显微超声监测普萘洛尔治疗婴幼儿血管瘤的病情演变

目的：应用显微超声监测腮腺区婴幼儿血管瘤患儿,在口服普萘洛尔前后病灶的变化情况。方法保存患儿普萘洛尔治疗前后的临床资料及超声图像并建立数据库,超声评价指标包括病灶深度、血管密度、血管阻力指数等,应用t检验分析治疗前后病灶变化情况。结果口服普萘洛尔后,血管瘤病灶深度、血管密度明显下降,血流阻力指数明显上升。结论普萘洛尔能够有效治疗婴幼儿血管瘤,显微超声能够有效监测服药后血管瘤病灶变化情况。     

Development and validation of an in vitro–in vivo correlation (IVIVC) model for propranolol hydrochloride extended-release matrix formulations

The objective of this study was to develop an in vitro–in vivo correlation (IVIVC) model for hydrophilic matrix extended-release (ER) propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8). In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR) commercial products. The similarity factor f₂ was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE) values of C_max and AUC_0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for C_max and AUC_0–∞ demonstrated that the propranolol IVIVC model was valid.     

普萘洛尔治疗婴幼儿肝脏血管瘤疗效初探

目的：观察口服普萘洛尔治疗婴幼儿肝脏血管瘤的疗效。方法：17例年龄15 d-11个月的多发性血管瘤患儿经彩色B超、CT、MRI检测诊断为肝脏血管瘤,其中女14例,男3例。所有患儿予以口服普萘洛尔治疗,每日维持剂量2 mg/kg,至少维持6个月,定期复诊,随访观察疗效。结果：17例患儿用药6个月后肝脏血管瘤均明显好转,B超提示结节较治疗前明显缩小,直径由2-44 mm缩小至0-20 mm,其中8例患儿皮肤血管瘤较治疗前明显缩小,颜色变浅。所有患儿用药过程中心电图、血压、血生化等检查均未出现明显异常,停药后病情均未出现反复。结论：普萘洛尔治疗婴幼儿肝脏血管瘤疗效确切且不良反应小,可作为一线治疗药物。     

Evaluation of the use of UPLC-TOFMS with simultaneous [14C]-radioflow detection for drug metabolite profiling: application to propranolol metabolites in rat urine

The non-selective beta-adrenergic receptor antagonist propranolol [1-(isopropylamino)-3-(1-naphthoxy)-2-propanol] is metabolised extensively in vivo. Enumerating and identifying the many metabolites that result from multiple biotransformations provides a considerable analytical challenge, greatly aided by efficient chromatography coupled to sensitive mass spectrometric detection. Here the use of the newly introduced high-resolution technique of "ultra performance liquid chromatography" (UPLC) linked to quadrupole time-of-flight mass spectrometry (TOFMS) with simultaneous [(14)C]-radioflow detection was applied to rapid metabolite profiling. [(14)C]-propranolol, dosed intraperitoneally to rat at 25mgkg(-1) and 200muCikg(-1) was used as a model compound for this evaluation. Some 14 metabolites were detected in the urine by this technique including a number of conjugated metabolites such as sulphates, several isobaric glucuronides and two novel di-glucuronides.     

L'azione del propranololo sulla glicemia e sull'insulina immunoreattiva in una paziente affetta da insulinoma

Riassunto Con la somministrazione orale di propranololo ad una paziente affetta da insulinoma si è notato un miglioramento delle condizioni cliniche e una minor frequenza delle crisi ipoglicemiche. I valori di glicemia e di IRI si sono portati nella norma. Vengono riportati e brevemente discussi i risultati delle prove del digiuno, del glucagone e della leucina praticate prima e durante la somministrazione del propranololo.

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Summary Oral administration of propranolol to a patient with insulinoma resulted in normalization of blood glucose and immunoreactive insulin and improvement in the patient's condition. Blood glucose and IRI levels returned normal. The results of fasting, glucagon and leucine tests performed before and during administration of propranolol are reported and briefly discussed.

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Zusammenfassung Nach der oralen Verabreichung von Propranolol in einer Patientin mit Insulinom wurde eine Besserung der klinischen Daten sowie eine verminderte Haeufigkeit der hypoglykaemischen Krisen festgestellt. Die Werte des Blutzuckers sowie der IRI kehrten zur Norm zurueck. Es werden die Resultate der Proben des Fastens, des Glukagons sowie des Leuzins vor und waehrend der Verabreichung von Propranolol mitgeteilt und kurz diskutiert.

