Indacrinone (MK-196) - a specific inhibitor of the voltage-dependent CI- permeability in toad skin

The effect of indacrinone (MK-196) on Cl^- transport through toad (Bufo bufo) skin epithelium was studied by the voltage clamping technique. At the transepithelial potential, V = 50 mV (serosal bath grounded) the unidirectional fluxes, governed by a Cl^- self-exchange diffusion pathway, were not affected by 1 mM racemic MK-196 in the outer bath. Likewise at V = 0 mV, the unidirectional fluxes as well as the active (net) inward flux of Cl^- were unaffected by MK-196. Voltage clamping the epithelium in the physiological range of potentials activated a Cl^- specific passive conductance that saturated for V ±– 90 mV. The influx and efflux of Cl^- through this pathway were inhibited by MK-196, and the (passive) Cl^- current was inhibited in a dose-dependent way for [MK-196] ± 50 μM with about 70% inhibition for [MK-196] = I mM. The maximum Cl^- conductance was decreased without shifting the position along the V-axis of the inverted S-shaped conductance–voltage relationship. The time constants for the voltage-stimulated Cl^- conductance activation were not affected by MK-196 (50 μM ± [MK-196] ± 1 mM). The (+) and (–) isomers and racemic MK-196 affected the voltage-dependent Cl^- conductance in similar ways. It is concluded that MK-196 has the properties of a Cl^- channel blocker which is specific for the voltage-dependent Cl^- permeability of the epithelium. The time course for development of inhibition exhibited a fast (min) and a slow (h) component. The fast component may reflect a direct interaction of MK-196 with an extracellular site of the Cl^- channel, whereas the slow one may reflect impairment of a metabolic pathway regulating the Cl^- permeability, or an interaction of MK-196 with a cytoplasmic site of the anion permeation pathway.     

A system of electronic records developed by a children's hospice

This paper describes the development, implementation and dissemination of an electronic data collection system for children's hospices in the UK. In 1999, CHASE Hospice Care for Children (CHASE) began providing support for life-limited children and their families in their own homes across south-west London, Surrey and West Sussex. CHASE community team is multidisciplinary and original members of the team had to create all of the necessary administrative systems for collecting and storing information about referrals and care provided to children and their families. The community team had the foresight to record activity statistics from day one of the service. The team worked together to identify information routinely collected that could usefully be stored on a computer database and a simple solution was created for this purpose using Microsoft Access version 2. CHASE was in a privileged position because the commitment to use information technology came from people providing care to children and their families.     

A comparison between naturally occurring macroamylasaemia and macroamylasaemia induced by hydroxyethyl-starch

Macroamylasaemia was produced in vitro by incubation of hydroxyethylstarch with serum, and in vivo by intravenous infusion of hydroxyethylstarch. Gel filtration on Sephadex G-100 revealed distinct differences in molecular size distribution between such hydroxyethylstarch-induced macroamylase and the usual form of naturally occurring macroamylase which was observed in a few patients from our hospital. Further studies demonstrated that the gel filtration elution pattern of amylase activity in serum containing hydroxyethylstarch-induced macroamylase is significantly altered with time in vitro and in vivo, probably because of an enzymatic degradation of the hydroxyethylstarch components of the macromolecular complexes. In a healthy volunteer the serum amylase activity was elevated to a maximum of 797 u/l and the renal clearance rate of amylase was diminished to a minimum of 0.3 ml/min after infusion of 500 ml of a 6% solution of hydroxyethylstarch, as compared to 300 u/l, and 0.95 ml/min, respectively, during the pre-infusion period.     

Familial hemiplegic migraine: a clinical comparison of families linked and unlinked to chromosome 19

We compared the clinical characteristics of 50 patients from three unrelated families with familial hemiplegic migraine (FHM) linked to chromosome 19, with those of 20 patients from two families with FHM not linked to chromosome 19. We found no significant differences for age at onset, frequency and duration of attacks, duration of the paresis, and occurrence of basilar migraine symptoms. In the linked families, significantly more patients reported unconsciousness during attacks (39%, vs 15%; p<0.05) and provocation of attacks by mild head trauma (70% vs 40%; p< 0.05). In one linked family patients also displayed chronic progressive cerebellar ataxia, whereas in one unlinked family benign infantile convulsions occurred in addition to FHM. Interestingly, so far an association with cerebellar ataxia was only described in chromosome 19-linked families. FHM linked to chromosome 19 and FHM unlinked to chromosome 19 do not differ with respect to clinical features.     

