Antagonism of novel inotropic agents at A1 adenosine receptors and m-cholinoceptors in human myocardium

Summary The effects of the new inotropic agents saterinone, sulmazole, UD-CG 212.C1 and milrinone at A₁ adenosine receptors and m-cholinoceptors were evaluated in human myocardium from patients with heart failure. At A₁ adenosine receptors, all compounds inhibited ³H-DPCPX-binding to ventricular membrane preparations at micromolar concentrations. As judged from the K_i-values, the rank order of potency was saterinone > sulmazole > UD-CG 212.C1 > milrinone. The new inotropic agents also displaced the binding of ³H-QNB at m-cholinoceptors. Except for saterinone, the concentration ranges of mean K_i-values were considerably higher at m-cholinoceptors than at A₁ adenosine receptors. The rank order of potency was saterinone > sulmazole > UD-CG 212.Cl > milrinone. Competition of the A₁ adenosine receptor agonist R-PIA to ³H-DPCPX-binding showed a biphasic curve with a shallow slope (Hill coefficient n_H = 0.63) and revealed two affinity states of the A₁ adenosine receptor. In the presence of guanine nucleotides [Gpp(NH)p], the competition curve showed one low affinity class of binding sites and was shifted to the right. In contrast, the competition curves of the new inotropic agents were characterized by a monophasic, steeper slope (mean Hill coefficient n_H = 0.98). Guanine nucleotides had no effect. Similar results were obtained with saterinone and carbachol at m-cholinoceptors. Competition with carbachol revealed three affinity states of the m-cholinoceptor, the superhigh affinity binding was reversed by Gpp(NH)p. Competition with saterinone revealed one class of binding sites which was not influenced by Gpp(NH)p. Accordingly, in isolated, electrically driven human atrial trabeculae, the negative inotropic effect of adenosine was antagonized concentration-dependently by saterinone, sulmazole and UD-CG 212.Cl. Similarly the negative inotropic effect of carbachol was antagonized concentration-dependently by saterinone. It is concluded that the new inotropic agents bind to A₁ adenosine receptors and that their interaction is of antagonist nature. This mechanism might contribute to their capacity to enhance force of contraction by stimulation of cAMP-formation in addition to phosphodiesterase inhibition. The effects of saterinone may be partially due to antagonism at m-cholinoceptors. This is presumably not the case with the other inotropic agents studied given their low affinity for this receptor.Send offprint requests to M. Böhm at the above addressSupported by the Deutsche Forschungsgemeinschaft     

药物浓度和病因对三磷酸腺苷治疗阵发性室上性心动过速的影响

本文报告23例次ATP治疗PSVT的效果,总有效率56.5％,9例次高浓度快速注射者8例转复。器质性心脏病者副作用较多,1例冠心速注高浓度ATP后,发生心室颤动和阿-斯氏综合征。这一结果提示:药物浓度和注射速度是影响疗效的主要因素,PSVT伴AVB者疗效也很低;病因和药物浓度是决定副作用的因素。因此,对于器质性心脏病者,尤其冠心病人,应避免高浓度快速静脉注射ATP。     

肟类药物对塔崩等神经性毒剂抑制的大鼠脑AChE的体外重活化作用

系统地研究了肟类药物对塔崩抑制的大鼠脑AChE的体外重活化作用,并与梭曼、沙林和VX进行了比较。结果表明,沙林和VX抑制的AChE较易被药物重活化,而塔崩和梭曼抑制的AChE则较难。37℃、pH7.2条件下,塔崩抑制的大鼠脑AChE可浓度依赖性地被TMB_r和LuH_6重活化,2-PAM在高浓度下也有一定作用,但HI-6在所用3个浓度下均无重活化。通过降低抑制温度成功地建立了未老化的梭曼膦酰化AChE模型。药物试验表明,未老化的梭曼膦酰化大鼠脑AChE可被高浓度(1mmol/L)HI-6重活化,而不被2-PAM、TMB_4及LuH_6重活化。提示药物自身内在活性在重活化作用中的重要性。TMB_4和LuH_6对塔崩磷酸化AChE有较强重活化,而对未老化梭曼膦酸化AChE无重活化,HI-6则相反,对未老化梭曼膦酰化AChE重活化效果好,而对塔崩磷酰化AChE无重活化作用。塔崩和梭曼膦酰化AChE在未老化以前对药物的响应就有所不同,毒剂残基的空间效应可能起重要作用。     

胃久灵抗溃疡、抗胃炎作用及毒性的初步研究

以中药验方胃久灵对大白鼠的两种急性溃疡模型、一种慢性溃疡模型及两种胃炎模型用药治疗,证明胃久灵确有抗溃疡抗胃炎作用.其中对慢性溃疡的治疗作用较为突出.经急、慢性毒性实验,未见对重要脏器有任何毒性损害.     