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Resumen Suministrando por vía oral propranololo a una paciente enferma de insulinoma, se ha notado mejoría de las condiciones clínicas y menor frecuencia de las crisis hipoglucémicas. Los valores de glucemia y de IRI volvieron a su normalidad. Se reportan, y se discuten brevemente, los resultados de las pruebas del ayuno, del glucagón y de la leucina, efectuadas antes y durante la suministración de propranololo.

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Resume Avec l'administration par voie orale de propranolole à une femme affecte de insulinome, les AA. ont observé une admélioration des conditions cliniques et une mineure fréquence des crises hipoglycémiques. Le taux de glycémie et de l'IRI sont redevenu normaux. On discute brièvement les résultats des épreuves du jeûne, du glucagone et de la léucine administrées avant et pendant le propranolole.

     

口服普萘洛尔治疗婴幼儿增殖期血管瘤:英国儿科皮肤病学会共识及临床指南

婴幼儿血管瘤(infantile hemangiomas, IH)是最常见的婴幼儿血管良性肿瘤。关于适应证、诊疗前检查、PHACES综合征的治疗、停药时间等,目前仍存在诸多分歧。本研究使用改进的德尔菲法(Delphi technique),包括国际性治疗方法调查,对已发表文献的系统评价、面对面多学科专家会谈以及匿名投票,就8大类条目共47项指南内容达成共识。本临床指南有助于标准化和简化口服普萘洛尔治疗婴幼儿血管瘤的过程,并且协助临床决策。     

Alpha adrenergic system in medial preoptic area involved in sleep-wakefulness in rats

The study is aimed at investigating the possible involvement of adrenergic mechanisms in the medial preoptic area (mPOA) for modulation of sleep-wakefulness in rats. In this study, saline, norepinephrine (NE), phenoxybenzamine (PBZ) and propranolol (PROP) were injected in the mPOA in different groups of male rats during the day and night. NE and PBZ were injected, during the day and the night respectively, in some control areas adjoining the mPOA in two other groups of animals. Arousal was produced by NE, and sleep by PBZ when they were applied in the mPOA. All other procedures, including application of NE and PBZ in the control areas and beta blocker (PROP) in the mPOA, did not produce alterations in sleep-wakefulness. These findings provide support for a physiological role played by the alpha adrenergic system in the mPOA for arousal, and area specificity of action of this system.     

L-5-hydroxytryptophan-induced drinking in rats: Possible mechanisms for induction

Administration of L-5-hydroxytryptophan (25 mg/kg body weight, SC) to female rats resulted in copious drinking. The dipsogenic response to administration of L-5-hydroxytryptophan (5-HTP) was blocked by propranolol (6 mg/kg body weight, IP), a β-adrenergic antagonist, and captopril (35 mg/kg body weight, IP), an angiotensin converting enzyme inhibitor. In addition, clonidine (12.5 and 25 μg/kg body weight, IP), a central α-adrenergic agonist known to inhibit renin release, attenuated drinking during 1, 2 and 3 hours after 5-HTP was administered. These results suggest that 5-HTP-induced drinking is mediated by way of the renin-angiotensin system. Haloperidol (150 μg/kg body weight, IP), a dopaminergic antagonist, also attenuated the dipsogenic response to administration of 5-HTP. In addition, incremental reductions in 5-HTP-induced drinking with increasing doses of spiperone (37.5 to 150 μg/kg body weight, IP), a more potent dopaminergic antagonist, were demonstrated. Thus, the dipsogenic response to administration of 5-HTP to rats is dependent on both the renin-angiotensin system and an intact dopaminergic pathway.     

回顾性分析口服普萘洛尔治疗婴幼儿血管瘤的疗效和安全性

目的 探讨分析普萘洛尔应用于婴幼儿血管瘤的治疗效果和安全性.方法 回顾性分析2014年1月至2015年12月广东省妇幼保健院血管瘤住院患儿,共计收治73例血管瘤患儿,按1.0 ～ 2.0 mg/kg,每天3次口服,住院治疗3～14d后,出院继续服药.每天定时观察和记录血管瘤质地、大小、颜色等变化,随时观察记录不良反应,并对其作及时处理.按Achauer 4级评分法对口服普萘洛尔的疗效进行评价.结果 服药24 h后,所有患儿瘤体颜色开始变浅,体积开始变小,张力均有所降低,在5～7d内变化最显著,不良反应轻微.随访1～ 10个月,疗效评定为:Ⅰ级1例,Ⅱ级6例,Ⅲ级31例,Ⅳ级35例.总有效率为90.4％.不良反应主要表现为心血管方面的改变:心率减慢;同时还伴有腹泻、睡眠改变等,但均未造成严重后果,经及时处理,均恢复正常.结论 口服普萘洛尔应用于婴幼儿血管瘤的治疗,用药安全,疗效明显,有望成为一线的治疗药物.