Similar bioavailability of single-dose oral and intravenous mesna in the blood and urine of healthy human subjects

Although mesna has been used for more than a decade to reduce the incidence of hemorrhagic cystitis induced by ifosfamide and cyclophosphamide, the disposition of i.v. and oral mesna has not been adequately described. To obtain accurate bioavailability data for the design of mesna regimens, we developed procedures to preserve and measure mesna and dimesna in the blood and urine and studied 25 volunteer subjects who received single doses of i.v. mesna and four different formulations of oral mesna in a five-way randomized crossover study. The dose-adjusted area under the blood concentration-time curve showed no difference in bioavailability for i.v. and oral mesna; however, the maximum mesna concentration after oral doses was 16% of that estimated for i.v. doses. The short initial half-life of i.v. mesna indicated that mesna was rapidly cleared; however, the blood concentrations of mesna uniformly exceeded those of dimesna after oral as well as i.v. doses, which suggested that reduced mesna and oxidized mesna disulfide are in equilibrium. The ratio of mesna:dimesna was higher in protein-free plasma than it was in the urine, which suggested that most urinary mesna is produced by glomerular filtration of mesna rather than by renal tubular reduction of dimesna. The sum of mesna and dimesna excretion after the i.v. doses (73% of the dose) and the four oral formulations (68-73%) showed no difference in urinary bioavailability, consistent with the blood data. However, the urinary bioavailability of the therapeutically active free-thiol mesna was greater after i.v. doses (40% of the dose) than it was after oral doses (31-33%). The ratio of oral:i.v. mesna excretion ranged from 0.52-1.23 (mean, 0.82) among the 24 subjects. Urinary mesna concentrations exceeded 50 microM in all subjects for up to 12 h after oral doses as compared to 4 h after i.v. doses. About 90% of this mesna was excreted by hour 2 after i.v. doses and by hour 9 after oral doses. The mean maximum concentration of mesna in blood and excretion into urine were both 2.6 h after dosing. The oral formulations thus showed sustained urinary excretion, and their urinary bioavailability approached that of i.v. mesna.     

Test quality of hierarchical defect-tolerant integrated circuits

This paper presents a theoretical expression to evaluate the test quality of hierarchical defect-tolerant integrated circuits. This expression, which is developed for circuits with two levels of hierarchy, is based on a defect model with which one can take into account the relative importance (probability of occurrence) of each defect and consequently of each fault. Results obtained from this expression show that, for a given test coverage, the addition of defect-tolerance mechanisms decreases the test quality of integrated circuits. These results are important because they indicate that fault coverage can be a misleading measure of the test quality of defect-tolerant integrated circuits.     

Sediment Monitoring Bias by Automatic Sampler in Comparison with Large Volume Sampling for Parking Lot Runoff

A field study was conducted to assess biases of suspended sediment concentration (SSC) analyses (ASTM Standard D3977-97) performed on discrete samples obtained by automatic sampler in comparison with actual sediment concentrations from large volume sampling. Research results indicate that the biases attributed to the monitoring of sediment event mean concentration (EMC) and median particle size in parking lot runoff by automated samplers (nonisokinetic) were minimal. Large volume samples ( ～ 15,000??L) of the first-flush event runoff were taken from a storm-water sewer system for eighteen storm events over two years. The intent was to obtain a complete portion of a storm to accurately determine EMCs and particle size distributions (PSDs). Concurrently, flow-weighted discrete samples were obtained by automatic samplers for the same portion of the events. Thus, characteristics of sediments from a whole-storm sample were compared with those of subsamples obtained by an automatic sampler using nonisokinetic sampling. SSCs and PSDs were compared for the two respective field sampling methods. The two methods showed a strong correlation for median sediment EMCs (R2 = 0.98, n = 18). Biases to particle size distributions were found to be both for the large particles (>75–150??μm) and smaller fines (<25??μm). Specific sediment size fractions captured by the large volume sampling and automatic sampler were not significantly different (α = 0.05) for D50, which = 58 and 46??μm, respectively.     

用预防性保养使造纸机网毯性能最佳化

造纸厂不断地努力减少生产成本和提高操作效率,而造纸机网毯使用寿命达到最佳而同时不影响成品质量也是可控制的参数中的一部分.本文着重于用预防性保养使造纸机网毯性能达到最佳化.     

Effect of growth media and washing on the spectral signatures of aerosolized biological simulants

We have evaluated the influence of growth media and washing on the laser-induced fluorescence spectra of bacteria. Three different bacterial simulants were cultured in three types of growth media. Three kinds of samples were generated from each culture: the culture itself, the growth medium alone, and a triple-washed sample. The materials were injected as aerosols in a lab-sized lidar aerosol chamber to obtain their spectra. Using two different analysis approaches, signature variations were observed between the three kinds of samples for most combinations of growth media/bacteria. This study concludes that the culture media used influences the spectral signatures.     

Reliability of a simple non-invasive method for the evaluation of 5-HT2 receptors using [18F]-setoperone PET imaging

This study was designed to determine the effects of oral administration of the copper(II) complex of amino acids, on gastric lesions induced by ethanol in rats and the possible mechanism(s) of protection. The copper(II) complex of L-tryptophan and L-phenylalanine is reported as the most effective in reducing ulcer numbers as well as ulcer severity of the many amino acid complexes studied. We investigated the role of PGE2 and nitric oxide (NO) in the protection afforded by Cu(II)(L-Trp)(L-Phe) against ethanol-induced damage. The involvement of endogenous eicosanoids and NO was evaluated with the respective inhibitors of prostaglandin and NO synthesis, indomethacin and NG-nitro-L-arginine (L-NNA). Ex vivo PGE2 accumulation in the rat gastric mucosa has also been determined. Pretreatment with indomethacin only partially counteracted the protective activity of Cu(II)(L-Trp)(L-Phe). L-NNA did not attenuate the protection by Cu(II)(L-Trp)(L-Phe), which was reduced but not prevented by indomethacin, suggesting that prostanoids contribute to the Cu(II)(L-Trp)(L-Phe) protective effect, together with some mechanism(s) other than NO synthesis.     

The seats of reason? An imaging study of deductive and inductive reasoning

We carried out a neuroimaging study to test the neurophysiological predictions made by different cognitive models of reasoning. Ten normal volunteers performed deductive and inductive reasoning tasks while their regional cerebral blood flow pattern was recorded using [15O]H2O PET imaging. In the control condition subjects semantically comprehended sets of three sentences. In the deductive reasoning condition subjects determined whether the third sentence was entailed by the first two sentences. In the inductive reasoning condition subjects reported whether the third sentence was plausible given the first two sentences. The deduction condition resulted in activation of the left inferior frontal gyrus (Brodmann areas 45, 47). The induction condition resulted in activation of a large area comprised of the left medial frontal gyrus, the left cingulate gyrus, and the left superior frontal gyrus (Brodmann areas 8, 9, 24, 32). Induction was distinguished from deduction by the involvement of the medial aspect of the left superior frontal gyrus (Brodmann areas 8, 9). These results are consistent with cognitive models of reasoning that postulate different mechanisms for inductive and deductive reasoning and view deduction as a formal rule-based process.