聚乙烯醇-盐酸普萘洛尔多孔水凝胶的制备及体外经皮渗透研究

目的：制备聚乙烯醇-盐酸普萘洛尔多孔水凝胶,并研究其体外经皮渗透性能。方法：采用循环冷冻-解冻法制备多孔水凝胶,采用改进的Franz扩散池进行体外透皮试验,以凝胶外观、致孔效果和累积渗透量为评价指标,优化水凝胶的处方和工艺。结果：壳聚糖与聚乙烯醇比例为1：3（W/W）时,凝胶具有较均匀的孔洞结构,平均孔径为10~50 μm,多孔凝胶的累积渗透量和皮肤滞留量均高于普通盐酸普萘洛尔凝胶。结论：所选处方工艺合理,制剂具有良好的透气性、经皮渗透性和皮肤粘着力,相较于普通凝胶,更适合婴幼儿患者使用。     

Propranolol inhibits angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell

Background: Oral propranolol (PRN) has recently been shown to be highly effective for infantile hemangiomas (IHs), and is currently recommended as the first-line treatment of complicated IHs. However, the therapeutic mechanism(s) still remain unclear. Methods: In this study, we tested hemangioma-derived stem cells for expression of vascular endothelial growth factor (VEGF) in vitro and studied the inhibition of VEGF expression. We used PCR, Elisa, Western blotting and immunohistochemistry in vivo and in vitro trial. Results: The study demonstrated that application of PRN at a “normal” concentration equivalent to plasma concentration did not inhibit proliferation or promote apoptosis of hemangioma derived stem cells (HemSCs) isolated from IH patients. PRN suppressed expression of vascular endothelial growth factor (VEGF) and basic Fibroblast Growth Factor (bFGF) in HemSCs in vitro. Morphological, histological and immunohistological improvement were observed in vivo using murine IH model in which HemSCs pre-treated with PRN were implanted into BALB/c-nu mice. In the pre-treated HemSC grafts, mean micro-vessel density (MVD) significantly decreased and protein levels of VEGF markedly decreased, while bFGF was still detectable. Conclusions: The results suggested PRN inhibited angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell. These findings provide critical insight into the potential mechanisms of PRN action on IH.     

心得安试验对功能性ST-T改变的临床价值

目的探讨口服心得安试验对功能性ST—T改变的临床价值。方法分析86例40岁以上伴有心悸、胸闷、气短症状,静息心电图有ST段水平或下斜型压低,T波低平的患者,通过口服心得安药物20mg,分别在30、60、90、120min描记心电图观察其变化。结果口服心得安20mg60min后描记心电图,86％女性S—T段恢复正常,呈阳性改变,与男性组相比有明显差异性（P〈0．05）;与男性不同年龄组相比,随年龄增加阳性率逐渐降低,无明显差异性（P〉0．05）。结论86％以上的女性ST—T改变是植物神经功能紊乱所致,为功能性改变,与器质性ST-T改变无相关性和必然联系,对冠心病诊断敏感性为92．3％．特异性为90．6％．阳性预测价值为88．9％．     

小剂量心得安加川芎嗪预防食管静脉曲张破裂出血的实验与临床研究

目的探讨小剂量心得安与川芎嗪联用预防肝硬变食管静脉曲张破裂出血(EVB)复发的疗效、副反应及其作用机制.方法在用药前后采用血管插管法对8只肝硬变犬血流动力学指标进行检测.在临床上对治疗组(n=38,po心得安10 mg+川芎嗪50 mg,3次/d)和安慰剂组(n=36,服维生素B110 mg+维生素PP 50 mg,3次/d)进行前瞻性对照研究,随访2 a,并用彩色多普勒超声仪监测其门脉系统血流动力学变化.结果小剂量心得安与川芎嗪联用可使肝硬变犬WHVP,HVPG,Rpv及Ppv明显降低,对HR,MAP无明显影响.用药4 wk后治疗组患者Qpv,Qsv,Dpv,Dsv及Qaz均显著下降(分别为1439±494 vs1152±387,948±436 vs 529±362,1.43±0.25vs1.36±0.28,1.20±0.24vs0.85±0.16,0.94±1.18vs0.71±1.04,P＜0.05/0.01);随访2 a,安慰剂组再出血率和死亡率均显著高于治疗组(P＜0.05);临床上未见明显副作用.结论小剂量心得安与川芎嗪联用预防EVB复发是安全有效的.     

