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排序方式: 共有1179条查询结果,搜索用时 31 毫秒
31.
Julia C Bartsch Pawel Fidzinski Jojanneke HJ Huck Heide H?rtnagl Richard Kovács Agustin Liotta Josef Priller Christian Wozny Joachim Behr 《Neuropsychopharmacology》2015,40(4):987-995
Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca2+ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system. 相似文献
32.
Complete recovery in plasma of enzymes lost from the heart after permanent coronary artery occlusion in the dog 总被引:2,自引:0,他引:2
W T Hermens F H van der Veen G M Willems M L Mullers-Boumans A Schrijvers-van Schendel R S Reneman 《Circulation》1990,81(2):649-659
Plasma activities of creatine kinase (CK) and alpha-hydroxybutyrate dehydrogenase (HBD) were measured after permanent coronary artery occlusion in the dog. Cumulative release of enzymes in plasma was calculated from these data by using a previously validated two-compartment model for circulating enzymes. Regional myocardial ischemia was measured by injection of radiolabeled microspheres. After 48 hours, the dogs were killed, and a detailed map of left ventricular enzyme activity was obtained from 108 tissue samples. Cumulative release into plasma of CK and HBD was 96 +/- 20% and 112 +/- 26%, respectively, of the total activities depleted from the heart (mean +/- SD, n = 11). The scatter in these values is inherent to the calculations, and it is concluded that both enzymes are recovered completely in plasma and, thus, can be used as quantitative markers of injury. Discrepancies between this result and earlier reports on the recovery of CK are only partly apparent and can be explained partly by underestimation of the elimination rate of CK from plasma, irregardless of tissue edema and incomplete extraction of enzyme activity from tissue. 相似文献
33.
Estimation of circulatory parameters in patients with acute myocardial infarction. Significance for calculation of enzymatic infarct size 总被引:5,自引:0,他引:5
Estimation of infarct size from enzyme activities in plasma or serum presupposes known values of circulatory parameters such as the extravascular distribution volume Ve and the permeability constant P for the transport of enzyme between intravascular volume Vi and Ve. In man, parameter values are used that are extrapolated either from values found in the dog or from turnover studies of non-myocardial proteins. Large systematic errors can be introduced in this way, as demonstrated in this study. It is shown that by simultaneous determination of two different enzymes in the same patient, estimates of circulatory parameters are obtained. The method is applied to creatine kinase (CK) and alpha-hydroxybutyrate dehydrogenase (HBDH) plasma activities in 36 patients with acute myocardial infarction (AMI). The following results are obtained: 1. Exchange of enzyme between Vi and Ve is much slower and clearance of CK is much faster than presently assumed in the literature. 2. Release of CK and HBDH into the circulation is proportional to the amounts of these enzymes present in the myocardium. This finding is supported by data on early enzyme release. 3. Quantitation of HBDH release needs a two-compartment model, while for CK a one-compartment model can be used in good approximation. 4. Release of CK and HBDH after AMI continues up to 96 hours. 5. Using obtained parameter values, a simulated model demonstrates that estimation of clearance rates of CK from exponential fits on plasma levels results in large errors. This may explain recent conflicting results in validation of enzymatic estimates of infarct size. 相似文献
34.
Enzymatic assessment of myocardial necrosis after cardiac surgery: differentiation from skeletal muscle damage, hemolysis, and liver injury 总被引:1,自引:0,他引:1
G M Willems F H van der Veen H A Huysmans W Flameng R de Meyere A van der Laarse G J van der Vusse W T Hermens 《American heart journal》1985,109(6):1243-1252
Plasma activities of various (iso)enzymes were measured in patients after cardiac surgery (n = 114) and after acute myocardial infarction (n = 40). From these activities, the cumulative release of enzymes in plasma was calculated with a two-compartment circulatory model. This model was adapted to transient postoperative changes in plasma volume and similar changes in the transcapillary escape rate of proteins, observed after cardiac surgery and verified in dogs after cardiopulmonary bypass (CPB). Comparison of cumulative release of enzymes with the enzyme content of myocardium, skeletal muscle, and blood cells allows identification of the various sources of enzyme release. Cardiac injury after uncomplicated bypass surgery is only 1.5 +/- 1.5 (mean +/- SD) gram equivalents (gmEq) of myocardium, compared to a loss of 31 +/- 13 gmEq of myocardium after AMI. Peroperative hemolysis is estimated at 68 +/- 15 ml of blood. Total loss of skeletal muscle amounts to 13 +/- 10 gmEq. Some hepatic enzyme release is observed after AMI but not after surgery. Large differences in time course exist between the release of enzymes from myocardium and skeletal muscle and also between myocardial release in the surgery group and in the AMI group. The accuracy of estimations is discussed and indicated as a function of the extent of cardiac injury. 相似文献
35.
