Pharmacological preconditioning by diazoxide downregulates cardiac L-type Ca2+ channels

BACKGROUND AND PURPOSE

Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K⁺ (mitoK_ATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca²⁺ homeostasis during PPC, particularly changes in Ca²⁺ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca²⁺ channels.

EXPERIMENTAL APPROACH

PPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca²⁺ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the α_1c subunit of L-type channels in the cellular membrane were measured by Western blot.

KEY RESULTS

PPC was accompanied by a 50% reduction in α_1c subunit levels, and by a reversible fall in L-type current amplitude and Ca²⁺ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoK_ATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the α_1c subunit and Ca²⁺ channel function were prevented in part by the protease inhibitor leupeptin.

CONCLUSIONS AND IMPLICATIONS

PPC downregulated the α_1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca²⁺ channel, which in turn reduced Ca²⁺ influx, which may attenuate Ca²⁺ overload during reperfusion.     

A supervised land cover classification of a western Kenya lowland endemic for human malaria: associations of land cover with larval Anopheles habitats

Background  

A supervised land cover classification was developed from very high resolution IKONOS satellite data and extensive ground truth sampling of a ca. 10 sq km malaria-endemic lowland in western Kenya. The classification was then applied to an investigation of distribution of larval Anopheles habitats. The hypothesis was that the distribution and abundance of aquatic habitats of larvae of various species of mosquitoes in the genus Anopheles is associated with identifiable landscape features.     

垂体催乳素瘤的诊断和治疗指南

首次测定确立高催乳血症必需避免过度的静脉穿刺压力,理想的情况是醒后或饭后致少1h来测试.     

Family physician views about primary care reform in Ontario: a postal questionnaire

Background  

Primary care reform initiatives in Ontario are proceeding with little information about the views of practicing family physicians.     

茶碱对有呼吸窘迫综合征的极早产儿患血管运动性肾病的预防作用研究：一项随机双盲安慰剂对照试验

背景:血管运动性肾病是早产儿常见的肾功能障碍性疾患。目的:确定茶碱是否可以预防有呼吸窘迫综合征的极早产儿罹患血管运动性肾病。方法:随机双盲安慰剂对照试验,50例胎龄≤32周须辅助通气的早产儿。婴儿接受3d茶碱(1m g/kg)或安慰剂静脉注射。每天测定其24h尿量。在第2、第5及第11天,收集血样及12h尿并进行电解质、肌酐、尿素分析。结果:茶碱组患儿的第1天排尿量的组别x(s)为2.4(0.9)m l/(kg·h),显著高于安慰剂组[1.6(1.0)m l/(kg·h);P=0.023]。茶碱组少尿或无尿的发生率(5%)显著低于安慰剂组(33%)。在第一次给予茶碱/安慰剂后24h,茶碱…     

Parvovirus: the expanding spectrum of disease

Treatment of parvovirus infections among immunocompromised hosts using immunoglobulin has provided the clinician with a useful therapeutic tool but has also highlighted the problems concerning chronic disease states. The discovery of the human parvovirus B19 in 1975 and subsequent studies of its effects in humans have identified this virus as the causative agent of a broad spectrum of diseases. Recent improvements regarding the development of sensitive PCR techniques and methods for cultivation have provided new insight into its pathogenic role, its virology and immunology, and the varied clinical manifestations. The current state of knowledge concerning parvovirus enabled us to divide the long list of diseases caused by this virus into three main categories: (1) diseases found among normal hosts (asymptomatic disease, erythema infectiosum, arthropathy, hydrops fetalis), (2) hematologic diseases (aplastic crisis, chronic anemia, idiopathic thrombocytopenic purpura, transient erythroblastopenia of childhood, Diamond-Blackfan anemia) and, finally, (3) a heterogeneous group of diseases, in which the etiologic role of parvovirus is less clear and sometimes putative (neurologic disease, rheumatologic disease, vasculitic and myocarditic syndromes). In particular, arthropathy, hydrops fetalis and the hematologic disorders may be of pediatric concern. Consequently, it is of paramount importance that in all of these cases the clinician includes parvovirus as a differential diagnosis.     

A case of neonatal bilateral diaphragmatic paralysis requiring surgery

Abstract Diaphragmatic paralysis may cause life threatening respiratory distress especially in infancy. A case is reported of a 32 week gestation infant with bilateral phrenic nerve palsies and associated brachial plexus injury who remained severely compromised despite spontaneous recovery of the right hemidiaphragm after 13 weeks. Operative plication of the left hemidiaphragm produced a marked improvement. Surgery should be considered after an adequate trial of expectant management in symptomatic patients.