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161.
Chronic clonazepam administration decreases gamma-aminobutyric acidA receptor function in cultured cortical neurons 总被引:1,自引:0,他引:1
Chronic benzodiazepine administration has been reported to decrease gamma-aminobutyric acidA (GABAA) receptor function in animals and may alter benzodiazepine binding in neuronal cultures. To assess GABAA receptor function in neuronal cultures exposed to chronic clonazepam, we measured muscimol-stimulated chloride uptake in chick cerebral cortical cultures treated acutely and for 2, 4, and 10 days. Acute clonazepam administration (1 microM) led to an increase in GABA-related chloride uptake at lower doses of muscimol. After chronic clonazepam (1 microM), maximal uptake was markedly decreased at day 10, but maximal uptake was unchanged after 2- and 4-day treatments. Benzodiazepine receptor binding was decreased by approximately 60% after 10 days due to a decrease in receptor number. Decreases in chloride uptake were also observed after 10 days of treatment with 0.1 and 10 microM clonazepam. Concomitant treatment with 0.1 microM Ro15-1788 abrogated the effect of 0.1 microM clonazepam on chloride uptake. Chronic clonazepam treatment (1 microM) did not alter total cellular protein, cellular protein synthesis or degradation or percentage of neuronal cells, as determined morphologically and by [3H]ouabain binding. 相似文献
162.
Although beta-adrenergic blockade may increase coronary vascular resistance in some patients with severe ischemic heart disease, the effects of beta blockade on the nitroglycerin (NTG)-induced augmentation of coronary blood flow have not been elucidated. Therefore, systemic hemodynamic and anterior left ventricular regional coronary blood-flow (thermodilution) data were measured during administration of NTG into the left coronary artery, before and 10 min after intravenous propranolol (0.1 mg/kg) in 22 patients. Six patients (Group 1) had normal left coronary arteries and nine (Group 2) had severe coronary artery disease with at least greater than 70% narrowing of the left anterior descending artery. In seven additional patients (three without and four with greater than 70% left anterior descending coronary artery disease), measurements were obtained with constant-paced heart rates (Group 3). Before beta blockade, NTG (200 mcg) significantly increased anterior regional great-vein flow [for Group 1, 84 +/- 38% (81 +/- 20 to 140 +/- 60 ml/min); Group 2, 39 +/- 41% (61 +/- 26 to 83 +/- 38 ml/min); and Group 3, 87 +/- 55% (75 +/- 36 to 144 +/- 86 ml/min)]. In Groups 1 and 2, beta-adrenergic blockade reduced heart rate 10% (p less than 0.01) but did not affect mean arterial or pulmonary artery pressures.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
163.
E P Dellinger M J Wertz S D Miller M B Coyle 《Archives of surgery (Chicago, Ill. : 1960)》1988,123(6):745-750
In a prospective, double-blind study, 193 patients hospitalized for established hand infections were randomized to receive either cefamandole intravenously followed by cephalexin by mouth or methicillin intravenously followed by dicloxacillin by mouth. Careful aerobic and anaerobic cultures were performed. Multiple organisms grew in cultures from 84% of the patients (over three isolates per infection on average). Human bite wounds contained anaerobes 43% of the time compared with 12% for other wounds. The majority of wounds (72%) required operative treatment. In 128 patients assessable for treatment outcome, results were unsatisfactory in 11 (9%). There was no difference in outcome between cefamandole (6/59, 10%) and methicillin (5/59, 8%). The presence of anaerobes, Eikenella corrodens, human bites, or an increasing number of organisms was associated with an unsatisfactory response. The presence of Staphylococcus aureus and/or beta-hemolytic streptococci was associated with a favorable response. The incidence of antibiotic-resistant isolates did not correlate with outcome. 相似文献
164.
165.
166.
R S Haluck W E Richenbacher J L Myers C A Miller R K Wise J A Waldhausen 《The Journal of surgical research》1990,48(6):611-614
The repair of complex coarctation of the aorta often requires an aortic patch. Prosthetic patches lack growth potential and are associated with an increased incidence of aneurysm formation opposite the patch. We compared buffered glutaraldehyde-fixed patches, used in six animals (group 1), and untreated autologous pericardial aortic patches, used in five animals (group 2). Weanling pigs underwent pericardial patch replacement of a 1 X 2-cm diamond-shaped segment of the lateral wall of the descending thoracic aorta at the level of the aortic isthmus. Six months following patch aortoplasty, the animals were killed and the in situ patch dimensions were measured and compared to the measurements obtained at implantation. The increases in length, recorded as mean percentage change +/- SEM, were 34.7 +/- 3.7% for group 1 and 102.8 +/- 20.3% for group 2 animals; the increases in width were 91.4 +/- 31.7% for group 1 and 192.4 +/- 31.4% for group 2. The percentage changes for both length and width were significantly different between groups (P less than 0.05). Pull strength testing of standard-size patch samples demonstrated no significant difference in tensile breaking load between groups: group 1 = 959 +/- 277 g, group 2 = 795 +/- 86 g. Thoracic aortography revealed no evidence of stenosis or aneurysmal dilation in either group. Autologous pericardium is resilient, strong, and readily available and has expansile potential that makes it an ideal aortic patch material. We conclude that glutaraldehyde fixation does not provide additional strength and limits graft expansile potential when compared to untreated pericardium. 相似文献
167.
