氯通道阻断剂对H_2O_2诱导的胰岛RIN-mβ细胞凋亡的影响

目的观察氯通道阻断剂对H2O2诱导的胰岛RIN-mβ细胞凋亡的影响,探讨氯通道在RIN-mβ细胞凋亡中的作用。方法采用H2O2诱导的胰岛RIN-mβ细胞凋亡模型,观察氯通道阻断剂(DIDS、NPPB和NFA)对细胞存活率、形态学变化、凋亡的影响。结果氯通道阻断剂单用时对胰岛RIN-mβ细胞活力无明显影响,但能明显提高H2O2处理的胰岛RIN-mβ细胞的存活率。与模型对照组相比,氯通道阻断剂DIDS、NPPB和NFA对抗组细胞存活率明显增加(P<0.01),细胞凋亡率明显降低(P<0.01)。结论氯通道阻断剂对H2O2诱导的RIN-mβ细胞损伤和凋亡具有明显的保护作用。     

抗帕金森病新药研究进展

帕金森病(Parkinson's disease,PD)是一种常见的神经退行性疾病,其特征为黑质纹状体通路的多巴胺能神经元的丢失。左旋多巴一直作为临床治疗的主导用药,然而,该药长期应用会引起症状波动和运动障碍。目前最有希望治疗帕金森病的药物包括能够阻碍或者降低神经退行性过程的神经保护性药物,能够恢复大脑功能的药物,多巴胺替代和保留的药物,作用于纹状体以外的非多巴胺的神经递质的抗运动障碍药物。此外,一些具有崭新作用机制的药物,如腺苷A_(2A)受体阻滞剂、抗细胞凋亡药物等,都可能以单用或合并用药治疗PD。现综述目前临床治疗和开发中的抗PD新药的研究进展。     

Postjunctional α2-adrenoceptors in blood vessels of human nasal mucosa

Summary Human nasal mucosa has various types of blood vessels and is a good tissue for demonstrating receptors for many vasoactive substances, including -adrenoceptors. In contrast to the large contractile response induced by ₂-agonists, our studies have shown that ₂-agonists produce a small maximal contraction. This ₂-induced response was easily blocked by ₁-antagonists, indicating that it is evoked, at least partially, by the stimulation of ₁-adrenoceptors. Noradrenaline (NA)-induced contractions could not be abolished by either ₁- or ₂-antagonists alone, but were almost completely blocked by the combination of both antagonists. This suggests the presence of postjunctional ₂-adrenoceptors. The low-maximal responsiveness to ₂-agonists and calcium independency of NA-induced contractions were distinct from our former results obtained on canine nasal specimens.     

Myocardial beta-1 adrenoceptor down-regulation in aging and heart failure: implications for beta-blocker use in older adults with heart failure

Heart failure is associated with increased sympathetic nervous stimulation that results in down-regulation of myocardial beta-1 receptors. The failing heart might depend more on beta-2 receptors for positive inotropic support than the normal heart. Suppression of both beta-1 and beta-2 adrenoceptors by a non-selective beta-blocker, such as carvedilol, is likely to eliminate the failing heart's much needed inotropic support, resulting in an exacerbation of symptoms. Use of a beta-1 selective blocker, such as metoprolol, on the other hand, is likely to be well tolerated. Unlike carvedilol, the use of metoprolol is associated with up-regulation of beta-1 receptors. The clinical significance of the pharmacodynamic differences between these two beta-blockers in terms of their short-term hemodynamic and long-term beneficial effects is not clearly understood. However, in clinical trials, both carvedilol and metoprolol improved left ventricular function, heart failure symptoms and survival. Both drugs are well tolerated as well. Aging itself is associated with elevated myocardial and serum norepinephrine levels, which is associated with down-regulation of beta-1 receptors. In this article, we reviewed the literature to examine the clinical implications of this dual (age- and heart failure-related) sympathetic stimulation and beta-1 receptor down-regulation on selection of beta-blockers in older adults with heart failure.     

Lamotrigine monotherapy for control of neuralgia after nerve section

BACKGROUND: We present six patients treated only with the new-generation anticonvulsant lamotrigine to define its sole effect on neuralgia after nerve section. METHODS: Previous surgical or pharmacological attempts failed to relieve this neuropathic pain in our patients. Before initiation of lamotrigine therapy, patients reported spontaneous and touch-evoked shooting pain followed by periods of burning pain. No breakthrough medication was needed during the maintenance phase of 1-23 months. Data were acquired by a pain diary on a weekly basis. RESULTS: With 75-300 mg of lamotrigine per day, the burning and shooting pain intensity was relieved by 33-100%. Most obviously, the attack frequency of the shooting pain was reduced by 80-100%. No adverse effects were observed. CONCLUSION: We conclude that lamotrigine may be beneficial in the treatment of neuralgia after nerve section following the failure of previous pharmacological or surgical attempts.     

