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971.
Kessler RC McLaughlin KA Green JG Gruber MJ Sampson NA Zaslavsky AM Aguilar-Gaxiola S Alhamzawi AO Alonso J Angermeyer M Benjet C Bromet E Chatterji S de Girolamo G Demyttenaere K Fayyad J Florescu S Gal G Gureje O Haro JM Hu CY Karam EG Kawakami N Lee S Lépine JP Ormel J Posada-Villa J Sagar R Tsang A Ustün TB Vassilev S Viana MC Williams DR 《The British journal of psychiatry : the journal of mental science》2010,197(5):378-385
972.
973.
Küster T Zumkehr B Hermann C Theurillat R Thormann W Gottstein B Hemphill A 《Journal of the American Association for Laboratory Animal Science》2012,51(2):219-223
The oral route is the most frequently used method of drug intake in humans. Oral administration of drugs to laboratory animals such as mice typically is achieved through gavage, in which a feeding needle is introduced into the esophagus and the drug is delivered directly into the stomach. This method requires technical skill, is stressful for animals, and introduces risk of injury, pain and morbidity. Here we investigated another method of drug administration. The benzimidazole derivative albendazole was emulsified in commercially available honey and administered to mice by voluntary feeding or gavage. Mice that received albendazole by either gavage or honey ingestion had virtually identical levels of serum albendazole sulfoxide, indicating that uptake and metabolism of albendazole was similar for both administration techniques. In addition, dosing mice with the albendazole-honey mixture for 8 wk had antiparasitic activity comparable to earlier studies using gavage for drug administration. Compared with gavage, voluntary ingestion of a drug in honey is more rapid, less stressful to the animal, and less technically demanding for the administrator. Because of its low cost and ready availability, honey presents a viable vehicle for drug delivery. 相似文献
974.
Lesseur C Gilbert-Diamond D Andrew AS Ekstrom RM Li Z Kelsey KT Marsit CJ Karagas MR 《Toxicology letters》2012,213(1):100-106
The phthalates DEHP (Diethylhexyl phthalate), DiNP (Diisononyl phthalate) and DiDP (Diisodecyl phthalate) are constituents of plastisols. We sought to obtain first data on occupational exposures to the above phthalates by analyzing their metabolites in pre- and post-shift urine samples from 5 workers in a car manufacturing plant engaged in seam sealing with a DINP based plastisol. Pre-shift samples were collected after a work-free period of at least 2 days. As a comparison group we investigated 10 employees from the same plant. The comparison group had phthalate exposures in the range of the general German population. All plastisol workers had post shift values of DiNP and DiDP metabolites that were approx. 20-times higher, and pre-shift values that were approx. 5-10 times higher than those of the general background exposure. Post-shift values of DiNP metabolites were (median [maximum]: OH-MiNP: 117 [442] μg/L; oxo-MiNP: 44.3 [175] μg/L; carboxy-MiNP: 57.8 [286]μg/L), pre shift values were (OH-MiNP: 26 [164] μg/L; oxo-MiNP 12.9 [68.6] μg/L; carboxy-MiNP: 32.3 [103] μg/L), compared to the comparison group (OH-MiNP: 6.2 [33]μg/L; oxo-MiNP: 2.8 [16] μg/L; carboxy-MiNP: 6.5 [31] μg/L). DiDP values were generally lower. Regarding DEHP we found no significant work related exposure. The dermal exposure route might play an important role for phthalates in plastisols, with possible influences on distribution and elimination kinetics and therefore data interpretation. 相似文献
975.
976.
977.
Batchinsky AI Burkett SE Zanders TB Chung KK Regn DD Jordan BS Necsoiu C Nguyen R Hanson MA Morris MJ Cancio LC 《Critical care medicine》2011,39(10):2314-2321
978.
Beasley CM Benson C Xia JQ Young SS Haber H Mitchell MI Loghin C 《Pacing and clinical electrophysiology : PACE》2011,34(9):1116-1127
Background: Many thorough QT (TQT) studies use a baseline day and double delta analysis to account for potential diurnal variation in QTc. However, little is known about systematic changes in the QTc across contiguous days when normal volunteers are brought into a controlled inpatient environment. Methods: Two separate crossover TQT studies included 2 days of no treatment lead‐in days with ECG collection preceding periods of drug treatment . In the first study, there were two pairs of such contiguous days with 10 replicate electrocardiograms (ECGs) collected at six time points, and in the second study, there were four pairs of contiguous days with nine replicate ECGs collected at five time points. These lead‐in day pairs provided the opportunity to evaluate any systematic changes across contiguous first and second days of an inpatient environment. Within‐patient consistency of change across pairs of days as well as within day, diurnal variation could also be evaluated. Results: Modest (4.2 ms [range 1.9–6.5 ms]) but consistent decreases (significant [P < 0.05] for all 32 comparisons) were observed (probability: ≤5.4 × 10?16). Although group behavior with respect to QTc was consistent, individual subjects demonstrated substantial variability across pairs of days. Evidence of diurnal variation was weak and inconsistent. Magnitude of any diurnal variation was less than magnitude of change across days. Conclusions: Subjects show a systematic decrease in QTc from first day to second day of inpatient status and do not demonstrate a significant diurnal pattern. The magnitude of this systematic change is sufficient to influence QTc study interpretation. (PACE 2011; 34:1116–1127) 相似文献
979.
Marta Weinstock Lisandro LuquesTatyana Poltyrev Corina BejarShai Shoham 《Neurobiology of aging》2011,32(6):1069-1078
Oxidative stress and glial activation occur in the aging brain. Ladostigil is a new monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitor designed for the treatment of Alzheimer's disease. It has neuroprotective and antioxidant activities in cellular models at much lower concentrations than those inhibiting MAO or AChE. When ladostigil (1 mg/kg/day) was given for 6 months to 16-month-old rats it prevented the age-related increase in activated astrocytes and microglia in several hippocampal and white matter regions and increased proNGF immunoreactivity in the hippocampus towards the levels in young rats. Ladostigil also prevented the age-related reduction in cortical AChE activity and the increase in butyrylcholinesterase activity in the hippocampus, in association with the reduction in gliosis. The immunological and enzymatic changes in aged rats were associated with improved spatial memory. Ladostigil treatment had no effect on memory, glial or proNGF immunoreactivity in young rats. Early treatment with ladostigil could slow disease progression in conditions like Alzheimer's disease in which oxidative stress and inflammatory processes are present. 相似文献
980.
The neonatal Fc receptor (FcRn) was demonstrated to play a role both in the recycling and thus the protection of immunoglobulin G (IgG) from catabolism and in the maternal-fetal transfer of IgG. The expression of this particular receptor was evidenced in a variety of cell types, but the endothelial cell was considered the main cell able to perform both recycling and IgG catabolism. Based on preliminary data obtained in adult human mammary glands and skin, this study focused on a number of neonatal human tissues, targeting FcRn expression mainly in epithelial versus endothelial cells. Our results demonstrate that in most of the investigated tissues, the neonatal Fc receptor is not detectable in the endothelial cells lining the capillaries, whereas most epithelial cells are positive. We could also observe the receptor's expression in most macrophages, smooth muscle cells, and neurons. Taken together, these data suggest that the main sites of IgG catabolism might in fact be other than endothelial cells in human neonates. 相似文献