Pulmonary valve stenosis associated with hypertrophic cardiomyopathy

Summary The association of pulmonic stenosis with hypertrophic cardiomyopathy is rare in infancy. Presented here is an infant with atypical picture of pulmonic stenosis and echocardiographic evidence of hypertrophic cardiomyopathy. At eight months of age, she had a successful percutaneous balloon valvuloplasty and has subsequently been managed with propranolol.     

雌二醇对大鼠离体胃平滑肌收缩活动的影响

目的 观察雌二醇对大鼠离体胃平滑肌收缩活动的影响，并探讨其可能的作用机制。方法 取大鼠离体平滑肌条，将其置于灌流肌槽中，经张力换能器将信号输入生理记录仪，记录股条的等长收缩活动。结果 雌二醇显著地降低胃底纵行肌及胃体纵行肌和环行肌张力，减少胃体、胃窦纵行肌和环行肌收缩波平均振幅及幽门环行肌运动指数，其作用不被六烃季胺、消炎痛、心得安、酚妥拉明及L-NNA所阻断。结论 雌二醇可抑制大鼠离体胃平滑肌收缩活动，可能是直接作用于胃平滑肌细胞或通过其他受体起作用。     

普萘洛尔联合硝酸异山梨酯预防食管胃底曲张静脉再出血疗效观察

目的探讨普萘洛尔和硝酸异山梨酯联合治疗预防肝硬化食管胃底曲张静脉再出血的有效性。方法122例肝硬化食管胃底曲张静脉出血的患者被随机分成三组,一组为普萘洛尔+硝酸异山梨酯;一组为普萘洛尔;一组为对照组,观察其疗效。结果普萘洛尔+硝酸异山梨酯组12个月、18个月、24个月再出血率分别为7%、12%、28%;普萘洛尔组分别为22%、37%、49%;对照组分别为46%、58%、79%,三组间差异有统计学意义(P<0.05)。结论普萘洛尔联合硝酸异山梨酯能明显降低肝硬化门脉高压患者的再出血率。     

Reducing liver metastases of colon cancer in the context of extensive and minor surgeries through β-adrenoceptors blockade and COX2 inhibition

Liver metastases are a major cause of colorectal cancer death, and the perioperative period is believed to critically affect the metastatic process. Here we tested whether blocking excess release of catecholamines and prostaglandins during surgical procedures of different extent can reduce experimental liver metastasis of the syngeneic CT26 colon cancer in female and male BALB/c mice. Animals were either treated with the beta-blocker, propranolol, the COX-2 inhibitor, etodolac, both drugs, or vehicle. The role of NK cells in controlling CT26 hepatic metastasis and in mediating the effect of the drugs was assessed by in vivo depletion or stimulation of NK cells, using anti-asialo GM1 or CpG-C, respectively. Surgical extent was manipulated by adding laparotomy to small incision, extending surgical duration, and enabling hypothermia. The results indicated that combined administration of propranolol and etodolac, but neither drug alone, significantly improved host resistance to metastasis. These beneficial effects occurred in both minor and extensive surgeries, in both sexes, and in two tumor inoculation approaches. NK cell-mediated anti-CT26 activity is involved in mediating the beneficial effects of the drugs. Specifically, CpG-C treatment, known to profoundly activate mice marginating-hepatic NK cytotoxicity, reduced CT26 hepatic metastases; and NK-depletion increased metastases and prevented the beneficial effects of the drugs. Overall, given prevalent perioperative psychological and physiological stress responses in patients, and ample prostaglandin release by colorectal tumors and injured tissue, propranolol and etodolac could be tested clinically in laparoscopic and open colorectal surgeries, attempting to reduce patients’ metastatic disease.     

The Role of the Beta-Adrenergic Receptor in the Secretion of Gastrin: Studies in Normal Subjects and in Patients with Duodenal Ulcers

Intravenous infusion of isoproterenol, a beta-adrenergic receptor stimulatory agent, increased serum gastrin concentration significantly more in patients with a duodenal ulcer than in healthy subjects. The rise in pulse rate, blood glucose concentration and in serum insulin was the same in both groups of subjects. Gastrin secretion was also increased significantly more in the patients than in the control subjects after a beef-meal. Basal serum gastrin concentrations were higher in the patients than in the control subjects and correlated to the rise in serum gastrin during both tests in the patients with a duodenal ulcer. Isoproterenol and meal stimulated gastrin secretion, expressed as percent of the basal value, were twice as high in the patients as in the control subjects. The combined administration of isoproterenol and the meal had an additive effect on the rise in serum gastrin. Isoproterenol stimulated gastrin secretion was completely suppressed by propranolol, a beta-adrenergic receptor blocking agent, which had no effect on meal stimulated gastrin secretion. It is concluded that the mechanism of the hypersecretion of gastrin in patients with a duodenal ulcer did not involve a specific abnormality of the beta-adrenergic receptor or the receptor which recognized proteins and their digested products. There is no established role of beta-adrenergic receptor activity in the hypersecretion of gastrin in patients with duodenal ulcers. It is suggested that the beta-adrenergic receptor may have some yet unknown function unrelated to the acute secretory response of gastrin.     

