Simultaneous determination of isosorbide dinitrate and its mononitrate metabolites in human plasma by capillary gas chromatography with electron-capture detection

A method for the simultaneous determination of isosorbide dinitrate (ISDN) and its mononitrate metabolites (2- and 5-ISMN) in human plasma by capillary gas chromatography with electron-capture detection was developed. Two internal standards were used: isomannide dinitrate (IMDN) for the determination of ISDN and isomannide mononitrate (IMMN) for the determinations of 2- and 5-ISMN. After addition of the internal standards, the compounds were isolated from plasma by solid-liquid extraction. They were determined by gas chromatography using an electron-capture detector. The reproducibility and accuracy of the method were found suitable in the range of concentrations 2.5–83 ng/ml for ISDN, 2.6–208 ng/ml for 2-ISMN and 2.3–1010 ng/ml for 5-ISMN. The limit of quantitation (LOQ) was about 2.5 ng/ml for each compound. The method was applied to clinical samples.     

Synthesis,antiplatelet and antithrombotic activities of resveratrol derivatives with NO-donor properties

Resveratrol (RVT) is a stilbene with a protective effect on the cardiovascular system; however, drawbacks including low bioavailability and fast metabolism limit its efficacy. In this work we described new resveratrol derivatives with nitric oxide (NO) release properties, ability to inhibit platelet aggregation and in vivo antithrombotic effect. Compounds (4a–f) were able to release NO in vitro, at levels ranging from 24.1% to 27.4%. All compounds (2a–f and 4a–f) have exhibited platelet aggregation inhibition using as agonists ADP, collagen and arachidonic acid. The most active compound (4f) showed reduced bleeding time compared to acetylsalicylic acid (ASA) and protected up to 80% against in vivo thromboembolic events. These findings suggest that hybrid resveratrol-furoxan (4f) is a novel lead compound able to prevent platelet aggregation and thromboembolic events.     

麝香保心丸和消心痛防治冠心病心绞痛的对比性研究

为了比较麝香保心丸和消心痛对防治冠心病心绞痛患者的疗效,本文观察了66例冠心病心绞痛患者,将他们随机分为麝香保心丸治疗组(30例)和消心痛对照组(30例)。心绞痛发作时首先舌下含服麝香保心丸2粒,然后以麝香保心丸2粒,3次1d;对照组则含服消心痛10 mg,然后以消心痛10 mg,3次/d,疗程均为四周。结果发现,含服麝香保心丸和消心痛均能迅速缓解心绞痛发作,对缺血性ST段压低和T波倒置,总有效率治疗组达93.3％和96.7％,对照组均达96.7％,两药疗效相当。经过四周冶疗两药均可显著降低心绞痛发作频率和硝酸甘油消耗量,改善心绞痛分级。治疗组心电图总有效率达93.9％～96.7％,24 h动态心电图显示两药均可明显改善缺血负荷,与对照组比较差别有显著性(420±271,411±291 VS 664±324 mm×min P值均小于0.05)。超声心动图示麝香保心丸可缩小左室收缩末和舒张末容积指数,并改善心功能。麝香保心丸副作用小,且依从性良好。     

Chronopharmacology of Oral Nitrates in Healthy Subjects

The pharmacokinetics and the hemodynamic effects (blood pressure, heart rate) of oral organic nitrates have been investigated in healthy subjects after oral single-dose application either in the morning or in the evening. Isosorbide-5-monitrate (IS-5-MN, 60 mg) was administered as an immediate-release tablet or as a slow-release formulation. Isosorbide dinitrate (ISDN, 20 mg) was ingested as an immediate-release tablet. After administration of IS-5-MN as an immediate-release tablet, the drug was more rapidly absorbed in the morning (t_max of 0.9 h) than in the evening (t_max of 2.1 h). The rapid absorption led to more pronounced effects in the morning, at which time maximum drug concentrations occurred at the same time as peak effects were observed. After evening administration, however, peak effects were in advance of the maximum drug concentrations. No chrono-kinetics were observed after application of the slow-release formulation of IS-5-MN. In accordance with the results of the immediate-release formulation, peak effects of the slow-release preparation occurred significantly earlier than peak drug concentrations after evening than after morning dosing. ISDN bioavailability was higher after morning than after evening administration and hemodynamic effects were more pronounced in the evening than in the morning. These results show that daily variations in pharmacokinetics and/or hemodynamic effects can be observed with oral nitrates. In addition, galenic formulation can influence the time-specified pharmacokinetics of IS-5-MN.     

Effects of nitric oxide synthase inhibitors and a substrate,L-arginine,on the cardiac function of juvenile salmonid fish

Control of cardiac function was investigated juvenile brown trout (Salmo trutta L.) and rainbow trout (Oncorhynchus mykiss Walbaum) using inhibitors of nitric oxide synthase (NOS), (L-NAME, NG-nitro-L-arginine and L-NMMA, NG-monomethyl-L-arginine) and a substrate of NOS (L-arginine). Salmonid alevins are excellent models for such studies since they are transparent, the beating heart is easily observed, diffusing distances are small, and they respond within a few seconds to exogenously administered chemicals. The response to inhibitors of NOS (L-NAME or L-NMMA) was tachycardia interpreted as vasoconstriction through lowered capacity for synthesis of NO. This could be reversed by addition of L-arginine and the subsequent bradycardia was explained as a vasodilation resulting from increased synthesis of NO. Blood flow into the heart is mainly via the vitelline vein and changes of flow resulting from constriction or dilation of this vessel may be probably major determinants of heart rate. The results provide evidence for the presence NOS in juvenile fish and indicate a physiological role for NO in cardiovascular control.     

