The negative inotropic action of canrenone is mediated by L-type calcium current blockade and reduced intracellular calcium transients

Background and purpose:

Adding spironolactone to standard therapy in heart failure reduces morbidity and mortality, but the underlying mechanisms are not fully understood. We analysed the effect of canrenone, the major active metabolite of spironolactone, on myocardial contractility and intracellular calcium homeostasis.

Experimental approach:

Left ventricular papillary muscles and cardiomyocytes were isolated from male Wistar rats. Contractility of papillary muscles was assessed with force transducers, Ca²⁺ transients by fluorescence and Ca²⁺ fluxes by electrophysiological techniques.

Key results:

Canrenone (300–600 µmol·L⁻¹) reduced developed tension, maximum rate of tension increase and maximum rate of tension decay of papillary muscles. In cardiomyocytes, canrenone (50 µmol·L⁻¹) reduced cell shortening and L-type Ca²⁺ channel current, whereas steady-state activation and inactivation, and reactivation curves were unchanged. Canrenone also decreased the Ca²⁺ content of the sarcoplasmic reticulum, intracellular Ca²⁺ transient amplitude and intracellular diastolic Ca²⁺ concentration. However, the time course of [Ca²⁺]_i decline during transients evoked by caffeine was not affected by canrenone.

Conclusion and implications:

Canrenone reduced L-type Ca²⁺ channel current, amplitude of intracellular Ca²⁺ transients and Ca²⁺ content of sarcoplasmic reticulum in cardiomyocytes. These changes are likely to underlie the negative inotropic effect of canrenone.     

The effect of changes in dietary fat on the food group and nutrient intake of 4- to 10-year-old children

OBJECTIVE: To determine how young children changed their overall diet when they changed their fat intake after 3 months of participating in a nutrition education demonstration study designed to lower low-density lipoprotein cholesterol and cardiovascular risk. METHODS: Three 24-hour dietary recalls were collected from 303 4- to 10-year-old children at baseline and 3 months later. At both times, mean number of servings from food groups, grams of fat contributed from food groups, and intake of calories and nutrients were calculated and compared among quartiles of children formed according to change in their percent of calories from total fat after 3 months. RESULTS: Children who reduced their percent of calories from total fat most (ie, by an average of 8.5%) after 3 months consumed fewer servings from meats, eggs, dairy, fats/oils, and breads but tended to increase their number of servings from lower-fat foods within those food groups, particularly from dairy foods. These children also increased their mean intake of fruits, vegetables, and desserts, and maintained average intakes of all nutrients (except vitamin D) in excess of two thirds of the respective recommended dietary allowance. CONCLUSIONS: Young children who reduced their percent of calories from total fat in accordance with the current National Cholesterol Education Program recommendations accomplished this by reducing their overall intake of higher-fat foods, replacing higher-fat foods with lower-fat foods within several food groups, particularly within the dairy group (eg, drinking skim milk instead of whole milk) and by consuming more servings of fruits, vegetables, and very-low-fat desserts. These behaviors did not compromise their mean calorie or nutrient intakes, showing that it is possible for young children to lower their fat intake safely to reduce their risk of future heart disease.     

Antitumor effectiveness of different amounts of electrical charge in Ehrlich and fibrosarcoma Sa-37 tumors

Background  

In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings.     

A preliminary modeling investigation into the safe correction zone for high tibial osteotomy

Background

High tibial osteotomy (HTO) re-aligns the weight-bearing axis (WBA) of the lower limb. The surgery reduces medial load (reducing pain and slowing progression of cartilage damage) while avoiding overloading the lateral compartment. The optimal correction has not been established. This study investigated how different WBA re-alignments affected load distribution in the knee, to consider the optimal post-surgery re-alignment.

Evaluation of an open access echocardiography service in the Netherlands: a mixed methods study of indications,outcomes, patient management and trends

Background  

In our region (Eastern South Limburg, The Netherlands) an open access echocardiography service started in 2002. It was the first service of this kind in The Netherlands. Our study aims were: (1) to evaluate demand for the service, participation, indications, echocardiography outcomes, and management by the general practitioner (GP); (2) to analyse changes in indications and outcomes over the years.     

A research algorithm to improve detection of delirium in the intensive care unit

Introduction  

Delirium is a serious and prevalent problem in intensive care units (ICUs). The purpose of this study was to develop a research algorithm to enhance detection of delirium in critically ill ICU patients using chart review to complement a validated clinical delirium instrument.     

血卟啉衍生物光动力效应对体外培养人鼻咽癌细胞株的杀伤作用

目的:通过探讨血卟啉衍生物光动力学效应对人鼻咽癌细胞株CNE2的生物作用,为光动力治疗放、化疗效果较差的鼻咽癌提供理论依据。方法:实验于2005-10/2006-06在南方医科大学南方医院肿瘤生物治疗中心实验室完成。对体外培养的人鼻咽癌细胞株CNE2分为光处理和无光处理各8个实验组及各分别设对照组和空白对照组,实验组分别加入0.5,1.0,1.5,2.0,2.5,3.0,3.5,4.0mg/L血卟啉衍生物100μL,每组设7个复孔;孵育4h,对照组除不加光敏剂外其他与实验组相同,空白对照组只加培养基不加细胞和光敏剂。光处理实验组给予波长为630nm的半导体激光进行照射,照射的功率密度为20mW/cm2,照射能量密度分别为20,10,5,2J/cm2,继续孵育24h,用四唑盐(MTT)比色法测定细胞存活率。细胞存活率(%)=(实验组A值-空白对照组A值)/(对照组A值-空白对照组A值)×100%。每次实验重复3次,取平均值。结果:①血卟啉衍生物与CNE2细胞共同孵育后,采用630nm的半导体激光照射可对其产生杀伤作用,杀伤作用大小与血卟啉衍生物的浓度和激光剂量成正相关(P<0.01),但血卟啉衍生物浓度达2.5mg/L以上时杀伤细胞作用无显著增加。激光能量为20J/cm2,血卟啉衍生物的浓度为2.5mg/L时,其杀伤CNE2细胞的作用最明显。②在加入血卟啉衍生物而无激发光的情况下,血卟啉衍生物对鼻咽癌细胞生存不产生明显影响(P>0.05)。结论:血卟啉衍生物介导的光动力在体外可以对CNE2细胞产生杀伤效应,在一定范围内杀伤作用大小与血卟啉衍生物的浓度和激光剂量成正相关。