尼莫地平对兔血中梭曼的消除及[^3H]梭曼在小鼠组织分布的影响

目的:考察尼莫地平对兔血中梭曼的消除及结合[~3H]梭曼在小鼠组织分布的影响,以探索尼莫地平对梭曼代谢解毒的作用.方法:以二异丙基氟磷酸酯(DFP)为内标,用大进样量手性毛细管柱气相色谱法测定兔梭曼静脉染毒后血中游离C(±)P(-)梭曼浓度.同位素示踪法测定结合[~3H]梭曼在小鼠组织中的分布.结果:尼莫地平(10 mg/kg,ip,预给药1小时)使兔梭曼染毒(43.2 μg/kg,iv)15 s后,血中游离C(±)P(-)梭曼浓度从(54±13)μg/L下降到(19±12)μg/L,使血中C(±)P(-)梭曼的清除率从(20.8±1.5)mL·kg~(-1)·s~(-1)增加到(31±11)mL·kg~(-1)·s~(-1),从而使AUC从(2.08±0.15)mg·s·L~(-1)降低到(1.6±0.4)mg·s·L~(-1).尼莫地平(10 mg/kg,ip,预给药1小时)能显著降低在[~3H]梭曼皮下染毒(0.544 GBq·119 μg/kg)0-120 min后小鼠血浆、脑、肺及肝脏中结合[~3H]梭曼的分布,而小肠中结合[~3H]梭曼的分布却显著升高.结论:尼莫地平可能通过改变梭曼的分布,降低了血中梭曼的初始浓度而起到促进梭曼代谢解毒的作用.     

苯巴比妥及氯贝丁酯对小鼠体内梭曼解毒作用的影响

考察了肝微粒体酶诱导剂苯巴比妥及氯贝丁酯对小鼠体内解毒酶的诱导作用及对小鼠体内梭曼解毒作用的影响 .结果表明 ,苯巴比妥 ,氯贝丁酯预处理均能显著提高小鼠肺脏 ,肝脏中羧酸酯酶及小鼠脑中胆碱酯酶活性 ,不同之处在于苯巴比妥亦能显著提高血中羧酸酯酶活性 .小鼠按 798μg·kg- 1梭曼iv后 0 .2 5～ 1.5min时 ,苯巴比妥能显著降低小鼠血中梭曼残留浓度 ,而氯贝丁酯则没有加速梭曼在小鼠体内消除的作用 .提示血中羧酸酯酶在梭曼解毒中发挥了重要的作用 ,针对提高血中羧酸酯酶活性为指标 ,有可能筛选出更为有效的解毒剂 .     

苯巴比妥及氯贝丁酯对小鼠体内梭曼解毒作用的影响

考察了肝微粒体酶诱导剂苯巴比妥及氯贝丁酯对小鼠体内解毒酶的诱导作用及对小鼠体内梭曼解毒作用的影响. 结果表明,苯巴比妥,氯贝丁酯预处理均能显著提高小鼠肺脏,肝脏中羧酸酯酶及小鼠脑中胆碱酯酶活性,不同之处在于苯巴比妥亦能显著提高血中羧酸酯酶活性.小鼠按798 μg·kg^-1梭曼iv后0.25～1.5 min时,苯巴比妥能显著降低小鼠血中梭曼残留浓度,而氯贝丁酯则没有加速梭曼在小鼠体内消除的作用. 提示血中羧酸酯酶在梭曼解毒中发挥了重要的作用,针对提高血中羧酸酯酶活性为指标,有可能筛选出更为有效的解毒剂.     

人肝梭曼水解酶的微量比色测定及性质

建立了人肝二异丙基氟磷酸酯酶（ＤＦＰａｓｅ，ＥＣ．３．１．８．２．）的微量比色测定法并探讨了此酶的部分生化性质。梭曼在过硼酸钠及丙酮存在时，可与盐酸联苯胺反应生成橙黄色偶氮化合物，橙黄色产物的量与梭曼量在１０－２００ｎｍｏｌ范围内呈正相关。本文将此呈色反应与酶反应相结合，通过测定剩余梭曼的量来测定酶活力，并探讨了测定的最适条件。测定的变异系数为５％，测得人肝ＤＦＰａｓｅ的Ｋｍ值为３ｍｍｏｌ·Ｌ－１，最适ｐＨ范围为７．０－７．２，酶反应时间为２５ｍｉｎ，在－２０℃保存７个月，或在３７℃保温１８ｈ活性无明显丧失，反复冻融３次活性不变，但经冻融６次时活性下降１／５．人肝ＤＦＰａｓｅ活性主要存在于细胞的可溶性部分。     

血浆内皮素及红细胞变形性的研究

内皮素是Yangzsawa等于1988年从培养的猪动脉内皮细胞分离得到的，作用强且持久的缩血管多肽。红细胞变形性（ED）是指红细胞在外力作用下改变自身形态的能力，是血液流变学的重要组成部分之一，对血液循环有重要影响。目前已有较多的研究证实，内皮素及红细胞变形性在缺血性脑血管病的发生发展中起重要作用，研究脑出血（CH）时血浆内皮素含量及红细胞变形性的变化，旨在了解脑出血后其病理变化机制。     