普萘洛尔在甲状腺功能亢进症孕产妇中的应用

甲状腺功能亢进症(甲亢)和妊娠同时存在的病例临床并不少见,这类孕妇的药物治疗中,普萘洛尔的适应证和禁忌证大多教科书常常没有提及,因此值得讨论.少数文献报道该药可增加自然流产几率,并可致胎儿宫内发育迟缓、心动过缓、出生后呼吸窘迫等异常.相关动物试验显示,普萘洛尔可减缓心率,且对胎肺β受体的阻滞可能导致胎儿出生后呼吸窘迫.大部分学者认为,在常规剂量下,该药没有临床致畸性,应用于妊娠期是相对安全的.也有专家认为,普萘洛尔应尽量短期使用以减少其可能的副作用,如在抗甲状腺药物起效之前的数周以及甲状腺危象时应用.胎儿在出生以后因药物在体内重新分布导致血浆药物浓度升高,建议产前减少药物用量.而在哺乳期,婴儿经乳汁摄取的药物极少,治疗剂量的产妇哺乳是安全的.另外,普萘洛尔还可安全地用于保守治疗难以控制的妊娠剧吐.     

去甲肾上腺素对胶质母细胞瘤侵袭迁移能力的影响及机制研究

目的   研究应激激素去甲肾上腺素(NE)对胶质母细胞瘤侵袭迁移能力的影响及机制,并探讨β受体阻断剂普萘洛尔(propranolol)抗应激所致肿瘤侵袭转移的可行性。方法   培养胶质母细胞瘤细胞系T98G、U251及U87,采用RT-PCR检测胶质瘤细胞系β肾上腺素能受体表达,Transwell评价NE对胶质瘤细胞侵袭迁移的影响,明胶酶谱法检测NE对胶质瘤细胞系MMP 2分泌水平影响。结果   随NE浓度增加(0.1~10μmol/L),胶质瘤细胞侵袭力逐渐增强(P>0.05),普萘洛尔(1nmol/L)可抑制此效应;随NE浓度增加(0.1~10μmol/L),胶质瘤细胞基质金属蛋白酶 2(MMP-2)分泌显著增多,普萘洛尔(1nmol/L)可抑制NE诱导的MMP 2分泌。结论   应激激素去甲肾上腺素可以促进胶质母细胞瘤MMP-2分泌酶活性从而增强其迁移能力,普萘洛尔可以抑制NE诱导的胶质瘤侵袭增强。     

小剂量普萘洛尔口服治疗婴儿血管瘤的近期疗效与安全性评价

目的 评价小剂量普萘洛尔口服治疗婴儿血管瘤的近期疗效与安全性.方法 2008年10月至2009年5月,共58例血管瘤患儿在山东省临沂市肿瘤医院和上海交通大学医学院附属第九人民医院接受并完成普萘洛尔治疗.男19例,女39例;年龄1～12个月,平均4个月;血管瘤大小为1.5 cm×1.0 cm～18.0 cm×5.0 cm,浅表血管瘤27例,深部血管瘤9例,混合型血管瘤22例;病变位于头颈部41例,四肢和躯干12例,阴唇2例,肛周、会阴、阴囊各1例.普萘洛尔1.0～1.5 mg/kg,每天1次顿服,连续服用.住院治疗7～10 d后,出院连续服药,每2周复诊,动态观察和记录血管瘤大小、质地、颜色变化,观察并随时处理治疗过程中出现的不良反应.按4级评分法对近期疗效进行评价.结果 服药后24 h,所有患儿瘤体张力均有不同程度减小,颜色开始变淡,体积开始缩小,5～7 d内变化最显著.服药2个月者7例,3个月者22例,4个月者21例,5个月者8例.随访5～9个月,疗效评定为Ⅳ级(优)者10例(17.2%),Ⅲ级(好)35例(60.4%),Ⅱ级(中)12例(20.7%),Ⅰ级(差)1例(1.7%).深部血管瘤的疗效显著优于浅表型血管瘤(P<0.05),但不同部位血管瘤之间疗效差异无统计学意义(P>0.05).主要不良反应为心率减慢(100%),腹泻(37例,63.8%)和睡眠改变(21例,30.2%),均未造成严重影响,经对症处理,全部恢复正常.结论 普萘洛尔小剂量口服治疗婴儿血管瘤近期疗效良好,不良反应轻微,可作为婴儿血管瘤的一线治疗药物.     

Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task

Rationale Atypical antipsychotics improve cognitive function, including working memory, in schizophrenia. Some atypical antipsychotics have been reported to activate the locus coeruleus and induce beta-adrenoceptor antagonist sensitive c-Fos-like immunoreactivity in the prefrontal cortex. Materials and methods The present study investigated the effects of chronic treatment of rats with risperidone (1 mg kg⁻¹ day⁻¹ s.c.), clozapine (10 mg kg⁻¹ day⁻¹ s.c.), or acidified saline vehicle control for 2, 4, or 8 weeks on spatial working memory performance in a delayed matching-to-place water maze task with a 60-s inter-trial retention interval with and without acute challenge with propranolol (10 mg/kg i.p.). Results Treatment with risperidone for 8 weeks, but not 2 or 4 weeks, significantly improved working memory performance. In contrast, treatment with clozapine for up to 8 weeks did not improve working memory. Acute challenge with propranolol blocked the improvement in working memory produced by chronic treatment with risperidone, but had no significant effect on performance in saline- or clozapine-treated animals. Conclusions The delayed matching-to-place water maze task may prove valuable in the investigation of the behavioural pharmacology of the cognitive effects of antipsychotic drugs. These data suggest that beta adrenoceptors may contribute to the cognitive effects of chronic treatment with atypical antipsychotics.