口服普萘洛尔联合聚桂醇局部注射治疗婴幼儿血管瘤的疗效评价

目的：评价普萘洛尔联合局部注射聚桂醇治疗婴幼儿血管瘤的临床疗效。 方法：收集2014-2018年我科就诊的婴幼儿血管瘤患者,分为口服普萘洛尔组和口服普萘洛尔联合聚桂醇局部注射治疗组,随访观察12个月。结果：共治疗婴幼儿血管瘤患者43例,其中口服普萘洛尔组21例,口服普萘洛尔联合聚桂醇局部注射治疗组22例。全部患儿随访观察12个月,瘤体均有不同程度缩小、颜色变浅。口服普萘洛尔组治疗时间(148±32)天,治愈率为61.9%;联合治疗组治疗时间为(62±24)天,治愈率为95.45%,两者间差异均有统计学意义（Ps＜0.05）。43例患儿中有4例在服口服普萘洛尔1小时后出现心率减慢,经观察3 h后自行恢复正常,35例患儿血糖轻微降低,降低幅度≤0.2 mmol/L,未给予特殊处理。22例联合聚桂醇局部注射治疗患儿,7例注射局部有少量渗血。结论：口服普萘洛尔联合局部注射聚桂醇治疗婴幼儿血管瘤较单用普萘洛尔治疗疗程缩短,临床疗效更佳。     

普萘洛尔对肾上腺素促大鼠动脉粥样硬化斑块进展的保护作用及其机制的研究

目的:探讨普萘洛尔对肾上腺素促大鼠动脉粥样硬化斑块进展的预防作用及其机制。方法:50只Wistar雄性大鼠经高脂喂养17周,制成动脉粥样硬化模型。随机分为对照组、肾上腺素组、普萘洛尔小剂量组、普萘洛尔中剂量组、普萘洛尔大剂量组,每组10只。所有大鼠在继续高脂喂养基础上,对照组皮下注射生理盐水0.5ml/d;肾上腺素组予肾上腺素0.5mg.kg-1.d-1皮下注射;普萘洛尔小、中、大剂量组分别予普萘洛尔2.5mg.kg-1.d-1、5mg.kg-1.d-1、7.5mg.kg-1.d-1灌胃,0.5h后皮下注射肾上腺素0.5mg.kg-1.d-1。分组处理1周,处死全部大鼠,取主动脉粥样斑块用免疫组织化学方法检测巨噬细胞(CD68)浸润及MMP-9表达。结果:肾上腺素组,CD68阳性细胞浸润及MMP-9的表达显著高于对照组;普萘洛尔小、中、大剂量组,CD68阳性细胞浸润程度及MMP-9的表达较肾上腺素组显著减少,且减少程度与普萘洛尔剂量呈正相关。结论:普萘洛尔可以减轻肾上腺素刺激后大鼠动脉粥样硬化斑块内巨噬细胞的浸润及其MMP-9表达,有延缓肾上腺素促大鼠动脉粥样硬化斑块进展的作用。     

"阶梯治疗方案"口服普萘洛尔治疗婴幼儿混合型和深层血管瘤的疗效评价

目的：采用"阶梯治疗方案"口服普萘洛尔治疗婴幼儿混合型和深层血管瘤,探讨其疗效及安全性。方法：治疗前对98例婴幼儿混合型和深层血管瘤患儿进行全面评估,并行心电图、心脏彩超、血糖、肝功能、肾功能、心肌酶和血常规检查,排除禁忌证后均给予"阶梯治疗方案"口服普萘洛尔治疗,剂量从0.5mg·kg^-1·d^-1逐渐增加至4.0 mg·kg^-1·d^-1,分3次口服,服药前和服药后1和2h监测心率,动态观察瘤体大小、质地、颜色等变化及患儿有无相关不良反应,每个月复诊,按4级评分法进行疗效评价。结果：服药后,98例患儿瘤体均出现不同程度颜色变浅或质地变软,普茶洛尔剂量增至4.0 mg·kg^-1·d^-1后瘤体性质变化最快。疗效评价,Ⅳ级（优）84例（85.71%）,Ⅲ级（好）2例（2.04%）,Ⅱ级（中）4例（4.08%）,Ⅰ级（差）8例（8.16%）。混合型血管瘤的疗效优于深层血管瘤（P<0.05）。74例血管瘤患儿痊愈时间为6个月。主要不良反应,心率下降5例（5/98,5.10%）,嗜睡3例（3/98,3.06%）,腹泻7例（7/98,7.14%）,食欲不振1例（1/98,1.02%）,抽搐2例（2/98,2.04%）,给予对症处理后均恢复正常。停药后2个月复发4例,继续服药仍然有效。结论："阶梯治疗方案"口服普萘洛尔治疗婴幼儿混合型和深层血管瘤疗效明显,且无严重不良反应发生。     

