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71.
Rectal cancer affects 40,000 people annually in the United States. Traditionally, operative therapy has involved abdominoperineal resection. This procedure results in a permanent colostomy and carries a high incidence of impotence and urinary retention. Because of improvements in operative techniques, perioperative care, and adjuvant tumor therapy, less invasive local techniques of tumor resection have become excellent options. 相似文献
72.
M Egertová DK Giang BF Cravatt MR Elphick 《Canadian Metallurgical Quarterly》1998,265(1410):2081-2085
CB1-type cannabinoid receptors in the brain mediate effects of the drug cannabis. Anandamide and sn-2 arachidonylglycerol (2-AG) are putative endogenous ligands for CB1 receptors, but it is not known which cells in the brain produce these molecules. Recently, an enzyme which catalyses hydrolysis of anandamide and 2-AG, known as fatty acid amide hydrolase (FAAH), was identified in mammals. Here we have analysed the distribution of FAAH in rat brain and compared its cellular localization with CB1-type cannabinoid receptors using immunocytochemistry. High concentrations of FAAH activity were detected in the cerebellum, hippocampus and neocortex, regions of the rat brain which are enriched with cannabinoid receptors. Immunocytochemical analysis of these brain regions revealed a complementary pattern of FAAH and CB1 expression with CB1 immunoreactivity occurring in fibres surrounding FAAH-immunoreactive cell bodies and/or dendrites. In the cerebellum, FAAH was expressed in the cell bodies of Purkinje cells and CB1 was expressed in the axons of granule cells and basket cells, neurons which are presynaptic to Purkinje cells. The close correspondence in the distribution of FAAH and CB1 in rat brain and the complementary pattern of FAAH and CB1 expression at the cellular level provides important new evidence that FAAH may participate in cannabinoid signalling mechanisms of the brain. 相似文献
73.
In studying the alcohol-morbidity association, a substantial amount of attention and efforts has been focused on volume of alcohol intake. Considerably less is known about the differential health effects of beverage types. The present study used a most recent national household survey of the U.S. general population on drinking practices, alcohol use disorders, and their associated disabilities. The prevalence of a broad range of alcohol-related diseases was examined with respect to preferred beverage type, as well as consumption level. Our findings showed a reduced health risk associated with beer and wine drinking for a number of physical disorders, and a somewhat favorable cardiovascular effect of these two beverage types in relation to abstention. Among preferrers of beer, wine, and liquor, the results indicate that liquor preference is associated with elevated morbidity for several medical consequences. However, interpretation of results and the public health implications of these findings need to be taken cautiously, because sociodemographic and other behavioral characteristics were not considered in this preliminary report. 相似文献
74.
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76.
Oxytocin analogues which combine high oxytocic activities with negligible antidiuretic and pressor activities have been studied. [4-Threonine,7-glycine]oxytocin, [1-(L-2-hydroxy-3-mercaptopropionic acid),4-threonine,7-glycine]oxytocin, and [1-(L-2-hydroxy-3-mercaptopropionic acid)]oxytocin were found to possess the following specific biological activities respectively: rat uterotonic, 270 +/- 10, 337 +/- 23, 1542 +/- 0.4; rat antidiuretic, 0.002 +/- 0.0008, 0.048 +/- 0.005, 40.3 +/- 2.4. The results are analyzed from a conformation-activity viewpoint in a continued attempt to evaluate the scope and limitations of this approach in comparison to structure-activity studies. 相似文献
77.
SA Kates BF McGuinness C Blackburn GW Griffin NA Solé G Barany F Albericio 《Canadian Metallurgical Quarterly》1998,47(5):365-380
In the rat dorsal hippocampus and dorsal raphe nucleus, the microiontophoretic application of ergotamine and 5-HT suppressed the firing activity of CA3 pyramidal neurons and 5-HT neurons, an effect antagonized by selective 5-HT1A receptor antagonists. Co-application of ergotamine prevented the inhibitory action of 5-HT on the firing activity of CA3 pyramidal neurons but not of 5-HT neurons, indicating that ergotamine acted as a partial 5-HT1A receptor agonist in the dorsal hippocampus and as a full agonist at 5-HT1A autoreceptors. Ergotamine decreased, in a concentration-dependent manner, the electrically evoked release of [3H]5-HT in preloaded rat and guinea pig hypothalamus slices; this effect was prevented by the nonselective 5-HT receptor antagonist methiothepin but not by the selective 5-HT1B/1D receptor antagonist GR 127935 or the alpha 2-adrenoceptor antagonist idazoxan. Although body temperature in humans remained unchanged following inhaled ergotamine, in the rat, subcutaneously injected ergotamine produced a hypothermia that was prevented by a pretreatment with the 5-HT1A/1B receptor/beta-adrenoceptor antagonist pindolol. Finally in humans, ergotamine did not alter prolactin or adrenocorticotropic hormone levels, but increased growth hormone level, which was prevented by pindolol. Cortisol level was increased in humans by ergotamine, but this enhancement was unaltered by pindolol. In conclusion, the present results suggest that ergotamine acted in the rat brain as a 5-HT1A receptor agonist and as an agonist of terminal 5-HT autoreceptor of a yet undefined subtype. In humans, ergotamine also displayed some 5-HT1A receptor activity but, probably because of lack of receptor selectivity, it did not present the same profile as other 5-HT1A receptor agonists. 相似文献
78.