抗癌药CA4P与不同种属血浆蛋白结合的规律

目的 研究抗癌药Combretastatin A4 phosphate(CA4P)与不同种属血浆蛋白结合的规律.方法 采用平衡透析法分离结合药物和游离药物,采用HPLC法测定Combretastafin A4(CA4)的浓度.结果 经24 h的透析,CA4在3种浓度下与大鼠血浆的蛋白结合率分别是77.86%、74.70%、64.46%;与Beagles犬血浆的蛋白结合率分别是81.70%、81.32%、79.68%;与人血浆的蛋白结合率分别是84.55%、77.04%、71.70%.结论 CA4 0.918～36.720 μg·ml-1,是一种中等程度蛋白结合的药物,虽随CA4浓度的增加结合率略下降,但不同浓度的CA4与大鼠、犬和人血浆蛋白的结合率无统计学差异(P>0.05).     

超滤法结合液质联用技术测定抗肿瘤化合物CJ-6在不同种属中的血浆蛋白结合率

目的:通过建立测定血浆中抗肿瘤化合物N-(4-((2-(环丙烷甲酰胺)吡啶-4-基)氧基)-3-氟苯基)-4-甲基-3,5-二氧基-2-苯基-2,3,4,5-四氢-1,2,4-三嗪-6-甲酰胺(CJ-6)的分析方法,测定CJ-6在不同种属(大鼠、猴、人)中的血浆蛋白结合率.方法:采取超滤法测定CJ-6在大鼠、猴、人血浆...     

成都地区医疗机构红细胞类及血浆类血液制品退回的现状分析

目的:分析成都地区医疗机构红细胞类、血浆类血液制品的退回情况.方法:收集2013-2019年成都地区医疗机构红细胞类、血浆类血液制品的退回数据,按类别、数量和原因进行统计分析.结果:2013-2019年,成都地区发放红细胞类血液制品共1245911袋,退回1125袋,平均退回率为0.09％,前3位退回原因依次为DAT阳性、抗筛阳性和脂肪血;发放血浆类血液制品共1144041袋,退回4485袋,平均退回率为0.39％,前3位退回原因依次为漏袋、絮状物、脂肪血.结论:成都地区医疗机构红细胞类、血浆类血液制品退回涉及多方面原因,应在血液制品制备、运输等各个环节加强落实《血站技术操作规程》《临床输血技术规范》相关要求,并根据不同退回原因采取针对性措施,以减少退回率.     

悬浮红细胞与异体血浆混合输注的危害性

目的 探讨悬浮红细胞与异体血浆混合输注的弊端,明确掌握输血适应证的重要性.方法 统计某医院2005年共1182份输血申请单的申请用血情况,分为单纯输注全血悬浮RBC血浆机采PC冰冻机采PC机采WBC以及悬浮红细胞与异体血浆混合输注全血与异体血浆混合输注.结果 1182份输血申请单中,悬浮红细胞与异体血浆混合输注的申请单数比例高达20.5%;其中实施输注的798份临床用血申请单中,混合输注的悬浮红细胞成分血输血率(RBC%)占比高达32.6%.结论 悬浮红细胞与异体血浆混合输注的危害性远远大于全血输注,混合输注的做法导致患者发生输血付反应和传播输血相关传染病的危险性成倍增加,同时又增加了患者的经济负担,而且容易引起柠檬酸钠中毒,导致患者凝血功能障碍.临床以悬浮红细胞与异体血浆混合输注来代替全血输注,以提高临床成分血输血率,这与国家推行成分输血的宗旨(使临床输血更安全、科学、合理、有效)不符.     

体外小鼠、豚鼠、犬及人血液对梭曼的解毒作用

目的　研究不同种属动物及人血液对梭曼的解毒能力与血液中几种梭曼解毒酶活性的关系。方法　测定血液中梭曼残留浓度及解毒酶活性。结果　小鼠、豚鼠、犬、人血浆对梭曼的解毒能力要明显高于其自身红细胞的解毒能力 ,血浆对梭曼的解毒能力依小鼠、豚鼠、犬、人的顺序由高到低依次排列。啮齿类动物血液中羧酸酯酶 (CaE)活性位点数目多且与梭曼结合快 ,因此在梭曼解毒中可发挥重要作用。犬、人血液中乙酰胆碱酯酶 (AChE)在梭曼解毒中占据了重要的解毒地位 ,犬、人血液中CaE基本没有参与梭曼解毒。结论　血液解毒能力的种属差异与种属间解毒酶结合位点数量的多少及梭曼与酶的结合速率密切相关     

大鼠心肌质膜[~3H]forskolin结合部位的特征(英文)

