Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome.
(65/1602)
AIM: To compare patient triggered, with conventional fast rate, ventilation in a randomised controlled trial using the incidence of chronic lung disease as the primary outcome measure. METHODS: Three hundred and eighty six preterm infants with birthweights from 1000 to 2000 g, and requiring ventilation for respiratory distress syndrome within 24 hours of birth, were randomised to receive either conventional or trigger ventilation with the SLE 2000 ventilator. RESULTS: There were no significant differences in the incidence of chronic lung disease (28 day and 36 week definitions), death, pneumothorax, intraventricular haemorrhage, number of ventilator days, or length of oxygen dependency between groups. CONCLUSIONS: Patient triggered ventilation in preterm infants with respiratory distress syndrome is feasible. No significant differences, when compared with conventional fast rate ventilation in important medium and longer term outcome measures, were evident. (+info)
Effects of corticotropin-releasing factor on neuronal activity in the serotonergic dorsal raphe nucleus.
(66/1602)
The present study examined the regional localization of corticotropin-releasing factor (CRF)- and 5-hydroxytryptamine (5-HT)-immunoreactive (IR) fibers within the rat dorsal raphe nucleus (DRN) using immunohistochemistry. Additionally, the effects of CRF, administered intracerebroventricularly (0.1-3.0 micrograms) or intraraphe (0.3-30 ng), on discharge rates of putative 5-HT DRN neurons were quantified using in vivo single unit recording in halothane-anesthetized rats. CRF-IR fibers were present at all rostrocaudal levels of the DRN and exhibited a topographical distribution. CRF produced predominantly inhibitory effects on DRN discharge at lower doses and these effects diminished or became excitatory at higher doses. Inhibition of DRN discharge by CRF was attenuated by the nonselective CRF antagonist, DPheCRF12-41 and the CRF-R1-selective antagonist, antalarmin, implicating the CRF-R1 receptor subtype in these electrophysiological effects. The present findings provide anatomical and physiological evidence for an impact of CRF on the DRN-5HT system. (+info)
Developmental toxicity studies in rats and rabbits with 3,5,6-trichloro-2-pyridinol, the major metabolite of chlorpyrifos.
(67/1602)
3,5,6-Trichloro-2-pyridinol (TCP), the primary metabolite of chlorpyrifos and chlorpyrifos-methyl, was evaluated for potential developmental toxicity. Groups of 32-34 bred female Fischer 344 rats were given 0, 50, 100, or 150 mg TCP/kg/day by gavage on gestation days 6-15; the fetuses were evaluated on gestation day 21. Similarly, groups of 16 inseminated female New Zealand White rabbits were given 0, 25, 100, or 250 mg TCP/kg/day by gavage on gestation days 7-19, and fetuses were evaluated on gestation day 28. No clinical signs of toxicity attributed to TCP were noted in either species. In rats, at 150 mg/kg/day, maternal effects included slight decreases in feed consumption, significantly depressed body weight gain (25% relative to controls) resulting in significantly lower maternal terminal body weights, and increased relative liver weight. At 100 mg/kg/day, maternal body weight gain in rats was depressed approximately 22%. Among rabbits, maternal effects were limited to the group given 250 mg/kg/day, which lost an average of approximately 70 g during the treatment period (vs. 140 g in the controls). There were no effects on fetal weight or viability, nor were there significant increases in any fetal alteration in either species. A slightly higher (not statistically significant) than usual incidence of central nervous system anomalies occurred in rabbits, but these anomalies were found in both treated and control groups in this study as well as contemporaneous studies of unrelated compounds. This, and the fact that these anomalies were not seen with the parent compound, chlorpyrifos, suggest that their origin was spontaneous. Thus, TCP was not considered fetotoxic or teratogenic in either rats or rabbits, even at dose levels that produced maternal toxicity. (+info)
Consequences of neural cell adhesion molecule deficiency on cell migration in the rostral migratory stream of the mouse.
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In vertebrates, interneurons of the olfactory bulb (OB) are generated postnatally and throughout life at the subventricular zone of the forebrain. The neuronal precursors migrate tangentially through the forebrain using a well defined pathway, the rostral migratory stream (RMS), and a particular mode of migration in a chain-like organization. A severe size reduction of the OB represents the most striking morphological phenotype in neural cell adhesion molecule (NCAM)-deficient mice. This defect has been traced back to a migration deficit of the precursors in the RMS and linked to the lack of the polysialylated form of NCAM. In this study we investigate the morphological alterations and functional properties of the RMS in mice totally devoid of all isoforms of NCAM and polysialic acid (PSA). We show that a morphologically altered, but defined and continuous pathway exists in mutants, and we present in vivo and in vitro evidence that PSA-NCAM in the RMS is not essential for the formation and migration of chains. Instead, we find a massive gliosis associated with the formation of membrane specializations in a heterotypic manner, linking precursors to astrocytes. This finding and the over-representation and defasciculation of axons in the pathway suggest that important interactions between migrating cells and their stationary environment are perturbed in the mutants. Finally, we used transplantation experiments to demonstrate that lack of PSA-NCAM leads to a decrease but not a total blockade of migration and demonstrate that the mutant RMS is functional in transporting normal neuronal precursors to the OB. (+info)
The role of CNS glucagon-like peptide-1 (7-36) amide receptors in mediating the visceral illness effects of lithium chloride.
