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991.
Logé C Siomboing X Wallez V Scalbert E Bennejean C Cario-Tourmaniantz C Loirand G Gressier B Pacaud P Luyckx M 《Journal of enzyme inhibition and medicinal chemistry》2003,18(2):127-138
With a view to specifying structure-activity relationships we have synthesised a new series of analogues of the Rho-kinase inhibitor 1-(5-isoquinolinesulfonyl)-homopiperazine (Fasudil). The structural modifications concerned the isoquinolinyl heterocycle and the sulfonyl group which are the two main features of this lead compound. These analogues were evaluated on the actin cytoskeleton and on the enzymatic activity of Rho-kinase. Most of the chemical modifications result in a loss of activity showing that interactions of Fasudil with the catalytic domain of Rho-kinase seem to be particularly definite and sensitive to structural variations. The presence of an isoquinolinyl nitrogen and a basic amino group separated by a spacer bearing a sulfonamide function are of utmost importance. Only the tetra-hydroisoquinoline analogue 3 shows the same activity as Fasudil. Moreover, this compound is unable to inhibit PKC biological activity contrary to Fasudil. The loss of the aromatic property could increase the selectivity level in favour of compound 3. 相似文献
992.
Chabane H Lamazzi C Thiery V Pierre A Leonce S Pfeiffer B Renard P Guillaumet G Besson T 《Journal of enzyme inhibition and medicinal chemistry》2003,18(2):167-174
Novel thiazolocarbazole derivatives have been synthesized via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor activity of these polyheterocyclic compounds was studied. 相似文献
993.
Charton I Suzenet F Boutin JA Audinot V Delagrange P Bennejean C Renard P Guillaumet G 《Journal of enzyme inhibition and medicinal chemistry》2003,18(2):187-193
The synthesis of benzoxathiins bearing a retroamide function is described from 8-hydroxythiochroman, the key step involving the synthesis of the benzoxathiin ring through a sulfonium salt. These new melatonin analogues were evaluated on human receptors MT1 and MT2 and have a similar affinity to that of melatonin itself. 相似文献
994.
995.
Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons 总被引:11,自引:0,他引:11
van den Munckhof P Luk KC Ste-Marie L Montgomery J Blanchet PJ Sadikot AF Drouin J 《Development (Cambridge, England)》2003,130(11):2535-2542
Mesencephalic dopaminergic (MesDA) neurons play crucial roles in motor and behavioral processes; their loss in Parkinson's disease (PD) results in striatal dopamine (DA) deficiency and hypokinetic movement disorder. The Pitx3 homeobox gene is expressed in the MesDA system. We now show that only a subset of MesDA neurons express Pitx3 and that in Pitx3-deficient aphakia mice, this subset is progressively lost by apoptosis during fetal (substantia nigra, SN) and postnatal (ventral tegmental area) development, resulting in very low striatal DA and akinesia. Similar to human PD, dorsal SN neurons (which are Pitx3 negative) are spared in mutant mice. Thus, Pitx3 defines a pathway for survival of neurons that are implicated in PD and that are required for spontaneous locomotor activity. 相似文献
996.
997.
Theoretical evaluation of cell membrane ion channel activation by applied magnetic fields 总被引:5,自引:0,他引:5
This letter re-examines a recently published calculation of the forces exerted on a membrane ion channel by a cation passing
through in the presence of an externally applied magnetic field. We show here, in contradiction to the originally published
calculation, that the forces generated due to the Lorentz force of the magnetic field on the cation are negligible compared
with the forces required to activate an ion channel protein conformation change associated with the gating of the channel.
Received: 11 August 1998 / Revised version: 25 October 1998 / Accepted: 11 November 1998 相似文献
998.
In order to assess the effects of weak-field magnetic stimulation on brain electrical activity in epileptics, three patients suffering from mesial temporal lobe epilepsy (MTLE) were exposed to DC magnetic fields of 0.9 and 1.8 millitesla (mT). The EEG activity was recorded simultaneously from intracranial electrodes inserted through the foramen ovale (FO) and scalp electrodes. Significant enhancement of interictal epileptiform activity was observed in two patients, while in one patient, magnetic stimulation resulted in the cessation of interictal spike/wave trains. 相似文献
999.
The dynamics of the "Etang de Berre", a brackish lagoon situated close to the French Mediterranean sea coast, is strongly disturbed by freshwater inputs coming from an hydroelectric power station. The system dynamics has been described as a sequence of daily typical states from a set of physicochemical variables such as temperature, salinity and dissolved oxygen rates collected over three years by an automatic sampling station. Each daily pattern summarizes the evolution, hour by hour of the physicochemical variables. This article presents results of forecasts of the states of the system subjected to the simultaneous effects of meteorological conditions and freshwater releases. We recall the main step of the classification tree method used to build up the predictive model (Classification and Regression Trees, Breiman et al., 1984) and we propose a transfer procedure in order to test the stability of the model. Results obtained on the Etang de Berre data set allow us to describe and predict the effects of the environmental variables on the system dynamics with a margin of error. The transfer procedure applied after the tree building process gives a maximum gain in prediction accuracy of about 15%. 相似文献
1000.
Véronique Zupan Joanna M. Hill Douglas E. Brenneman †Illana Gozes ‡Mati Fridkin §Patrick Robberecht Philippe Evrard Pierre Gressens 《Journal of neurochemistry》1998,70(5):2165-2173
Abstract: At the end of neuronal migration, the neopallial germinative zone produces glial cells destined to colonize the upper layers of neocortex. High densities of binding sites for vasoactive intestinal peptide (VIP) have been found in the rodent germinative zone just after completion of neuronal migration, suggesting a possible role of VIP in neocortical astrocytogenesis. In the present study, administration of a VIP antagonist at embryonic days 17 and 18 to pregnant mice was followed by a dramatic depletion of astrocytes in the upper cortical layer of the offspring. The depletion of astrocytes was dose-dependent, with a 42% reduction in the density of astrocytes observed with 50 µg of antagonist. The antagonist effect was reversed by cotreatment with VIP or pituitary adenylate cyclase-activating polypeptide (PACAP), suggesting the involvement of a receptor common to these two neuropeptides. VIP antagonist-induced inhibition of astrocytogenesis was also blocked by Ro 25-1553, a long-acting cyclic VIP analogue selective for the PACAP II VIP2 receptor subclass. Our results demonstrate that VIP and/or PACAP play a crucial physiological role in neocortical astrocytogenesis, possibly through interaction with PACAP II VIP2 receptors. 相似文献