聚多卡醇联合阿替洛尔治疗婴幼儿腮腺区血管瘤的临床研究

［摘要］ 目的 探讨聚多卡醇联合阿替洛尔治疗婴幼儿腮腺区血管瘤的疗效及其对环氧化酶2（cyclooxygenase 2,COX-2）、结缔组织生长因子（connective tissue growth factor,CTGF）、血管内皮生长因子（vascular endothelial growth factor,VEGF）的影响。 方法 选取腮腺区血管瘤患儿76例,随机分为对照组（38例）和观察组（38例）,对照组患儿给予阿替洛尔治疗,观察组患儿在此基础上给予瘤内局部注射1%聚多卡醇治疗。比较2组临床疗效及不良反应发生情况,比较治疗前后2组患儿COX-2、CTGF阳性率、VEGF水平及免疫功能。 结果 2组患儿平均服用阿替洛尔6个月,观察组患儿平均注射1%聚多卡醇3个疗程。76例患儿均完成治疗,随访12个月无失访。观察组总有效率显著高于对照组（P＜0.05）。治疗完成后观察组VEGF水平及COX-2、CTGF阳性率显著低于对照组,观察组IgA、IgG及IgM水平均显著高于对照组（P＜0.05）。治疗期间,观察组不良反应发生率显著低于对照组（P＜0.05）。 结论 聚多卡醇联合阿替洛尔治疗婴幼儿腮腺区血管瘤效果良好,且安全性高,具有抑制COX-2、CTGF及VEGF表达的作用。     

难溶性药物阿替洛尔单层芯渗透泵片的制备

 目的以阿替洛尔为模型药物,通过酸碱反应提高难溶性药物的溶解能力并制备单层芯渗透泵片。方法在处方中加入酒石酸使其与阿替洛尔的碱性基团反应从而增强药物的溶解性,用自行设计的带针冲头压制带孔片芯,以乙基纤维素为膜材包衣制备渗透泵片,采用相似因子作为指标筛选处方。结果在酒石酸溶液中阿替洛尔的溶解能力大幅度提高,制备的阿替洛尔单层芯渗透泵片能在24h内匀速释放药物,且释药行为不受桨转速和释放介质的影响。结论用酒石酸提高阿替洛尔的溶解能力并进而制备单层芯渗透泵片的方法是可行的。酸碱反应增溶药物的方法可望推广到其他难溶于水,但具有酸碱反应能力药物的增溶和渗透泵片的制备。     

尼群地平（98例）与阿替洛尔（92例）治疗老年高血压病的比较

目的：比较尼群地平与阿替洛尔治疗老年高血压病的疗效。方法：老年高血压病人９８例（男性７９例，女性１９例；年龄６４±ｓ９ａ）给予尼群地平１０ｍｇ，ｐｏ，ｔｉｄ，共服１ｍｏ。对照组为同样的病人９２例（男性７７例，女性１５例；年龄６０±９ａ）给予阿替洛尔２５ｍｇ，ｐｏ，ｔｉｄ，共服１ｍｏ。结果：尼群地平组显效６８％，有效２４％，总有效率９２％；阿替洛尔组显效４１％，有效２６％，，总有效率６７％；２组总有效率差异非常显著（Ｐ＜０．０１）。结论：尼群地平治疗老年高血压病优于阿替洛尔。     

Effects of atenolol,labetalol and propranolol on the peripheral circulation in hypertensive patients without obstructive vascular disease

Summary In an observer-blind, randomised cross-over trial, in 12 patients, the effects on the peripheral circulation of antihypertensive doses of atenolol, labetalol and propranolol and placebo were compared. After a placebo period of at least 4 weeks, patients were allocated at random to one of the three active drug treatments. After active treatment for at least 6 weeks and a fall in diastolic pressure (DP) to less than 90 mmHg subjects were switched to the next medication. At the end of each period, photoelectric plethysmography (PHELP) was done on all fingers of one hand cooled over 4 min in water in steps of 3°C from 33° to 12°C, and subsequently warmed in room air (20°C) for a period of 10 min. Blood flow changes during cooling were expressed as a percentage of the initial PHELP value (% PHELP). Areas under the curves, representing the % PHELP/cooling period and % PHELP/warming-up period, showed that within the temperature range normally encountered in daily life, labetalol preserved finger blood flow significantly better than propranolol and marginally better than placebo. With atenolol, finger blood flow was not significantly different from that during the three other regimens, but there were significantly fewer other side-effects. It is concluded that labetalol may be the drug of choice for hypertensive patients treated with beta-blocking agents whose peripheral arterial circulation seems inadequate at low temperatures.     

