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排序方式: 共有335条查询结果,搜索用时 19 毫秒
91.
Fan H Kotsikorou E Hoffman AF Ravert HT Holt D Hurst DP Lupica CR Reggio PH Dannals RF Horti AG 《European journal of medicinal chemistry》2009,44(2):593-608
Cyano analogs of Rimonabant with high binding affinity for the cerebral cannabinoid receptor (CB1) and with optimized lipophilicity have been synthesized as potential positron emission tomography (PET) ligands. The best ligands of the series are optimal targets for the future radiolabeling with PET isotopes and in vivo evaluation as radioligands with enhanced properties for PET imaging of CB1 receptors in human subjects. Extracellular electrophysiological recordings in rodent brain slices demonstrated that JHU75528, 4, the lead compound of the new series, has functional CB antagonist properties that are consistent with its structural relationship to Rimonabant. Molecular modeling analysis revealed an important role of the binding of the cyano group with the CB1 binding pocket. 相似文献
92.
Meike AQ Mutsaerts Henk Groen Nancy CW ter Bogt Johanna HT Bolster Jolande A Land Wanda JE Bemelmans Walter KH Kuchenbecker Peter GA Hompes Nick S Macklon Ronald P Stolk Fulco van der Veen Jacques WM Maas Nicole F Klijn Eugenie M Kaaijk Gerrit JE Oosterhuis Peter XJM Bouckaert Jaap M Schierbeek Yvonne M van Kasteren Annemiek W Nap Frank J Broekmans Egbert A Brinkhuis Carolien AM Koks Jan M Burggraaff Adrienne S Blankhart Denise AM Perquin Marie H Gerards Robert JAB Mulder Ed TCM Gondrie Ben WJ Mol Annemieke Hoek 《BMC women's health》2010,10(1):1-9
Background
In the Netherlands, 30% of subfertile women are overweight or obese, and at present there is no agreement on fertility care for them. Data from observational and small intervention studies suggest that reduction of weight will increase the chances of conception, decrease pregnancy complications and improve perinatal outcome, but this has not been confirmed in randomised controlled trials. This study will assess the cost and effects of a six-months structured lifestyle program aiming at weight reduction followed by conventional fertility care (intervention group) as compared to conventional fertility care only (control group) in overweight and obese subfertile women. We hypothesize that the intervention will decrease the need for fertility treatment, diminish overweight-related pregnancy complications, and will improve perinatal outcome.Methods/Design
Multicenter randomised controlled trial in subfertile women (age 18-39 year) with a body mass index between 29 and 40 kg/m2. Exclusion criteria are azoospermia, use of donor semen, severe endometriosis, premature ovarian failure, endocrinopathies or pre-existent hypertensive disorders. In the intervention group the aim is a weight loss of at least 5% to10% in a six-month period, to be achieved by the combination of a diet, increase of physical activity and behavioural modification. After six months, in case no conception has been achieved, these patients will start fertility treatment according to the Dutch fertility guidelines. In the control group treatment will be started according to Dutch fertility guidelines, independently of the patient's weight.Outcome measures and analysis
The primary outcome measure is a healthy singleton born after at least 37 weeks of gestation after vaginal delivery. Secondary outcome parameters including pregnancy outcome and complications, percentage of women needing fertility treatment, clinical and ongoing pregnancy rates, body weight, quality of life and costs. Data will be analysed according to the intention to treat principle, and cost-effectiveness analysis will be performed to compare the costs and health effects in the intervention and control group.Discussion
The trial will provide evidence for costs and effects of a lifestyle intervention aiming at weight reduction in overweight and obese subfertile women and will offer guidance to clinicians for the treatment of these patients.Trial registration
Dutch Trial Register NTR1530 相似文献93.
Phillips TJ Symons J Menon S;HT Study Group 《Journal of the American Academy of Dermatology》2008,59(3):397-404.e3
94.
95.
萘甲异喹(NI)呈浓度依赖性地降低离体豚鼠心房收缩力和频率。其拮抗豚鼠左房肌Iso正性肌力作用的PD22′值为5.4,Ver为5.8。NI10μmol/L明显降低豚鼠乳头肌收缩力;缩短快反应APD,以对APD20影响最大,但不影响APA和Vmax。对高K+去极化慢反应动作电位,NI产生浓度依赖性负性肌力作用,同时明显降低APA,Vmax,缩短APD;提高细胞外液Ca2+浓度可使其抑制作用逆转。结果提示NI具有钙通道阻滞作用。 相似文献
96.