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Peripheral administration of large doses of lithium chloride (LiCl) to rats causes a spectrum of effects that are consistent with visceral illness. LiCl reduces food intake, decreases salt ingestion after sodium depletion, induces pica, and produces robust conditioned taste aversions. Because some of the effects of peripheral LiCl are mimicked by centrally administered glucagon-like peptide-1 (7-36) amide (GLP-1), we hypothesized that this peptide is involved in the neural pathways by which LiCl causes visceral illness. To test this hypothesis, we pretreated rats with a selective and potent GLP-1 receptor antagonist given directly into the third ventricle via an indwelling cannula before administration of peripheral LiCl. The GLP-1 receptor antagonist completely blocked the effect of LiCl to reduce food intake, induce pica, and produce a conditioned taste aversion. The same dose of GLP-1 receptor antagonist did not reverse the LiCl-induced reduction in NaCl intake. The data indicate a role for GLP-1 receptors in the CNS pathway that mediates some of the effects of visceral illness. (+info)
Sympathoinhibition by central and peripheral infusion of nifedipine in spontaneously hypertensive rats.
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The present study assessed whether central mechanisms may contribute to the hypotensive effect of the calcium channel blocker nifedipine. In conscious, spontaneously hypertensive rats (SHR) on a high-salt diet, hemodynamic (mean arterial pressure [MAP] and heart rate) and sympathetic (renal sympathetic nerve activity) responses to low, central, intracerebroventricular infusion rates (25 microg. kg(-1). h(-1) for 2 hours) and peripheral intravenous rates (50 microg. kg(-1). h(-1) for 3 hours and then 100 microg. kg(-1). h(-1) for 2 hours) of nifedipine were evaluated. The distribution of nifedipine in the blood and tissues was assessed at the end of the infusions. Nifedipine significantly inhibited renal sympathetic nerve activity and lowered MAP in SHR beginning 30 minutes after the start of the intracerebroventricular infusion. The decrease of MAP by intravenous infusion began at 60 minutes and was more profound with 100 microg. kg(-1). h(-1). Inhibition of sympathetic activity preceded and then paralleled the decrease in blood pressure; it occurred earlier with central (15 to 30 minutes) than with peripheral (30 to 60 minutes) infusion. Intravenous infusion resulted in concentrations of nifedipine in brain structures (brain stem, midbrain, and cortex) that were 30% to 40% of those in the heart, kidneys, and liver. From the hemodynamic and sympathetic responses and the distribution of nifedipine into the central nervous system, we conclude that the peripheral infusion of nifedipine at relatively low rates may evoke a hypotensive response in SHR, not only via peripheral mechanisms, but also through central mechanisms, which will lead to an inhibition of sympathetic outflow and, therefore, a lowering of blood pressure. (+info)
Behavioral effects of central administration of the novel CRF antagonist astressin in rats.
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Astressin, a novel corticotropin releasing factor (CRF) antagonist, has been found to be particularly potent at inhibiting the hypothalamo-pituitary-adrenal axis. The aim of the present study was to determine the effects in rats of astressin in attenuating the anxiogenic-like response produced by social stress and intracerebroventricular (ICV) CRF administration on the elevated plus-maze, and ICV CRF-induced locomotor activation in the rat. Astressin significantly reversed the anxiogenic-like response induced by both social stress and ICV rat/humanCRF (r/hCRF) on the elevated plus-maze, but failed to block the effects of r/hCRF-induced locomotor activity in a familiar environment. When these results were compared to previous studies performed with the same paradigms using other CRF antagonists, astressin showed effects similar to those of D-PheCRF(12-41) on plus-maze performance. However, contrary to alpha-helicalCRF(9-41) and D-PheCRF(12-41), astressin had no effect on CRF-induced locomotor activity. These results suggest that astressin may have a unique anti-CRF profile compared to previously tested antagonists. (+info)
Morphologic characteristics of subcortical heterotopia: MR imaging study.
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BACKGROUND AND PURPOSE: Gray matter heterotopia have been divided into three groups based on clinical and imaging characteristics: subependymal, subcortical, and band heterotopia. Nonetheless, subcortical heterotopia can have variable morphologic findings. The purpose of this study was to perform a morphologic analysis of a series of cases of subcortical heterotopia based on MR images, to correlate the morphologic appearance with clinical characteristics, and to speculate about the embryologic implications of our results. METHODS: The MR imaging studies and clinical records of 24 patients with subcortical heterotopia were retrospectively reviewed. The morphologic findings of the heterotopia were recorded along with presence and type of associated malformations. These results were correlated with available data on development and neurologic status. RESULTS: Analysis revealed that, in six cases, the heterotopia were composed exclusively of multiple nodules, in 13, they appeared primarily as curvilinear ribbons of cortex extending into the white matter, and in five, they had deep nodular regions with curvilinear areas more peripherally. All of the curvilinear regions were contiguous with the cerebral cortex in at least two locations. In eight cases, curvilinear heterotopia contained curvilinear areas of flow void that were thought to be blood vessels; in 10, they contained fluid resembling CSF. No difference in developmental or neurologic manifestations was noted among patients with heterotopia of different morphologic appearances. CONCLUSION: Subcortical heterotopia can have nodular or curvilinear morphologic appearances. Although no difference was found in the clinical conditions of the patients with differing morphologic appearances, additional analysis of these patients or studies of animal models of these malformations may further our understanding of normal and abnormal brain development. (+info)