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排序方式: 共有738条查询结果,搜索用时 15 毫秒
71.
72.
Evidence from endothelium of gastric absorption of heparin and of dextran sulfates 8000 总被引:2,自引:0,他引:2
L B Jaques L M Hiebert S M Wice 《The Journal of laboratory and clinical medicine》1991,117(2):122-130
Heparin, hydrogenated dextran sulfate 8000 (Usherdex 8), and dextran sulfate 8000 were administered to rats, and the total drug was separated and determined in endothelium and plasma. A large amount of each drug was recovered from endothelium 2.4 and 6 minutes after intravenous injection. This accounted for the drug missing from plasma. The drugs in water were placed in the stomach by catheter. All three drugs were recovered from the endothelium and identified unchanged by electrophoresis and specific staining. The amounts that were recovered at 2.4 and 6 minutes were equivalent to most of the drug administered. Thus heparin, Usherdex 8, and dextran sulfate 8000 enter the body immediately on oral administration. At longer time intervals after intravenous and oral administration, much of each drug was not demonstrable in endothelium by the method used. Some drug could be detected in endothelium after 4 hours. After oral administration, plasma levels of each drug were rarely more than 0.5% of the dose. Formalin-alcohol was applied to the jugular veins of anesthetized rats to produce a thrombus, (see Blake et al. J Clin Path 1959;12:118-22) and the drugs were immediately introduced into the stomach. Four hours later the injured veins were inspected for thrombi. Incidence of thrombotic plug was 80% in rats that received saline solution, 4% with Usherdex 8, 0% with dextran sulfate 8000, and 0% with heparin. Usherdex 8, dextran sulfate 8000, and heparin demonstrate low, moderate, and high in vitro anticoagulant activity, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
73.
Tolerability and steady-state pharmacokinetics of everolimus in maintenance renal transplant patients. 总被引:1,自引:0,他引:1
Klemens Budde Hans-Hellmut Neumayer Gustav Lehne Michael Winkler Ingeborg Anni Hauser Arno Lison Lutz Fritsche Jean-Paul Soulillou Per Fauchald Jaques Dantal 《Nephrology, dialysis, transplantation》2004,19(10):2606-2614
BACKGROUND: Current immunosuppressant regimens need to be improved to prevent acute and chronic graft rejection. The novel macrocyclic immunosuppressant everolimus (Certican, RAD) is currently in clinical development to address this issue. METHODS: The primary objective of this multicentre, randomized, double-blind, placebo-controlled, dose-escalating phase 1 study was to evaluate the safety and tolerability of everolimus at four dose levels (0.75, 2.5, 5 and 10 mg/day) in maintenance renal transplant patients receiving cyclosporin and steroids. The secondary objective was to assess the pharmacokinetic profile of two different formulations (capsule and tablet) of everolimus. RESULTS: Fifty-four subjects were randomized for 4 weeks treatment with everolimus (n = 44) or placebo (n = 10). Dose levels of everolimus between 0.75 and 5 mg daily were well tolerated, permitting dose escalation to the highest everolimus dose of 10 mg daily. At this dose, everolimus was associated with a higher incidence and severity of adverse events, most notably thrombocytopenia. Pharmacodynamic assessment showed a relationship between drug exposure and thrombocytopenia. Notable reversible elevations of cholesterol were also observed at the 10 mg/day dose. Other changes in laboratory evaluations, including triglycerides, were minor, reversible and did not appear to be dose dependent. The bioavailability of the tablet formulation was 2.6-fold higher compared with the capsule, with evidence for dose proportionality over the dose range tested. Within-subject pharmacokinetic variability was low (coefficient of variation: 10-19%); however, between-subject variability ranged from 34 to 60% for AUC and C(max). CONCLUSIONS: These results indicate that up to 5 mg/day everolimus results in a dose-proportional exposure, and is adequately well tolerated in renal transplant recipients receiving cyclosporin and steroids. 相似文献
74.
Administration of nitrilotriacetic acid is known to cause the appearance of a mucopolysaccharide in blood and urine. The urinary excretion product has now been examined more specifically, has been shown to be degraded by chondroitinase AC, and is therefore chondroitin sulfate. 相似文献
75.
Heparin was demonstrated by the microelectrophoresis procedure of Jaques &; Wollin in endothelial powders obtained after acetone extraction of Häutchen preparations after injection of 1,000 units in rats. Concentrations of heparin calculated for the endothelium was 30 to 7,500 times greater than the concentration of heparin in blood at a given time with a comparable dose. An electron micrograph of preparations stained with Ruthenium Red taken at five minutes after intravenous injection of heparin, demonstrated a marked increase in electron density, as compared to normal endothelium, at the cell membrane and in vesicles near the luminal surface of the cell. 相似文献
76.
77.
Raymond F. Morgan Richard M. Hirata Darrell A. Jaques John R. Saunders 《American journal of surgery》1983,146(4):439-440
This study was carried out to determine the merit of contralateral supraomohyoid neck dissection in the clinically negative neck. When performed in conjunction with a standard radical neck dissection on the ipsilateral side, a yield of 2.8 percent pathologically positive nodes (5 of 177) was obtained in the contralateral neck. Little difference was noted in the yield of midline lesions versus unilateral lesions which approached the midline (3 and 2.6 percent, respectively). Similarly, the yield with preoperative radiation was close to that of the nonradiated group (3 and 2.7 percent, respectively). Additionally, in 1.7 percent of patients (3 of 177) with both clinically and pathologically negative nodes, metastases later developed in the contralateral neck, which indicates that the dissection is not necessarily effective in preventing future disease. The contralateral supraomohyoid neck dissection in the treatment of malignancies of the oral cavity, pharynx, and larynx does not appear to be of significant therapeutic value. 相似文献
78.
79.
Several hypotheses have been advanced for disorders of lipid metabolism such as atherosclerosis. However, these have not led to any significant means of control or cure. A reappraisal of the situation in the light of recent observations has led us to believe that lipid absorption and redistribution is under the control of a histamine-glycosaminoglycan-histaminase system which regulates vascular permeability. Failure of this control mechanism may lead to pathological conditions. 相似文献
80.