97.
Kan Takeda Keisuke Ueda Ursula Scheffel Hayden Ravert Norman D. LaFrance William A. Baumgartner Bruce A. Reitz Ahvie Herskowitz Henry N. Wagner Jr. 《European journal of nuclear medicine and molecular imaging》1991,18(7):461-466
111In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r=0.88) but was poorly correlated with labelled antibody uptake (r=0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin.
Offprint requests to: U. Scheffel, Sc.D. 相似文献
98.
In vivo investigation of estrogen regulation of adrenal and renal angiotensin (AT1) receptor expression by PET. 总被引:1,自引:0,他引:1
Taofeek K Owonikoko Maria E Fabucci Philip R Brown Nighat Nisar John Hilton William B Mathews Hayden T Ravert Paige Rauseo Kathryn Sandberg Robert F Dannals Zsolt Szabo 《Journal of nuclear medicine》2004,45(1):94-100
The renin angiotensin system (RAS) has been implicated as one mediator of the cardiovascular effects of estrogen. Since changes in angiotensin type 1 (AT(1)) receptor expression are central to modulation of the RAS, we used the noninvasive PET imaging technique to study for the in vivo effects of estrogen on membrane and intracellular AT(1) receptors. METHODS: Dynamic PET measurements of canine AT(1) (cAT(1)) receptors using the radiolabeled AT(1) receptor antagonist, (11)C-L-159,884, were performed during 2-wk consecutive periods of estrogen deprivation induced by ovariectomy and 17beta-estradiol (E(2)) replacement. RESULTS: Kinetic modeling of time-activity curves in the kidney and adrenal showed lower receptor expression in the estrogen replete state (21% and 30% decrease in Gjedde-Patlak slope, influx constant, respectively). These in vivo findings correlated with in vitro radioligand-binding assays with (125)I-[Sar(1),Ile(8)]angiotensin II showing reduced AT(1) receptor number in the adrenal (35%), glomeruli (30%), myocardium (35%), and liver (21%) in the estrogen-replenished compared with estrogen-depleted animals. CONCLUSION: Although other endogenous systems are known to regulate AT(1) receptors and could compete with estrogenic actions, these PET studies reveal that estrogen attenuates AT(1) receptor expression in vivo. Thus, estrogen modulation of AT(1) receptors may contribute to the cardiovascular protective effects associated with estrogen. 相似文献
99.
Recombinant human granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem/progenitor cells (PBPC) have replaced bone marrow (BM) harvests for autologous transplantation after myeloablative therapy in cancer patients. G-CSF-mobilized PBPC from healthy donors contain one log excess of T lymphocytes representing a potential risk for graft-versus-host disease (GVHD). However, recent pilot clinical studies of G-CSF-mobilized allogeneic PBPC transplantation have shown rapid haematological recovery and no severe acute GVHD except in a very few cases. Therefore, the risk of inducing severe acute GVHD is not as high as was expected during the pioneering period of allogeneic PBPC transplantation.The present study was performed to address the possible reasons for the rapid haematological recovery and the absence of severe acute GVHD observed after allogeneic PBPC transplantation by comparing the contents and subsets of CD3+ and CD34+ G-CSF-mobilized PBPC (n = 31) with those of BM (n = 26) allografts from healthy adult donors. The present results revealed that the phenotypic profiles of CD3+ and CD34+ cells differ between PBPC and BM allografts. The single PBPC leukapheresis product contained 10 times more mononuclear cells, 1.5 times more CD34+ cells, 5.5 times more CD3+ T lymphocytes, 3 times more CD19+ B lymphocytes and 3.8 times more CD14+ monocytes than the single BM harvest. Both CD34+CD33+ myeloid progenitor cells and CD34+HLA-DR- long-term reconstituting haemopoietic stem cells were significantly increased in the CD34+ G-CSF-mobilized PBPC compared with the CD34+ BM cells; median 73.1% and 30.4% vs 60.6% and 5.0%, respectively, P < 0.01.The percentage of CD3+ cells coexpressing CD4 (T helper/inducer) was similar in both PBPC and BM allografts, 47.2% and 45.6%, respectively, whereas the percentage of CD3+ cells coexpressing CD8 (T suppressor/cytotoxic) was significantly decreased in PBPC compared with BM; 37.0% vs 55.9%, p < 0.01. 相似文献
100.
Dopamine receptor binding of C-11-3-N-methylspiperone in the caudate in schizophrenia and bipolar disorder: a preliminary report 总被引:1,自引:0,他引:1