Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans.

Experimentally increasing metabolic flux in a pathway in which an essential step is catalyzed by a vitamin-dependent enzyme (a challenge test) has been used in assessing functional vitamin status and elucidating common and alternate metabolic pathways. Conversion of 3-methylcrotonyl CoA to 3-methylglutaconyl CoA in the leucine catabolic pathway is catalyzed by the biotin-dependent enzyme methylcrotonyl-CoA carboxylase (MCC). Marginal biotin deficiency reduces MCC activity and increases urinary excretion of 3-hydroxyisovaleric acid (3HIA) and 3-hydroxyisovaleryl carnitine (3HIA-carnitine) measured in 24-h urine collections.

Cholinergic modulation of GABAergic and glutamatergic transmission in the dorsal subcoeruleus: mechanisms for REM sleep control.

Study Objectives: Dorsal subcoeruleus (SubCD) neurons are thought to promote PGO waves and to be modulated by cholinergic afferents during REM sleep. We examined the differential effect of the cholinergic agonist carbachol (CAR) on excitatory and inhibitory postsynaptic currents (PSCs), and investigated the effects of CAR on SubCD neurons during the developmental decrease in REM sleep.

Design: Whole-cell patch clamp recordings were conducted on brainstem slices of 7- to 20-day-old rats.

Insulin-like growth factor binding protein-5 influences pancreatic cancer cell growth.

Aim: To investigate the functional significance of insulin-like growth factor binding protein-5 (IGFBP-5) overexpression in pancreatic cancer (PaC).

Methods: The effects of IGFBP-5 on cell growth were assessed by stable transfection of BxPC-3 and PANC-1 cell lines and measuring cell number and DNA synthesis. Alterations in the cell cycle were assessed by flow cytometry and immunoblot analyses.

Predictors of short-term course of drinking in untreated rural and urban at-risk drinkers: effects of gender, illegal drug use and psychiatric comorbidity.

Objective: The purpose of this study was to examine predictors of changes in drinking and drinking consequences in untreated at-risk drinkers in a community sample.

Method: Four waves of telephone interviews were conducted at 6-month intervals with a probability sample of at-risk drinkers in the rural and urban South (initial N = 733). Participants were interviewed at each wave regarding concurrent drug use, psychopathology and social support, as well as alcohol service use.