羧甲基-β-环糊精取代度对毛细管电泳手性拆分普罗帕酮和普萘洛尔对映体的影响

目的：研究羧甲基-β-环糊精取代度对毛细管电泳手性拆分普罗帕酮和普萘洛尔对映体的影响。方法：在氢氧化钠溶液中β-环糊精被氯乙酸直接羧甲基化,很方便地合成了不同取代度的羧甲基-β-环糊,并应用红外光谱和核磁共振对它们的平均取代度和取代位置进行表征,以不同取代度的羧甲基-β-环糊精为手性选择剂,系统考察运行缓冲液的浓度和pH值、手性选择剂浓度、石英毛细管温度和运行电压等因素对毛细管电泳手性拆分的影响。结果：随着羧甲基-β-环糊精取代度的增大,普罗帕酮和普萘洛尔对映体的分离随之改善;在优化条件下,两个消旋化合物都获得很好的拆分。结论：羧甲基-β-环糊精的取代度对毛细管电泳手性拆分和运行缓冲液的离子强度有重要影响,因此在手性分离中使用表征清晰的环糊精衍生物是非常重要的。     

可乐定和普萘洛尔对实验性肾性高血压糖尿病性心肌病的影响

可乐定和普萘洛尔治疗肾性高血压糖尿病性心肌病大鼠的心肌组织学改变,表明可乐定和普萘洛尔均使大鼠血压下降,体重恢复,心肌灶性坏死和纤维化减少。普萘洛尔组血管周围纤维化好转比可乐定组明显,可乐定组心肌纤维化改善较普萘洛尔组明显。其机制可能与抗交感紧张和减少儿茶酚胺对心肌损伤有关。     

Hypertrophic cardiomyopathy in childhood and adolescence – strategies to prevent sudden death

Clinically overt hypertrophic cardiomyopathy is the most common cause of sudden unexpected death in childhood and has significantly higher sudden death mortality in the 8‐ to 16‐year age range than in the 17‐ to 30‐year age range. A combination of electrocardiographic risk factors (a limb‐lead ECG voltage sum >10 mV) and/or a septal wall thickness >190% of upper limit of normal for age (z‐score > 3.72) defines a paediatric high‐risk patient with great sensitivity. Syncope, blunted blood pressure response to exercise, non‐sustained ventricular tachycardia and a malignant family history are additional risk factors. Of the medical treatments used, only beta‐blocker therapy with lipophilic beta‐blockers (i.e. propranolol, metoprolol or bisoprolol) have been shown to significantly reduce risk of sudden death, with doses ≥6 mg/kg BW in propranolol equivalents giving around a tenfold reduction in risk. Disopyramide therapy is a very useful adjunct to beta‐blockers to improve prognosis in those patients that have dynamic outflow obstruction in spite of large doses of beta‐blocker, and its use in patients with hypertrophic cardiomyopathy is not associated with significant pro‐arrhythmia mortality. Calcium‐channel blockers increase the risk of heart failure‐associated death in hypertrophic cardiomyopathy (HCM) patients with severe generalized hypertrophy and should be avoided in such patients. Amiodarone does not protect against sudden death, and long‐term use in children usually has to be terminated because of side effects. Therapy with internal cardioverter defibrillator implantation has high paediatric morbidity, 27% incidence of inappropriate shocks, and does not absolutely protect against mortality but is indicated as secondary prevention or in very high‐risk patients.