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排序方式: 共有10000条查询结果,搜索用时 15 毫秒
981.
982.
Predicting Oral Absorption of Drugs: A Case Study with a Novel Class of Antimicrobial Agents 总被引:3,自引:0,他引:3
Hilgers AR Smith DP Biermacher JJ Day JS Jensen JL Sims SM Adams WJ Friis JM Palandra J Hosley JD Shobe EM Burton PS 《Pharmaceutical research》2003,20(8):1149-1155
Purpose. The purpose of this work was to evaluate an oral absorption prediction model, maximum absorbable dose (MAD), which predicts a theoretical dose of drug that could be absorbed across rat intestine based on consideration of intestinal permeability, solute solubility, intestinal volume, and residence time.
Methods. In the present study, Caco-2 cell permeability, as a surrogate for rat intestinal permeability, and aqueous solubility were measured for 27 oxazolidinones. The oxazolidinones are a novel class of potential antibacterial agents currently under investigation. These values were used to estimate MAD for each of the compounds. Finally, these predicted values were compared to previously measured bioavailability data in the rat in order to estimate oral absorption properties.
Results. A reasonably good correlation between predicted dose absorbed and bioavailability was observed for most of the compounds. In a few cases involving relatively insoluble compounds, absorption was underestimated. For these compounds while aqueous solubility was low, solubility in 5% polysorbate 80 was significantly higher, a solvent possibly more representative of the small intestinal lumen.
Conclusions. These results suggest that MAD may be useful for prioritizing early discovery candidates with respect to oral absorption potential. In the case of compounds with poor aqueous solubility, additional factors may have to be considered such as solubility in the intestinal lumen. 相似文献
983.
Rosacea fulminans is characterized by the sudden onset of large, coalescing nodules and draining sinuses on the face. A few reports have linked medications to this condition, but none have described the onset of rosacea fulminans with pegylated interferon or ribavirin therapy. We report a patient who presented with rosacea fulminans after initiation of therapy for Hepatitis C. 相似文献
984.
Heitbrink WA Moyer ES Jensen PA Watkins DS Martin SB 《AIHA journal : a journal for the science of occupational and environmental health and safety》2003,64(3):394-400
To evaluate filter efficiency and performance of environmental enclosures for tractors, 3- to 4-year-old tractor enclosure combinations (cabs retrofitted to tractors after manufacturing) were studied at a custom pesticide applicators facility. Optical particle counters were used to measure the aerosol number concentration inside and outside the cab. The ratio of these concentrations multiplied by 100 is termed percentage penetration, the amount of the aerosol that penetrates into the enclosure. For particles in the 0.3 to 0.4 microm range, penetration into the cab was reduced from 11 to 0.4% in the following sequential steps. First, manufacturing mistakes were corrected by fixing a bowed flange and inappropriate sealing of the sheet metal used to separate incoming air from air that had passed through the filter. This reduced aerosol penetration from 11 to 4.8%. Replacing gasket material on the used filter reduced penetration from 4.8 to 0.65%. This suggests that the filter gaskets are deforming and allowing leakage. Also, the filter media were evaluated for aerosol penetration as a function of particle size and were tested per the criteria stipulated in 42 CFR 84 for negative pressure air-purifying particulate respirators. These results showed penetration through the filter media of less than 0.03%, indicating that filter media were not a major source of aerosol leakage into the cab. The results suggest that the manufacturer should implement a quality control program to ensure that minimal aerosol penetration criteria into the cabs are met and an acceptable maintenance program exists to ensure compliance. Furthermore, the degradation of filter gasket material over time needs to be minimized to ensure that the environmental cabs continue to provide acceptable performance. 相似文献
985.
986.
