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61.
Michel O Petereit H Klemm E Walther LE Bachmann-Harildstad G 《The Journal of laryngology and otology》2005,119(10):765-769
A diagnosis of perilymphatic fistula is still controversial. Recently, a case report indicated that beta-trace protein (prostaglandin D synthase) might be a potential marker for perilymphatic fluid. In this multicentre clinical case series study beta-trace protein was used as a marker for perilymphatic fluid fistula. Fifteen fluid samples were collected during diagnostic tympanoscopy. In addition, five samples were collected from patients with tympanic membrane perforation for use as as negative controls. Samples were obtained using precision glass capillaries and were analysed for beta-trace protein using laser nephelometry. The diagnosis of perilymphatic fistula was defined by the patient's history, the audiological and vestibular investigation and the findings at tympanoscopy. The cut-off level of beta-trace protein for perilymph-positive samples was chosen at 1.11 mg/l. The sensitivity and specificity were calculated using a 2 x 2 contingency table. There was no false positive result, but in two cases a false negative result was found. The specificity was 1 and the sensitivity was 0.81. The material of this first clinical study is small owing to the rarity of patients undergoing diagnostic tympanoscopy for perilymphatic fluid fistula. However, according to these preliminary results beta-trace protein might be a promising marker in the diagnosis of perilymphatic fluid fistulas. 相似文献
62.
Memantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons 总被引:4,自引:0,他引:4
Maler JM Esselmann H Wiltfang J Kunz N Lewczuk P Reulbach U Bleich S Rüther E Kornhuber J 《Brain research》2005,1052(2):156-162
The present study examined the effect of memantine, an uncompetitive NMDA receptor antagonist, on ethanol-induced NMDA receptor up-regulation. Primary glutamatergic rat hippocampal neurons were exposed to ethanol and memantine for 5 days. The ethanol-sensitive NMDA receptor subunits NR1, NR2A and NR2B were quantified by Western immunoblot analysis. Exposure to ethanol (50 mM) caused an increase in the levels of NR1 (137 +/- 11% of untreated control, P = 0.009), NR2A (128 +/- 14%, P = 0.022) and NR2B (136 +/- 19%, P = 0.012). Coincubation with memantine (10 microM) completely blocked the ethanol-induced up-regulation of NR1 (102 +/- 4%), NR2A (95 +/- 7%) and NR2B (105 +/- 13%). No effect of memantine on NR subunit expression was observable, except for NR2A, where a decrease (79 +/- 6%, P = 0.034) was noted. Neither ethanol nor memantine alone or in combination were toxic in the concentrations tested. These results may provide a molecular explanation for beneficial effects of memantine on ethanol-induced glutamatergic hyperexcitability reflected in the ethanol withdrawal syndrome and on the development of ethanol dependence. 相似文献
63.
Polyclonal antithymocyte globulins (ATGs) are immunosuppressive drugs widely used in transplantation and hematologic disorders. Treatment with ATGs can induce side effects such as neutropenia and thrombocytopenia because of unspecific antibodies directed against nonmyeloid cells present in these preparations. Depletion, activation, and expression of adhesion molecules on platelets in vitro were studied in the whole blood of healthy volunteers by means of flow cytometry after incubation with different doses of three polyclonal ATGs. Our data show no ATG-mediated cytotoxic activity against platelets. ATGs are able to induce activation of platelets through increased expression of P-selectin and hLAMP-1 and higher percentages of gated thrombocytes expressing these molecules. Furthermore, increased expression of hLAMP-1 presented a dose-dependent pattern. ATGs induced activation and enhanced expression of adhesion molecules in unstimulated platelets. Increased adhesion may be responsible for undesirable side effects such as thrombocytopenia and reticulopenia. 相似文献
64.
