Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 181 records · Page 10Linked to original sources

PubMed1997

A prospective randomized study of three types of platelet concentrates in patients with haematological malignancy: corrected platelet count increments and frequency of nonhaemolytic febrile transfusion reactions.

We prospectively randomized 51 patients with haematological malignancy requiring platelet concentrates (PCs) to receive either single donor platelet-pheresis products (SD-PC), PCs made from pooled buffy coats (BC-PC) or pooled units of platelets made by the platelet-rich plasma method (PRP-PC). The leucocyte content of each type of PC was 0.33 (0.03-13.5), 5.68 (0.19-99.0) and 365 (65-910) x 10(6); median (range), respectively; P < 0.0001. All red cell transfusions were leucodepleted by filtration. Statistical comparison of the probability of the occurrence of a nonhaemolytic febrile transfusion reaction (NHFTR) following transfusion of PCs in patients in each group showed a significant decrease for the SD-PC and BC-PC groups (0.031 and 0.038, respectively) when compared with PRP-PC (0.171); P = 0.0001. The actual corrected platelet count increments (CCI) at 1-6 and 18-24 h post-transfusion for all three types of PC did not differ significantly. We conclude that transfusion of PRP-PC is associated with a significant increase in NHFTR.

Adult↗

PubMed1997

Stress-induced alterations of somatodendritic 5-HT1A autoreceptor sensitivity in the rat dorsal raphe nucleus--in vitro electrophysiological evidence.

Somatodendritic 5-HT1A autoreceptors play a key role in the control of the electrical and metabolic activity of serotoninergic neurons in the dorsal raphe nucleus. These neurons also possess intracellular glucocorticoid receptors which may be involved in the well established modulation of serotonin (5-hydroxytryptamine, 5-HT) metabolism by corticosterone in stressed animals. The possible mediation by somatodendritic 5-HT1A autoreceptors of such corticosterone-dependent changes in serotoninergic neuron activity was investigated using an in vitro electrophysiological approach. 5-HT1A autoreceptor-mediated inhibition of the firing of serotoninergic neurons was examined in brain stem slices from rats whose serum corticosterone concentrations had been markedly increased (+100-200%) by two different stressful conditions. Immobilization for 30 or 90 min (restraint stress) did not modify the concentration-dependent inhibition of the firing of serotoninergic neurons by the 5-HT1A receptor agonist ipsapirone. In contrast, placing the rats in novel uncontrolled environmental conditions for 16 h significantly reduced the cell response to ipsapirone, indicating a decreased sensitivity of somatodendritic 5-HT1A autoreceptors. Such a change was not observed in adrenalectomized rats subjected to the same stressful conditions. These data show that some forms of stress can reduce the 5-HT1A autoreceptor-dependent inhibitory control of the electrophysiological activity of serotoninergic neurons in the dorsal raphe nucleus. Both the nature and duration of stress seem to be critical factors for triggering the (corticosterone-dependent) mechanism(s) responsible for the functional desensitization of 5-HT1A autoreceptors in stressed rats.

Adrenalectomy↗

PubMed1997

Association of angiotensin converting enzyme and angiotensin II type 1 receptor genotypes with left ventricular function and mass in patients with angiographically normal coronary arteries.

OBJECTIVE: To analyse the potential association of the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) gene polymorphisms on left ventricular function and mass in patients with normal coronary arteries. DESIGN: Consecutive sample. SETTING: University hospital. SUBJECTS: 141 consecutive white patients referred for coronary angiography and with angiographically normal coronary arteries. Patients with valvar diseases, cardiomyopathies, or a history of myocardial infarction were excluded. MAIN OUTCOME MEASURES: Left ventricular variables were measured for all patients. The ACE and AT1R genotypes were determined with a polymerase chain reaction based protocol using DNA prepared from white blood cells. A general linear model was used to compare data according to the ACE and to the AT1R genotypes. RESULTS: A strong association was observed between left ventricular mass and systemic hypertension (mean (SD) hypertension: 114 (31) g/m2; no hypertension 98 (23) g/m2; P < 0.003). However, no influence of ACE and AT1R polymorphisms on left ventricular mass was found, regardless of systemic hypertension. The subjects homozygous for the AT1R CC mutation had a significantly lower ejection fraction than those with allele A (AC+AA) (mean (SD) 62(12)% and 68(10)%, respectively, P < 0.05). No synergistic interaction of ACE and AT1R gene polymorphisms on left ventricular function and mass was found. CONCLUSIONS: These data do not support an association of the ACE and AT1R genotypes on left ventricular hypertrophy in white patients with normal coronary arteries.