Influence of oxygen tension on the viscoelastic behavior of red blood cells in sickle cell disease 总被引:2,自引:0,他引:2
Although the rheological behavior of sickle cell suspensions and of hemoglobin S solutions is known to be strongly dependent on oxygen tension (PO2), little data exist concerning the influence of PO2 on the viscoelasticity of individual HbSS RBC. We have used micropipette aspiration techniques to test the deformation response of both HbSS and control HbAA RBC over a wide range of PO2 at 23 degrees C. Sickled, spiculed HbSS cells were present for PO2 approximately less than 35 mm Hg; for a number of these cells, the deformation response was essentially elastic and an effective membrane rigidity (EMR) was calculated. EMR increased with decreasing PO2 and was approximately 5 to 50 times higher than the equivalent rigidity of oxygenated HbSS RBC. In addition, the rate of membrane deformation was very slow for sickled cells; the half-time for the deformation process increased as PO2 was lowered and was about two orders of magnitude longer than the equivalent time for normal RBC. Other sickled cells exhibited plastic deformation when subjected to comparable deforming forces and experienced irreversible membrane deformation and budding. At all PO2 levels tested, some HbSS RBC remained as discocytes; these cells had normal membrane elasticity and membrane viscosity. Furthermore, changes in PO2 did not affect the membrane properties of HbAA RBC. Thus, gross abnormalities in the deformation response of HbSS RBC were only detected after morphological sickling had occurred. These abnormalities most likely arose from changes in the cytoplasmic HbS viscoelasticity and, if present in vivo, would be expected to impair the flow of HbSS cells in the microcirculation. 相似文献
36.
Ehninger G; Schuler U; Renner U; Ehrsam M; Zeller KP; Blanz J; Storb R; Deeg HJ 《Blood》1995,85(11):3247-3249
In a canine model we investigated the toxicity and pharmacokinetics of a water soluble busulfan preparation. Busulfan was dissolved in dimethylsulfoxide (DMSO) and administered either orally or intravenously in a single dose of 1 mg/kg. The application in either preparation was well tolerated. In seven dogs, peak levels in the range of 730 ng/mL to 1,000 ng/mL were measured after intravenous injection with an area under curve (AUC) of 75 ng.h/kg.mL to 146 ng.h/kg.mL. It was of note that even the oral administration of the same busulfan preparation resulted in AUC values in the same range as observed after parenteral application. The absorption rate of busulfan tablets in our model was as unpredictable as documented in clinical trials. On the basis of the present study, clinical trials using busulfan dissolved in DMSO given either intravenously or orally appear warranted. This approach should lead to predictable blood levels, reduced toxicity, and increased efficacy of busulfan-containing regimens. 相似文献
37.
Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease 总被引:7,自引:2,他引:7
Gruss HJ; Hirschstein D; Wright B; Ulrich D; Caligiuri MA; Barcos M; Strockbine L; Armitage RJ; Dower SK 《Blood》1994,84(7):2305-2314
CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H- RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD. 相似文献
38.
39.
Historically, brain tumour resection has relied upon standardised anatomical atlases and classical mapping techniques for successful resection. While these have provided adequate results in the past, the emergence of new technologies has heralded a wave of less invasive, patient-specific techniques for the mapping of brain function. Functional magnetic resonance imaging (fMRI) and, more recently, diffusion tensor imaging (DTI) are two such techniques. While fMRI is able to highlight localisation of function within the cortex, DTI represents the only technique able to elucidate white matter structures in vivo. Used in conjunction, both of these techniques provide important presurgical information for thorough preoperative planning, as well as intraoperatively via integration into frameless stereotactic neuronavigational systems. Together, these techniques show great promise for improved neurosurgical outcomes. While further research is required for more widespread clinical validity and acceptance, results from the literature provide a clear road map for future research and development to cement these techniques into the clinical setup of neurosurgical departments globally. 相似文献