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131.
OBJECTIVE: Dopamine D2 receptor occupancy measurements provide a valid predictor of antipsychotic response, extrapyramidal side effects, and elevation of prolactin levels. The new antipsychotics clozapine, risperidone, and olanzapine obtain antipsychotic response with few extrapyramidal side effects and little prolactin elevation. The purpose of this study was to compare the D2 and serotonin 5-HT2 receptor occupancies of these drugs in patients receiving multiple-dose, steady-state regimens. METHOD: Forty-four patients with schizophrenia (16 taking risperidone, 2-12 mg/day; 17 taking olanzapine, 5-60 mg/day; and 11 taking clozapine, 75-900 mg/day) had their D2 and 5-HT2 occupancies determined with the use of [11C]raclopride and [18F]setoperone, respectively, and positron emission tomography imaging. RESULTS: Clozapine showed a much lower D2 occupancy (16%-68%) than risperidone (63%-89%) and olanzapine (43%-89%). Risperidone and olanzapine gave equal D2 occupancies at doses of 5 and 20 mg/day, respectively. All three drugs showed greater 5-HT2 than D2 occupancy at all doses, although the difference was greatest for clozapine. CONCLUSIONS: Clozapine, at doses known to be effective in routine clinical settings, showed a D2 occupancy clearly lower than that of typical antipsychotics, while risperidone and olanzapine at their usual clinical doses gave the same level of D2 occupancy as low-dose typical antipsychotics. The results also suggest that some previous clinical comparisons of antipsychotics may have been confounded by different levels of D2 occupancy. Clinical comparisons of these drugs, matching for D2 occupancy, may provide a better measure of their true "atypicality" and will help in understanding the contribution of non-D2 receptors to antipsychotic effects. 相似文献
132.
Neutral glycolipids (NGL) are promising diagnostic markers of human gliomas, but differences in NGL with age and sex have
not been examined. Previous work demonstrated that ceramide dihexosides (CDH) levels in mouse kidney are age- and sex-dependent,
probably due to levels of sex hormones. We quantitated CDH in 181 human gliomas and found significant differences with sex
and age, particularly menopause and male puberty. This emphasizes the importance of assessing results of studies on glycolipids
in disease states with respect to age and sex in order to avoid erroneous conclusions concerning the relationship of glycolipid
composition with diagnosis and pathogenesis. 相似文献
133.
Rios M.A. Kirschen D.S. Jayaweera D. Nedic D.P. Allan R.N. 《Power Systems, IEEE Transactions on》2002,17(3):543-548
Deterministic security criteria provide a degree of security that may be insufficient under some operating conditions and excessive for others. To determine an appropriate level of security, one should perform a probabilistic cost/benefit analysis that balances the cost of the security margin against its benefits, i.e., the expected societal cost of the avoided outages. This paper shows how a previously published method based on Monte Carlo simulation can be enhanced to take into account time-dependent phenomena (TDP) such as cascade tripping of elements due to overloads, malfunction of the protection system, and potential power system instabilities. In addition, the importance of using failure rates that reflect the weather conditions is discussed. Studies based on the South-Western part of the transmission network of England and Wales demonstrate the validity of the models that have been developed. 相似文献
134.
RB Goldberg 《Canadian Metallurgical Quarterly》1998,82(4):805-821
Type 2 diabetes is a major cause of morbidity and mortality resulting from its microangiopathic and macroangiopathic complications. Current approaches to its management and to the prevention of diabetic complications are difficult to implement effectively, and there is little evidence to date that these approaches are reducing the impact of this disease. The recognition that type 2 diabetes usually has a prolonged prediabetic phase raises the possibility that the emergence of hyperglycemia and the atherosclerotic complications associated with diabetes may be preventable by the institution of early treatment modalities. Sufficient data suggest that life-style modification or pharmacotherapy directed at improving insulin sensitivity or insulin secretion in subjects with impaired glucose tolerance may reduce progression to diabetes. Two long-term prospective, controlled trials have been initiated to test this hypothesis. 相似文献
135.
ML Wei F Bonzelius RM Scully RB Kelly GA Herman 《Canadian Metallurgical Quarterly》1998,140(3):565-575
The trafficking of GLUT4, a facilitative glucose transporter, is examined in transfected CHO cells. In previous work, we expressed GLUT4 in neuroendocrine cells and fibroblasts and found that it was targeted to a population of small vesicles slightly larger than synaptic vesicles (Herman, G.A, F. Bonzelius, A.M. Cieutat, and R.B. Kelly. 1994. Proc. Natl. Acad. Sci. USA. 91: 12750-12754.). In this study, we demonstrate that at 37 degrees C, GLUT4-containing small vesicles (GSVs) are detected after cell surface radiolabeling of GLUT4 whereas uptake of radioiodinated human transferrin does not show appreciable accumulation within these small vesicles. Immunofluorescence microscopy experiments show that at 37 degrees C, cell surface-labeled GLUT4 as well as transferrin is internalized into peripheral and perinuclear structures. At 15 degrees C, endocytosis of GLUT4 continues to occur at a slowed rate, but whereas fluorescently labeled GLUT4 is seen to accumulate within large peripheral endosomes, no perinuclear structures are labeled, and no radiolabeled GSVs are detectable. Shifting cells to 37 degrees C after accumulating labeled GLUT4 at 15 degrees C results in the reappearance of GLUT4 in perinuclear structures and GSV reformation. Cytosol acidification or treatment with hypertonic media containing sucrose prevents the exit of GLUT4 from peripheral endosomes as well as GSV formation, suggesting that coat proteins may be involved in the endocytic trafficking of GLUT4. In contrast, at 15 degrees C, transferrin continues to traffic to perinuclear structures and overall labels structures similar in distribution to those observed at 37 degrees C. Furthermore, treatment with hypertonic media has no apparent effect on transferrin trafficking from peripheral endosomes. Double-labeling experiments after the internalization of both transferrin and surface-labeled GLUT4 show that GLUT4 accumulates within peripheral compartments that exclude the transferrin receptor (TfR) at both 15 degrees and 37 degrees C. Thus, GLUT4 is sorted differently from the transferrin receptor as evidenced by the targeting of each protein to distinct early endosomal compartments and by the formation of GSVs. These results suggest that the sorting of GLUT4 from TfR may occur primarily at the level of the plasma membrane into distinct endosomes and that the organization of the endocytic system in CHO cells more closely resembles that of neuroendocrine cells than previously appreciated. 相似文献
136.
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139.
A Carroccio M Fontana MI Spagnuolo G Zuin G Montalto RB Canani F Verghi A Bavusotto K Bastoni MC Boccia A Guarino 《Canadian Metallurgical Quarterly》1998,33(9):998-1001
Obstructive sleep apnea (OSA) syndrome occurs in 4% to 9% of middle-aged men and in 1% to 2% of middle-aged women. The incidence of OSA among morbidly obese patients is 12- to 30-fold higher. The pathophysiology of OSA is complex and incompletely understood. The important clinical symptoms of OSA include snoring, daytime sleepiness, restless sleep, morning fatigue, and headaches. The diagnosis is made by polysomnography. The possible sequelae of OSA are hypertension, left and right ventricular hypertrophy, sudden cardiovascular death, and increased risk for brain infarction. Nasal continuous positive airway pressure (nCPAP) appears to be the recommended treatment for OSA. Morbidly obese patients may also benefit from weight reduction gastric surgery. 相似文献
140.
RB Cohen JP Dormans ME Guttenberg JV Hunter 《Canadian Metallurgical Quarterly》1997,(343):249-52, 256-9