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排序方式: 共有188条查询结果,搜索用时 15 毫秒
1.
Naloxone inhibits superoxide release from human neutrophils 总被引:12,自引:0,他引:12
Using the superoxide dismutase inhibitable reduction of cytochrome c assay, we studied, the effect of (-) naloxone on N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated superoxide (O2-) release from human neutrophils. Neutrophils were pre-incubated with the range of concentrations of (-) naloxone that is administered in models of experimental sepsis (10(-6) - 10(-4.5) M). (-) Naloxone inhibited O2- release in a dose dependent manner. 02- produced by a cell-free xanthine-xanthine oxidase system was not inhibited by (-) naloxone, indicating that (-) naloxone was not scavanging O2-. There was no difference between the effect of (-) and (+) naloxone suggesting that the inhibition of O2- was not specific for an opiate receptor. Another opiate antagonist, nalorphine, as well as the opiate agonist, morphine, also inhibited O2- release in the same concentration range. There was no difference between the effect of naloxone and morphine. 相似文献
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Tissue distribution of cocaine in the pregnant rat 总被引:2,自引:0,他引:2
Cocaine hydrochloride was administered by single intraperitoneal (IP) doses to pregnant rats at day 18 or 19 of gestation. Plasma and tissue cocaine and norcocaine concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic analysis of concentration versus time data showed rapid distribution of cocaine and its metabolite to maternal and fetal tissues. The area under the cocaine concentration versus time curve (AUC) in fetus compared to maternal plasma was 3.33. The half-life of cocaine in the maternal plasma and fetus was 46 and 55 minutes, respectively, similar to values reported for cocaine elimination half-life in human plasma. The order of cocaine concentrations was placenta greater than fetal liver greater than maternal heart greater than whole fetus greater than fetal brain greater than maternal brain = maternal plasma. Norcocaine concentrations were usually less than 20% of cocaine concentrations in plasma and tissues. These results support extensive fetal exposure to cocaine following administration to pregnant rodents. Pharmacodynamic studies of cocaine in pregnancy should consider the effects of the drug on the developing fetus. 相似文献
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Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans 总被引:13,自引:3,他引:10
Recent studies of mitochondrial DNA (mtDNA) variation in mammals and
Drosophila have shown an excess of amino acid variation within species
(replacement polymorphism) relative to the number of silent and replacement
differences fixed between species. To examine further this pattern of
nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5
genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans.
Of interest are the frequency spectra of silent and replacement
polymorphisms, and potential variation among genes and taxa in the
departures from neutral expectations. The Drosophila ND3 and ND5 data show
no significant excess of replacement polymorphism using the
McDonald-Kreitman test. These data are in contrast to significant
departures from neutrality for the ND3 gene in mammals and other genes in
Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however,
both Drosophila and human mtDNA show very significant excesses of amino
acid polymorphism. Silent polymorphisms at ND5 show a significantly higher
variance in frequency than replacement polymorphisms, and the latter show a
significant skew toward low frequencies (Tajima's D = -1.954). These
patterns are interpreted in light of the nearly neutral theory where mildly
deleterious amino acid haplotypes are observed as ephemeral variants within
species but do not contribute to divergence. The patterns of polymorphism
and divergence at charge-altering amino acid sites are presented for the
Drosophila ND5 gene to examine the evolution of functionally distinct
mutations. Excess charge-altering polymorphism is observed at the carboxyl
terminal and excess charge-altering divergence is detected at the amino
terminal. While the mildly deleterious model fits as a net effect in the
evolution of nonrecombining mitochondrial genomes, these data suggest that
opposing evolutionary pressures may act on different regions of
mitochondrial genes and genomes.
相似文献
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Michael A. Simpkins David E. Withrow Jack C. Cesarone Peter L. Boveng 《Marine Mammal Science》2003,19(4):791-805
We monitored the haul-out behavior of 68 radio-tagged harbor seals ( Phoca vitulina ) during the molt season at two Alaskan haul-out sites (Grand Island, August-September 1994; Nanvak Bay, August-September 2000). For each site, we created a statistical model of the proportion of seals hauled out as a function of date, time of day, tide, and weather covariates. Using these models, we identified the conditions that would result in the greatest proportion of seals hauled out. Although those "ideal conditions" differed between sites, the proportion of seals predicted to be hauled out under those conditions was very similar (81.3% for Grand Island and 85.7% for Nanvak Bay). The similar estimates for both sites suggest that haul-out proportions under locally ideal conditions may be constant between years and geographic regions, at least during the molt season. 相似文献
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Longer lifespan in male mice treated with a weakly estrogenic agonist,an antioxidant,an α‐glucosidase inhibitor or a Nrf2‐inducer 下载免费PDF全文
Adam Antebi Clinton M. Astle Molly Bogue Martin S. Denzel Elizabeth Fernandez Kevin Flurkey Karyn L. Hamilton Dudley W. Lamming Martin A. Javors João Pedro de Magalhães Paul Anthony Martinez Joe M. McCord Benjamin F. Miller Michael Müller James F. Nelson Juliet Ndukum G. Ed. Rainger Arlan Richardson David M. Sabatini Adam B. Salmon James W. Simpkins Wilma T. Steegenga Nancy L. Nadon David E. Harrison 《Aging cell》2016,15(5):872-884
The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin – the latter with and without rapamycin, and two drugs previously examined: 17‐α‐estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17‐α‐estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male‐specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α‐glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies. 相似文献
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