近年来从植物研究中发现的一种二萜衍生物(forskolin)是一种新型作用于心血管系统的药物。质膜中forskolin结合部位被认为是腺苷酸环化酶(EC4.6.1.1.)的催化亚单位。我们已经证明了它对大鼠心肌质膜腺苷酸环化酶的激活作用呈剂量效应相关。本文用〔1,2-~3H〕forskolin研究了大鼠心肌质膜for-skolin结合部位的特征。实验结果表明:〔~3H〕forskolin结合量和膜蛋白呈线性相关;其特异结合是快速的、可饱和的、可逆的、依赖温度的;结合反应的平衡解离常数(Ka)为0.21±SD 0.08μmol/L,其最大结合浓度为3.3±SD1.2 pmol/mg蛋白,Hill系数为1.07±SD0.05;37℃时缔合速率常数为0.0013(nmol/L)~(-1)·min~(-1),30 min达到平衡状态;心肌质膜结合的〔1,2-~3H〕forskolin被forskolin取代的解离速率常数:37℃时为0.22 min~(-1)(t_(1/2)=3.2 min),0℃时为0.03 min~(-1)(t_(1/2)=25.8min),IC_(50)为1.6μmol/L。本文实验结果提示:心肌质膜〔~3H〕forskolin结合分析可以作为研究激素和药物对心肌腺苷酸环化酶催化亚基作用的良好模型。     

Properties of [3H]flunitrazepam binding to different benzodiazepine binding proteins

Membranes from cerebellum or hippocampus were incubated with various concentrations of [³H]flunitrazepam in the absence or presence of diazepam, Cl 218 872 or ethyl-β-carboline-3-carboxylate (β-CCE). After binding equilibrium of [³H]flunitrazepam had been established, the membranes were either filtered for determination of reversible binding or were irradiated with UV light for determination of irreversible binding. Irradiated membranes were then subjected to SDS-polyacrylamide gel electrophoresis and fluorography. Individual photolabeled proteins were identified, appropriate sections cut out of the gel, and the radioactivity in the gel pieces measured. The results indicate that [³H]flunitrazepam binding to individual benzodiazepine binding proteins and its inhibition by various drugs can be measured by the present technique and support previous evidence for the independent existence of various proteins irreversibly labeled by [³H]flunitrazepam and their possible association with different benzodiazepine receptors.     

Distribution of [3H]diisopropylfluorophosphate, [3H]soman, [3H]sarin, and their metabolites in mouse brain

The brain area distribution of [3H]diisopropylfluorophosphate, [3H]soman, and [3H]sarin and their metabolites in mice was studied after iv administration of sublethal doses. At the appropriate time after the injection of the radiolabeled organophosphate, the mice were decapitated and their brains were dissected into seven areas. There was a relatively even distribution of the parent compounds and their metabolites in all brain areas except the hypothalamus, which contained concentrations of parent compounds the metabolites that were 2-5 times greater than those in other brain areas. Concentrations of the parent compounds and free metabolites declined steadily throughout the time course, whereas concentrations of the bound metabolites remained relatively constant between 6 and 24 hr. There was no correlation between the disposition of soman, and its metabolites, and cholinesterase inhibition in brain areas, which implicates other central mechanisms in the production of organophosphate effects. However, the higher concentrations of organophosphates and their metabolites in the hypothalamus suggest that this area might be important with respect to the pharmacological effects or the toxicity of these compounds.     

The binding of [3H]prazosin and [3H]clonidine to rat jejunal epithelial cell membranes

The binding of [3H]prazosin and [3H]clonidine to rat jejunal epithelial cell membranes has been studied. The membrane preparation was enriched in baso-lateral components as determined by Na+, K+ ATPase and alkaline phosphatase activities. The membranes possessed two saturable specific binding sites for [3H]prazosin, a high affinity (Kd 0.17 nM) low capacity (Bmax 27.3 fmole bound per mg protein) and a low affinity (Kd 5.0 nM) high capacity (Bmax 276 fmole bound per mg protein) site. The specificity of both sites was similar and was related to alpha 1-adrenoceptors. [3H]Clonidine bound to the membranes in a saturable fashion (Kd 7.3 nM). The specificity of this site was related to alpha 2-adrenoceptors. The [3H]clonidine binding site was present in the membranes in much lower density (Bmax 22.8 fmole bound per mg protein) suggesting that alpha 1-adrenoceptors predominate in this tissue.     

The nature of [3H]imipramine binding to synaptosomes

In contrast to serotonin “uptake”, the saturable binding of imipramine to rat brain synaptosomes does not involve an active transport process, since it is independent of time, temperature and Na⁺ K⁺-ATPase. It is moreover unaffected by a high concentration of serotonin. confirming that the “uptake” site for this amine is not implicated. Analysis of the saturation curve for binding of imipramine to intact synaptosomes gives a binding constant of 3.5 ± 1.0 × 10^?5 M. Identical binding characteristics are found with a synaptosomal membrane “ghost” fraction. When the membrane fraction is solubilized in Triton X-100, saturable binding is still observed but the affinity for imipramine decreases while the number of binding sites increases. Diverse psychoactive compounds effectively compete with imipramine for binding to synaptosomal membranes and the order of their activity is correlated with their lipophilicity. It is suggested that these compounds interact with a lipophilic pocket of low affinity and low specificity. If a more specific interaction exists and is associated with inhibition of transmitter amine “uptake” by tricyclic antidepressants, it could be masked by this process.