Effect of Nebivolol and Atenolol on Brachial Artery Flow-Mediated Vasodilation in Patients with Coronary Artery Disease

Summary Endothelial dysfunction is considered to be the first step in atherogenesis as well as a predictor of adverse cardiovascular events in patients with coronary artery disease (CAD), while endothelial function improvement is associated with improved clinical outcome. Nebivolol is a beta₁-adrenoreceptor antagonist with an independent beneficial action on endothelial function, increasing nitric oxide bioavailability. The aim of the present study was to examine the effects of nebivolol on endothelial function in the brachial artery in patients with CAD compared with another selective beta₁ adrenergic receptor antagonist, atenolol. Thirty-five patients with stable CAD were randomized to receive either 5 mg nebivolol (n = 17) or 50 mg atenolol (n = 18) daily for 4 weeks. Each patient underwent measurement of endothelial function by means of flow-mediated dilatation (FMD) of the brachial artery before and after 4 weeks of treatment. All vasoactive drugs and cardiovascular risk factors were comparable in the two groups. No significant differences were observed between the two groups at baseline in FMD. In the atenolol group FMD remained unchanged at the end of the 4-week treatment, but in patients treated with nebivolol FMD showed a significant increase by the end of the treatment period (3.9 ± 2.7% vs. 5.6 ± 2.9%, p = 0.047) leading to a significantly higher value compared to patients treated with atenolol (5.6 ± 2.9% vs. 3.4 ± 3.2%, p = 0.041). Beta₁ blockade by nebivolol but not atenolol improves endothelial dysfunction in patients with CAD, an effect that might further reduce the risk for cardiovascular events in patients with CAD.     

Serum lipoprotein changes during atenolol treatment of essential hypertension

Summary Serum lipoproteins were determined in 15 patients before and during antihypertensive treatment with atenolol 0.1–0.2 g/day for a mean of 8 months. The mean blood pressure fell from 171/103 to 154/93 mm Hg (p<0.05). Significant lipoprotein changes were an increase in very low density triglycerides (VLDL-TG) from 1.21±0.95 (SD) to 1.62±1.24 mmol/l (p<0.01) and in low density (LDL) TG from 0.46±0.12 to 0.51±0.12 mmol/l (p<0.05). Together, these TG increases resulted in development of hypertriglyceridaemia in 7/15 patients during atenolol treatment. No effect on whole serum cholesterol or on the high density lipoprotein cholesterol concentrations were found. Thus, some patients on long term treatment with atenolol seem to receive the benefit of normotension at the cost of hypertriglyceridaemia. This may have practical implications, since hypertriglyceridaemia constitutes an important risk factor for atherosclerosis.     

Functional characterization of beta-adrenoceptors mediating relaxation in sheep gallbladder

The purpose of this study was to characterize beta-adrenoceptor subtype(s) mediating relaxation in smooth muscle strips of the sheep gallbladder. Experiments were performed on isolated smooth muscle strips suspended in tissue baths containing Krebs' solution. Isoprenaline (10(-8) M-10(-5) M) and salbutamol (10(-7) M-10(-4) M) produced concentration-dependent relaxation of carbachol (10(-7) M-3 x 10(-7) M) contracted smooth muscles of the sheep gall bladder. Isoprenaline-induced relaxation was significantly antagonized by propranolol with -logKB values of 7.81 +/- 0.11 (n = 7) and 7.73 +/- 0.12 (n = 6) in the fundic and ductal strips respectively. Atenolol (10(-5) M), a selective beta 1-adrenoceptor antagonist, also significantly antagonized isoprenaline-induced relaxation with -logKB values of 5.82 +/- 0.11 and 6.09 +/- 0.09 in the fundic and ductal strips respectively. However, ICI 118551, a selective beta 2-adrenoceptor antagonist, at concentrations up to 10(-6) M had little or no effect on isoprenaline-induced relaxation in either of these preparations. BRL 37344A, a selective beta 3-adrenoceptor agonist produced concentration-dependent relaxation of carbachol-precontracted fundic and ductal strips. BRL 37344 was approximately 9-fold more potent in the ductal than fundic strips. In both preparations, BRL 37344-induced relaxation was not significantly (p > 0.05) antagonized by propranolol (3 x 10(-7) M). This would confirm that the response was mediated via beta 3-adrenoceptors. It was concluded that beta 1- and beta 3-adrenoceptors coexist in the sheep gallbladder and mediate smooth muscle relaxation.     

Does α1-adrenergic blockade influence regional blood flow regulation in hearts with coronary artery occlusion?

