ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS AND KININ METABOLISM: EVIDENCE THAT ACE INHIBITORS MAY INHIBIT A KININASE OTHER THAN ACE

1. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, and also metabolizes bradykinin-(1–9) to bradykinin-(1–7) and bradykinin-(1–7) to bradykinin-(1–5). Increases in endogenous kinin levels may contribute to the therapeutic effects of ACE inhibitors. 2. ACE inhibitors increase vascular levels of both bradykinin-(1–9) and its ACE cleavage product bradykinin-(1–7), at doses below the threshold for ACE inhibition, leading to the proposal that ACE inhibitors may also inhibit a non-ACE kininase which cleaves both kinin peptides; this non-ACE kininase may be the major pathway of kinin metabolism in the vasculature and some other tissues. 3. In support of this proposal, ACE inhibitors potentiate bradykinin-(1–9) effects at doses which have little or no effect on ACE activity, as indicated by angiotensin I conversion to angiotensin II. ACE inhibitors also potentiate the actions of ACE-resistant kinin analogues, which may be susceptible to metabolism by a non-ACE kininase. 4. Identification and characterization of the putative non-ACE kininase which is inhibited by ACE inhibitors may reveal novel approaches to the tissue-specific modulation of kinin levels.     

Acute and chronic losartan administration: effect on angiotensin II content and modulation of [3H]norepinephrine release from rat interscapular brown adipose tissue

Summary To determine if acute or chronic (21 days) losartan (10mg/kg, s.c.) regulates the renin-angiotensin system in interscapular brown adipose tissue, angiotensin II (AII) content and [³H]overflow from slices preloaded with [³H]norepinephrine were examined. Acute or chronic losartan administration had no effect on AII content. AII increased evoked [³H]overflow from slices from control rats. Losartan administration did not alter basal [³H]outflow or evoked [³H]overflow. Acute losartan administration inhibited AII-induced enhancement of evoked [³H]overflow. Tolerance developed to the inhibitory effect of losartan following chronic administration.Supported by a grant from the American Heart Association (Local Kentucky Affiliate) and by a gift from DuPont Merck Pharmaceuticals. Portions of this work have been presented in abstract form [The Pharmacologist 34(3): 157, 1992]     

Quality of life on enalapril after acute myocardial infarction

Quality of life was assessed 4–6 months after an acutemyocardial infarction in a randomized double-blind study ofenalapril versus placebo. Quality of life was evaluated usingthe Nottingham Health Profile (NHP), the Physical Symptoms DistressIndex (PSDI), the Work Performance Scale (WPS) and the LifeSatisfaction Index (LSI). The study comprised 36 women (aged46–85 years, mean 68) and 96 males (aged 39–81 years,mean 62). Quality of life did not differ significantly between patientstreated with enalapril versus placebo. The scores were (enalaprilvs placebo, mean± SE): average NHP 15.4 ± 2.3vs 17.1 ± 2.3; PSDI 9.5± 1.0 vs 10.8 ±0.9; WPS 19.8 ± 2.0 vs 19.4 ± 1.4; LSI 24.1 ±1.0 vs 22.5 ±1.4. Men reported a better quality of lifethan women on most assessments, and non-smokers and ex-smokersbetter than smokers. Patients with moderate or severe anginapectoris had a worse quality of life measured by PSDI and NHPthan patients with minimal or no angina pectoris. Patients withcongestive heart failure had a higher PSDI than those without(13.6 ± 1.7 vs 9.4 ± 0.7, P<0.05), while nosignificant differences were observed in the NHP scores. In conclusion, quality of life was similar in enalapril andplacebo- treated patients after an acute myocardial infarction.However, it was reduced in patients with angina pectoris orheart failure and in those who continued smoking.     

罗比卡因与布比卡因硬膜外麻醉剖宫产术时心电图及心肌酶的变化

目的　比较硬膜外麻醉剖宫产术时罗比卡因和布比卡因对心电图及心肌酶的影响。方法　择期剖宫产手术病人 30例 ,硬膜外麻醉时Ⅰ组 (15例 )用 0 5 %罗比卡因 ,Ⅱ组 (15例 )用0 5 %布比卡因。观察麻醉手术期间心电图P R、QRS波间期以及肌酸磷酸激酶 (CK)和同工酶 (CK MB)的变化 ,同时观察麻醉镇痛、肌松效果和不良反应。结果　两组病人P R、QRS波间期均在正常范围内 (P >0 0 5 )。两组病人CK术后 2 4h值明显高于术前 (P <0 0 5 ) ,但反映心肌受损特异性较高的CK MB则无明显变化 (P >0 0 5 ) ,两组间亦无差异 (P >0 0 5 )。麻醉效果及不良反应两组间无差异。结论　硬膜外麻醉时罗比卡因与布比卡因对心电图及心肌酶影响无明显差异     

Cross-neutralisation of Australian brown and tiger snake venoms with commercial antivenoms: Cross-reactivity or antivenom mixtures?

