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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aim of this study was to investigate the effects of different doses of exogenous recombinant human tissue plasminogen activator (rt-PA) on the endogenous cerebral plasminogen–plasmin system in focal ischemia in rats. Ischemia was induced using the suture model. Each group of rats (n = 6) received either treatment (0.9, 9 or 18 mg rt-PA/kg body weight) or saline (control group) at the end of ischemia; a sham-operated group was added. The activity of the plasminogen activators was measured by casein-dependent plasminogen zymography. In the cortex urokinase (u-PA) rose from sham (no ischemia), 91 ± 7% to ischemia, 176 ± 10% (P 〈 0.005). Increasing rt-PA doses led to further significant (P 〈 0.001) cortical u-PA activation which was maximal at 18 mg: 249 ± 13%. An extreme increase in the u-PA activity was observed in the basal ganglia to 1019 ± 22% (P 〈 0.001). This increase was further aggravated by higher rt-PA doses (18 mg, 1236 ± 15%; P 〈 0.001). The t-PA level did not change I3R24 during (3 h ischemia followed by reperfusion for 24 h); however, during low and moderate doses of rt-PA, endogenous t-PA was reduced. In conclusion, while ischemia leads to a significant increase in u-PA, mainly in the basal ganglia, t-PA is not altered. Increasing doses of rt-PA lead to a further elevation of u-PA. Thus, u-PA seems to play a major role in the endogenous plasminogen activator system following focal cerebral ischemia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Principal neurons of the medial nucleus of the trapezoid body (MNTB) receive a synaptic input from a single giant calyx terminal that generates a fast-rising, large excitatory postsynaptic current (EPSC), each of which are supra-threshold for postsynaptic action potential generation. Here, we present evidence that MNTB principal neurons receive multiple excitatory synaptic inputs generating slow-rising, small EPSCs that are also capable of triggering postsynaptic action potentials but are of non-calyceal origin. Both calyceal and non-calyceal EPSCs are mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-d-aspartate (NMDA) receptor activation; however, the NMDA receptor-mediated response is proportionally larger at the non-calyceal synapses. Non-calyceal synapses generate action potentials in MNTB principal neurons with a longer latency and a lower reliability than the large calyceal input. They constitute an alternative low fidelity synaptic input to the fast and secure relay transmission via the calyx of Held synapse.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Focal cerebral ischemia leads to the gradual disruption of the extracellular matrix. A key role in the turnover of the extracellular matrix is played by the system of matrix metalloproteinases (MMPs). In this study we describe changes of the MMP inducer protein (EMMPRIN) following experimental cerebral ischemia (induced for 3 h and followed by 24 h reperfusion, suture model) in rats. Extracellular EMMPRIN was measured by Western blot of the ischemic and nonischemic basal ganglia and cortex separately. Compared with the contralateral nonischemic area, the ischemic hemisphere showed a significant increase in EMMPRIN: basal ganglia, 158% ± 4% (P 〈 0.05); cortex, 128% ± 25% (P 〈 0.05). Immunohistochemistry was used to localize EMMPRIN on cerebral microvessels. EMMPRIN-positive microvascular structures were quantified by automatic morphometric video-imaging analysis and a significant increase in the number of cerebral microvessels staining positive for EMMPRIN in the ischemic basal ganglia was shown. The significant loss of microvascular basal lamina antigen collagen type IV in ischemic cortex and basal ganglia was calculated by Western blot. Measured by gelatin zymography, we demonstrated an MMP-2 and MMP-9 increase in the ischemic brain regions (P 〈 0.05). For the first time the MMP activation system EMMPRIN was shown to be relevant in cerebral ischemia. These results raise the possibility that the increased expression of EMMPRIN, the increase in MMPs and the damage of the basal lamina following cerebral ischemia are connected and part of a network of related changes.
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  • 4
    ISSN: 1468-2982
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To investigate sympathetic nervous system and neuroendocrine changes in idiopathic trigeminal neuralgia, we determined the plasma level of the catecholamines norepinephrine and epinephrine, as well as cortisol and ACTH in 16 patients (55.38.3 years) with trigeminal neuralgia at four different times during the day (7.00, 13.00, 17.00 and 23.00). Morning and evening values of plasma norepinephrine as well as the daily mean value (dmv) were significantly higher (p〈0.01) in patients with trigeminal neuralgia than in an age- and gender-matched control group. Moreover, morning, afternoon and dmv epinephrine values were also significantly elevated. The dmv norepinephrine levels correlated with the intensity of the attacks (r=0.68, p〈0.01), the frequency of the attacks (r=0.75, p〈0.01) and the duration of the disease (r=0.78, p〈0.01). In addition to elevated catecholamines, trigeminal neuralgia patients also demonstrated significantly increased morning, evening and daily mean values of plasma cortisol. Thus, patients with trigeminal pain have an increased sympathetic nervous system activity for an extended period of time without a direct link to pain attacks, which suggests that the sympathetic nervous system itself is at least co-activated in trigeminal neuralgia and perhaps plays a role in the induction and maintenance of trigeminal pain. The neuroendocrine changes are similar to cluster headache and point to a central dysregulation of the hypothalamic-pituitary-adrenal axis, possibly due to the cyclic phenomena in idiopathic trigeminal neuralgia.
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Histopathology 34 (1999), S. 0 
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To determine the significance of proliferative activity (PA) in endometrial carcinomas, we analysed the expression of cell cycle-related antigens in routinely processed tissue.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsSerial sections of 164 endometrial carcinoma specimens were immunostained with the monoclonal antibodies (MoAb) Ki-S4 (specificity for p170) and Ki-S5 (specificity for p320/350). The Ki-S4 PA (median value 18.3%) and Ki-S5 PA (median value 25.0%) in endometrial carcinomas showed a significant correlation (r = 0.89, P 〈 0.001). A significantly lower median value of Ki-S4 and Ki-S5 immunoreactivity was ascertained in endometrial carcinomas stage I vs. 〉 I (P 〈 0.05), in tumours with myometrial invasion ≤ 50% vs. 〉 50% (P 〈 0.03), and in grade 1 vs. grade 2 and 3 tumours (P 〈 0.001). Univariate analysis showed that age, FIGO stage and grade, histopathological subtype, myometrial invasion, Ki-S4 and Ki-S5 PA provided prognostic information on the adjusted overall survival, whereas FIGO stage (P = 0.002) and Ki-S4 PA (P = 0.008) were independent prognosticators for adjusted overall survival in multivariate analysis.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionsThe association with established prognosticators for endometrial carcinomas, and the results of uni- and multivariate analysis indicates that the additional evaluation of Ki-S4 PA is useful for classifying patients into subgroups with low and high risk of relapse which might help individualizing the therapeutic strategy in endometrial cancer patients.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford : Blackwell Science Ltd
    Anaesthesia 53 (1998), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sodium channel antagonists have been used in the management of neuropathic pain for several years. Recent evidence suggests that lamotrigine, which is active at glutaminergic excitatory synapses, is very effective in producing pain relief. We have successfully used lamotrigine in two patients suffering from neuropathic pain. Our results suggest that this novel channel antagonist can be used to treat neuropathic pain. Double blind placebo control studies are therefore needed to substantiate these findings.
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