Andres?Beiras-FernandezEmail author Eckart?Thein Daniel?Chappel Rosalía?Gallego Dolores?Fernandez-Roel Gregor?Kemming Claus?Hammer 《Transplant international》2004,17(8):453-457
Reperfusion triggers the expression of inflammatory cytokines and adhesion molecules that increase the rate of apoptosis in the reperfused tissues after ischaemia, thus worsening the outcome of the grafts. Polyclonal anti-thymocyte globulins (pATGs) are able to reduce the number of lymphocytes as well as block adhesion molecules and induce apoptosis in T-lymphocytes through Fas-ligand. The aims of this study were to investigate the influence of pATGs on the prevention of apoptosis of reperfused tissues after ischaemia and to monitor their capability to enhance lymphocyte apoptosis thus decreasing the deleterious effects of ischaemia/reperfusion injury (IRI). Extremities of cynomolgus monkeys (n=8) were flushed via either the femoral or the brachial artery. After 60 min of ischaemia the limbs were reperfused with human blood. ATG was added to the blood in a therapeutic dose 20 min prior to reperfusion of the extremities. Surgically available limbs (n=20) were assigned to the following groups: ATG group (n=10) and control group (without ATG; n=10). DNA fragmentation analysis was performed in situ to detect apoptosis at the single-cell level. Our study shows an increased rate of muscle and connective tissue apoptosis in the control group compared with the ATG-treated group. Cells found in the vascular areas present different rates of apoptosis, with enhanced cellular death of endothelium and connective perivascular areas being observed in the control group. The group treated with ATG shows an increased rate of white blood cell (WBC) apoptosis in vascular and perivascular areas. Previous studies have shown that pATGs are able to induce apoptosis as well as complement-mediated cell death in peripheral T-lymphocytes in vitro. Our results confirm that pATGs not only increase the rate of apoptosis of WBCs in vivo but also have a protective effect on the reperfused tissue. This may alleviate the damage after reperfusion of solid-organ transplantation. 相似文献
65.
Kirov R Kinkelbur J Heipke S Kostanecka-Endress T Westhoff M Cohrs S Ruther E Hajak G Banaschewski T Rothenberger A 《Journal of sleep research》2004,13(1):87-93
The aim of the study was to characterize the sleep pattern in children with attention deficit/hyperactivity disorder (ADHD). By means of polysomnography (PSG), sleep patterns were studied in 17 unmedicated preadolescent boys rigorously diagnosed with ADHD and 17 control boys precisely matched for age and intelligence. Although ADHD children did not display a general sleep alteration, major PSG data showed a significant increase in the duration of the absolute rapid eye movement (REM) sleep and the number of sleep cycles in ADHD group when compared with controls. In addition, REM sleep latency tended to be shorter in ADHD children. These results suggest that in ADHD children, a forced REM sleep initiation may produce a higher incidence of sleep cycles and may also contribute to an increased duration of the absolute REM sleep. The overall pattern of the findings implies that a forced ultradian cycling appears characteristic for the sleep in ADHD children, which may be related to alterations of brain monoamines and cortical inhibitory control accompanying the ADHD psychopathology. 相似文献
66.
67.
Wagner T Krampe H Stawicki S Reinhold J Jahn H Mahlke K Barth U Sieg S Maul O Galwas C Aust C Kröner-Herwig B Brunner E Poser W Henn F Rüther E Ehrenreich H 《Journal of psychiatric research》2004,38(6):619-635
It is far from clear how comorbidity changes during alcoholism treatment. This study investigates: (1) the course of comorbid Axis I disorders in chronic alcoholics over 2 years of controlled abstinence in the outpatient long-term intensive therapy for alcoholics (OLITA) and (2) the effect of comorbid Axis I and II disorders in this group of patients on subsequent drinking outcome over a four-year follow-up. This prospective treatment study evaluates psychiatric variables of 89 severely affected chronic alcohol dependent patients on admission (t1), month 6 (t2), 12 (t3) and 24 (t4). Drinking outcomes have been analyzed from 1998 to 2002. On admission, 61.8% of the patients met criteria for a comorbid Axis I disorder, 63.2% for a comorbid personality disorder. Axis I disorders remit from t1 (59.0% ill), t2 (38.5%), t3 (28.2%) to t4 (12.8%) (p<0.0001). Anxiety disorders remit more slowly from t1 (43.6%) to t3 (20.5%, p=0.0086), whereas mood disorders remit early between t1 (23.1%) and t2 (5.1%, p=0.0387) with a slight transient increase at t3 (10.3%). During the four-year follow-up, the cumulative probability of not having relapsed amounts to 0.59. Two predictors have a strong negative impact on abstinence probability: number of inpatient detoxifications (p=0.0013) and personality disorders (p=0.0106). The present study demonstrates a striking remission of comorbid Axis I disorders upon abstinence during comprehensive long-term outpatient alcoholism treatment. The presence of an Axis II rather than an Axis I disorder on admission strongly predicts drinking outcome over a four-year follow-up. 相似文献
68.
