硝苯地平控释片联合替米沙坦对老年高血压患者动态血压及左室舒张功能的影响

目的:研究硝苯地平控释片联合替米沙坦对老年高血压患者动态血压以及左室舒张功能的影响。方法:选择我院2012年12月至2013年11月收治的轻、中度老年高血压合并左室舒张功能不全的患者84例为研究对象,并将其随机分为两组。对照组给予硝苯地平控释片30~60 mg/d,观察组在对照组的基础上,加用替米沙坦40 mg/d,降压未达疗效者,改为80 mg/d,疗程12周。期间观察和比较两组患者的动脉血压波动情况、左心室舒张功能及疗效。结果:对高血压的控制,观察组总有效率显著高于对照组(P0.05),显效率高于对照组,但无统计学意义(P0.05)。动态血压监测及血压负荷结果提示两组治疗后的24 h收缩压平均值(24hm SBP)、24 h舒张压平均值(24hm DBP)、日间收缩压平均值(dm SBP)、日间舒张压平均值(dm DBP)、夜间收缩压平均值(nm SBP)、夜间舒张压平均值(nm DBP)均显著低于治疗前,且观察组显著优于对照组(P0.05)。两组的左心室射血分数(LVEF)、左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、舒张期左室后壁厚度(LVPWD)、舒张期室间隔厚度(IVST)水平均较治疗前有所改善,但差异无统计学意义(P0.05);观察组各指标水平优于对照组,但差异亦无统计学意义(P0.05)。结论:硝苯地平控释片联合替米沙坦治疗老年高血压有助于更加有效地控制其动态血压波动,且在一定程度上可改善左心室舒张功能。     

硫酸镁联合硝苯地平治疗中重度妊娠高血压综合征患者的疗效观察

目的:探讨硫酸镁联合硝苯地平治疗中重度妊娠期高血压综合征的临床疗效。方法:选取2013年5月-2014年10月我院收治的中重度妊娠期高血压综合征患者70例,随机将患者分为研究组和对照组,每组35例。对照组患者应用硫酸镁治疗,研究组患者给予硫酸镁联合硝苯地平治疗,比较两组患者的临床疗效、血压变化、血液粘度、24 h尿蛋白含量以及血细胞压积情况。结果:研究组治疗总有效率显著优于对照组,差异具有统计学意义(P0.05);两组患者治疗后的血压水平显著低于治疗前,且研究组显著优于对照组,差异具有统计学意义(P0.05);两组患者治疗后的血液粘度、24 h尿蛋白含量及血细胞压积显著优于治疗前,且研究组优于对照组,差异具有统计学意义(P0.05)。结论:硫酸镁联合硝苯地平治疗中重度妊娠期高血压具有较好的临床疗效,能够显著改善患者的临床症状。     

硝苯地平片联合酒石酸托特罗定片对TURP术后膀胱过度活动症的应用效果分析

目的:探讨硝苯地平片联合酒石酸托特罗定片用于经尿道前列腺电切术(TURP)术后膀胱过度活动症的临床效果及安全性。方法:选择2015年8月至2017年8月我院接诊的103例TURP术后出现膀胱过度活动症的患者作为本研究对象,通过随机数表法将其分为试验组52例和对照组51例。两组均给予常规处理,对照组在此基础上口服酒石酸托特罗定片,2 mg/次,2次/d;试验组在对照组基础上联合硝苯地平片口服,5 mg/次,3次/d;两组均连续用药7d。比较两组临床疗效,治疗前后膀胱过度活动症(OABSS)评分、国际前列腺症(IPSS)评分、膀胱痉挛次数、排尿情况的变化以及不良反应的发生情况。结果:治疗后,试验组和对照组临床疗效总有效率分别为92.31%(48/52)和76.47%(39/51),OABSS评分分别为(2.69±0.58)分和(4.76±0.62)分,IPSS评分分别为(5.02±0.80)分和(7.86±1.15)分,24h膀胱痉挛次数分别为(0.65±0.48)次和(1.10±0.61)次,24h尿急次数分别为(0.88±0.32)次和(1.59±0.54)次,24h排尿次数分别为(5.52±1.02)次和(7.24±0.97)次,夜间排尿次数分别为(0.73±0.45)次和(1.39±0.70)次,24 h平均尿量分别为(227.07±16.68)mL和(196.65±15.07)mL,试验组临床总有效率和24 h平均尿量均显著高于对照组(P0.05),OABSS评分、IPSS评分、24 h膀胱痉挛次数、24 h尿急次数及24h排尿次数均显著低于对照组(P0.05)。两组不良反应发生率比较差异无统计学意义(P0.05)。结论:硝苯地平片联合酒石酸托特罗定片治疗TURP术后膀胱过度活动症患者的临床疗效明显优于单用酒石酸托特罗定片,其可更有效促进膀胱功能恢复,且不增加不良反应。     