Hatsukami DK Jensen J Brauer LH Mooney M Schulte S Sofuoglu M Pentel PR 《Pharmacology, biochemistry, and behavior》2003,75(1):1-7
Previous studies have shown that cotinine, a metabolite of nicotine, may antagonize some of the therapeutic effects of nicotine. The mechanisms underlying cotinine's effects are unclear, but cotinine has been observed to increase serotonin levels in the brain. Thus, it is possible that blocking serotonin effects may antagonize the actions of cotinine, thereby reducing its impact on responses to nicotine. This study determined whether granisetron, a 5HT(3) receptor antagonist, would enhance the efficacy of the nicotine patch. Subjects were randomly assigned to one of the three granisetron conditions (N=43 for 2 mg/day; N=43 for 1 mg/day; N=42 for 0 mg/day) and asked to take the assigned medication daily during 15 days of tobacco abstinence. Because we were interested in interactions between cotinine and serotonin, all groups were also treated with a 21-mg nicotine patch. Assessments of withdrawal symptoms were made for 1 week during baseline smoking and several times during the experimental period. There was a near but nonsignificant difference among groups on a measure of tobacco withdrawal and no significant differences on global measures of drug effects or physiological measures. The data do not strongly support the hypothesis that 5HT(3) agonism is the mechanism by which cotinine offsets the effects of nicotine. 相似文献
987.
Prescott E Holst C Grønbaek M Schnohr P Jensen G Barefoot J 《International journal of epidemiology》2003,32(6):990-997
BACKGROUND: Vital exhaustion, a psychological measure characterized by fatigue and depressive symptoms, has been suggested to be an independent risk factor for ischaemic heart disease (IHD) but the generality of the phenomenon remains in question. The aim of this study is to describe prevalence of these symptoms in a community sample and determine whether they prospectively predict increased risk of IHD and all-cause mortality in men and women. METHODS: The study base was 4084 men and 5479 women aged 20-98 free of IHD examined in 1991-1993 in the Copenhagen City Heart Study. Events were ascertained through record linkage until 1998 for IHD and September 2000 for all-cause mortality. There were 483 first hospital admissions and deaths caused by IHD and 1559 deaths from all causes during follow-up. RESULTS: The 17 items on the vital exhaustion questionnaire were frequently endorsed with prevalence ranging from 6 to 47 per cent, higher in women. All but 4 of the 17 items were significantly associated with IHD with significant relative risks (RR) ranging between 1.36 (95% CI: 1.08, 1.72) and 2.10 (95% CI: 1.63, 2.71). Associations with all-cause mortality were also observed, but were weaker. RR of both IHD and all-cause mortality increased with increasing item sum score and were similar in men and women. For IHD, RR reached a maximum of 2.57 (95% CI: 1.65, 4.00) for subjects endorsing >9 items. The similar RR for all-cause mortality was 2.50 (95% CI: 2.09, 2.99). Multivariate adjustment for biological, behavioural, and socioeconomic risk factors did not substantially affect the association for IHD but attenuated the association with all-cause mortality. CONCLUSIONS: Measures of fatigue and depression were common symptoms in this population sample and convey increased risk of IHD and of all-cause mortality. We propose this knowledge begin to be implemented in risk assessment in clinical practice. 相似文献
988.
Jensen GL Friedmann JM Henry DK Skipper A Beiler E Porter C Boyd-Kantoff D 《JPEN. Journal of parenteral and enteral nutrition》2003,27(1):89-90
BACKGROUND: Body weight provides vital information for patient care; therefore, measurement at hospital admission should be standard practice. Our objective was to test compliance with this standard. METHODS: This was a study of 300 patients, aged > or = 18 years, admitted to general medicine and surgery services of 3 tertiary care teaching hospitals in Nashville, Chicago, and San Francisco. At 24 to 36 hours after admission, participants were queried as to whether they had been weighed, and if not, they were asked whether they had been questioned by nursing personnel about their weight. Subjects were then weighed by research personnel using identical protocol at all 3 institutions. Any admission body weight documented by nursing was noted. RESULTS: Compliance was similar at all 3 institutions, with only 197 (65.7%) of patients reporting being weighed. There were 213 (71.0%) patients who had a weight documented in the nursing record. Of those who had not been weighed, 69 (67.0%) indicated that they had been queried about their weight. Comparison of documented weights in the nursing records with those measured by research personnel revealed that 55 (25.9%) differed by > or = 5 pounds (2.27 kg). Those who had a documented weight in the nursing record but were not weighed by nursing personnel were also more likely to deviate from the weight measured by research personnel by > or = 5 pounds (2.27 kg) in comparison with those who had been weighed by nursing personnel (42.8% versus 21.8%, respectively, p < .0147). CONCLUSION: Overall compliance with weight measurement is poor. Recorded weights are often inaccurate. 相似文献
989.