Inhibition and subsequent enhancement of platelet responsiveness by prostacyclin in the rabbit. Relationship to platelet adenosine 3'',5''-cyclic monophosphate.

Methods were developed for measuring changes in platelet sensitivity to a release-inducing stimulus and in platelet cyclic AMP in fresh whole blood samples from rabbits. These techniques permitted detection of the effects of exogenous and endogenous prostacyclin on circulating platelets. In these methods, rabbit platelets were labeled in vitro by incubation with [14C]serotonin and [3H]adenine and then transfused into other rabbits. Release of platelet [14C]serotonin by a standard dose of synthetic platelet-activating factor (40 pmol/ml) and the platelet cyclic [3H]AMP levels were then measured in citrated blood from the conscious animals within 2 min of arterial puncture. Bolus intravenous injections of prostacyclin (1-10 nmol/kg) caused concentration-dependent increases in platelet cyclic AMP after 2 min, which decreased approximately 75% by 5 min, and disappeared after 30 min. Significant inhibition of the platelet release reaction was detected 2 min but not 5 min after injection of 10 nmol of prostacyclin per kilogram. With lower doses, significant enhancement of the release of [14C]serotonin was observed after 5 min. Similar changes in platelet responsiveness and cyclic [3H]AMP were observed after release of endogenous prostacyclin by intravenous injection of angiotensin II (5 nmol/kg); inhibition of the release of [14C]serotonin after 2 min was followed by potentiation after 5 min, though platelet cyclic [3H]AMP remained above control values. In these experiments, the time course of the changes in platelet cyclic [3H]AMP correlated closely with values for blood prostacyclin obtained previously (Haslam, R.J., and M.D. McClenaghan, 1981, Nature [Lond.]., 292:364-366). Prostacyclin also had a biphasic effect on the release of [14C]serotonin when added to citrated blood in vitro, though both the increase in sensitivity to platelet-activating factor and the return of platelet cyclic [3H]AMP towards control values took place more slowly. At all times, addition of platelet-activating factor decreased platelet cyclic [3H]AMP towards but not below the control level observed in the absence of prostacyclin. Our results indicate that although transient increases in platelet cyclic AMP cause an immediate decrease in platelet responsiveness in vivo or in vitro, a period of enhanced platelet sensitivity follows as platelet cyclic AMP falls.     

中国城市地区0~5岁儿童养育实践相关因素分析

目的 了解我国城市地区0~5岁儿童养育实践情况及其影响因素,为促进我国儿童早期发展、开展父母积极养育指导和服务提供依据。方法 2017年8-12月在我国14省15个城市4 515名0~5岁的儿童家长中进行自填式问卷调查,采用父母养育与家庭适应量表（PAFAS）评价父母对儿童的养育实践情况,包括养育一致性、强迫性、鼓励性和亲子关系以及父母的情绪适应、家庭关系和相互协助等多个维度,通过单因素分析和多重线性回归探索儿童个体、父母和家庭因素对父母养育实践的影响。结果 我国城市地区0~5岁儿童的父母在PAFAS量表中的总得分为21.00（15.00~28.00）分,该得分的变化与儿童年龄、独生子女、分娩方式、父亲文化程度、家长育儿信心、家长情绪、家庭年收入、家庭结构以及寻求专业支持等因素有关,提示我国儿童养育实践情况存在较大差异并受多种因素影响。结论 我国城市地区0~5岁儿童养育实践整体情况良好,养育实践与儿童个体、父母和家庭环境等多种因素有关,关注多重因素的影响有利于提高父母养育技能的培训效果,更好地促进儿童早期发展。