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61.
The dentate gyrus is one of the few brain regions that show proliferation of neuronal precursors postnatally and in adult life. Proliferation in the dentate gyrus has been shown to be influenced by exercise, stress and drugs such as antidepressants. Traditionally, proliferation studies rely on the time consuming and subjective manual count of labeled cells. Here we adapted the Metamorph software to automatically count cells labeled in the S phase in the developing dentate gyrus of mice. The validity of the computer-assisted method was established by showing an outcome similar to that obtained with the established manual counting procedure. In addition, by using a genetically modified mouse line with increased proliferation, the ability of the computer-assisted method to detect changes in proliferation was demonstrated. 相似文献
62.
Guiard BP Guilloux JP Reperant C Hunt SP Toth M Gardier AM 《Molecular pharmacology》2007,72(6):1411-1418
Preclinical studies suggest that substance P (SP) neurokinin 1 (NK1) receptor antagonists are efficient in the treatment of anxiety and depression. This therapeutic activity could be mediated via stimulation of serotonin (5-HT) neurons located in the dorsal raphe nucleus (DRN), which receive important SP-NK1 receptor immunoreactive innervations. The present study examined the effects of intraraphe injection of SP on extracellular 5-HT levels in the frontal cortex, ventral hippocampus, and DRN by using intracerebral microdialysis in conscious mice. Intraraphe SP injection dose dependently decreased cortical 5-HT release, whereas no effects were detected in the ventral hippocampus. Cortical effects were blocked by the selective NK1 receptor antagonist N-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenylpiperidin-3-amine (GR205171) and completely dampened in mice lacking NK1 receptors. Furthermore, genetic (in knockout 5-HT1A(-/-) mice) or pharmacological inactivation of 5-HT1A autoreceptors blocked cortical responses to SP. Contrasting with its cortical effects, intraraphe SP injection increased 5-HT outflow in the DRN in wild-type mice; this effect was potentiated by a local perfusion of the selective 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635). Finally, SP-induced changes in frontal cortex and DRN dialysate 5-HT levels were blocked by the DRN perfusion of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate ionotropic receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). These data support the hypothesis that SP-induced over-activation of 5-HT1A autoreceptors within the DRN limits cortical 5-HT release. A better knowledge of the complex relationship between tachykininergic, serotonergic, and glutamatergic systems within the DRN might help better understand the pathophysiology and subsequent treatment of depression. 相似文献
63.
François Lüthi Miklos Pless Serge Leyvraz Beat Biedermann Emilie Müller Richard Hermann Christian Monnerat 《Supportive care in cancer》2010,18(12):1515-1520
Introduction
Anaemia during chemotherapy is often left untreated. Erythropoiesis-stimulating agents are frequently used to treat overt anaemia. Their prophylactic use, however, remains controversial and raises concerns about cost-effectiveness. Therefore, we assessed the efficacy of a dose-reduction schedule in anaemia prophylaxis. 相似文献64.
65.
Miklos D. Kertai Sreekanth Cheruku Wenjing Qi Yi-Ju Li G. Chad Hughes Joseph P. Mathew Jörn A. Karhausen 《The Journal of thoracic and cardiovascular surgery》2017,153(1):68-76.e2
Objective
Aortic surgeries requiring hypothermic circulatory arrest evoke systemic inflammatory responses that often manifest as vasoplegia and hypotension. Because mast cells can rapidly release vasoactive and proinflammatory effectors, we investigated their role in intraoperative hypotension.Methods
We studied 31 patients undergoing proximal aortic repair with hypothermic circulatory arrest between June 2013 and April 2015 at Duke University Medical Center. Plasma samples were obtained at different intraoperative time points to quantify chymase, interleukin-6, interleukin-8, tumor necrosis factor alpha, and white blood cell CD11b expression. Hypotension was defined as the area (minutes × millimeters mercury) below a mean arterial pressure of 55 mm Hg. Biomarker responses and their association with intraoperative hypotension were analyzed by 2-sample t test and Wilcoxon rank sum test. Multivariable logistic regression analysis was used to examine the association between clinical variables and elevated chymase levels.Results
Mast cell-specific chymase increased from a median 0.97 pg/mg (interquartile range [IQR], 0.01-1.84 pg/mg) plasma protein at baseline to 5.74 pg/mg (IQR, 2.91-9.48 pg/mg) plasma protein after instituting cardiopulmonary bypass, 6.16 pg/mg (IQR, 3.60-9.41 pg/mg) plasma protein after completing circulatory arrest, and 7.64 pg/mg (IQR, 4.63-12.71 pg/mg) plasma protein after weaning from cardiopulmonary bypass (each P value < .0001 vs baseline). Chymase was the only biomarker associated with hypotension during (P = .0255) and after (P = .0221) cardiopulmonary bypass. Increased temperatures at circulatory arrest and low presurgical hemoglobin levels were independent predictors of increased chymase responses.Conclusions
Mast cell activation occurs in cardiac surgery requiring cardiopulmonary bypass and hypothermic circulatory arrest and is associated with intraoperative hypotension. 相似文献66.