Summary. The effects of selective α₁-adrenergic blockade with doxazosin on regional myocardial tissue blood flow was studied in anaesthetized cats with acute coronary artery occlusion. Reflex tachycardia was prevented by selective β₁-adrenergic blockade with atenolol and coronary perfusion pressure was kept constant by partial stenosis of the descending aorta. Administration of atenolol reduced cardiac mechanical work-load by its negative inotropic and chronotropic effects, and reduced myocardial tissue blood flow in normally perfused myocardium. This reduction was most pronounced in the endocardial half-layer of the myocardium adjacent to the ischaemic region. Administration of doxazosin in this situation clearly reduced peak systolic and coronary perfusion pressure. But when coronary perfusion pressure was raised to pre-administration values, measurements of regional blood flow revealed no changes either in ischaemic or non-ischaemic myocardium. Also, there was no sign of redistribution of blood flow between endocardial and epicardial tissue in any area. This study, therefore, indicates that α₁-adrenoceptors play a minor role in the regulation of coronary blood flow in normal myocardium as well as ischaemic myocardium.     

Types of Adrenoreceptors Mediating Responses of Rabbit Gastric Muscularis Mucosae

This study investigated adrenoreceptor-mediated responses of muscularis mucosae from the fundic and antral ends of the rabbit gastric corpus. Norepinephrine-induced fundic muscularis mucosae contractions were enhanced by propranolol and converted to relaxations by phentolamine. Methoxamine, but not clonidine, elicited large fundic contractions. Fundic muscle responded to low isoproterenol concentrations with atenolol- and butoxamine-resistant relaxations, and to high concentrations with atenolol-sensitive contractions. Norepinephrine evoked propranolol-resistant relaxations of antral muscularis mucosae that were enhanced by phentolamine. Methoxamine and clonidine elicited small antral contractions. Lower concentrations of isoproterenol caused atenolol-resistant antral relaxations that were enhanced by butoxamine; higher concentrations produced weak excitation. Fundic and antral relaxations to isoproterenol were abolished by cyanopindolol. Fundic muscularis mucosae possesses excitatory ₁-, ₁- and inhibitory ₃-adrenoreceptors. Excitatory ₂- and inhibitory ₃-adrenoreceptors predominate in the antral region. The heterogeneous adrenoreceptor-mediated responses of the gastric muscularis mucosae suggest that adrenergic modulation of its motor activity is unlikely to be linked to acid secretion.     

Comparative study of the effects of acebutolol,atenolol, d-propranolol and dl,-propranolol on the alterations in energy metabolism caused by ischemia and reperfusion: A 31P NMR study on the isolated rat heart

Summary 31-P NMR spectroscopy data recorded for the isolated heart were analyzed, in conjunction with functional and biochemical variables, in order to investigate the effect observed for several different beta-adrenoceptor antagonists on the alterations provoked by global partial ischemia (37°C, 24 minutes, 1% residual coronary flow) and reperfusion in the metabolism of the myocardium. During ischemia: intracellular acidosis, adenosine triphosphate (ATP) degradation, and inorganic phosphate (Pi) accumulation were found to be reduced whether the perfusion fluid contained: acebutolol 2.7×10^-5 M, atenolol 10^-5 M, d-propranolol 10^-5 M, or dl-propranolol 10^-5 M. On reperfusion metabolic and functional variables were variously affected by the different drugs, except the Pi level which was, in all series, significantly lower compared with control hearts. The adenylate charge and the glycogen stores were protected in the acebutolol, dl-propranolol, and d-propranolol groups. The ATP level was higher than in controls only in the acebutolol and atenolol groups. The intracellular pH recovered to values non-significantly different from preischemic values in the acebutolol and dl-propranol-treated hearts only. The mechanical performance, expressed as the rate-pressure product, was unaltered by the ischemia-reperfusion sequence in the acebutolol and d-propranolol series, while decreasing significantly in controls and in the atenolol group. In dl-propranolol-treated hearts the mechanical activity, which in normoxic conditions was already halved during the effect of the drug, remained at this same level after ischemia. From these observations, it appears that the nonspecific properties of the drugs, as distinct from beta-blockade, play an important part in attenuating the ischemia-induced alteration in myocardial metabolism. Thus, it can be postulated that (1) the metabolic effects of dl-propranolol probably result largely from the reduction of heart work induced by this drug; (2) the maintenance of energy metabolism associated with the preservation of the myocardial activity, as observed in the case of acebutolol and d-propranolol, is possibly a consequence of the existence of a membrane-stabilizing activity.