高血压合并心力衰竭患者应用ACEI和ACEI联合ARB的随机对照研究

目的探讨高血压合并心力衰竭的患者治疗中联合应用血管紧张素转换酶抑制剂(ACEI)和血管紧张素II受体拮抗剂(ARB)的安全性和对心功能的影响。方法自2005年2月~2006年2月共入选91例高血压合并心力衰竭患者。采用随机对照方法,将入选患者分为ACEI组46例和ACEI联合ARB组45例。2组均应用氢氯噻嗪25mg/d,用药前血钾、肝功能、肾功能均正常。ACEI组给予培哚普利,4mg/d;ACEI联合ARB组给予培哚普利,4mg/d,缬沙坦80mg/d,均以血压降至140/90mmHg以下为达标。监测用药1个月前后的血钾、C反应蛋白(CRP)、血肌酐水平及心功能变化。结果(1)未见血钾及血肌酐的异常增高。(2)与治疗前比较,2组患者治疗后血浆CRP浓度差异有显著意义(P<0.05),2组间比较亦有显著差异(P<0.05)。(3)2组患者治疗后心脏收缩功能改变差异有显著意义(P<0.05),但2组间比较无显著差异(P>0.05)。(4)2组治疗前后心室舒张功能改变差异有显著意义(P<0.05)。2组间比较亦有显著差异(P<0.05)。结论在应用排钾利尿剂的基础上,联合应用ACEI和ARB治疗高血压合并心力衰竭的患者,不但可以增加控制高血压的疗效,而且不会导致血钾、血肌酐水平的异常增高,并且可降低血清CRP浓度,在改善心脏收缩功能的同时,明显改善心脏的舒张功能。     

特发性长QT综合征QT离散度与尖端扭转性室性心动速的关系

目的探讨QT离散度与特发性长QT综合征（LQT1）发生尖端扭转性室性心动过速的关系.方法79例基因（11p15.5）携带者根据晕厥发作的频度和程度分为3组：轻度（0～4次,n=59）,中度（5～100次,n=14）和重度（有心脏骤停史,n=5）.比较：3组首次心电图QT离散度的差异;19例小于35岁的中、重度患者长期用β阻滞剂后QT离散度的变化;9例患者用β阻滞剂前后踏车试验QT离散度的变化.结果（1）3组间QT离散度有显著差异（P＜0.01）;（2）13例长期用β阻滞剂者,10例QT离散度缩小（P＜0.05）;（3）患者用β阻滞剂前,QT离散度与运动负荷呈正相关,用β阻滞剂后,呈负相关.结论QT离散度是估计病情的敏感而可靠的指标;小于35岁的中、重度LQT1（包括“无症状”者）应长期用β阻滞剂.     

坎地沙坦联合胺碘酮转复房颤及预防房颤复发疗效观察

目的:探讨坎地沙坦联合胺碘酮转复房颤及预防房颤复发的疗效。方法:将持续性房颤患者87例随机分为坎地沙坦-胺碘酮联合治疗组(即治疗组)与胺碘酮治疗组(即对照组),进行转复治疗及预防复发治疗,共观察8个月,观察转复率、转复周期及复发率、复发时限并进行对比分析。结果:联合治疗组与胺碘酮治疗组相比,其房颤转复率无显著性差异(72.7%vs 51.2%,P>0.05),而转复周期显著缩短〔(12.6±4.1)d vs(15.3±5.5)d,P<0.05〕,复发率显著降低(34.4%vs63.6%,P<0.05),复发时限显著延长〔(175.3±41.5)d vs(90.9±36.5)d,P<0.05〕。结论:血管紧张素受体拮抗剂坎地沙坦在转复及维持房颤患者窦性节律方面有辅助作用。     

萘甲异喹对大鼠心肌细胞Ca~(2+)内流的影响

目的研究萘甲异喹（NI）对大鼠心肌细胞外Ca(2+)内流的影响。方法：应用钙离子荧光指示剂Fura－2检测。结果：NI（3，10μmol·L(-1)）和维拉帕米（0．3μmol·L(－1)）对静息状态下心肌细胞内Ca(2+)浓度无影响，但可浓度依赖地抑制高钾（60mmol·L(-1)）和异丙肾上腺素（lμmol·L(－1)）引起的心肌细胞内Ca(2+)浓度的升高，抑制率分别为29％±6％、49％±9％和26％±6％、40％±8％；NI对两种激动剂作用的抑制百分率无明显差异，而维拉帕米对高钾作用的抑制大于对异丙肾上腺素作用的抑制。结论：NI对心肌细胞电压依赖性钙通道以及和β受体有关的钙通道有阻断作用，NI可能是非选择性钙通道阻滞剂。     

The effect of nifedipine on monocrotaline-induced pulmonary hypertension in rats

Effective drug therapy for pulmonary hypertension has not yet been developed. This study was designed to estimate the long-term hemodynamic and histopathological effects of nifedipine on severe pulmonary hypertension using animal models. Injection of one dose of monocrotaline produced subacute pulmonary hypertension in 7 week old Sprague-Dawley rats. Nifedipine (10 mg/kg) was administered intraperitoneally every day. For 5 weeks, bodyweight and hemodynamic parameters were measured, and right ventricle (RV) and left ventricle with septum (LV + S) were weighed separately. Medial thickness of the small pulmonary arterial wall was calculated by Suwa's method. Compared with the control group, the increase in right ventricular systolic pressure, total pulmonary resistance index, weight ratio of RV/(LV + S) and medial hypertrophy in the nifedipine-treated rats were significantly limited without causing systemic hypotension. These results suggest that treatment with nifedipine may also be effective in attenuation of pulmonary hypertension when applied to humans.