Angiotensin II↗

PubMed1997

bFGF restores endothelium-dependent responses of hypercholesterolemic rabbit thoracic aorta.

In animal models, a hypercholesterolemic diet induces areas of deendothelialization and impairs endothelium-dependent vasorelaxation. Angiogenic growth factors increase endothelial cell growth in vivo. This study was thus designed to test the hypothesis that chronic administration of basic fibroblast growth factor (bFGF) in hypercholesterolemic rabbits might restore normal physiological responses to endothelium-dependent agonists. After feeding on a 2% cholesterol diet for 6 wk, 14 New Zealand White rabbits received twice-weekly intravenous boluses of either 2.5 microg bFGF (hypercholesterolemic bFGF group, n = 6) or placebo (hypercholesterolemic control group, n = 8) for 3 wk and were killed for assessment of in vitro vasoreactivity and for histological analysis. Six animals fed with standard rabbit diet were used to assess normal responses. Endothelium-dependent responses to acetylcholine and to the calcium ionophore A-23187 were reduced in the hypercholesterolemic control group compared with normal rabbits. Hypercholesterolemic animals treated with bFGF had significantly better endothelium-dependent responses than hypercholesterolemic rabbits not treated with bFGF. Endothelium-independent responses did not differ significantly among the three groups. A similar degree of plaque formation was observed in control- and bFGF-treated hypercholesterolemic rabbits. These results show that, in this model of atherosclerosis, bFGF has a highly beneficial effect on the functional responses of atherosclerotic vessels and does not have a deleterious effect on the degree of plaque formation.

Acetylcholine↗

PubMed1997

Role of serotonin3 receptors in the nucleus tractus solitarii on the carotid chemoreflex.

The effects of serotonin3 (5-HT3)-receptor stimulation in the nucleus tractus solitarii (NTS) on the cardiovagal, sympathetic, and respiratory responses to activation of carotid body chemoreceptors were investigated in anesthetized rats. The chemoreflex responses were triggered by an intravenous administration of KCN (40 microg/kg) in spontaneously breathing urethan-chloralose-anesthetized rats or by an intracarotid administration of saline saturated with 100% CO2 in pancuronium bromide-paralyzed and artificially ventilated urethan-anesthetized rats. Microinjections of 5-HT (2.5-5 nmol) or the 5-HT3 agonist 1-(m-chlorophenyl)-biguanide (CPBG, 300-1,200 pmol) into the commissural NTS blocked in a dose-dependent manner the atropine-sensitive chemoreflex bradycardia elicited by KCN. However, neither 5-HT nor CPBG affected the KCN-induced increase in respiratory volume and the CO2-induced increases in blood pressure and lumbar sympathetic nerve discharge. The inhibitory effect of 5-HT or CPBG on KCN-induced bradycardia was blocked by prior intra-NTS microinjection of a 5-HT3 antagonist, such as zacopride (100 pmol) or ondansetron (100 pmol), or the A-type gamma-aminobutyric acid (GABA(A)) antagonist bicuculline (10 pmol). In contrast, local microinjections of antagonists acting at 5-HT1 and 5-HT2 receptors, such as methysergide (100 pmol) and ketanserin (10 pmol), respectively, did not prevent the actions of 5-HT or CPBG. These data show that the stimulation of 5-HT3 receptors in the NTS exerted an inhibitory influence, probably through the activation of a local GABAergic system, on the cardiovagal component of the chemoreflex. Because similar effects of 5-HT3-receptor stimulation in the NTS were previously found on the baroreflex and Bezold-Jarisch reflex responses, it can be inferred that NTS 5-HT3 receptors play a key modulatory role in the reflex control of the heart rate.

Animals↗

PubMed1997

[Pituitary radiotherapy. Current data and future prospects].

