Pflügers Archiv : European journal of physiology
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Comparative Study
Xenon-induced inhibition of Ca2+-regulated transitions in the cell cycle of human endothelial cells.
Xenon is an anesthetic with very few side-effects, yet its targets at the cellular level are still unclear. It interferes with many aspects of intracellular Ca2+ homeostasis, but so far no specific event or defined regulatory complex of the Ca2+-signaling system has been identified. Specific effects of xenon were found by investigating its effects on the cell cycle in human endothelial cells: there is a relationship between two cell cycle transition points, their regulation by Ca2+, and specific blocks induced by xenon. ⋯ An artificial increase of intracellular Ca2+ in the submicromolar range, using a very low dose of the Ca2+ ionophore ionomycin, or a threefold increase of the external Ca2+ concentration suffices to lift the xenon-induced metaphase block; the cells enter anaphase despite the presence of xenon and complete cell division. Thus, the specific but completely reversible inhibition by xenon of the G2-M transition and the block at metaphase suggest an interaction with a Ca2+-dependent event involved in the control of these processes. The results are consistent with the hypothesis that suppression of Ca2+ signals can be considered as a common denominator of the effects of xenon on the cell cycle and on the neuronal system during anesthesia.
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The present study was undertaken to examine the effects of microinjection of sodium nitroprusside (SNP), which releases nitric oxide (NO) spontaneously, into the nucleus tractus solitarii (NTS) on cerebral circulation. Cerebral blood flow (CBF) was measured in urethane-anesthetized (1.5 g middle dotkg-1, i.p.), paralysed and artificially ventilated rats using labeled microspheres or laser Doppler flowmetry. The CBF was significantly decreased by microinjection of SNP (5 nmol, n=10, microsphere technique; 0.5 nmol, n=6, laser Doppler flowmetry) into the unilateral NTS. ⋯ Unilateral microinjections of L-NMMA into the NTS (n=9), of SNP into the area adjacent to the NTS (n=9), of vehicle solution into the NTS (n=10), and of light-inactivated SNP into the NTS (n=6) had no effect on cerebral circulation. Cerebral autoregulation was well maintained in our protocols (n=9). These results indicate that microinjection of SNP, an NO donor, into the NTS decreases CBF.
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The present study was carried out to investigate the contribution of the Ca2+-transport ATPase of the sarcoplasmic reticulum (SR) to caffeine-induced Ca2+ release in skinned skeletal muscle fibres. Chemically skinned fibres of balb-C-mouse EDL (extensor digitorum longus) were exposed for 1 min to a free Ca2+ concentration of 0.36 microM to load the SR with Ca2+. Release of Ca2+ from the SR was induced by 30 mM caffeine and recorded as an isometric force transient. ⋯ Increasing CPA concentrations prolonged the time-to-peak in a dose-dependent manner, following a Hill curve with a half-maximal value of 6.5 +/- 3 microM CPA and a Hill slope of 1.1 +/- 0.2, saturating at 100 microM. The effects of CPA could be simulated by an extended three-compartment model representing the SR, the myofilament space and the external bathing solution. In terms of this model, the SR Ca2+-ATPase influences the Ca2+ gradient across the SR membrane in particular during the early stages of the Ca2+ transient, whereas the subsequent relaxation is governed by diffusional loss of Ca2+ into the bathing solution.
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There is accumulating evidence from in vitro experiments that the gene expression of the vascular endothelial growth factor (VEGF) is, like that of the erythropoietin (EPO) gene, regulated by the oxygen tension and by divalent cations such as cobalt. Since the information about the regulation of VEGF gene expression in vivo is rather scarce, this study aimed to examine the influence of hypoxia and of cobalt on VEGF gene expression in different rat organs and to compare it with that on EPO gene expression. To this end male Sprague-Dawley rats were exposed to carbon monoxide (0.1% CO), hypoxia (8% O2 ) or to cobalt chloride (12 and 60 mg/kg s.c.) for 6 h. mRNA levels for VEGF- 188, -164, and -120 amino acid isoforms in lungs, hearts, kidneys and livers were semiquantitated by RNase protection. ⋯ Only in the livers did hypoxia lead to a significant (50%) increase of VEGF mRNA. These findings suggest that, in contrast to the in vitro situation, the expression of the VEGF gene in normal rat tissues is rather insensitive to hypoxia. In consequence, the in vivo regulation of the VEGF and the EPO genes appear to differ substantially, suggesting that the regulation of the VEGF and EPO genes may not follow the same essential mechanisms in vivo.
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Clinical Trial
Brainstem auditory evoked potentials and somatosensory evoked potentials in prediction of posttraumatic coma in children.
Follow-up brainstem auditory evoked potential (BAEP) and somatosensory evoked potential (SEP) studies were performed within 72 hours after admission in 127 children with severe head injury (Glasgow Coma Scale score of < or = 8) in order to predict quo ad vitam outcome of posttraumatic coma. Outcomes were categorised as brain death and survival. ⋯ All of them died. Thus, comatose children with normal EP studies have in 78% good prognosis and a bad outcome can be reliably predicted.