两种钙离子拮抗剂联用治疗尿毒症合并难治性高血压的临床研究

目的：探讨联用两种钙离子拮抗剂（calciumchannelblocker,CCB）治疗尿毒症合并难治性高血压的临床疗效。方法：选择广东省湛江市廉江市人民医院血液净化中心2010年10月至2011年9月收治的72例终末期肾病维持性血液透析合并难治性高血压患者作为观察对象,并随机分为A、B、C三组,每组24例,A组和B组病分别用硝苯地平缓释片和苯磺酸氨氯地平治疗8周,C组联合应用硝苯地平缓释片和苯磺酸氨氯地平治疗8周,观察各组血压变化情况及不良反应的发生情况。结果：C组病例治疗完成时收缩压、舒张压、平均动脉压较A组和B组病例治疗前的血压明显降低,总有效率明显高于A组和B组,差异有统计学意义（P〈0．05）。三组治疗过程中,均无严重不良反应发生。结论：联合应用两种CCB治疗尿毒症顽固性高血压,降压效果明显,且可耐受性好。     

Determination of hyperforin in human plasma using solid-phase extraction and high-performance liquid chromatography with ultraviolet detection

The role of the Mg2+ cation on antihypertensive molecule binding on human serum albumin (HSA) was studied by affinity chromatography. The thermodynamic data corresponding to this binding were determined for a wide range of Mg2+ concentrations (c). For the nifedipine molecule, an increase in the Mg2+ concentration produced a decrease in binding due to a decrease in the electrostatic interactions. For verapamil and diltiazem, which have the highest solvent accessible surface area, the solute binding on HSA was divided into two Mg2+ concentration regions. For a low c value below c(c) (approximately 1.6 mmol/l), the binding dependence with c was similar to that of nifedipine. For c above c(c) the hydrophobic effect created in the bulk solvent associated with a decrease in the van der Waals interactions between the solute molecule and the HSA implied a decrease in its binding. These results showed that for patients with hypertension, an Mg2+ supplementation during treatment with these antihypertensive molecules can increase the active pharmacological molecule concentration.     

Active calcium ion transport in Xenopuslaevis skin

The skin of intact, free-swimming Xenopus laevis transports Ca²⁺ inwardly in a manner that is proportional to the external [Ca²⁺] up to about 0.3 mmol · l⁻¹, saturates above 0.3 mmol · l⁻¹, and is opposed to the electrochemical gradient. Efflux is relatively constant at external concentrations between 0.016 and 0.6 mmol · l⁻¹; net flux which is negative below 0.125 mmol · l⁻¹ becomes positive above this external [Ca²⁺]. Allometric analysis suggests that both Ca²⁺ influx and efflux scale to the 2/3 power approximately like surface area. There were no significant differences in influx between summer and fall animals; however, efflux was greater in the fall and this resulted in a change from positive balance in the summer to negative balance in the fall. Isolated skins were shown to support a Ca²⁺ uptake rate of nearly 30 nmol · cm⁻² · h⁻¹. The phenylalkylamine verapamil in the apical bathing solution significantly inhibited this at 25 μmol · l⁻¹. The benzothiazepine diltiazem was also effective at 50 μmol · l⁻¹ while the dihydropyradine nifedipine was ineffective up to 100 μmol · l⁻¹. The inorganic ion La³⁺ was effective at blocking Ca²⁺ uptake at 300 μmol · l⁻¹; Ni²⁺ was also effective at 500 μmol · l⁻¹ but Co²⁺ was ineffective up to 500 μmol · l⁻¹. These results suggest that apical calcium channels in Xenopuslaevis skin have properties similar to mammalian L-channels and fish gill Ca²⁺ channels. Accepted: 23 January 1997     

Blockade by NS-7, a neuroprotective compound, of both L-type and P/Q-type Ca2+ channels involving depolarization-stimulated nitric oxide synthase activity in primary neuronal culture

The effect of 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride (NS-7), a neuroprotective compound, on Ca2+ channels involving the activation of nitric oxide synthase (NOS) was investigated in primary neuronal culture. The NOS activity was estimated from the cyclic GMP formation. The KCl (25 mM)-stimulated cyclic GMP formation was totally abolished by a combined treatment with nifedipine and omega-agatoxin IVA (omega-Aga), whereas spontaneous cyclic GMP formation was partially but significantly reduced by nifedipine. In contrast to nifedipine, NS-7 blocked KCl-stimulated cyclic GMP formation without affecting spontaneous cyclic GMP formation. Subsequently, the effects of nifedipine and NS-7 on L-type Ca2+ channels were compared. Nifedipine blocked equally the cyclic GMP formation stimulated by various concentrations of (+/-)-Bay K 8644, whereas NS-7 inhibited the maximal response without affecting the responses induced by low concentrations of (+/-)-Bay K 8644. The effects of NS-7 on L-type and P/Q-type Ca2+ channels involving KCl-stimulated cyclic GMP formation were subsequently examined. NS-7 suppressed the KCl-stimulated cyclic GMP formation measured in the presence of omega-Aga to almost the same extent as that determined in the presence of nifedipine. In contrast, NS-7 had no influence on ionomycin-induced enhancement of cyclic GMP formation. Finally, NS-7 reversed KCl-induced elevation of the intracellular free Ca2+ concentration. These findings suggest that NS-7 inhibits NOS activation in primary neuronal culture by reducing Ca2+ entry through L-type and P/Q-type Ca2+ channels, in which the inhibition is largely dependent on Ca2+ channel activity.     

