The β‐adrenoceptor blocker propranolol ameliorates compulsive‐like gambling behaviour in a rodent slot machine task: implications for iatrogenic gambling disorder

Previous work has shown that chronic administration of the dopamine D_2/3 receptor agonist ropinirole invigorates performance on a rodent slot machine task (rSMT). This behavioural change appears superficially similar to the iatrogenic gambling disorder (GD) observed in a sub‐set of patients with Parkinson's disease (PD), and has been associated with increased activation of the intra‐cellular signalling proteins GSK3β and CREB in the striatum. Here, we wanted to determine whether this response to ropinirole could be attenuated by targeting these signalling proteins, and if the loss of dopaminergic innervation characteristic of PD would alter ropinirole's effects on the rSMT. Male Long Evans rats were trained on the rSMT. Dopaminergic terminals innervating the dorsolateral striatum were then lesioned bilaterally using the neurotoxin 6‐hydroxydopamine hydrochloride (6‐OHDA). Subsequently animals were implanted with osmotic mini‐pumps delivering ropinirole. Lastly, animals were given dietary lithium (Li⁺), to inhibit the activation of GSK3β, or injections of the ß‐adrenoceptor antagonist propranolol, which potently inhibits CREB as a secondary mechanism of action, and any changes in ropinirole‐induced increases in compulsive‐like engagement in the rSMT evaluated. Chronic ropinirole increased the number of trials animals completed, reproducing our original finding. This increase in task engagement was not altered in animals with 6‐OHDA lesions, a putative model of early PD. In addition, the effects of ropinirole were not attenuated by administration of Li⁺, but were ameliorated by propranolol. These data suggest that propranolol may represent a potential pharmacotherapy for the treatment of iatrogenic gambling.     

β-blocker therapy for infantile hemangioma

ABSTRACT

Introduction

Fifteen percent of proliferating infantile hemangioma (IH) require intervention because of the threat to function or life, ulceration, or tissue distortion. Propranolol is the mainstay treatment for problematic proliferating IH. Other β-blockers and angiotensin-converting enzyme (ACE) inhibitors have been explored as alternative treatments.     

不同治疗方法在偏头痛治疗中的疗效研究

目的观察托吡酯和普奈洛尔在偏头痛治疗中的临床效果。方法选取医院收治的80例偏头痛患者;将40例采用普萘洛尔进行治疗的患者作为对照组;将40例采用托吡酯联合普萘洛尔进行治疗的患者作为研究组;分析研究组与对照组患者治疗前后的脑血管血流速度以及两组患者治疗后脑电图与脑白质变性情况。结果治疗前,两组患者在各项脑血管血流速度中均没有明显差异(P>0.05);治疗后,研究组患者在椎动脉、基底动脉、大脑前动脉、大脑中动脉以及大脑后动脉血管血流速度中均显著优于对照组(P<0.05);且治疗后,两组患者在脑白质变性率中没有明显差异(P>0.05);研究组患者在α波频率变慢、δ波增多以及θ波增多中均显著高于对照组(P<0.05)。结论在针对偏头痛患者进行治疗的过程中,采用托吡酯联合普萘洛尔进行治疗能够有效提高患者的治疗效果,改善患者的脑血管病变情况。     

普萘洛尔联合其他治疗措施治疗婴幼儿血管瘤有效率的网状Meta分析

目的:采用网状Meta分析方法,将普萘洛尔联合其他治疗与各对照治疗措施进行对比。方法:以“普萘洛尔”,“血管瘤”为关键词检索CNKI、VIP、万方数据;以“propranolol”“hemangioma”为关键词检索Cochrane Library、Embase、pubmed。检索期限为建库至2019年6月1日。采用STATA14.0软件Network程序包进行数据分析。结果:共纳入18篇文献,涉及8项治疗措施,共纳入1469例血管瘤患者。网状Meta分析结果显示:4种联合治疗方式与单纯口服普萘洛尔相比疗效均优于单纯口服普萘洛尔治疗。普萘洛尔联合注射平阳霉素、普萘洛尔联合外用噻吗洛尔、普萘洛尔联合敷贴器的有效率均优于对应的注射平阳霉素、外用噻吗洛尔及敷贴器。各治疗措施的有效性排序为:普萘洛尔联合敷贴器>普萘洛尔联合外用噻吗洛尔>普萘洛尔联合口服糖皮质激素>普萘洛尔联合注射平阳霉素>敷贴器照射>外用噻吗洛尔>口服普萘洛尔>注射平阳霉素。结论:对于婴幼儿血管瘤的治疗,普萘洛尔联合治疗措施疗效均优于单纯的口服普萘洛尔治疗,其中普萘洛尔联合敷贴器的疗效最佳。     

Value of Doppler ultrasound scans in deciding whether to treat infantile haemangioma with oral propranolol

BackgroundOral propranolol (Pr) must be administered until the end of the proliferation phase of infantile haemangioma (IH). This phase may be difficult to assess, particularly where a deep component is involved. Doppler ultrasound scans (DUS), which identify vascular activity (VA), could assist the clinician in making the correct therapeutic decision (CTD).Patients and methodsAll children with IH treated with Pr for at least 3 months and up to the age of 9 months, and who also underwent DUS, were enrolled in this retrospective, single-centre, observational study. The quality of DUS as a binary diagnostic test for IH proliferation was assessed, together with its value in deciding whether to discontinue Pr (at the end of the presumed proliferation phase) or resume this drug (in the case of suspected recurrence).ResultsA total of 29 children were enrolled and 45 DUS were performed. Thirty-nine (87%) DUS were of high quality (80% sensitivity, 95% specificity) and made a major, moderate, or minimal contribution to the CTD in respectively 20%, 60% and 7% of cases.DiscussionDUS proved to be a high-value tool. They were essential in some cases of IH, mainly periocular and localised forms, and those involving deep components, in which the question of discontinuing Pr arose (age > 1 year) and where clinical examination had not been sufficient to make the CTD. Furthermore, in the vast majority of cases, they provide a helpful examination and complement clinical findings in terms of patient follow-up and reaching a CTD.ConclusionDUS is an effective and complementary tool to clinical investigation.     