Therapeutic drug monitoring of mirtazapine and its metabolite desmethylmirtazapine by HPLC with fluorescence detection 总被引:1,自引:0,他引:1
A selective and sensitive HPLC method is described for therapeutic drug monitoring of the antidepressant drug mirtazapine and its active metabolite desmethylmirtazapine. Liquid/solid extraction with C18 cartridges was used for cleanup of plasma samples. The chromatographic separation was carried out on a phenylhexyl column. No interference from other coadministered antidepressants has been observed in 234 samples from 184 patients. The calibration range used was from 1 ng/mL to 100 ng/mL. The analytic method has proven robust and well suited for therapeutic drug monitoring. In addition to qualitative and quantitative validation data for the assay method, concentration measurements in samples from patients on mirtazapine therapy and the relevant dosing information are presented. Median drug levels after a 15-mg dose were 37 ng/mL mirtazapine and 20 ng/mL desmethylmirtazapine. When a 60-mg dose was administered, median concentrations of 83 ng/mL mirtazapine and 65 ng/mL desmethylmirtazapine were found. 相似文献
69.
Corticotropin-releasing factor (CRF) and the CRF-like peptide urocortin I (UcnI) exert their activity through two different CRF receptors, CRF1 and CRF2. Recently, UcnII and UcnIII have been discovered as potential endogenous agonists selective for CRF2 known to be involved in brain functions such as learning and anxiety, as well as in cardiovascular functions. A structure-affinity relationship study using chimeric peptides was designed to characterize mouse UcnII (mUcnII) and mUcnIII further and to investigate the structural basis of their receptor subtype selectivity. In the framework of this study, mUcnII (IC50 = 4.4 nM) but not mUcnIII was identified as high-affinity ligand for the rat CRF binding protein. Such affinity had previously not been observed for the human version of this protein. On the basis of secondary structure predictions, it was hypothesized that the amino acid motifs Pro-Ile-Gly of mUcnII and Pro-Thr-Asn of mUcnIII decrease alpha-helicity and thereby impair binding to CRF1. In support of this hypothesis, binding affinity to CRF1 of the chimeric peptides [Pro11Ile12Gly13]h/rCRF, [Pro11Thr12Asn13]h/rCRF, and the corresponding rUcnI analogs was found to be decreased by three orders of magnitude, whereas binding affinity to CRF2 was much less affected. The dramatic decrease in binding affinity to CRF1 correlated with a decrease in alpha-helicity as indicated by the data of circular dichroism spectroscopy. 相似文献
70.
Although the role of CD8 as a supplier of lck is unchallenged, its role in contributing to the formation of a stable complex between class I molecules and the TCR, as well as its role as an adhesion molecule, is less clear. To address the role of CD8/MHC-I interactions, we generated tetramers composed of H2-K(b) molecules with mutations in the alpha 3 domain of H2-K(b) that abolish CD8 binding. We show that the ability of tetramers to stain and activate CD8 T cells is strongly dependent on binding of CD8 to the same class I molecule engaged by the TCR. We characterize a mutation in the alpha 3 domain that results in H2-K(b) molecules capable of staining specific CD8 T cells with little ensuing activation. Although CD8 to some extent serves an adhesive function, this contribution is modest and does not substitute for lack of binding of CD8 to the class I molecule engaged by the TCR. We show that CD8 and the TCR associate in a process independent of binding of CD8 to class I. Our data support the notion that CD8 is required to form a stable complex between class I and the TCR. 相似文献