Picrotoxin-sensitive receptors mediate gamma-aminobutyric acid-induced modulation of synaptic plasticity in rat superior cervical ganglion

Activity-dependent changes of synaptic efficacy in the superior cervical ganglion (SCG) can be prevented by gamma-aminobutyric acid (GABA). We have studied the effects of picrotoxin (PTX) on GABA-mediated inhibition of long-term potentiation (LTP) of synaptic transmission in the rat SCG. Compound action potentials were recorded extracellularly in the postganglionic internal carotid nerve in response to preganglionic nerve stimulation. PTX (100 microM) antagonized the inhibition by exogenous GABA (250 microM) of LTP induced by strong tetanic stimulation (20 Hz, 20s, supramaximal stimulation, partial blockade of transmission by hexamethonium). Additionally, PTX alone (50 microM) facilitated the induction of LTP by a weak tetanus (20 Hz, 5 s, submaximal stimulation). These results further support previous data indicating that activation of GABAA-like receptors can prevent the occurrence of synaptic plasticity at this peripheral synapse.     

Fetal death in mice lacking 5alpha-reductase type 1 caused by estrogen excess

Female mice deficient in steroid 5alpha-reductase type 1 have a decreased litter size. The average litter in homozygous deficient females is 2.7 pups vs. 8.0 pups in wild type controls. Oogenesis, fertilization, implantation, and placental morphology appear normal in the mutant animals. Fetal loss occurs between gestation days 10.75 and 11.0 commensurate with a midpregnancy surge in placental androgen production and an induction of 5alpha-reductase type 1 expression in the decidua of wild type mice. Plasma levels of androstenedione and testosterone are 2- to 3-fold higher on gestation day 9, and estradiol levels are chronically elevated by 2- to 3-fold throughout early and midgestation in the knockout mice. Administration of an estrogen receptor antagonist or inhibitors of aromatase reverse the high rate of fetal death in the mutant mice, and estradiol treatment of wild type pregnant mice causes fetal wastage. The results suggest that in the deficient mice, a failure to 5alpha-reduce androgens leads to their conversion to estrogens, which in turn causes fetal death in midgestation. These findings indicate that the 5alpha-reduction of androgens in female animals plays a crucial role in guarding against estrogen toxicity during pregnancy.     

Risk-benefit analysis for industrial and social needs

This study develops a decision method for evaluating the social acceptability of industrial controls on hazardous materials. Decisions are based on a "multiple criteria approach" that jointly considers measures such as risk-benefit tradeoff, minimum reducible health risk, maximum acceptable cost and implicit value of human life. Health risks are calculated by combining separate estimates of production and usage patterns, emissions to air and water, effectiveness of controls, pollutant dispersion and human susceptibility. Economic benefits consider employment, trade and consumer impacts, as well as direct costs of controls. The analysis focuses on asbestos as an example hazard. Relative values of hazard reduction alternatives are examined for asbestos manufacturing exhaust filters and for asbestos substitutes in brake linings. Preliminary calculations indicate risk reductions of these alternatives cannot justify their social costs.     

Brief hierarchical assessment of potential treatment components with children in an outpatient clinic

Seven patients conducted assessments in an outpatient clinic using a prescribed hierarchy of antecedent and consequence treatment components for their children's problem behavior. Brief assessment of potential treatment components was conducted to identify variables that controlled the children's appropriate behavior. Experimental control via a brief reversal was achieved for 6 of the 7 children, (1 child continued to behave appropriately following initial improvement in behavior). For these 6 children, improved behavior occurred with changes in treatment components. Our results extend previous studies of direct assessment procedures conducted in outpatient clinic settings.     

Survival in lung reperfusion injury is improved by an antibody that binds and inhibits L- and E-selectin

The selectins are a three-member family of leukocyte, platelet, and endothelial cell adhesion proteins that mediate leukocyte traffic into normal and inflamed tissues. P-selectin is expressed by endothelial cells and platelets, E-selectin by endothelial cells, and L-selectin by circulating leukocytes. To determine if selectin-mediated leukocyte adhesion influences the development of lung reperfusion injury, we studied hemodynamics and respiratory and inert gas exchange in sheep subjected to 3-hour in situ left lung ischemia followed by 6-hour left lung reperfusion with the right lung excluded. Ten minutes before reperfusion, eight animals received EL-246 (1 mg/kg intravenously), a novel antihuman selectin antibody that recognizes and blocks both L- and E-selectin and cross-reacts in sheep. Eight control animals with ischemia received no treatment, whereas three received an isotype-matched antihuman L-selectin antibody that does not cross-react in sheep (DREG-56, 1 mg/kg intravenously). Eight sham control sheep underwent an identical operative procedure but were never subjected to ischemia. Volume-cycled, pressure-limited (20 cm H2O) mechanical ventilation was consistent in all animals throughout the experiment. Six-hour survival in EL-246 recipients (100%) was significantly higher than in either ischemic control sheep (37.5%) or DREG-56 recipients (33.3%), but gravimetric lung water was equivalent in EL-246 recipients (5.9 +/- 1.7 ml/kg), ischemic control sheep (8.3 +/- 3.0 ml/kg), and DREG-56 recipients (9.1 +/- 2.6 ml/kg).(ABSTRACT TRUNCATED AT 250 WORDS)     

The uptake of 3-deoxy-3-fluoro-D-glucose by synaptosomes from rat brain cortex

D-[3-3H]-3-deoxy-3-fluoroglucose was synthesized chemically and shown to be transported into rat brain synaptosomes by a saturable process with a Km 6.2 x 10(-4) M and a Vmax 2.8 nmole x mg protein-1. After an initial, rapid period of transport, further uptake of the fluorosugar is restricted by the rate of its phosphorylation. Both D-glucose and cytochalasin B are competitive inhibitors of 3-deoxy-3-fluoro-D-glucose transport with Ki values of 93 micron and 6.0 x 10(-7) M, respectively. Phloretin, N-ethylmaleimide and p-chloromercuribenzoate also inhibit the fluorosugar uptake, whereas ouabain and changes in K+, Na+, Mg2+ and Ca2+ ions have only a small effect. The recorded 3-deoxy-3-fluoro-D-glucose influx is slightly reduced by potassium cyanide, antimycin A, 2,4-dinitrophenol, and rotenone. The uptake reduction caused by these four reagents is relieved by the addition of exogenous ATP. The possible influence of hexokinse activity on the uptake process is discussed.