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。     

An infant with localized vasoconstriction following topical propranolol exposure for infantile hemangioma

We describe a 3‐month‐old child with an infantile hemangioma on the forehead with a blanched macule provoked by topical treatment with propranolol. This observation demonstrates that topically applied (non‐selective) beta‐blockers may induce blanched macules at the site of application, a side effect due to peripheral vasoconstriction of blood vessels by non‐selective beta‐2 blockade. This side effect was linked due to overuse and was reversible. This case illustrates the importance of providing thorough instructions regarding topical propranolol application.     

口服普萘洛尔治疗婴幼儿血管瘤的效果观察

目的 观察普萘洛尔治疗婴幼儿血管瘤的临床疗效。 方法 回顾性分析在我院门诊收治的血管瘤婴儿300例,其中观察组150例口服普萘洛尔治疗,对照组150例口服泼尼松治疗。2组患儿定期门诊复诊,采用直观、手工测量、彩色多普勒超声或MRI等方法动态观察患者血管瘤范围、颜色变化、质地及不良反应。 结果 观察组与对照组相比,瘤体明显缩小,瘤体缩短消退时间明显缩短,差异有统计学意义（P＜0.001）。此外,观察组的治疗有效率（94.00%）显著高于对照组（82.67%）,且观察组服用普萘洛尔后发生的不良反应明显低于对照组（P＜0.01）。 结论 口服普萘洛尔治疗婴儿血管瘤疗效显著,且无明显不良反应。     

普萘洛尔治疗新疆地区婴幼儿血管瘤的临床疗效观察

目的:研究普萘洛尔治疗新疆地区婴幼儿血管瘤的临床疗效。方法:选择2012年3月~2014年3月于新疆医科大学第一附属医院颌面肿瘤外科接受口服普萘洛尔治疗的血管瘤患儿42例,年龄1~14个月,服药剂量:小于3个月的患儿口服剂量为0.5mg/kg/天;3~6个月的患儿口服剂量为1mg/kg/天;大于6个月的患儿口服剂量为2mg/kg/天。2次/日、饭后30min服药,两次给药间隔6~8h。连续服用1年,服药后1个月、3个月、6个月、9个月、12个月复诊,动态评估患儿瘤体大小、质地、颜色及不良反应,并对出现的不良反应积极处理。以Achauer疗效评定法及服药前后彩色多普勒B超检查结果进行临床疗效评估。结果:42例患儿服药观察12个月后,疗效I级(差)3例,II级(中)16例,III级(好)13例,IV级(优)10例;所有患者均无严重并发症;不同性别、民族、瘤体部位与血管瘤分型治疗效果之间无统计学差异(P0.05);42例患者治疗前PSV(46.47±26.87)与治疗后PSV(17.67±8.05)之间有统计学差异(P0.05);42例患者治疗前RI指数(0.54±0.12)与治疗后RI指数(0.82±0.15)之间有统计学差异(P0.05)。结论:口服普萘洛尔治疗婴幼儿血管瘤作用显著且不良反应轻。     

内镜干预联合普萘洛尔治疗食管胃底静脉曲张破裂出血的临床研究

目的评价内镜套扎术和(或)硬化剂注射结合组织胶黏合剂联合普萘洛尔治疗食管胃底静脉曲张破裂出血患者的疗效。方法2017年10月—2019年10月同济大学附属第十人民医院崇明分院收治的食管胃静脉曲张破裂出血(esophagogastric variceal bleeding, EVB)患者共120例,将患者随机分为研究组和对照组,每组60例。两组患者在治疗前的年龄、性别、体质量指数、病因、Child-Pugh评分、静脉曲张严重程度、血液学检查(血红蛋白、C-反应蛋白(C-reactive protein, CRP)、肝酶水平、凝血酶原时间(prothrombin time, PT)、电解质）和影像学检查(静脉曲张直径、门静脉宽度、脾静脉宽度、门静脉流速)等基线资料均一致。研究组给予内镜下套扎术和(或)硬化剂注射结合组织胶黏合剂联合普奈洛尔治疗,而对照组长期口服普奈洛尔,根据最大耐受量调整剂量,术后随访24个月。评价患者的死亡率、再出血率以及实验室指标。结果研究组与对照组死亡率差异无统计学意义(P>0.05);研究组输血量、止血时间和住院日与对照组相比明显减少,差异具有统计学意义(P<0.05);研究组的Child-Pugh评分、PT、血钠水平、炎症指标CRP、静脉曲张直径、门静脉和脾静脉宽度改善较为明显,差异具有统计学意义(P<0.05);血红蛋白、肝酶、血钾水平和门静脉流速在两组间无明显差异(P>0.05);术后18个月和24个月,研究组再出血发生率显著低于对照组,差异具有统计学意义(P<0.05);治疗前Child-Pugh评分、PT、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase, AST)、血钠水平、静脉曲径直径大小对预后具有重要意义,差异具有统计学意义(P<0.05);Chlid-Pugh评分、PT、血钠水平、静脉曲径直径大小可能是肝硬化静脉曲张预后不良的独立影响因素(OR>1,P<0.05)。结论内镜干预联合普萘洛尔治疗方案用于防治食管胃底静脉曲张再出血的效果确切,安全性较高,值得广泛推广。