Some technical improvements have allowed to minimize the frequency of severe complications following fractionated pituitary conventional radiotherapy, without altering its efficiency. "Conformational" radiotherapy is currently under development, aiming at the best fitting of the tumor borders to the irradiation zone, by the means of stereotactic imaging. More recently, radiosurgery has been proposed for pituitary adenomas. It consists in a single high radiation dose to the tumor, by the means of either cobalt minibeams (Gamma Unit) or photon beams from a linear particle accelerator. These techniques require the use of a stereotactic frame and precise 3D imaging in order to tightly superimpose the target volume to the reference isodose. They must not be viewed as an alternative to conventional radiotherapy. They can be applied only to small lesions (less than 20 mm in their maximal axis) which are distant (> 5 mm) from the optic chiasma and nerves. Their efficiency is similar to the one of fractionated conventional radiotherapy, with a shorter response time. In conclusion, radiotherapy can be used safely for pituitary adenomas. It remains however a second line treatment, when surgery has been incomplete and when a simple, effective and inexpensive medical treatment is not possible.

Adenoma↗

PubMed1996

Ultrastructural localization of 5-hydroxytryptamine1A receptors in the rat brain.

5-Hydroxytryptamine1A (5-HT1A) receptors have been visualized at the electron microscopic level in selected areas (dorsal raphe nucleus, hippocampus, septum) of the rat brain using specific anti-peptide antibodies. 5-HT1A receptor immunoreactivity was found almost exclusively in the somatodendritic compartment of neurons and was very rarely observed within processes possibly belonging to glial cells. The immunoenzymatic reaction product was associated exclusively with dendritic spines in the dorsal hippocampus, whereas in the dorsal raphe nucleus and the septal complex, immunoreactivity was found in both dendritic processes and somata. Although some immunolabeling was observed within the cytoplasm of cell bodies, 5-HT1A receptor immunoreactivity was essentially confined to the plasma membrane where it was unevenly distributed. It was frequently associated with synapses (except in the dorsal raphe nucleus), but was also found extrasynaptically in both somata and dendrites. These data suggest that the action of serotonin via 5-HT1A receptor could occur through junctional as well as nonjunctional transmission.

Animals↗

PubMed1996

Interaction of S 21007 with 5-HT3 receptors. In vitro and in vivo characterization.

The interaction of S 21007 [5-(4-benzyl piperazin-1-yl)4H pyrrolo [1,2-a]thieno[3,2-e]pyrazine] with serotonin 5-HT3 receptors was investigated using biochemical, electrophysiological and functional assays. Binding studies using membranes from N1E-115 neuroblastoma cells showed that S 21007 is a selective high affinity (IC50 = 2.8 nM) 5-HT3 receptor ligand. As expected of an agonist, S 21007 stimulated the uptake of [14C]guanidinium (EC50 approximately 10 nM) in NG 108-15 cells exposed to substance P, and this effect could be prevented by the potent 5-HT3 receptor antagonist ondansetron. In addition, like 5-HT and other 5-HT3 receptor agonists (phenylbiguanide and 3-chloro-phenylbiguanide), S 21007 (EC50 = 27 microM) produced a rapid inward current in N1E-115 cells. The 5-HT3 receptor agonist action of S 21007 was also demonstrated in urethane-anaesthetized rats as this drug (120 micrograms/kg i.v.) triggered the Bezold-Jarisch reflex (rapid fall in heart rate), and this action could be prevented by pretreatment with the potent 5-HT3 receptor antagonist zacopride. Finally, in line with its 5-HT3 receptor agonist properties, S 21007 also triggered emesis in the ferret. Evidence for 5-HT3 receptor antagonist-like properties of S 21007 was also obtained in some of these experiments since previous exposure to this compound prevented both the 5-HT-induced current in N1E-115 cells and the Bezold-Jarisch reflex elicited by an i.v. bolus of 5-HT (30 micrograms/kg) in urethane-anaesthetized rats. These data suggest that S 21007 is a selective 5-HT3 receptor agonist which can exhibit antagonist-like properties either by triggering a long lasting receptor desensitization or by a partial agonist activity at 5-HT3 receptors in some tissues.

Animals↗

PubMed1996

Reduced inhibitory potency of serotonin reuptake blockers on central serotoninergic neurons in rats selectively deprived of rapid eye movement sleep.