Epidural pethidine and bupivacaine in labour

A double-blind randomised study was performed to assess the value of the addition of pethidine 50 mg to the initial dose of bupivacaine given for epidural analgesia in labour. Forty-nine patients received either 1 ml of saline (n = 24), or 50 mg of pethidine (n = 25), added to 9 ml of 0.25% bupivacaine as an initial injection for intrapartum epidural analgesia. There was a significant increase in the mean duration of analgesia in the pethidine group. However, pethidine did not increase the speed of onset of analgesia, or improve the quality of analgesia.     

植物化学物对健康影响的研究进展

近年来人们逐渐认识到多吃蔬菜和水果有益于健康，因为这些植物性食物中含有一些生物活性物质——植物化学物(phytochemicals)，它们具有保护人体和预防诸如心血管病和癌症等慢性疾病的作用。本将对植物化学物的总体研究状况加以综述。     

抗人精浆蛋白McAb的制备及其特性研究

本文报道用杂交瘤技术建立了２株分泌抗人精浆蛋白单克隆抗体的细胞株Ｄ１和Ｃ１２。Ｄ１株分泌的抗体为ＩｇＭ，Ｃ１２株为ＩｇＧ３。这两株均能与正常人精浆和无精子症患者的精浆产生特异性免疫反应。Ｄ１株单抗具有补体依赖性制动人精子的作用，间接免疫荧光试验表明，它能结合到人精子颈部和顶体后区。这充分说明２株单抗是特异性抗人精浆的，Ｄ１是精子制动抗体，其相应的精子抗原属于精子外套抗原成分之一。     

Contrast agents in functional MR imaging

Contrast agents have greatly expanded the role of MR imaging (MRI) to allow assessment of physiologic, or “functional,” parameters. Although activation mapping generally does not require contrast agents, other forms of functional MRI, including mapping of cerebral hemodynamics (eg, perfusion imaging), are best done with the use of contrast agents. Serial echo planar images are obtained after bolus injection of lanthanide chelates. Application of susceptibility contrast physics and standard tracer kinetic principles permits generation of relative cerebral blood volume maps. Deconvolution of cerebral blood flow and mean transit time parameters is also possible within technical limitations. By using diffusion and perfusion pulse sequences, an imaging correlate to the ischemic penumbra can be identified. Functional MRI perfusion imaging of intraaxial tumors is analogous to positron emission tomography for delineation of metabolic activity, yet may be even more sensitive to neovascularity and possesses improved image quality. Clinical applications include biopsy site selection and postirradiation follow-up. Further improvements in data analysis and map generation techniques may improve diagnostic accuracy and utility.     

Evaluation of portal MR angiography using superparamagnetic iron oxide

The purpose of our research was to determine the effects of superparamagnetic iron oxide on MR imaging of the portal venous system. Eight piglets were examined in deep anaesthesia and respiratory arrest using a time-of-flight magnetic resonance fast low angle shot, two-dimensional angiography sequence at 1.5T. MR angiograms were acquired precontrast and after intravenous administration of a cumulative dose of 10, 20 and 40 μmol/kg SHU 555A, a superparamagnetic iron oxide contrast agent for MR imaging with a particle size of 60 nm. For each dose, two subsequent sets of scans were obtained and reconstructed by a maximum-intensity-projection algorithm. Hepatic parenchymal and portal venous signal intensities were measured, and portal vein contrast calculated for each set of scans. All examinations were visually rated as to portal vein contrast and homogeneity by two blinded observers. Receiver operating characteristics of both observers were analyzed. The contrast agent reduced hepatic parenchymal signal in a dose-dependent way. After a cumulative dose of 10 μmol iron oxide, hepatic parenchymal signal intensity decreased to 63 ± 6% (average of measurements at 4 and 14 minutes, mean ± standard error of the mean), after 20 μmol to 24 ± 3%, and after 40 μmol to 12 ± 1% of control. Intra-vascular signal in the left main portal vein branch increased to 117 ± 6%, 127 ± 10%, and 133 ± 9% of control, respectively. The contrast-to-noise ratio of the portal vein improved (521 ± 90%, 891 ± 178%, and 995 ± 201% of control in the left portal vein main branch). Intravascular signal intensities increased slightly. The combined effect improved contrast of the portal vein stem and its branches. Receiver operating characteristics analysis documented dose-dependency of contrast medium effects on portal venous contrast and intravascular homogeneity. Visual rating also indicated a positive effect on portal venous contrast. The superparamagnetic iron oxide agent improved portal venous contrast with surrounding hepatic parenchyma in this normal animal model, and could potentially result in more accurate diagnosis of portal venous pathology.     

润滑油抗泡机理的研究 Ⅱ.助泡剂对泡沫倾向的影响及抗泡剂配伍性能

考察了各类添加剂在不同浓度、温度及不同基础油中的泡沫倾向,并测定了这些条件下体系的表面张力。从表面化学角度解释了添加剂对泡沫性质的影响,并通过对抗泡剂配伍性能的研究,验证了消泡机制:抗泡剂须具备高的表面活性才能吸附于泡膜表面,降低泡膜的表面粘弹性,改变膜的流变性能,从而起消泡作用。