RC Ribeiro RR Cavalieri N Lomri CM Rahmaoui JD Baxter BF Scharschmidt 《Canadian Metallurgical Quarterly》1996,271(29):17147-17151
Actions of thyroid hormones (THs) are determined by intracellular free hormone concentration. Here we report that enhanced TH extrusion via a saturable, cold-sensitive mechanism lowers intracellular TH and causes TH resistance in hepatoma cells. Since these cells overexpress multidrug resistance P-glycoproteins and TH extrusion and resistance are blunted by verapamil, P-glycoproteins may mediate this resistance. Verapamil-inhibitable TH efflux was also found in primary hepatocytes, cardiocytes, and fibroblasts. These findings demonstrate that TH extrusion can modulate TH availability and action in mammalian cells. 相似文献
79.
BF Bebo E Zelinka-Vincent G Adamus D Amundson AA Vandenbark H Offner 《Canadian Metallurgical Quarterly》1998,84(2):122-130
Rotational atherectomy is effective acutely in treating complex coronary disease, but less is known about its long-term clinical outcome. We examined the acute results and late clinical outcome in 178 patients undergoing treatment with this device. Rotational atherectomy was used to treat 240 lesions in 178 individual patients. Nineteen percent had multilesion or staged multivessel procedures, and 71% had AHA-ACC Type B2/C lesions. The procedure was completed successfully in 94% of patients. Major complications occurred in 6% (death 1%, Q-MI 2.8%, and emergency bypass surgery 2.2%). Clinical follow-up was available for 167 (94%) patients at 13+/-6 months. Thirty-five percent required additional catheterization because of recurrent symptoms or an abnormal stress test. Clinical restenosis was confirmed in 18%, and an additional 2.2% of patients had progression of disease in previously untreated segments. At the end of 1 year, 14% had undergone repeat target vessel revascularization. Cumulatively at follow-up, approximately 80% had avoided an acute major complication and repeat revascularization for restenosis. Rotational atherectomy provides excellent acute and good late clinical results. At 1 year follow-up, the likelihood of developing clinical restenosis or significant progression of disease was 1 in 5, and patients had a 1 in 7 chance of requiring revascularization because of restenosis. These findings are encouraging and indicate that rotational atherectomy can be performed safely and with a high degree of acute and late clinical success in complex coronary disease characterized by multivessel or multilesion involvement and a predominance of B2 and C lesions. 相似文献
80.
This study examined the cardioprotective effects and pharmacology of the novel adenosine A1/A2 receptor agonist ([1S-[1a,2b,3b, 4a(S*)]]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-3H-imida zo[4,5-b] pyridyl-3-yl] cyclopentane carboxamide) (AMP 579), in a model of myocardial infarction. Experiments were performed in pentobarbital-anesthetized pigs in which myocardial infarction was induced by a 40-min occlusion of the left anterior descending coronary artery, followed by 3 hr of reperfusion. This procedure resulted in approximately 20% of the left ventricle being made ischemic in all test groups. In untreated animals, an infarct size equal to 56 +/- 5% of the ischemic area was observed. Preconditioning, with two cycles of 5 min of ischemia followed by 10-min reperfusion, resulted in a 70% reduction in infarct size (17 +/- 5%) relative to risk area. Administration of AMP 579 30 min before ischemia (3 microg/kg i.v. followed by 0.3 microg/kg/min i.v. through 1 hr of reperfusion) did not change blood pressure, HR or coronary blood flow but resulted in marked cardioprotection: a 98% reduction in infarct size (1 +/- 1%) relative to risk area. Moreover, whereas approximately 90% of control pigs suffered ventricular fibrillation during ischemia, no fibrillation was observed in animals treated with AMP 579. Further experiments determined the effects of AMP 579 when administered 30 min after the onset of myocardial ischemia, 10 min before reperfusion. Two doses were studied: a low hemodynamically silent dose (3 microg/kg + 0.3 microg/kg/min through 1 hr of reperfusion) and a 10-fold higher dose that did cause reductions in blood pressure and HR. Both doses of AMP 579 produced a comparable cardioprotective effect, reducing infarct size to approximately 50% of that observed in control animals. The cardioprotective effect of AMP 579 was a consequence of adenosine receptor stimulation, because it was completely inhibited by pretreatment with the specific adenosine receptor antagonist CGS 15943 (1 mg/kg i.v.). However, the selective A1 receptor agonist GR 79236 (3 microg/kg + 0.3 microg/kg/min i.v.) did not reduce infarct size, which suggests that under these experimental conditions, stimulation of adenosine A2 receptors is important for the cardioprotective effect of AMP 579. The adenosine-regulating agent acadesine (5 mg/kg + 0.5 mg/kg/min i.v.) also failed to reduce infarct size. In conclusion, the novel adenosine A1/A2 receptor agonist AMP 579 produces marked cardioprotection whether administered before myocardial ischemia or reperfusion. Cardioprotection is not dependent on changes in afterload or myocardial oxygen demand and is a consequence of adenosine receptor stimulation. The pharmacological profile of AMP 579 in this model is consistent with its potential utility in the treatment of acute myocardial infarction. 相似文献