Effects of opioid blockade with nalmefene in older impotent men

We evaluated the effect of the opioid antagonist nalmefene on the HPG axis and on food consumption in 14 older impotent men. These patients had low to low normal mean serum testosterone values and normal gonadotrophin levels on screening evaluation. Normal response to GnRH was demonstrated in all the men. The protocol called for 24 hours of evaluation before and during administration of nalmefene 2.0 mg IV every 8 hours for 3 doses. During each 24 hour period, the following determinations were made: serum testosterone, FSH, and LH by five separate determinations between 8 AM and noon; 8 AM and 11 PM serum cortisols; 24 hour urine collections for free cortisol; and nocturnal penile tumescence (NPT). Food consumption was measured from 4 PM to 10 AM during the two periods. Nalmefene resulted in significant rises in testosterone, LH, and FSH. Nalmefene significantly elevated morning and evening cortisol measurements in all the patients. Nalmefene decreased total calorie consumption, principally by decreasing fat consumption. There was no effect on NPT. We conclude that in older impotent men, nalmefene acutely increases activity of the HPG axis and decreases calorie intake predominantly by decreasing fat consumption.     

A novel probe for phosphatidylinositol 4-phosphate reveals multiple pools beyond the Golgi

Polyphosphoinositides are an important class of lipid that recruit specific effector proteins to organelle membranes. One member, phosphatidylinositol 4-phosphate (PtdIns4P) has been localized to Golgi membranes based on the distribution of lipid binding modules from PtdIns4P effector proteins. However, these probes may be biased by additional interactions with other Golgi-specific determinants. In this paper, we derive a new PtdIns4P biosensor using the PtdIns4P binding of SidM (P4M) domain of the secreted effector protein SidM from the bacterial pathogen Legionella pneumophila. PtdIns4P was necessary and sufficient for localization of P4M, which revealed pools of the lipid associated not only with the Golgi but also with the plasma membrane and Rab7-positive late endosomes/lysosomes. PtdIns4P distribution was determined by the localization and activities of both its anabolic and catabolic enzymes. Therefore, P4M reports a wider cellular distribution of PtdIns4P than previous probes and therefore will be valuable for dissecting the biological functions of PtdIns4P in its assorted membrane compartments.     

The formation of a test system for assessing the safety of different types of pertussis preparations: their cytotoxic action on mouse thymocytes in vitro

The test for the evaluation of the toxicity of different types of pertussis preparations as manifested by their in vitro influence on mouse thymic cells (T test) has been finally worked out. The use of the T test has made it possible to reveal the nonstandard character of the production lots of adsorbed diphtheria-pertussis-tetanus vaccines, both whole-cell vaccine and Japanese acellular vaccine. The degree of the in vitro damaging action of pertussis preparations on mouse thymic cells greatly depends on the residual content of Bordetella pertussis nontoxoidized toxin which, in contrast to B. pertussis lipopolysaccharide and filamentous hemagglutinin, produces pronounced cytotoxic action on mouse thymic cells.