Burger J Dixon C Shukla T Tsipoura N Jensen H Fitzgerald M Ramos R Gochfeld M 《Archives of environmental contamination and toxicology》2003,44(1):0036-0042
We examined the concentrations of arsenic, cadmium, chromium, lead, manganese, mercury, and selenium in the eggs, leg muscle,
and apodeme (carapace musculature) in horseshoe crabs (Limulus polyphemus) from eight places on the New Jersey and Delaware sides of Delaware Bay to determine whether there were locational differences.
Although there were locational differences, the differences were not great. Further, contaminant levels were generally low.
The levels of contaminants found in horseshoe crabs were well below those known to cause adverse effects in the crabs themselves
or in organisms that consume them or their eggs. Contaminant levels have generally declined in the eggs of horseshoe crabs
from 1993 to 2001, suggesting that contaminants are not likely to be a problem for secondary consumers or a cause of their
decline.
Received: 25 January 2002/Accepted: 2 June 2002 相似文献
990.
Giguère A Couillard Y Campbell PG Perceval O Hare L Pinel-Alloul B Pellerin J 《Aquatic toxicology (Amsterdam, Netherlands)》2003,64(2):185-200
The present study was designed to assess the environmental effects of metals in a field setting. We explored exposure-->bioaccumulation-->effects relationships in freshwater molluscs exposed to metals in their natural habitat. Indigenous floater mussels (Pyganodon grandis) were collected from ten limnologically similar lakes located along a Cd, Cu and Zn gradient. Ambient free-metal ion concentrations were estimated as a measure of metal exposure. Metallothionein (MT) was measured in mussel gills and metal partitioning among the various cytosolic protein pools was determined by size exclusion chromatography. Various biomarkers were also measured, including malondialdehyde (MDA) concentrations in the gills and in the digestive gland, glutathione-peroxidase and glutathione-reductase activities in the digestive gland, and lipid concentrations in the gonad. Cadmium and MT concentrations in the gill cytosol increased along the contamination gradient, but Cu and Zn levels were independent of the ambient free-metal ion concentrations. The distribution of Cd among the various cytosolic complexes remained quite constant: 80% in the MT-like pool, 7% in the low molecular weight pool (LMW<1.8 kDa) and 13% in the high molecular weight pool (HMW>18 kDa). For these chronically exposed molluscs there was thus no threshold exposure concentration above which spillover of Cd occurred from the MT pool to other cytosolic ligands. However, the presence of Cd in the LMW and HMW fractions suggests that metal detoxification was imperfect, i.e. that P. grandis was subject to some Cd-related stress at low chronic exposure concentrations. Consistent with this suggestion, MDA concentrations, an indicator of oxidative stress, increased with gill cytosolic Cd. In the digestive gland, MDA concentrations were unrelated to any of the measured metals, but glutathione-peroxidase and glutathione-reductase activities increased with gill cytosolic copper. We speculate that cytosolic Cu catalyses the production of reactive oxygen species, to which the organism reacts by increasing activities of the two enzymes, thus preventing the accumulation of reactive oxygen species. Lipid concentrations in the gonad did not decrease with any of the measured toxicological parameters, suggesting that energy reserves for reproduction were not compromised in the metal-contaminated mussels. The results of the present study, where chronically exposed bivalves were collected from their natural habitat along a metal contamination gradient, contrast markedly with what would have been predicted on the basis of experimental metal exposures, and clearly demonstrate the need to study metal exposure-->bioaccumulation-->effects relationships in natural populations. 相似文献