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11.
J W Cox L G Dring L C Ginsberg P G Larson D A Constable R G Ulrich 《Drug metabolism and disposition》1990,18(5):726-731
Trospectomycin sulfate is an experimental, aminocyclitol antibiotic. It has been shown in preclinical, chronic safety studies in the dog and rat to elicit a reversible, lysosomal phospholipidosis in liver. The present experiments were conducted to characterize the tissue distribution and disposition of 3H]trospectomycin sulfate in the male rat, perfused rat, perfused rat liver, and cultured rat hepatocytes. Following a 5 mg/kg iv dose to four rats, approximately 70% of the dose was recovered within 24 hr primarily in urine as unchanged drug, and the remainder was eliminated with a terminal phase half-life in blood and tissues of 3 days. Fecal excretion was relatively minor (16% of the dose recovered in feces in 7 days) until later timepoints, when it was the principal pathway of terminal phase elimination. The liver sequestered approximately 10% of the dose and had the highest tissue levels of drug at all times measured. Liver perfusion experiments indicated that trospectomycin accumulated in a hepatic depot compartment as parent drug by a first-order process which was nonsaturable up to a 1 mM concentration of drug. Biliary excretion of unchanged trospectomycin by the perfused liver was slow (approximately 3% of the dose in 2 hr) and occurred by both paracellular and transcellular mechanisms. The hepatic depot compartment appeared to be responsible for transcellular biliary excretion, and thus for the sustained fecal excretion observed in vivo. Subcellular distribution experiments indicated that at least 50% of the drug in the hepatic depot was sequestered in organelles having a broad density range. The existence of a trospectomycin depot compartment was also demonstrated in cultured hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
12.
Summary— To investigate if the functional alterations observed in resistance arteries of spontaneously hypertensive rats (SHRs) were also present at the coronary level, in vitro experiments were performed in mesenteric resistance arteries (MRA) and in right (RIC) and left interventricular coronary (LIC) arteries taken from 15–25-week-old SHR and age-matched Wistar Kyoto rats WKYs. Using a passive extension protocol, internal diameters corresponding to 100 mmHg intraluminal pressure (D100) were determined and vessels were set up to a normalized internal diameter (0.9 D100). SHR mesenteric resistance arteries had a significantly smaller diameter compared to WKY arteries, whereas both types of SHR coronary arteries had a greater diameter compared to those of WKY rats. In arteries in the absence of contracting agonist, nitro-L-arginine (NOLA, 100 μM) induced a progressive rise in basal tone, which could be reversed by subsequent addition of L-arginine (100 μM) but not D-arginine (100 μM). When expressed as percent of maximal contractions induced by agonists (noradrenaline, NA [10 μM] in MRA; serotonin, 5-HT [10 μM], in RIC and LIC), these contractions were significantly stronger in WKY compared to SHR coronary and mesenteric resistance arteries. In NA-precontracted MRA and 5HT-precontracted coronary arteries in the presence of indomethacin (10 μM), the magnitude of acetylcholine-induced maximal relaxations (expressed as percent of maximal contractions induced by agonists) was greater in WKY compared to SHR arteries. After a 30-min incubation period, NOLA (100 μM) completely inhibited relaxations induced by acetylcholine (0.01–10 μM) in all types of precontracted arteries. Subsequent additions of sodium nitroprusside, (SNP, 10 μM) induced complete relaxations in all preparations. These results show that a basal release of NO or NO-like compound by endothelial cells is present in isolated mesenteric resistance and coronary arteries of WKY rats and SHRs. The contribution of endothelium-derived relaxing factor-nitric oxide (EDRF-NO) to arterial tone was lower in MRA compared to coronary arteries in both strains and in SHR compared to WKY arteries. In the SHR preparations, the impaired relaxation induced by acetylcholine appeared to be due to a functional alteration of the endothelium in the presence of normal reactivity of the smooth muscle cells. 相似文献
