with improved properties. In such a way, substitution of both piperazine N atoms was first optimized by using various alkyl, branched or not, and benzyl groups. Second, some modifications of the imidazoline ring and its replacement by isosteric heterocycles were carried out, proceeding from PMS 812, to evaluate their influence on the antidiabetic activity. The importance of the distance between the imidazoline ring and the piperazine skeleton was studied third. Finally, the influence of the N-benzyl moiety was also analyzed compared to a direct N-phenyl substitution. The pharmacological evaluation was performed in vivo using glucose tolerance tests on a rat model of type II diabetes. The most active compounds were 1,4-diisopropyl-2-(4', 5'-dihydro-1'H-imidazol-2'-yl)piperazine (41a), PMS 847 (S-22068), and 1,4-diisobutyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazine (41b), PMS 889 (S-22575), which strongly improved glucose tolerance without any side event or hypoglycemic effect. More particularly, PMS 847 proved to be as potent after po (100 micromol/kg) as after ip administration and appears as a good candidate for clinical investigations.     

Age and gender-related incidence of chronic renal failure in a French urban area: a prospective epidemiologic study

OBJECTIVE.: To determine the age- and gender-related incidence of chronicrenal failure in a French urban area. METHODS.: Prospective study of adult patients newly identified as havingestablished, chronic renal failure defined by serum creatinine(Scr) 200 µmol/l, with the cooperation of all nephrologyand dialysis units in the Ile de France district (10,660,000inhabitants) during a 1-year period. RESULTS.: 2775 patients (1780 males, 995 females) were referred with Scr200 µmol/l between July 1991 and June 1992, an overallincidence of 260/million population. 847 had advanced renalfailure (Scr 500 µmol/l) and 541 patients (19.5%) were75 years of age. The age-related incidence was 92, 264, 523and 619/million population in the age groups 20–39, 40–59,60–74 and 75 years old, respectively. The annual incidencewas twice as high in males than in females up to 75 years andthree times as high in patients 75 years (1124 vs 356/millionpopulation). Based on the proportion of patients reaching end-stagerenal failure within one year of referral, the minimal estimationof the need for supportive therapy is 81/million/year. CONCLUSIONS.: This epidemiological study in a large French urban area indicatesan incidence of 260 patients per million population annuallyreferred to nephrology units for chronic renal failure definedby Scr 200 µmol/l, with a marked preponderance of malesand a dramatic increase of incidence with age in both genders.     

荆州市乡村卫生室用药情况调查分析

目的：调查分析荆州市乡村卫生室用药情况，为有关部门制定农村医疗卫生政策提供依据。方法：抽样调查荆州市72个乡村卫生室1999—2000年用药情况，采用Microsoft Access2000及Microsoft Excel2000对调查结果进行数据录入、整理和统计处理。结果：荆州市农村用药处于较低水平，2000-1999年用量有一定增长。用药品种以国家基本药物为主，使用率较高的药物主要为抗感染药、解热镇痛抗炎抗痛风药、维生素、消化系统药、呼吸系统药等。结论：荆州市乡村卫生室药物应用基本合理。农村合作医疗政策是切实可行的。     

慢性中耳炎活动期听力重建的研究

目的 :探讨慢性化脓性中耳炎活动期听力重建的可能性。方法 :对 34例慢性中耳炎患者于活动期行鼓室探查 ,取出锤、砧骨 ,开放鼓峡 ,行鼓室成形术。其中 ,2 3例用自体听骨重建听骨链 (自体听骨组 ) ,1 1例用人工钛听骨重建听骨链 (人工钛听骨组 )。结果 :34例术后 3个月平均气导听力提高 1 5～ 30dBHL。术后 1年 ,自体听骨组 2 3例中 ,6例听力下降至术前水平 ,其中 1例穿孔 ;人工钛听骨组 1 1例中 ,1例听力明显下降 ,移植物完整 ,位置正常。 34例听力提高 (1 5dB以上 )率为 79.4 % (2 7/ 34) ,其中人工钛听骨组听力提高率为 90 .9% (1 0 /1 1 ) ,未见排斥 ;自体听骨组为 73.9% (1 7/ 2 3)。人工钛听骨组听力提高明显优于自体听骨组 ,差异有极显著性意义 (P <0 .0 1 )。结论 :慢性化脓性中耳炎活动期行鼓室成形听力重建是可行的 ;彻底开放鼓峡 ,清除上鼓室、鼓窦入口病灶 ,选择良好的听骨赝复物 ,是手术取得成功的关键     

