Changes in the rate of hexobarbital detoxication in rats during postnatal ontogenesis

Studies have been made on changes in detoxication rate of hexenal in male and female rats ageing from 1 day to 32 months as revealed by the duration of sleep after the injection of a standard dose (100 mg/g) of the drug. It was shown that in the newborn rats of both sexes, the detoxication rate is the highest, decreasing 3-fold to the age of 45 days. Sexual differences were observed beginning from the 55-60th day, resulting originally from the increase in the duration of sleep in females during their earlier sexual maturation, and being significantly enhanced to the 75th day due to a sharp decrease of the duration of sleep in males. From the 3-4th day up to the 20-32nd month, sexual differences in the duration of sleep increase due to its progressive increase in females. In 3-32-month males, significant changes in the duration of sleep were not noted. Sexual differences in detoxication rate of hexenal persist also in old animals.     

Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma

Plasmid DNA vectors have been constructed with minigenes encoding a single cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of respiratory syncytial virus (RSV) or from the nucleoprotein of measles virus (MV) with or without a signal sequence (also called secretory or leader sequence). Following intradermal immunization, plasmids in which the CTL epitopes were expressed in-frame with the signal sequence were more effective at inducing peptide- and virus-specific CTL responses than plasmids expressing CTL epitopes without the signal sequence. This immunization resulted in protection against MV-induced encephalitis and a significant reduction in viral load following RSV challenge. The reduction of viral load following RSV challenge was abrogated by prior injection with anti-IFN-gamma antibodies. These results highlight the ability of epitope-based DNA immunization to induce protective immune responses to well-defined epitopes and indicate the potential of this approach for the development of vaccines against infectious diseases.     

Endothelin-induced inositol phosphate formation in rat kidney. Studies on receptor subtypes, G-proteins and regulation during ontogenesis

The aim of this study was to characterize the properties of endothelin (ET)-receptor subtypes mediating inositol phosphate (IP)-formation in rat kidney and their regulation during ontogenesis. In renal cortical slices of adult rats (12-16 weeks old) ET's concentration-dependently increased IP-formation with an order of potency ET-1 > ET-3. While the non-selective ET-receptor antagonist bosentan (10 microM) completely suppressed ET-induced IP-formation, the ETA-receptor antagonist BQ-123 (10 microM) inhibited it only by 70%, the ETB-receptor antagonist IRL 1038 (1 microM) by 25%; combined application of BQ-123 + IRL 1038 caused complete inhibition of ET-1-induced IP-formation. Pretreatment of isolated renal cells with pertussis toxin (PTX, 500 ng/ml) overnight did not attenuate but significantly increased ET-1-induced IP-formation. Ontogenetic studies in renal sites from neonatal, 1, 2, 3, 6, 12 and 24 weeks old rats revealed that ET-1-induced IP-formation maturation-dependently declined being highest in neonatal rats (increase: 169% over basal) and lowest in 24 weeks old rats (increase: 47% over basal). This decline in ET-induced IP-formation was accompanied by a decrease in renal ET-receptor number and the amount of immunodetectable Gq/11 (assessed by Western-blotting using the QL-antiserum). Moreover, ET-receptor subtypes changed during the maturation process: from neonates to 12 weeks old rats number and functional responsiveness of ETA-receptors declined, while that of ETB-receptors increased. We conclude that in adult rat renal cortex ET-induced IP-formation is mediated by activation of both ETA- and ETB-receptors and does not involve a PTX-sensitive G-protein. ET-induced IP-formation declines during the maturation process; this is associated with a decrease in ET-receptor number and the immunodetectable amount of Gq/11.     

Clinical diagnosis of deep venous thrombosis after hip replacement surgery

Hip replacement surgery is associated with a high frequency of postoperative deep vein thrombosis. This prospective study was performed in order to investigate if routine bedside questioning and examination by the visiting doctor could reveal deep vein thrombosis in the legs of patients who had received a hip replacement. 258 patients were evaluated. Thromboprophylaxis (dextran-70, low molecular weight heparin and graded elastic stockings) was given during the first week after operation. Bilateral venography was performed in all patients on day seven after operation, and showed an overall deep vein thrombosis incidence of 16%. The visiting doctors had not suspected deep vein thrombosis in any of the patients. This may have been because postoperative painful and swollen legs effectively masked any signs and symptoms of deep vein thrombosis. Our results show that deep vein thrombosis during the first week after hip replacement surgery cannot be discovered by clinical diagnostics. The high subclinical frequency of deep vein thrombosis indicates the importance of improving thromboprophylaxis in order to further minimise the occurrence of deep vein thrombosis and the risk of thromboembolic complications.