Carnosine and Homocarnosine,the Forgotten,Enigmatic Peptides of the Brain

Carnosine (beta-alanyl-histidine) and homocarnosine (gamma-aminobutyryl-histidine) are major constituents of excitable tissues, brain and skeletal muscles, but their physiological functions are yet unknown. Using primary cell culture systems, synthesis and uptake of carnosine exclusively by glial cells could be demonstrated. Uptake of carnosine was found to be mediated by a high affinity, energy-dependent dipeptide transport system, subsequently identified as the peptide transporter PepT2. With the synthesis of beta-Ala-Lys-Nepsilon-AMCA as a fluorescent reporter molecule, accumulation of this dipeptide derivative could be monitored under viable conditions not only in astroglia cells but also in folliculostellate cells of the anterior pituitary and in gonadal resident macrophages. This reporter dipeptide provided a most valuable tool to identify an intrapituitary communication system by tracing folliculostellate cells in acute slice preparation. Moreover, this substance could also be used to prepare pituitary cell cultures enriched with or depleted of folliculostellate cells that are needed for further studies.     

Clinical Experience with an Oral Diuretic,Trichlormethiazide

The main objective of this study was to observe the long-term effects of the administration of trichlormethiazide on the urine and blood. Fourteen patients suffering from essential hypertension or edema requiring diuretic therapy were treated for periods of one to 12 months (mean 5.4 months). There were no significant changes in urine values, blood counts, or serum sodium or potassium levels. Additional nitrogen retention occurred in two patients with renal failure, but no significant changes in blood urea nitrogen occurred in the remainder. Serum uric acid levels were lower at the end of treatment than before. The blood pressure fell in nine patients. No toxic effects were observed.     

Clinical Trial of Mefruside,a New Diuretic

A controlled clinical trial of a new diuretic—mefruside—is reported, in which it was compared with frusemide in 15 normal subjects and 15 patients with fluid retention. It was found to be an effective diuretic which, in the patients, produced a significantly greater excretion of water and electrolytes than an equal dose of frusemide. Its smooth prolonged action, maximal in the first 12 hours, made it of particular value for maintenance therapy. In a short-term trial on a further 15 hypertensive patients mefruside was shown to have a useful hypotensive action. The drug was well tolerated with minimal side effects.