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1.
Trawat Attarbaschi Julia Sacher Thomas Geiss-Granadia Nikolas Klein Nilufar Mossaheb Rupert Lanzenberger Susanne Asenbaum Robert Dudczak Siegfried Kasper Johannes Tauscher 《European neuropsychopharmacology》2007,17(2):102-107
We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes. 相似文献
2.
Rupert R Lanzenberger Markus Mitterhauser Christoph Spindelegger Wolfgang Wadsak Nikolas Klein Leonhard-Key Mien Alexander Holik Trawat Attarbaschi Nilufar Mossaheb Julia Sacher Thomas Geiss-Granadia Kurt Kletter Siegfried Kasper Johannes Tauscher 《Neuropsychopharmacology》2007,61(9):1081-1089
BACKGROUND: Results from studies in serotonin-1A (5-HT1A) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT1A receptor binding potential (BP) in social anxiety disorder (SAD). METHODS: Using PET and [carbonyl-11C]WAY-100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HC). A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed. RESULTS: We found a significantly lower 5-HT1A BP in several limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD patients. The difference in 5-HT1A binding was most significant in the amygdala (-21.4%; p = .003). There was also a more than 20% lower 5-HT(1A) BP of SAD patients in the anterior cingulate cortex (p = .004), insula (p = .003), and dorsal raphe nuclei (p = .030). CONCLUSIONS: The lower 5-HT1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT1A binding, thus corroborating the potential validity of 5-HT1A receptors as targets in the treatment of human anxiety disorders. 相似文献
3.
Cortical spreading depression in the feline brain following sustained and transient stimuli studied using diffusion-weighted imaging 总被引:1,自引:0,他引:1
4.
Steffen Roiner Nikolas Bakinde Ulrike Zeitschel Reinhard Schliebs Volker Bigl 《International journal of developmental neuroscience》1998,16(7-8):669-673
The present study was conducted to test the hypothesis that cholinergic basalforebrain neurons are a major source of cerebrospinal fluid (CSF) cholinesterases. To address thisquestion enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inboth CSF and parietal cortex were assayed following selective lesion of basal forebrain cholinergicneurons by a single intracerebroventricular application of the cholinergic immunotoxin192IgG-saporin. Cholinergic immunolesions led to a dramatic decrease in total AChE activity inparietal cortex, which was due to the specific loss of the G4 molecular form while the activity ofthe G1 form was increased as compared to nonlesioned animals. In contrast, the total enzymeactivity of BChE and its molecular forms were not affected by cholinergic lesion in both parietalcortex and CSF. The data suggest, that cholinergic basal forebrain neurons are seemingly not amajor source of cholinesterases in the CSF, and do not provide any evidence for using CSFcholinesterases as a diagnostic marker of basal forebrain cholinergic cell loss in humans. 相似文献
5.
Principal neuron spiking: neither necessary nor sufficient for cerebral blood flow in rat cerebellum 总被引:1,自引:0,他引:1
Neuronal activity, cerebral blood flow, and metabolic responses are all strongly coupled, although the mechanisms behind the coupling remain unclear. One of the key questions is whether or not increases in spiking activity in the stimulated neurons are sufficient to drive the activity-dependent rises in cerebral blood flow (CBF) that form the basis of the signals used in functional neuroimaging such as the blood oxygen level-dependent (BOLD) signal. To this end the present study examined the effect of enhanced spike activity per se on CBF in rat cerebellar cortex under conditions of disinhibition, achieved by blocking GABAA receptors using either bicuculline or picrotoxin. Purkinje cell spiking activity and local field potentials were recorded by glass microelectrodes, and laser Doppler flowmetry was used to monitor CBF. Disinhibition increased Purkinje cell spiking rate to 200–300% of control without incurring any increase in basal CBF. This demonstrates that increased spike activity per se is not sufficient to affect basal CBF. The neurovascular coupling between excitatory synaptic activity and CBF responses evoked by inferior olive (climbing fibre) stimulation was preserved during disinhibition. Thus, the unchanged basal CBF in the presence of the dramatic rise in Purkinje cell spiking rate was not explained by impaired synaptic activity–CBF coupling. On the basis of our previous and the present studies, we conclude that increased spiking activity of principal neurons is neither sufficient nor necessary to elicit CBF responses and in turn BOLD signals, and that activation-dependent vascular signals reflect excitatory synaptic activity. 相似文献
6.
Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion 下载免费PDF全文
Smalley KS Brafford P Haass NK Brandner JM Brown E Herlyn M 《The American journal of pathology》2005,166(5):1541-1554
During the process of malignant transformation, nascent melanoma cells escape keratinocyte control through down-regulation of E-cadherin and instead communicate among themselves and with fibroblasts via N-cadherin-based cell-cell contacts. The zonula occludens (ZO) protein-1 is a membrane-associated component of both the tight and adherens junctions found at sites of cell-cell contact. In most cancers, levels of ZO-1 are typically down-regulated, leading to increased motility. Here we report the novel observation that ZO-1 expression is up-regulated in melanoma cells and is located at adherens junctions between melanoma cells and fibroblasts. Immunofluorescence and co-immunoprecipitation studies showed co-localization of ZO-1 with N-cadherin. Down-regulation of ZO-1 in melanoma cells through RNA interference produced marked changes in cell morphology--leading to a less-dendritic, more rounded phenotype. Consistent with a role in N-cadherin-based adhesion, RNAi-treated melanoma cells were less adherent and invasive when grown in a collagen gel. These data provide the first evidence that increased ZO-1 expression in melanoma contributes to the oncogenic behavior of this tumor and further illustrate that protein products of genes, such as ZO-1, can function in either a pro- or anti-oncogenic manner when expressed in different cellular contexts. 相似文献
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9.
Nikolas A. Jagodzinski Adrian Hughes Niel P. Davis Michael Butler Ian G. Winson Stephen W. Parsons 《Foot and Ankle Surgery》2013,19(2):125-130
BackgroundSymptomatic tarsal coalitions failing conservative treatment are traditionally managed by open resection. We describe an arthroscopic technique for excising talocalcaneal coalitions and present a retrospective two-surgeon case series of the first eight patients (nine feet).MethodsOutcome measures include restoration of subtalar movements, return to work and sports, visual analogue pain scales and Sports Athlete Foot and Ankle Scores (SAFAS). Follow-up ranges from 1 to 5.5 years.ResultsPain and SAFAS improved in 7 patients. Subtalar movements were improved in all feet. All patients achieved early good function but one relapsed requiring subsequent fusions. One posterior tibial nerve was damaged.ConclusionsMinimal destruction of bone and soft tissues allows early mobilization and minimizes pain. Patient selection and preoperative planning are crucial to avoid relapse and complication. This series from two independent surgeons supports the feasibility and effectiveness of this technique. 相似文献
10.
Nikolas L. Krott Gunnar M. Bloyinski Erik Cattrysse 《Journal of manipulative and physiological therapeutics》2018,41(4):304-314