Previous studies showed that chronic deprivation of rapid eye movement (REM) sleep had the same behavioral effects as antidepressant drugs in helpless rats. Since long-term treatment with antidepressants is known to affect central serotoninergic neurotransmission, we investigated whether REM sleep deprivation also exerts an influence on the activity of serotoninergic neurons within the dorsal raphe nucleus (DRN) in rats. REM sleep deprivation was performed using the platform technique. Recording of serotoninergic neurons in the DRN revealed no difference in the basal firing rate, but a reduced inhibitory response to the selective serotonin (5-HT) reuptake blockers cericlamine and citalopram after repeated but not acute REM sleep deprivation. These observations suggest that REM sleep deprivation renders serotoninergic DRN neurons less sensitive to the inhibitory effect of 5-HT reuptake blockers, probably because of functional desensitization of somatodendritic 5-HT1A autoreceptors, like that previously reported after chronic treatment with several antidepressants. Accordingly, REM sleep deprivation might alleviate depression through neurophysiological mechanisms similar to those induced by antidepressants.

Animals↗

PubMed1996

ACE polymorphism, a genetic predictor of occlusion after coronary angioplasty.

In this study, restenosis after coronary angioplasty is evaluated in a series of 291 consecutive patients according to ACE genotypes. The authors conclude that the ACE 2ID polymorphism has no effect on progressive restenosis after balloon angioplasty, but it is implicated in a distinct mechanism of restenosis (thrombosis and occlusion) that could explain discrepancies among previously published studies.

Angioplasty, Balloon, Coronary↗

PubMed1996

Medullary pathways of cardiovascular responses to 5-HT2 and 5-HT3 receptor stimulation in the rat nucleus tractus solitarius.

As previously found for the baroreceptor reflex, microinjection of kynurenic acid (KYN, 2 nmol), a glutamate receptor antagonist, into the caudal ventrolateral medulla (CVL) blocked the hypotension and bradycardia elicited by microinjections of a 5-HT2 receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI, 0.5 pmol) into the nucleus tractus solitarius (NTS). In addition, as previously observed with the sympathetic chemoreflex response, microinjections of KYN into the RVI, blocked the increase in blood pressure elicited by microinjections of 1-m-(chlorophenyl)-biguanide (1200 pmol), a 5-HT1 receptor agonist, into the NTS. These results suggest that medullary pathways involved in the responses to 5-HT2 and 5-HT3 receptor stimulation in the NTS are similar to those that mediate the baroceptor and chemoreceptor reflex responses, respectively.

Amphetamine↗

PubMed1996

Sumatriptan inhibits the release of CGRP and substance P from the rat spinal cord.

The possible presynaptic action of the anti-migraine drug sumatriptan on primary afferent fibres containing substance P and/or calcitonin gene-related peptide was investigated on superfused rat horizontal spinal cord slices with attached dorsal roots. Electrical stimulation of dorsal roots triggered a significant overflow of both peptides; this could be reduced by sumatriptan in a concentration-dependent manner. As expected from the involvement of 5-HT1B/1.D beta receptors, methiothepin, (-)tertatolol and GR 127,935, but not WAY 100,635, prevented the inhibitors effect of sumatriptan. These data support the idea that the anti-migraine action of sumatriptan may involve, at least in part, a presynaptic inhibitory control of nociceptive (trigeminovascular) substance P- and/or calcitonin gene-related peptide-containing sensory fibres.

Animals↗

PubMed1996

Novel selective and partial agonists of 5-HT3 receptors. Part 1. Synthesis and biological evaluation of piperazinopyrrolothienopyrazines.

A series of piperazinopyrrolo[1,2-a]thieno[3,2-e]- and -[2,3-e]pyrazine derivatives were prepared and evaluated in order to determine the necessary requirements for high affinity on the 5-HT3 receptors and high selectivity versus other 5-HT receptor subtypes. Various substitutions on the piperazine and the thiophene ring of the pyrrolothienopyrazine moieties were systematically explored as well as replacement of the piperazine by other cyclic amines. The best compounds are in the nanomolar range of affinity of 5-HT3 receptors with high to very high selectivity (up to 10,000 for 14b). These high-affinity compounds have in common a benzyl- or allylpiperazine substituent with no substitutions on the thiophene ring. Five of these compounds (1a, 4b, 13a,b, and 14b) have been evaluated on the Von Bezold-Jarisch reflex and were characterized as partial agonists. One of them, 13a, has shown in vivo at very low dose a potent anxiolytic-like activity in the light/dark test.

Animals↗

PubMed1996

Immunocytochemical localization of serotonin1A receptors in the rat central nervous system.

