How does the distention of urinary bladder cause arousal?

Abstract Under urethane anesthesia, the urinary bladder of male rats was distended by 0.3-0.5 mL of saline. When the animals displayed large amplitude delta waves, the distention caused tonic excitation in 76% (19/25) of the noradrenergic neurons in the locus coeruleus and in 53% (16/30) of the cholinergic neurons in the laterodorsal tegmental nucleus. The response was followed by a shift of electroencephalogram (EEG) pattern to faster waves of smaller amplitude. When EEG amplitude was faster and smaller, the same stimuli caused no response. Neurons in Barrington's nucleus were excited by a small amount of bladder distention independent of EEG patterns. These results suggest that the transition of state, caused by bladder distention, from deep sleep to light sleep is mediated by noradrenergic and cholinergic neurons in the brainstem.     

Solid phase peptide synthesis of human endothelin precursor peptide using two-step hard acid deprotection/cleavage methods

Syntheses are described for the putative human and porcine biosynthetic precursors (hET-38 and pET-39) of endothelin, with the sequence previously deduced from human- and porcine-cDNA coding for prepro-endothelin. The Boc based solid phase synthetic method was applied, followed by weak hard acid, trimethylsilyl bromide, cleavage. The peptide removal from the resin was optimally accomplished with hydrogen fluoride. Disulfide bridges were formed by air-oxidation, and the linkage modes determined by enzymic (Endoproteinase Asp-N) digestion and HPLC. Five additional C-terminally elongated endothelin homologs were also synthesized. For alternative synthesis of pET-39, the use of trimethylsilyl tri-fluoromethanesulfonate for the removal of peptide from the resin generated a major side product, which was characterized. hET-38 was found to be less effective in vitro, when compared to endothelin. The vasoconstrictor activity in vitro of other related peptides was comparable to that of hET-38.     

Diltiazem Facilitates Endothelin Clearance from the Blood Stream to Reduce Toxic Elevation of Plasma Endothelin Level in Rodents*

Abstract— Pretreatment with diltiazem at a dose of 2 mg kg^?1 intravenously protected against sudden death induced by intravenous administration of endothelin-1 (ET-1, 5 nmol kg^?1), with an apparent decrease in the plasma immunoreactive-ET-1 (IR-ET-1) in mice. These effects, which were also observed in anaesthetized rats, disappeared in rats with bilateral ligation of the renal arteries. In the latter, the exogenous ET-1-induced elevation of plasma IR-ET-1 tended to be higher than that in the sham-operated controls. Furthermore, in anaesthetized rats, diltiazem inhibited ET-1-induced decreases in renal blood flow and increased renal accumulation of IR-ET-1. These results indicate that part of the clearance of ET-1 from the bloodstream occurs in the kidney, and that diltiazem enhances the elimination of the peptide, presumably by improvement in the renal circulation, this action leading to alleviation of the toxic effects of ET-1.     

New Japanese pediatric guidelines for the treatment and management of bronchial asthma

There have been a number of guidelines for asthma treatment published throughout the world. However, childhood asthma guidelines must be developed in consideration of the background of the individual countries. The second version of the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2002 (JPGL 2002) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) in November 2002, and was popular among Japanese physicians. After the publication of the JPGL, the incidence of pediatric asthma deaths decreased in Japan. In JPGL 2005 the recommendations were re-edited based on Global Initiative for Asthma (GINA) and the JPGL 2002. In comparison to the GINA guidelines, the JPGL 2005 include a classification system of asthma severity, recommendations for long-term management organized by age, a special mention of infantile asthma, and an emphasis on prevention and early intervention.     

Proarrhythmic ECG Deterioration Caused by Myocardial Ischemia of the Conus Branch Artery in Patients with a Brugada ECG Pattern

The Brugada‐type electrocardiogram (ECG) is characterized by ST‐segment elevation in the right precordial ECG leads and has been reported to have the potential of sudden death. Right ventricular outflow tract supplied from the conus branch of the coronary artery (CB) is considered as the anatomopathologic substrate of Brugada syndrome. We experienced two asymptomatic patients with a saddleback Brugada‐type ECG who exhibited a dynamic ECG conversion to a coved type following a ventricular fibrillation/ventricular tachycardia (VT/VF) episode when myocardial ischemia occurred exclusively at the CB. Some types of Brugada syndrome might be caused VT/VF by selective myocardial ischemia at the CB. (PACE 2011; 34:e26–e29)