Gonadotropin releasing hormone (GnRH), as well as an antagonist [Ac-D2Nal,1 D4ClPhe,2 D3Pal,3 NicLys,5 DNicLys,6 ILys,8 DAla10] GnRH.HOAc (1) and a superagonist [DTrp6, Pro9-NHEt]GnRH (2), have been electrochemically driven across excised hairless mouse skin. Determined by HPLC analysis, the delivery rate from aqueous solution into isotonic saline at 0.5 mA cm-2 was as high as 19 nM cm-2 h-1 for 2. Because of its insolubility in water, analogue 1 could only be delivered from an acidic donor solution. Analogue 2 was also delivered in pulsatile fashion using current on/off cycles. For all three peptides, passive transport was negligible and stability is evident when in contact with the stratum corneum. Slow metabolism occurs when GnRH contacts the dermal side of hairless mouse skin. 相似文献
168.
B Zumoff G W Strain L K Miller W Rosner C D Levit E H Miller R S Rosenfeld 《International journal of obesity (2005)》1988,12(6):525-531
Obese men have hyperestrogenemia-induced hypogonadotropic hypogonadism (HHG), due, we believe, to increased rarmatization of adrenal androgens by the increased bulk of aromatase-containing adipose tissue. We studied the effects of corticosuppressive doses of dexamethasone (D) on 24-h mean plasma total and free estradiol (E2), estrone (E1), LH, FSH, total and free testosterone, delta 4-androstenedione (delta 4), and sex-hormone-binding globulin (SHBG) in nine obese men and five normal-weight controls. In the obese men, the following hormones fell: E2 [59 +/- 19 to 39 +/- 11 pg/ml (P less than 0.01)], E1 [93 +/- 41 to 50 +/- 25 pg/ml; (P less than 0.01)], delta 4-androstenedione [120 +/- 80 to 55 +/- 27 ng/dl; (P less than 0.02)]; free E2 [1.6 +/- 0.4 to 1.1 +/- 0.2 pg/ml; (P less than 0.01)], SHBG [12.8 +/- 5.3 to 8.2 +/- 3 nM/l; (P less than 0.04)]. FSH rose from 4.8 +/- 3.2 to 7.6 +/- 4.2 miu/ml (P less than 0.01). LH, total and free testosterone showed no significant change. In the nonobese men, there were decreases in total E2 [(34 +/- 6.8 to 25 +/- 10 pg/ml; P less than 0.04)], SHBG [16.8 +/- 7.5 to 10.4 +/- 2.0 nM/l: P less than .05.], free E2 [0.9 +/- 0.2 to 0.7 +/- 0.3 pg/ml: P less than 0.05], delta 4 [91.4 +/- 3.6 to 33.4 +/- 16.7 ng/dl; P less than .01] and total T [492 +/- 44 to 393 +/- 121 ng/dl; P less than 0.04]. There was no significant change in E1, FSH, LH or free T.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
169.
170.
Tamara M Paravicini Alyson A Miller Grant R Drummond Christopher G Sobey 《Journal of cerebral blood flow and metabolism》2006,26(6):836-845
Reactive oxygen species (ROS) such as superoxide (O2*-) and hydrogen peroxide (H2O2) are known cerebral vasodilators. A major source of vascular ROS is the flavin-containing enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase. Activation of NADPH-oxidase leads to dilatation of the basilar artery in vivo via production of H2O2, but the endogenous stimuli for this unique vasodilator mechanism are unknown. Shear stress is known to activate both NADPH-oxidase and phosphatidylinositol-3 kinase (PI3-K) in cultured cells. Hence, this study used a cranial window preparation in anesthetized rats to investigate whether increased intraluminal blood flow could induce cerebral vasodilatation via the activation of NADPH-oxidase and/or PI3-K. Bilateral occlusion of the common carotid arteries to increase basilar artery blood flow caused reproducible, reversible vasodilatation. Topical treatment of the basilar artery with the NADPH-oxidase inhibitor diphenyleneiodonium (DPI) (0.5 and 5 micromol/L) inhibited flow-induced dilatation by up to 50% without affecting dilator responses to acetylcholine. Treatment with the H2O2 scavenger, catalase similarly attenuated flow-induced dilatation, suggesting a role for NADPH-oxidase-derived H2O2 in this response. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) partially reduced flow-induced dilatation, and combined treatment with a ROS inhibitor (DPI or catalase) and L-NAME caused a greater reduction in flow-induced dilatation than that seen with any of these inhibitors alone. Flow-induced dilatation was also markedly inhibited by the PI3-K inhibitor, wortmannin. Increased O2*- production in the endothelium of the basilar artery during acute increases in blood flow was confirmed using dihydroethidium. Thus, flow-induced cerebral vasodilatation in vivo involves production of ROS and nitric oxide, and is dependent on PI3-K activation. 相似文献