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C. S. Peretti J. M. Danion F. Kauffmann-Muller D. Grangé A. Patat P. Rosenzweig 《Psychopharmacology》1997,129(4):329-338
Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid
dependence. The purpose of this study was to determine the abuse liability of parenteral buprenorphine in volunteers maintained
on daily sublingual (SL) buprenorphine (8 mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges
two times per week. Medication challenges were 16 h after the daily dose of buprenorphine, and consisted of double-blind IM
injections of buprenorphine (4, 8, 16 mg), the prototypic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessments
consisted of physiologic monitoring, subjects’ self-reports, and a trained observer’s ratings of drug effects, and were collected
for 0.5 h before and 2.0 h following injection. Supplemental doses of IM buprenorphine produced opioid agonist-like effects,
indicating some abuse potential of parenteral buprenorphine in buprenorphine-maintained patients. There was incomplete cross-tolerance
to the effects of hydromorphone, suggesting that higher maintenance doses of buprenorphine may be needed to maximize clinical
efficacy. However, there was a lack of graded dose-effects for hydromorphone, suggesting that buprenorphine’s combination
of partial agonist effects and high affinity for opioid receptors may limit the magnitude of effects of supplemental full
agonists. Finally, participants tolerated cumulative doses of maintenance buprenorphine plus challenge buprenorphine without
adverse effects, suggesting higher doses of buprenorphine can be safely administered to opioid dependent patients.
Received: 22 February 1996/Final version: 23 August 1996 相似文献
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A. I. Fabra De Peretti G. B. Mori De Moro N. E. Ghittoni A. M. Evangelista De Duffard R. O. Duffard 《Environmental toxicology》1987,2(2):217-228
The effects of 2,4-Dichlorophenoxyacetic acid on the growth rate, chemical composition, 14C-2,4-dichlorophenoxyacetic acid and 45Ca2+ uptake by Rhizobium sp. M 4 able to nodulate Arachis hypogaea were determined. Cellular growth was diminished by the presence of 10?3 M 2,4-dichlorophenoxyacetic acid in the medium. Alterations in cellular chemical composition, in 14C-2,4-dichlorophenoxyacetic acid and in 45Ca2+ uptake were found. 相似文献
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Epidermal growth factor directly stimulates steroidogenesis in primary cultures of porcine Leydig cells: actions and sites of action 总被引:7,自引:0,他引:7
The actions and the mechanisms of action of epidermal growth factor (EGF) in testicular steroidogenesis were investigated using a model of primary culture of purified porcine Leydig cells from immature intact animals. EGF decreased (1.7-fold) human CG (hCG)-induced dehydroepiandrosterone (DHEA) accumulation in the medium whereas it enhanced (2.5-fold) that of testosterone. The maximal and half-maximal effects on both DHEA and testosterone secretions were observed at similar concentrations which were, respectively, 3 (5 x 10(-10) M) and 0.7 (11 x 10(-11) M) ng/ml EGF, after 72-h treatment. EGF effect on DHEA and testosterone secretion was similarly observed whether the cells were acutely (3 h) stimulated with hCG (1 ng/ml) or with 8-bromo-cAMP (10(-3) M). To further localize the steroidogenic biochemical steps affected by EGF, the growth factor action on steroidogenic enzyme activities was investigated. EGF increased delta 5 steroid intermediate (i.e. pregnenolone and DHEA) formation [evaluated in the presence of 10(-5) M of WIN 24540, an inhibitor of 3 beta-hydroxysteroid dehydrogenase/iosomerase (3 beta-HSDI) activity]. However, this stimulation was observed in cells when acutely (3 h) stimulated with hCG (0.01-1 ng/ml) but not when incubated with 22R-hydroxycholesterol (0.01-10 micrograms/ml). Such findings indicate that EGF did not affect cholesterol side chain cleavage cytochrome P450 activity but probably increased cholesterol substrate availability for this enzyme in the inner mitochondria. Moreover, EGF significantly (P less than 0.001) increased delta 5 steroid intermediate (i.e. pregnenolone and DHEA) but not delta 4 steroid intermediate (i.e. progesterone and androstenedione) conversion into testosterone, indicating that EGF enhances 3 beta-HSDI activity. Such effects of EGF are directly exerted on Leydig cells since EGF receptors (Kd = 16 x 10(-11) M) are present in primary cultures of purified porcine Leydig cells. Together, the present findings show that in Leydig cells from intact animals, EGF enhances the gonadotropin action on testosterone formation through an increase in the availability of cholesterol substrate in the mitochondria as well as an increase in the activity of 3 beta-HSDI. 相似文献
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Kinnison ML; Perler BA; Kaufman SL; Mitchell SE; Kadir S; Williams GM; White RI Jr 《Radiology》1986,160(3):727-730
In situ saphenous vein grafts are being used with increasing frequency for bypass procedures involving the femoral and popliteal arteries. Complications of these procedures include anastomotic stenoses and persistent arteriovenous fistulae that may result in failure of the graft. Balloon angioplasty and embolotherapy with detachable balloons were employed successfully in three or four recent cases of patients with complications from in situ grafts. Tailored angiography is essential for evaluating in situ grafts, and interventional techniques are extremely useful for managing complications. 相似文献
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