Tarek Alhamad Michelle Lubetzky Krista L. Lentine Emmanuel Edusei Ronald Parsons Martha Pavlakis Kenneth J. Woodside Deborah Adey Christopher D. Blosser Beatrice P. Concepcion John Friedewald Alexander Wiseman Neeraj Singh Su-Hsin Chang Gaurav Gupta Miklos Z. Molnar Arpita Basu Edward Kraus Song Ong Arman Faravardeh Ekamol Tantisattamo Leonardo Riella Jim Rice Darshana M. Dadhania 《American journal of transplantation》2021,21(9):3034-3042
Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care. 相似文献
67.
68.
69.
Biagini E Elhendy A Bax JJ Rizzello V Schinkel AF van Domburg RT Kertai MD Krenning BJ Bountioukos M Rapezzi C Branzi A Simoons ML Poldermans D 《Journal of the American College of Cardiology》2005,45(1):93-97
OBJECTIVES: The aim of this study was to investigate the effects of gender on long-term prognosis of patients undergoing dobutamine stress echocardiography (DSE). BACKGROUND: Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease undergoing DSE have not been adequately studied. METHODS: We studied 2,276 men and 1,105 women with known or suspected coronary artery disease who underwent DSE. Follow-up events were cardiac death and nonfatal myocardial infarction (MI). RESULTS: Dobutamine stress echocardiography was normal in 687 men (30%) and 483 women (44%) (p <0.0001). Ischemia on DSE was present in 1,194 men (52%) and 416 women (38%) (p <0.001). During a mean follow-up of 7 +/- 3.4 years, there were 894 (26%) deaths (442 attributed to cardiac causes) and 145 (4%) nonfatal MIs. The annual cardiac event rate was 2.5% in men and 1.2% in women with normal DSE. Independent predictors of cardiac events in patients with normal DSE using a Cox proportional hazards regression analysis were male gender (hazard ratio [HR]: 1.7 [range 1.1 to 2.8]), age (HR: 1.02 [range 1.01 to 1.04]), history of heart failure (HR: 3.4 [range 1.5 to 7.9]), previous MI (HR: 1.7 [range 1.1 to 2.8]), and diabetes (HR: 2.4 [range 1.3 to 4.5]). Independent predictors of cardiac events in patients with an abnormal DSE were age (HR: 1.03 [range 1.02 to 1.04]), history of heart failure (HR: 1.7 [range 1.3 to 2.1]), diabetes (HR: 1.4 [range 1.1 to 1.8]), heart rate at rest (HR: 2.8 [range 1.4 to 5.8]), wall motion abnormalities at rest (HR: 1.06 [range 1.04 to 1.09]), and ischemia on DSE (HR: 1.04 [range 1.02 to 1.07]). Myocardial ischemia was an independent predictor of cardiac events in both men and women. CONCLUSIONS: Dobutamine stress echocardiography provides independent prognostic information in both men and women. In patients with normal DSE, gender is independently associated with cardiac events. The outcome of patients with abnormal DSE is not related to gender, after adjusting for stress echocardiographic abnormalities. 相似文献
70.
Sirolimus,tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation 总被引:9,自引:2,他引:9 下载免费PDF全文
Antin JH Kim HT Cutler C Ho VT Lee SJ Miklos DB Hochberg EP Wu CJ Alyea EP Soiffer RJ 《Blood》2003,102(5):1601-1605
We studied the feasibility and activity of adding sirolimus to tacrolimus and low-dose methotrexate as graft-versus-host disease (GVHD) prophylaxis in recipients of alternative donor transplants. Forty-one patients with hematologic malignancies were conditioned with cyclophosphamide and total body irradiation. Marrow stem cells were from an HLA-A, -B, and -DR compatible, unrelated donor (n = 26, 68%), from a 5 of 6 antigen-matched unrelated donor (n = 8, 20%), or from a 5 of 6 antigen-matched family member (n = 5, 12%). Therapeutic serum levels of sirolimus were attained in most patients. All evaluable patients engrafted. An absolute neutrophil count of 500/microL was achieved on day +18 (range, 11-32 days). Sustained platelet counts of more than 20 000/ microL were attained on day +29 (range, 14-98 days). Grades 0-I acute GVHD occurred in 75% of patients. Grades II, III, and IV acute GVHD occurred in 13%, 8%, and 5%, respectively (total grades II-IV GVHD, 26%). Median survival is 366 days (95% CI 185, not estimable) and actuarial survival at 1 year is 52%. Oral sirolimus is tolerable, adequate blood levels are achievable, and there is a low rate of acute GVHD compared with historical data in this high-risk population. This novel agent is worthy of further study in allogeneic transplantation. 相似文献