中国健康志愿者单次静滴甲磺酸加替沙星氯化钠注射液耐受性研究

目的在中国健康成年志愿者中评价单次静滴甲磺酸加替沙星氯化钠注射液的安全性、耐受性.方法根据新药临床试验指导原则设计试验方案,并获得伦理委员会批准.受试者须自愿签署知情同意书.选择48名18～50岁健康成人,经体检及实验室检查均在正常范围内.用区组随机化设计方法,将受试者随机分配至100mg、200mg、300mg、400mg、500mg、600mg、700mg、800mg剂量组中,每组6名,男女各半.观察指标为临床症状体征,实验室指标包括心电图、脑电图、血常规、凝血功能、尿常规、肝功能、肾功能、电解质等.严密观察记录试验期间发生的不良事件.结果各组入选受试者体检及实验室检查各项指标测定值均在正常范围,条件均衡,具较好可比性.给药后体温、呼吸频率、脉搏、血压、血常规、尿常规、肾功能、电解质、心电图、脑电图等未见有临床意义的改变.试验中未见严重的临床不良反应,只发现3例次可能与药物有关的轻度-过性不良反应,分别表现为面部瘙痒、皮疹、GOT或GPT升高.结论健康受试者单次静滴甲磺酸加替沙星氯化钠注射液,最大剂量至800mg,比较安全、耐受性较好.推荐临床使用剂量为400mg/次/日.     

中国健康志愿者单剂静滴甲磺酸加替沙星注射液的药代动力学

目的:研究中国健康成年男性志愿者单剂静滴甲磺酸加替沙星注射液的药代动力学。方法:按药物临床试验管理规范(GCP)指导原则设计试验方案。选择9名受试者分别依次单刘静滴100,200和400mg的甲磺酸加替沙星注射液后,应用HPLC测定血药浓度,采用3P97软件进行数据处理,求出药代动力学参数。结果:受试者分别给药后,药-时曲线符合二房室模型,主要药代动力学参数C_(max)分别为1.10±0.19,2.17±0.33和3.16±0.47mg·L~(-1);t_(1/2)β分别为7.42±1.99,8.41±2.72和8.46±2.83h;AUC_(0-∞)分别为4.45 ±0.71,11.10±1.81和23.03±3.83mg h·L~(-1)。原形药主要经肾排泄,48h尿药累积排泄率分别为(43.08±15.79)％,(51.33±23.69)%和(45.67±18.22)％。结论:9名静滴甲磺酸加替沙星注射液后,药-时曲线符合二房室模型。提示甲磺酸加替沙星在100～400mg剂量内药物体内过程基本呈线性动力学特征而无饱和性,主要排泄途径为肾脏。     

依那普利对2型糖尿病大鼠肠系膜血管内皮细胞的保护作用

目的　糖尿病血管病变的初始原因是血管内皮细胞损害。本研究观察依那普利对糖尿病大鼠肠系膜血管内皮细胞是否有保护作用。方法　大鼠用高脂饮食饲养 4周后 ,ip链佐霉素 30mg·kg- 1诱导 2型糖尿病 ,继续饲以高脂饮食 4周后 ,依那普利组给予依那普利 10mg·kg- 1·d- 1,ig ,连续 4周。采用大鼠离体肠系膜血管灌流技术 ,用去甲肾上腺素 1μmol·L- 1预收缩血管 ,再给予乙酰胆碱 (ACh) 1μmol·L- 1使血管舒张。观察ACh的舒张率来反映内皮细胞功能。结果　糖尿病大鼠肠系膜血管ACh舒张率为 (33±8) % ,较对照组 (79± 8) %明显降低 ,依那普利治疗组血管ACh舒张率为 (5 2± 6 ) % ,较糖尿病组明显改善。用皂素去内皮后 ,三个组肠系膜血管对ACh舒血管的反应性均明显降低 ,三组间无显著性差异。去内皮前后 ,三个组肠系膜血管对硝普钠舒张血管的反应性无显著变化。结论　依那普利对 2型糖尿病大鼠肠系膜血管内皮细胞具有保护作用。     

Induction of carbohydrate‐specific antibodies in HLA‐DR transgenic mice by a synthetic glycopeptide: a potential anti cancer vaccine for human use

Abstract: Over the last few years, anticancer immunotherapy has emerged as a new exciting area for controlling tumors. In particular, vaccination using synthetic tumor‐associated antigens (TAA), such as carbohydrate antigens hold promise for generating a specific antitumor response by targeting the immune system to cancer cells. However, development of synthetic vaccines for human use is hampered by the extreme polymorphism of human leukocyte‐associated antigens (HLA). In order to stimulate a T‐cell dependent anticarbohydrate response, and to bypass the HLA polymorphism of the human population, we designed and synthesized a glycopeptide vaccine containing a cluster of a carbohydrate TAA B‐cell epitope (Tn antigen: α‐GalNAc‐Ser) covalently linked to peptides corresponding to the Pan DR ‘universal’ T‐helper epitope (PADRE) and to a cytotoxic T lymphocyte (CTL) epitope from the carcinoembryonic antigen (CEA). The immunogenicity of the construct was evaluated in outbred mice as well as in HLA transgenic mice (HLA‐DR1, and HLA‐DR4). A strong T‐cell dependent antibody response specific for the Tn antigen was elicited in both outbred and HLA transgenic mice. The antibodies induced by the glycopeptide construct efficiently recognized a human tumor cell line underlying the biological relevance of the response. The rational design and synthesis of the glycopeptide construct presented herein, together with its efficacy to induce antibodies specific for native tumor carbohydrate antigens, demonstrate the potential of a such synthetic molecule as an anticancer vaccine candidate for human use.