The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

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喘息是儿童时期常见的症状之一,支气管扩张药物在年幼儿童中使用的有效性是多年来颇有争议的一个临床问题。争论的焦点在于,以往认为婴儿支气管平滑肌发育不成熟,喘息时气道动态闭合度增高和相对显著的黏膜水肿使其对支气管扩张剂的反应较弱。而近年的研究显示,虽然婴幼儿对支气管扩张剂的治疗反应弱于年长儿童和成年人,但在婴儿时期气道就存在对支气管扩张剂的反应[1],合理使用支气管扩张剂有利于改善喘息儿童的临床症状。1临床常用的支气管扩张剂1.1β2肾上腺素受体激动剂选择性β2受体激动剂是强效支气管扩张剂,支气管扩张作用是氨茶碱的…     

Sideropenic Dysphagia综合征膜性蹼26例分析

目的 :研究SideropenicDysphagla (S -D)综合征膜性蹼产生的机制。方法 :回顾分析S -D综合征2 6例的临床资料。结果 :影像学检查显示膜性蹼在颈段食道前壁呈 2mm深的模样陷凹。血液学检查为缺铁性低血红蛋白性贫血改变。结论 :缺铁性贫血是S -D综合征的原因 ,铁剂治疗有效     

斯氏狸殖吸虫感染多种动物及体内发育的研究

目的 :以不同数量斯氏狸殖吸虫囊蚴 ,分别感染大白鼠 ,小白鼠和豚鼠 ,定期解剖观察虫体。方法 :经1 5、30、45、60、75、90、1 1 0和 1 2 5d分别解剖观察虫体在实验动物体内发育 ,分布及虫体检出率。结果 :大鼠在感染 90d后虫体可以逐步发育成熟并产卵 ,而小白鼠和豚鼠体内只能查到童虫阶段。结论 :初步证实大白鼠是斯氏狸殖吸虫的适宜宿主 ,小白鼠和豚鼠体内的虫体全部处于滞育阶段 ,不能发育为成虫     

不同负荷运动训练对大鼠红细胞膜特性的影响

本文采用实验研究方法,通过对大鼠运动后红细胞数量,Hb浓度及体重等一般情况的检测,拟对其施加不同负荷的训练,观察训练后大鼠红细胞膜流动性及红细胞膜脂质成分的变化,进一步讨论运动后红细胞功能及机体机能所发生的变化。实验结果表明,小负荷的运动训练通过改善RBCM脂质组成,增加p/c比值、增强其抗氧化能力等增加RBCM流动性,使红细胞的变形能力增加,有利于其运氧功能的发挥。大负荷训练后RBCM流动性下降,提示不同负荷的运动训练会引起机体产生不同的变化,进而导致机体运动水平上的差异,整体携氧能力下降。     

颈椎术后病人首次下床活动的感受及需求的调查

早期下床活动的必要性已得到大家认可,但术后早期病人常常较虚弱,且下床活动时会引发一些不适,病人也会有一些担心和顾虑,这在一定程度上会影响病人下床活动的积极性。颈椎手术本身有其特殊性,术后对颈部的稳定要求较高,因此此类病人活动有其特点。本研究以颈椎术后已下床活动的病人为研究对象,通过问卷调查,了解颈椎手术后病人首次下床的感受和相关需求,为进一步提高颈椎术后护理质量提供依据。1资料和方法1.1对象采用方便取样,选取2005年4月—2005年6月在某三甲医院因颈椎病入院、术后已下床活动的病人75例。其中男54例,女21例;年龄28岁~7…     

急性脑血管病患者血清肌钙蛋白Ⅰ的检测及临床意义

目的 探讨血清肌钙蛋白Ⅰ(cTn-I)对急性脑血管病(ACVD)后心肌损伤的诊断价值.方法 检测160例ACVD患者入院后24h内、3d、7d的血清cTn-I和肌酸激酶同工酶(CK-MB),比较不同病程、不同类型、不同病情程度ACVD患者血清cTn-I和CK-MB的测定结果,观察预后与cTn-I、CK-MB的关系.结果 病后24h内和7d血清cTn-I较CK-MB的阳性率高;脑出血和重症患者病后7d cTn-I仍增高;病后30d内死亡者的cTn-I和CK-MB增高比例高于存活者.结论 血清cTn-I对ACVD后心肌损伤的检测具有比CK-MB更高的敏感性、特异性和更宽的诊断窗口.     

Immunoregulatory effects of phospholipase A2 (PLA2) on the proliferation of human lymphocytes

Extracellular phospholipase A2 (PLA2) is a proinflammatory enzyme found especially in the inflammatory exudate to modulate blood flow to areas of antigen stimulation. In this study we found that PLA2 exerted a biphasic effect on the proliferation of phytohemagglutinin (PHA)-stimulated human mononuclear cells (PHA MNC). At low concentrations range from 0.001 to 1 U/ml, PLA2 enhanced the proliferation of PHA MNC (maximal increase was 37.0 +/- 5.67%). Conversely, at concentrations over 10 U/ml, PLA2 markedly suppressed the PHA-induced MNC proliferation (maximal decrease was 88.86 +/- 2.89%). PLA2 was non-toxic to lymphocytes after three days culture, unless the concentration was higher than 100 U/ml. The membrane polarization of PHA-stimulated lymphocytes was also increased by PLA2 at a low concentration. In addition, PLA2 displayed a similar effect on the proliferation of streptokinase-streptodornase (SK/SD) or allogeneic cell stimulated lymphocytes. The change of lymphocyte proliferation by PLA2, was parallel to the change of percentage of helper T cells. Furthermore--a CD4-rich population was proved more susceptible to PLA2 effect than a CD8-rich population. Para-bromophenacyl bromide (pBPB), an irreversible inhibitor of PLA2, abrogated the biphasic effect of PLA2 on PHA MNC proliferation. These results suggest that PLA2 plays a regulatory role on immune reactions by modulating the percentage of helper T cells.