前列地尔联合硝酸异山梨酯对不稳定性心绞痛患者血清细胞因子及血液流变学的影响

目的:探讨前列地尔联合硝酸异山梨酯对不稳定性心绞痛(UAP)患者血清细胞因子及血液流变学的影响。方法:选取2015年3月-2016年12月期间我院收治的UAP患者86例为研究对象,按照治疗方式的不同分为对照组和实验组,每组各43例。对照组给予硝酸异山梨酯治疗,实验组在硝酸异山梨酯的基础上加用前列地尔治疗,两组均连续治疗14d。对比两组治疗前后血清细胞因子水平变化、血液流变学参数变化、临床疗效以及不良反应发生情况。结果:治疗后两组白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)水平均明显降低,白细胞介素-10(IL-10)水平明显升高(P0.05),且实验组IL-6、TNF-α、hs-CRP水平较对照组降低,IL-10水平较对照组升高(P0.05)。治疗后两组舒张功能指数(O/C)、总电机械收缩期(QA2)、总外周阻力(TPR)均降低,每搏做功(SW)、搏功指数(SWI)、心脏指数(CI)、主动脉血管顺应性(AC)均升高(P0.05),治疗后实验组O/C、QA2、TPR较对照组降低,SW、SWI、CI、AC较对照组升高(P0.05)。实验组总有效率为95.35%,高于对照组的81.40%(P0.05)。两组治疗期间不良反应发生率比较差异无统计学意义(P0.05)。结论:前列地尔联合硝酸异山梨酯治疗UAP患者具有较好的疗效,可以控制患者的炎症反应,改善患者的血液流变学,无严重不良反应发生,值得临床推广。     

New biosourced chiral molecularly imprinted polymer: Synthesis,characterization, and evaluation of the recognition capacity of methyltestosterone

New biosourced chiral cross‐linkers were reported for the first time in the synthesis of methyltestosterone (MT) chiral molecularly imprinted polymers (cMIPs). Isosorbide and isomannide, known as 1,4:3,6‐dianhydrohexitols, were selected as starting diols. The cMIPs were synthesized following a noncovalent approach via thermal radical polymerization and monitored by Raman spectroscopy. These cross‐linkers were fully characterized by ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy and high‐resolution mass spectrometry. The cross‐polarization magic angle spinning ¹³C NMR, Fourier transform infrared spectroscopy, scanning electron microscopy, and specific surface areas following the Brunauer‐Emmett‐Teller (BET) method were used to characterize the cMIPs. The effect of stereochemistry of cross‐linkers on the reactivity of polymerization, morphology, and adsorption‐recognition properties of the MIP was evaluated. The results showed that the cMIP exhibited an obvious improvement in terms of rebinding capacity for MT as compared with the nonimprinted polymer (NIP). The highest binding capacity was observed for cMIP‐Is (27.298 mg g⁻¹) for high concentrations (500 mg L⁻¹). However, the isomannide homologue cMIP‐Im showed higher recovery—up to 65% and capacity for low concentrations (15 mg L⁻¹). The experimental data were properly fitted by the Freundlich adsorption isothermal model.     

Chronopharmacology of Oral Nitrates in Healthy Subjects

The pharmacokinetics and the hemodynamic effects (blood pressure, heart rate) of oral organic nitrates have been investigated in healthy subjects after oral single-dose application either in the morning or in the evening. Isosorbide-5- monitrate (IS-SMN, 60 rng) was administered as an immediate-release tablet or as a slow-release formulation. Isosorbide dinitrate (ISDN, 20 mg) was ingested as an immediate-release tablet. After administration of IS-5-MN as an immediate-release tablet, the drug was more rapidly absorbed in the morning (t_max of 0.9 h) than in the evening (t_max of 2.1 h). The rapid absorption led to more pronounced effects in the morning, at which time maximum drug concentrations occurred at the same time as peak effects were observed. After evening administration, however, peak effects were in advance of the maximum drug concentrations. No chronokinetics were observed after application of the slow-release formulation of IS-5- MN. In accordance with the results of the immediate-release formulation, peak effects of the slow-release preparation occurred significantly earlier than peak drug concentrations after evening than after morning dosing. ISDN bioavailability was higher after morning than after evening administration and hemodynamic effects were more pronounced in the evening than in the morning. These results show that daily variations in pharmacokinetics and/or hemodynamic effects can be observed with oral nitrates. In addition, galenic formulation can influence the time-specified pharmacokinetics of IS-5-MN.     

催化山梨醇脱水制备异山梨醇的固体酸催化剂

为提高目标产物异山梨醇的产率,考察多种固体酸催化剂催化山梨醇脱水的反应性能。结果表明:催化剂酸性与其催化性能之间有密切联系,酸性较强的H3PO4/Nb2O5催化剂显示出比其他催化剂更优异的催化性能。对磷酸负载量进行优化后,在n(P)/n(Nb)为0.8的H3PO4/Nb2O5催化剂上得到了100%的山梨醇转化率和63%的异山梨醇选择性。