Recently it has been suggested that the Australian snake antivenoms made by CSL Ltd. are in fact not truly monovalent and may contain antibodies to other snake venoms because the horses are injected with multiple snake venoms. It is unclear to what extent various monovalent antivenoms can neutralise the effect of other venoms, whether this is due to a mixture of antibodies or true cross-reactivity, and whether this has any clinical significance. We aimed to study the immunological and functional properties of brown snake (Pseudonaja spp.) antivenom (BSAV) and tiger snake (Notechis spp.) antivenom (TSAV) against their respective venoms using enzyme immunoassays (EIA) and in vitro clotting studies. There was significant overlap between the two antivenoms with both TSAV and BSAV being detected by EIA on brown snake venom (BSV)-coated and tiger snake venom (TSV)-coated wells, respectively. In a competition EIA, increasing amounts of immunoaffinity-purified hen anti-brown antibodies (IgYp) mixed with TSAV reduced TSAV measured on TSV-coated wells. Both BSAV and TSAV prevented the clotting activity of both venoms. IgYp also prevented the clotting activity of TSV, suggesting true cross-reactivity. The cross-reactivity of TSAV and BSAV with BSV and TSV, respectively, was likely due to each being a mixture of anti-brown and anti-tiger antibodies, but there was partial cross-reactivity demonstrated by the effect of IgYp. Single-polyvalent antivenom for brown snake and tiger snake may be feasible in the future.     

人参二醇组皂甙对精索静脉曲张大鼠的保护作用及其机制

把56只成年Wistar大鼠分为如下3组:①精索静脉曲张组(VG)30只;②精索静脉曲张人参二醇组皂甙组(VPG)8只;③假手术组(SOG)18只。实验结果表明,人参二醇组皂甙可显著提高精索静脉曲张大鼠睾丸ACE活力并降低睾丸LPO含量,但3组动物睾丸的SOD水平无明显差异。作者认为人参二醇组皂甙可能是通过减少LPO产生以提高ACE活力,从而实现对精索静脉曲张大鼠的保护作用。     

卡托普利对血管成形术后再狭窄作用的实验研究

目的探讨卡托普利对血管成形术后再狭窄的干预作用。方法SD雄性大鼠60只,分单损组、干预组和对照组。单损组采用改良导丝法制作大鼠颈动脉再狭窄模型。干预组将卡托普利研磨成粉状,生理盐水稀释配制成5mg/ml溶液,分别于制模前6 d开始按10 mg/(kg.d)剂量经灌胃针给予大鼠至术后各时间点。对侧颈总动脉作为假手术对照组。每组各时间点6只大鼠,于制模后1天、4天、7天、14天及28天原位灌注固定取材。根据HE染色标本情况,选血管形态结构完整的50个标本,进行HE染色,采用病理图像分析系统染色片进行形态计量分析。结果损伤后从第7天起新生内膜厚度和面积逐渐增加,到28天达峰值;与单损组比较,干预组血管壁三层厚度无显著差别,干预组第14、28天新生内膜面积显著减低。狭窄率于血管损伤后逐渐增加,到28天达峰值,与单损组比较,干预组在14天和28天狭窄率明显变小,各时间点内弹力板面积、外弹力板面积及重塑指数两组之间无显著差别。结论卡托普利减小大鼠颈动脉损伤后新生内膜面积及狭窄率,抑制新生内膜形成,但不改变内、外弹力板面积及重塑指数,不影响血管收缩性重塑。     

A novel improved design for the first-generation glucose biosensor

A novel improved design for the first-generation glucose biosensor@Wang J     

蛇毒抗高凝状态酶、氟尿嘧啶对BEL-7404细胞作用的实验研究

目的通过蛇毒抗高凝状态酶（AHCSE）、氟尿嘧啶（5-FU）对人肝癌细胞BEL-7404（简称7404细胞）、正常LO2肝细胞（简称LO2细胞）作用的比较，研究AHCSE对肝癌的作用以及探讨其可能的作用机制。方法应用光学显微镜、透射电镜、MTT法、TUNEL、FCM等方法观察7404细胞、LO2细胞经过AHCSE、5-FU处理后，细胞形态学、生物化学等方面的变化。结果7404细胞、LO2细胞经过AHCSE、52FU处理后，发生了形态学改变；小剂量AHCSE对7404细胞具有很强的抑制作用，但对LO2细胞几乎无影响；随着剂量的加大，AHCSE对7404细胞抑制率上升不明显，但是出现对LO2细胞的抑制作用。经AHCSE作用后，7404细胞发生了凋亡，凋亡率随AHCSE浓度的增加而增加；与5-FU对7404细胞作用相似，但5-FU对LO2细胞抑制作用明显增强。结论AHCSE、5-FU对BEL-7404细胞均有很强的抑制作用，诱导细胞凋亡是其作用机制之一，AHCSE可能成为一种新的肝癌细胞凋亡的诱导剂。     

代谢酶基因多态性与胰腺癌易感性研究进展

代谢酶基因多态性与肿瘤的关系是近来国内外研究的热点。代谢酶基因多态性使酶的活性发生改变，是胰腺癌遗传易感性的重要机制。现综述了与胰腺癌癌变过程中有关的代谢酶基因多态性与其易感性的关系。