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The effects of neuropeptide Y and its fragments upon basal and electrically stimulated ion secretion in rat jejunum mucosa. 总被引:3,自引:3,他引:0
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1. The effects of acute or chronic morphine treatment on the changes in blood pressure and pulse rate in response to ganglionic stimulation or blockade and to vagal stimulation, and of isolated atria to field stimulation or noradrenaline, were studied. 2. In pithed rats, intravenously injected hexamethonium significantly depressed the blood pressure responses to sympathetic nerve stimulation. The ganglionic blocking effects of hexamethonium were significantly greater in chronically morphine-treated rats, but were not significantly affected by acute morphine administration in naive animals. 3. Intravenous administration of nicotine dose-dependently increased blood pressure and pulse rate. The magnitudes of these changes were not significantly affected by acute or chronic morphine pretreatment. 4. Studies with rat isolated atrial preparations revealed that the changes in atrial contractile rate and force in response to noradrenaline or field stimulation were not influenced by either acute or chronic morphine treatment. 5. Cervical vagal stimulation produced voltage- or frequency-dependent decreases in pulse rate and blood pressure. The responses were not significantly affected by chronic morphine treatment. 6. These findings suggest that the site of the changes in sympathetic function following prolonged exposure to the opiate appears to be on the preganglionic nerve fibres. 相似文献
17.
T M Crombleholme A A deLorimier N S Adzick M T Longaker M R Harrison K L Cox M B Heyman 《Journal of pediatric surgery》1990,25(8):843-845
Mediastinal pseudocyst is an unusual complication of pancreatitis, with only four cases previously reported in children. The extent of the pseudocyst can be defined by computed tomography or magnetic resonance imaging scan and preoperative aspiration of cyst fluid for amylase level can establish the diagnosis. Endoscopic retrograde cholangiopancreatography to define ductal anatomy can help plan the appropriate drainage procedure. Although exceedingly rare, the diagnosis of pseudocyst should be considered for any cystic mass in the abdomen or thorax, even in the absence of elevated amylase or history suggesting pancreatitis. 相似文献
18.
表小檗碱对α受体的作用 总被引:2,自引:0,他引:2
表小檗碱(epiberberine,EB)是从湖北产黄连(Coptis chinensis Franch)中提取的一种生物碱,属苯喹嗪类原小檗碱,对其药理作用的研究资料甚少,未见其对α肾上腺素体作用的报道。资料表明,许多原小檗碱类化合物有α受体阻滞作用,为从该类化合物中选择 相似文献
19.
G. J. Cox G. J. Bates A. B. Drake-Lee D. J. Watson 《Annals of the Royal College of Surgeons of England》1988,70(6):361-362
Acute epiglottitis is a potentially fatal upper respiratory tract infection. In this paper, we describe the use of flexible nasoendoscopy, both in establishing the diagnosis and during the subsequent airway management of adults with acute epiglottitis. 相似文献
20.
I Cox 《Optometry and vision science》1990,67(4):277-282
Although previous investigators have attempted to calculate the longitudinal spherical aberration inherent in soft and rigid contact lenses both on and off the eye, the use of inappropriate assumptions on which to base their calculations has left the problem unresolved. In this study, the longitudinal spherical aberration of both soft and rigid contact lenses was calculated surface by surface both in air and on the eye using a two-dimensional, exact ray tracing program. The erroneous assumptions made by previous investigators were avoided by using an elliptical model for the anterior corneal surface and assuming that the posterior surfaces of soft lenses aligned exactly with the anterior corneal surface after flexure onto the eye. The results demonstrated that, with a 6-mm pupil, contact lenses induce significant levels of spherical aberration in the ocular system for soft lenses of back vertex power greater than +3.00 D or -6.00 D and for rigid lenses of powers more positive than -3.00 D. It is suggested that visual disturbance due to induced spherical aberration has not been a major clinical problem in the past because these conditions fall outside those experienced by a large proportion of the contact lens-wearing public. 相似文献