44 research outputs found

    Current concepts in clinical radiation oncology

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    Serotonin levels are abnormally elevated in the fetus of the monoamine oxidase-A-deficient transgenic mouse.

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    Developmental changes in levels of serotonin, L-tryptophan and 5-hydroxyindol acetic acid (5-HIAA) were measured by high pressure liquid chromatography (HPLC) in the forebrain, brainstem and cervical cord of fetal, neonatal and adult mice from the wild strain C3H and the transgenic strain Tg8, created from the C3H line by the disruption of the gene encoding monoamine oxidase A. The results indicated that the absence of monoamine oxidase A activity in Tg8 mice results in abnormally high 5-hydroxytryptamine (5-HT) levels in all the central nervous structures and at all the studied developmental ages. Since serotonin levels were 4-5 times larger in Tg8 than in C3H mice at gestational day 20, comparing the central network function at birth of C3H and Tg8 neonates should shed some light on the role of serotonin in prenatal network maturation

    Serotonergic inhibition of phrenic motoneuron activity: an in vitro study in neonatal rat.

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    In vitro experiments were conducted on neonatal rat brainstem-spinal cord preparations to test the hypothesis of an inhibitory modulation of phrenic activity by serotonin (5-HT) via non-5-HT2A receptors [Lindsay, A.D. and Feldman, J.L., Modulation of respiratory activity of neonatal rat phrenic motoneurones by serotonin, J. Physiol., 461 (1993) 213-233]. The changes induced by 5-HT and related agents on phrenic root discharges and membrane currents in identified phrenic motoneurons were analysed after blockade of spinal 5-HT2A receptors. Spinal application of 5-HT1B (but not 5-HT1A) receptor agonists depressed the phrenic activity and the effect was prevented by pretreatment with 5-HT1B (but not 5-HT1A, 5-HT2A and 5-HT3) receptor antagonists. Results from phrenic motoneuron whole cell recordings do not reject a presynaptic location of the 5-HT receptors responsible for this depression

    Abnormal phrenic motoneuron activity and morphology in neonatal monoamine oxidase A-deficient transgenic mice: possible role of a serotonin excess.

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    In rodent neonates, the neurotransmitter serotonin (5-HT) modulates the activity of both the medullary respiratory rhythm generator and the cervical phrenic motoneurons. To determine whether 5-HT also contributes to the maturation of the respiratory network, experiments were conducted in vitro on the brainstem-spinal cord preparation of neonatal mice originating from the control strain (C3H) and the monoamine oxidase A-deficient strain, which has a brain perinatal 5-HT excess (Tg8). At birth, the Tg8 respiratory network is unable to generate a respiratory pattern as stable as that produced by the C3H network, and the modulation by 5-HT of the network activity present in C3H neonates is lacking in Tg8 neonates. In addition, the morphology of the phrenic motoneurons is altered in Tg8 neonates; the motoneuron dendritic tree loses the C3H bipolar aspect but exhibits an increased number of spines and varicosities. These abnormalities were prevented in Tg8 neonates by treating pregnant Tg8 dams with the 5-HT synthesis inhibitor p-chlorophenylalanine or a 5-HT(2A) receptor antagonist but were induced in wild-type neonates by treating C3H dams with a 5-HT(2A) receptor agonist. We conclude that 5-HT contributes, probably via 5-HT(2A) receptors, to the normal maturation of the respiratory network but alters it when present in excess. Disorders affecting 5-HT metabolism during gestation may therefore have deleterious effects on newborns

    Analysis of Perfluorinated Compounds: comparison between Liquid Chromatography coupled to Tandem Mass Spectrometry and High Resolution Mass Spectrometry

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    Perfluorinated compounds, described by some scientist as the “PCBs of the twenty-first century”, are a group of contaminants which present bioaccumulative and persistent properties. Significant amounts of these compounds were detected in human blood and in the liver of many species, and it appears that a potential risk could exist for developmental and other adverse effects associated with exposure in humans. Due to the high affinity of these compounds with the proteins, milk appears to be a highly exposed matrix. Contamination could be present naturally (transfer from cow to milk) or during the processing of milk. The potential toxicity of this matrix is of high concern, considering the large amounts of milk consumed by children. A sensitive and specific method has to be used in order to quantify accurately these compounds in cow milk. Extraction and purification processes present major problems due to the high complexity of the matrix, and they have been optimized using different protocols. A detection method by liquid chromatography coupled to tandem mass spectrometry has been developed, which enables the quantification of 15 perfluorinated compounds, especially PFOS and PFOA. The advantages of using a high resolution system are described in terms of sensitivity and specificity
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