Embryotoxic doses of vitamin A to rabbits result in low plasma but high embryonic concentrations of all-trans-retinoic acid: risk of vitamin A exposure in humans

Retinoid pharmacokinetics were examined in plasma, placenta and embryos of gestational d 12 rabbits following application of an embryotoxic dosing regimen (10 mg retinyl palmitate/kg body wt per day from gestational d 7 to 12). Vehicle-treated or untreated rabbits served as controls. Physiological concentrations of all-trans-retinoic acid (all-trans-RA) and 13-cis-RA in rabbit plasma (5-8.33 nmol/L) were very close to the endogenous levels in human plasma. In addition, we identified endogenous all-trans-RA, 3,4-didehydroretinol and 3,4-didehydroretinoic acid in rabbit embryo. Following the last retinyl palmitate administration, apparent steady-state concentrations of all retinoids were reached in the examined compartments of rabbits. The major polar retinoid in plasma was 9, 13-di-cis-RA, but its embryonic concentrations were only about 6% of those in plasma. In the embryo, retinol and its esters were found at high concentrations; lower amounts of all-trans-4-oxo-RA and the newly identified 14-hydroxy-4, 14-retro-retinol could also be measured. Embryonic concentrations of all-trans-RA were about 100% higher than endogenous levels. The overall exposure of the embryo to this retinoid was, however, substantial. Embryonic area under the concentration time curve values strongly suggest that the embryotoxicity of the applied dosing regimen is mainly due to the action of all-trans-RA. A very remarkable finding of this study is the marginal increase of plasma concentrations of all-trans-RA over their endogenous levels, which is comparable to the human situation after vitamin A intake. This analogy indicates that high vitamin A intake may be associated with a higher risk for teratogenic effects in humans even in the absence of high elevation of plasma all-trans-RA levels.     

LEICA: a low energy ion composition analyzer for the study of solarand magnetospheric heavy ions

The SAMPEX (Solar, Anomalous, and Magnetospheric Particle Explorer) LEICA instrument is designed to measure ~0.5-5-MeV/nucleon solar and magnetospheric ions over the range from He-Ni. The instrument is a time-of-flight (TOF) mass spectrometer, which measures particle TOF over an ~0.5-m path and the residual energy deposited in an array of Si solid state detectors. Large-area microchannel plates are used, resulting in a large geometrical factor for the instrument (0.6 cm² sr), which is essential for accurate compositional measurements in small solar flares and in studies of precipitating magnetospheric heavy ions     

Hip impact velocities and body configurations for voluntary falls from standing height

OBJECTIVE: To determine prevalence of various pheno- and genotypes of Serpulina sp in young pigs in relation to diarrhea and feed medication in Swedish pig-rearing herds. DESIGN: Isolation of spirochetes. Phenotypical and genotypical classification. SAMPLE POPULATION: Young pigs (n = 358) in 19 pigrearing herds. PROCEDURE: Serpulina isolates were classified according to a biochemical scheme based on hemolysis, indole production, hippurate hydrolysis, and alpha-galactosidase, alpha-glucosidase, and beta-glucosidase activities. The 16S rRNA sequences for 10 of the field strains and 2 type strains of Serpulina spp were aligned and compared. Minimum inhibitory concentrations of olaquindox for 9 of the strains were determined. RESULTS: Weakly beta-hemolytic intestinal spirochetes (WBHIS) were isolated from 17 of the herds and 65% of the samples. More than 1 phenotype of WBHIS was found in 12 of the 19 herds. S hyodysenteriae was not isolated in any of the herds. Hippurate-positive WBHIS were isolated in 6 of 7 herds affected by diarrhea, but in only 1 of 8 herds without diarrhea. Hippurate-positive strains were closely related to the pathogenic strain P43 if judged from sequence comparisons. Strains with the same biochemical profile isolated within a herd had identical sequences, but when isolated from different herds, sequence differences were observed. The prevalence of WBHIS was reduced in herds medicated with olaquindox. Investigated field strains had minimum inhibitory concentration values < or = 1 microgram/ml for olaquindox. CONCLUSION: The presence of WBHIS, with the ability to hydrolyze hippurate, was related to diarrhea in pig herds. CLINICAL RELEVANCE: Potentially pathogenic WBHIS can be distinguished from nonpathogenic strains by the hippurate hydrolysis test.     

Renewable energy in competitive electricity markets

A restructured electricity system may undervalue renewable energy. We remain wary of unregulated markets, but urge the renewable energy community to begin considering how they could adapt to increasing customer choice.     

On the effects of background selftests on system performance

Systems which perform built-in tests to provide continuous monitoring of system reliability are of increasing interest. To minimize the test overhead it is appropriate to divide the entire system test into several subtests, which are executed during the idle times of the system, i.e., in background mode. In this paper a model using renewal theory is described to determine the probability distribution function and the mean of the duration of an entire system selftest. Finally, we evaluate the effects of selftesting on system performance, expressed by the delays occurring and the decreased throughput of user tasks. Our analysis allows us to compare the performance effects of various test policies. At the end of the paper we deal with optimal subtest lengths.     

Conceptual design of a high-efficiency absorption cooling cycle

The search for high-efficiency, gas-fired cooling cycles has led to the development of dual-loop absorption machines with cooling coefficients of performance (COPs) in the 1.2 to 1.7 range. This increased performance may call for high generator temperatures, new working fluids or new materials of construction. In most cases, two different sets of working fluids are required. The conceptual design presented here is aimed at obtaining high efficiencies with relatively low temperatures, employing only one set of fluids. The concept consists of two loops coupled in a configuration aimed at minimizing the loss of thermodynamic availability incurred when transferring refrigerant between the loops. The working fluid pair is a solution of lithium bromide-water. The calculated COPs are of the order of 1.8. The cycle relies on an elaborate evaporator-absorber combination. The paper presents the conceptual design, the critical assumptions, and the performance calculations for the concept.