Morphological effects in rats following a 22-day space flight

A morphological examination of 27 rats flown onboard the biosatellite and sacrificed on the 1st-2nd and 26-27th postflight days demonstrated no significant changes in the structural organization of the vital organs and systems of the animal body. It was, however, found that the space exposure induced morphologically detectable changes in the musculo-skeletal system, hemo- and lymphopoiesis, hypothalamic-pituitary-adrenal system and the juxtaglomerular apparatus of the kidneys. The changes were reversible and nonspecific, and could be seen in animals exposed to ground-based hypokinetic and other stress experiments. Postflight the animals developed some reactions that were similar to those in humans. This helps to identify the morphological substrate of certain changes in the human body and to investigate their pathogenesis.     

Interactions between drops of a molten aluminum-lithium alloy and liquid water

Formerly Member of Technical Staff with Sandia National Laboratories     

The replacement of accessory T-lymphocytes by synthetic peptides during the formation of splenic hematopoietic colonies

Whether accessory T cells can be replaced by the synthetic immunomodulators thymogen (Glu-Trp) and thymohexin (Arg-Lys-Asp-Val-Tyr-Arg) was studied. The latter immunomodulator was found to show a 3-fold increase in splenic colony formation after incubation of bone marrow cells with rabbit antimouse brain serum (RAMBS). The former preparation failed to show the same action. Its effect was close to that of thymocytes. When the recipients exposed to lethal irradiation were administered the RAMBS-treated bone marrow cells and one of the peptides, it was shown that in concomitant administration, thymohexin and thymocytes lost their ability to restore colony formation by RAMBS-treated bone marrow. Thymogen did not suppress the stimulating activity of thymocytes. It is suggested that the differences observed between the tested peptides in their ability to recover colony formation were determined by their structure.     

Detection of the change point in oxygen uptake during an incremental exercise test using recursive residuals: relationship to the plasma lactate accumulation and blood acid base balance

BACKGROUND: Lovastatin is oxidized by cytochrome P4503A to active metabolites but pravastatin is active alone and is not metabolized by cytochrome P450. Diltiazem, a substrate and a potent inhibitor of cytochrome P4503A enzymes, is commonly coadministered with cholesterol-lowering agents. METHODS: This was a balanced, randomized, open-label, 4-way crossover study in 10 healthy volunteers, with a 2-week washout period between the phases. Study arms were (1) administration of a single dose of 20 mg lovastatin, (2) administration of a single dose of 20 mg pravastatin, (3) administration of a single dose of lovastatin after administration of 120 mg diltiazem twice a day for 2 weeks, and (4) administration of a single dose of pravastatin after administration of 120 mg diltiazem twice a day for 2 weeks. RESULTS: Diltiazem significantly (P < .05) increased the oral area under the serum concentration-time curve (AUC) of lovastatin from 3607 +/- 1525 ng/ml/min (mean +/- SD) to 12886 +/- 6558 ng/ml/min and maximum serum concentration (Cmax) from 6 +/- 2 to 26 +/- 9 ng/ml but did not influence the elimination half-life. Diltiazem did not affect the oral AUC, Cmax, or half-life of pravastatin. The average steady-state serum concentrations of diltiazem were not significantly different between the lovastatin (130 +/- 58 ng/ml) and pravastatin (110 +/- 30 ng/ml) study arms. CONCLUSION: Diltiazem greatly increased the plasma concentration of lovastatin, but the magnitude of this effect was much greater than that predicted by the systemic serum concentration, suggesting that this interaction is a first-pass rather than a systemic event. The magnitude of this effect and the frequency of coadministration suggest that caution is necessary when administering diltiazem and lovastatin together. Further studies should explore whether this interaction abrogates the efficacy of lovastatin or enhances toxicity and whether it occurs with other cytochrome P4503A4-metabolized 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, such as simvastatin, fluvastatin, and atorvastatin.