The drug epidemic: effects on newborn infants and health resource consumption at a tertiary perinatal centre.

OBJECTIVES: Illicit drug taking in Australia, with its attendant social and medical consequences, is increasing and the effects extend to maternity hospitals where infants born to addicted mothers have more health problems in the neonatal period. The aims of this study were to evaluate (1) the patterns of illness of such infants and (2) the burden imposed on the neonatal department of a large tertiary maternity centre. METHODOLOGY: An audit was conducted of all Chemical Dependency Unit (CDU) mothers and babies delivered at the Royal Women's Hospital, Melbourne, Australia during 1997. Data were compared with those from a concurrent control group of mothers and babies randomly generated from the hospital's obstetric database. RESULTS: Ninety-six infants born to CDU mothers were compared with a control group of 200 infant/mother pairs. The majority of women in the CDU clinic were treated for narcotic addiction with methadone (90%) but most continued to use heroin during pregnancy (68%). Infants born to CDU mothers were significantly less mature and lighter than control infants. Fifty-three (55%) CDU infants required admission to the Special Care Nursery either because of neonatal abstinence syndrome (n = 29) or other medical reasons (n = 24). The median length of hospital stay was significantly longer in CDU compared with control infants (8 vs 3 days, P < 0.01). CONCLUSIONS: Infants born to drug dependent mothers have more neonatal problems requiring specialized medical and nursing expertise, compared with control infants. These infants are large consumers of scarce health resources.

Oxidized glutathione decreases luminal Ca2+ content of the endothelial cell ins(1,4,5)P3-sensitive Ca2+ store.

The model oxidant, t-butyl hydroperoxide (t-buOOH), inhibits Ins(1,4,5)P3-dependent Ca2+ signalling in calf pulmonary artery endothelial cells. Metabolism of t-buOOH within the cytosol is coupled to the oxidation of glutathione. In this study, we investigated whether oxidized glutathione (GSSG) is the intracellular moiety responsible for mediating the effects of t-buOOH on Ca2+ signalling. The increase in cytosolic [Ca2+] stimulated by application of 2,5-di-t-butylhydroquinone (BHQ) was used to estimate the luminal Ca2+ content of the Ins(1,4,5)P3-sensitive store in intact cells. Luminal Ca2+ content was unaffected by t-buOOH (0.4 mM, 0-3 h) unless intracellular GSSG content was concomitantly elevated. The effect was specific for increased GSSG and was not replicated by depletion of GSH. These results suggest that cytosolic GSSG, produced endogenously within the endothelial cell, decreases the luminal Ca2+ content of Ins(1,4,5)P3-sensitive Ca2+ stores. Depletion of internal Ca2+ stores by GSSG may represent a key mechanism by which some forms of oxidant stress inhibit signal transduction in vascular tissue. At the plasma membrane, t-buOOH is known to inhibit the capacitative Ca2+ influx pathway. Increased intracellular GSSG potentiated the inhibitory effect of t-buOOH on Ca2+ influx, thereby providing the first evidence that activity of the capacitative Ca2+ influx channel is sensitive to thiol reagents formed endogenously within the cell.

Reductant substrate for glutathione peroxidase modulates oxidant inhibition of Ca2+ signaling in endothelial cells.

Oxidant stress mediated by tert-butyl hydroperoxide (t-BOOH) inhibits agonist-stimulated Ca2+ entry and internal store Ca2+ release in cultured endothelial cells. The role of intracellular glutathione in modulating the effects of oxidant stress on Ca2+ signaling was determined in cells preincubated with buthionine-[S,R]-sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, or 1-chloro-2,4-dinitrobenzene (CDNB), a cosubstrate for glutathione-S-transferase. BSO and CDNB decreased endothelial cell glutathione content by 85 and 97%, respectively (control glutathione, 21.5 +/- 2.3 nmol/mg protein). Each agent accelerated the time-dependent effects of t-BOOH on Ca2+ signaling in fura 2-loaded cells and potentiated the inhibition of bradykinin-stimulated 45Ca2+ efflux induced by t-BOOH. These results indicate that decreased availability of reduced glutathione, the primary cosubstrate for glutathione peroxidase, potentiates the effect of hydroperoxide oxidant stress on receptor-operated Ca2+ entry across the plasmalemma and Ca2+ release from internal stores. The present findings suggest that intracellular glutathione availability and/or glutathione redox cycle activity are critically important modulators of oxidant inhibition of Ca(2+)-dependent signal transduction.