Transepithelial transport of zinc and <Emphasis Type="SmallCaps">l</Emphasis>-histidine across perfused intestine of American lobster, <Emphasis Type="Italic">Homarus americanus</Emphasis>

The intestine of the American lobster, Homarus americanus, was isolated and perfused in vitro with a physiological saline, based on the ion composition of the blood, to characterize the mechanisms responsible for transmural transport of zinc and how the amino acid, l-histidine, affects the net movement of the metal across the tissue. Previous studies with this preparation, focusing on the characteristics of unidirectional mucosa to serosa (M to S) fluxes of ⁶⁵Zn²⁺ and ³H-l-histidine, indicated the presence of a brush border co-transport process responsible for simultaneously transferring the metal and amino acid across this tissue as an apparent bis-complex (Zn-[His]₂) using a PEPT-1-like dipeptide carrier mechanism. In addition, both zinc and l-histidine were also transferred toward the blood by separate transporters that were independent of the other substrate. The focus of the present study was to characterize the serosa to mucosa (S to M) flux of ⁶⁵Zn²⁺ under a variety of conditions, and use these values in conjunction with those from the previous study, to assess the direction and magnitude of net metal movement across the tissue. Transmural S to M transport of ⁶⁵Zn²⁺ was markedly reduced with the addition of the serosal inhibitors ouabain (32%), excess K⁺ (25%), excess Ca²⁺ (30%), Cu²⁺ (38%), nifedipine (21%), and vanadate (53%). In contrast, this flux was markedly stimulated with the serosal addition of ATP (24%) and excess Na⁺ (28%). These results suggest that S to M fluxes of zinc occurred by the combination of the basolateral Na/Ca exchanger (NCX), where zinc replaced calcium, and a basolateral nifedipine-sensitive calcium channel. Transmural M to S ⁶⁵Zn²⁺ fluxes (5–100 μM) were threefold greater than S to M metal transport, and the addition of luminal l-histidine doubled the net M to S zinc flux over its rate in the absence of the amino acid. The results of this paper and those in its predecessor indicate that zinc transport by the lobster intestine is absorptive and significantly enhanced by luminal amino acids.     

Dose- and administration time-dependent effects of nifedipine gits on ambulatory blood pressure in hypertensive subjects

Previous chronotherapy studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium channel blockers (CCB), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the antihypertensive efficacy and safety profile of the slow-release, once-a-day nifedipine gastrointestinal therapeutic system (GITS) formulation administered at different times with reference to the rest-activity cycle of each participant. We studied 80 diurnally active subjects (36 men and 44 women), 52.1±10.7 yrs of age, with grade 1-2 essential hypertension, who were randomly assigned to receive nifedipine GITS (30 mg/day) as a monotherapy for eight weeks, either upon awakening in the morning or at bedtime at night. Patients with uncontrolled BP were up-titrated to a higher dose, 60 mg/day nifedipine GITS, for an additional eight weeks. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours before and after therapy with either dose. The BP reduction after eight weeks of therapy with the lower dose of 30 mg/day was slightly, but not significantly, larger with bedtime dosing. The efficacy of 60 mg/day nifedipine GITS in non-responders to the initial 30 mg/day dose was twice as great with bedtime as compared to morning dosing. Moreover, bedtime administration of nifedipine GITS reduced the incidence of edema as an adverse event by 91%, and the total number of all adverse events by 74% as compared to morning dosing (p=0.026). Independent of the time of day of administration, a single daily dose of 30 mg/day of nifedipine GITS provides full 24 h therapeutic coverage. The dose-dependent increased efficacy and the markedly improved safety profile of bedtime as compared to morning administration of nifedipine GITS should be taken into account when prescribing this CCB in the treatment of essential hypertension.     

Synthesis and antioxidant activity of new lipophilic dihydropyridines

Dihydropyridines (DHPs) obtained from Hantzsch multicomponent reactions are an important pharmaceutical class of compounds marketed as antihypertensive (e.g., nifedipine, nitrendipine, and amlodipine) drugs. This study synthesized new symmetrical and unsymmetrical long-chain fatty DHPs using multicomponent reactions under metal-free conditions with sulfamic acid as a catalyst. The DHPs were tested for antioxidant activity using three different methods. The insertion of a long chain into the DHP core contributed to antioxidant potential, and compounds derived from nitro aldehydes have better antioxidant potential than the antihypertensive drug nifedipine. In addition, fatty analogs to nifedipine derived from palmitic and oleic chains showed similar antioxidant activity to the common standards butylated hydroxytoluene and vitamin E. These results showed that our new synthesized products may find novel applications as antioxidant additives or for tools for use in drug discovery.