Specific anti-rat 5-hydroxytryptamine1A (serotonin1A) receptor antibodies raised in a rabbit injected with a synthetic peptide corresponding to a highly selective portion of the third intracellular loop of the receptor protein (El Mestikawy et al. [1990] Neurosci. Lett. 118:189-192) were used for immunohistochemical mapping of serotonin1A receptors in the brain and spinal cord of adult rats. The highest density of immunostaining was found in limbic areas (lateral septum, CA1 area of Ammon's horn and dentate gyrus in the hippocampus, and frontal and entorhinal cortices), in the anterior raphe nuclei, and in the interpeduncular nucleus, in agreement with previous autoradiographic studies with selective radioligands showing the enrichment of these regions in serotonin1A receptor binding sites. Serotonin1A receptor-like immunoreactivity was also present, but at a moderate level, in the neocortex, in some thalamic and hypothalamic nuclei, in the nucleus of the solitary tract, in the dorsal tegmentum, in the nucleus of the spinal tract of the trigeminal nerve, and in the superficial layers of the dorsal horn in the spinal cord. In contrast, extrapyramidal areas, including the caudate putamen, the globus pallidus, and the substantia nigra as well as the cerebellum, exhibited very low to no immunostaining by antiserotonin1A receptor antibodies. At the cellular level, both the plasma membrane of neuronal perikarya and fine neuronal processes probably corresponding to dendritic fields were found to bind antiserotonin1A receptor antibodies. Regional differences were noted regarding these two types of immunostaining, because only dendrites bound antibodies within the hippocampus and the lateral septum, whereas both dendrites and neuronal cell bodies were immunoreactive in the medial septum, in the diagonal band of Broca, and in the dorsal and median raphe nuclei. Therefore, differential addressing of serotonin1A receptors could occur from one neuron to another. In general, the distribution and density of serotonin1A receptor-like immunoreactivity in the whole brain and in spinal cord were consistent with the mapping of serotonin1A receptor binding sites and serotonin1A receptor mRNA previously established by immunoautoradiographic and in situ hybridization procedures.

Animals↗

PubMed1996

Basic fibroblast growth factor restores endothelium-dependent responses after balloon injury of rabbit arteries.

BACKGROUND: After experimental angioplasty, partial or complete reendothelialization of the denuded surface occurs; the function of the regenerated endothelium has, however, been shown to be abnormal. Basic fibroblast growth factor (bFGF) is mitogenic for endothelial cells in vitro and in vivo. We investigated whether chronic administration of bFGF in a rabbit model of balloon denudation might not only improve endothelial regrowth but also restore normal physiological responses to endothelium-dependent agonists. METHODS AND RESULTS: Thirty-nine New Zealand White rabbits underwent balloon denudation of the right iliac artery. Twenty rabbits received intravenous administration of bFGF (2.5 micrograms twice a week for 2 weeks). Nineteen rabbits receiving saline injections served as controls. Animals were killed on day 28 for assessment of reendothelialization and neointimal thickening and for analysis of in vitro vasoreactivity. Animals in the bFGF group had a significantly (P<.005) greater degree of reendothelialization than controls (115 +/- 13 versus 55 +/- 6 mm2). Neointimal thickening was similar in the two groups. Four weeks after denudation, endothelium-independent responses did not differ significantly between the two groups. In contrast, the maximal endothelium-dependent acetylcholine-induced relaxation of the bFGF-treated animals (Emax, 40 +/- 7%) was significantly greater than that of the control group (Emax, 11 +/- 9%; P<.05). CONCLUSIONS: Systemic administration of bFGF restores, in large part, the responses of previously denuded arterial segments to endothelium-dependent vasodilators. Angiogenic growth factors may help to reestablish normal endothelial cell function in patients who have undergone angioplasty.

Acetylcholine↗

PubMed1996

Quantitative RT-PCR distribution of serotonin 5-HT6 receptor mRNA in the central nervous system of control or 5,7-dihydroxytryptamine-treated rats.

Possible adaptive changes of the recently cloned serotonin 5-HT6 receptor after the selective lesion of serotoninergic neurons by an intracerebral administration of 5,7-dihydroxytryptamine were investigated using competitive RT-PCR (reverse transcription followed by polymerase chain reaction) for the measurement of 5-HT6-mRNA in various areas of the rat central nervous system. In control rats, 5-HT6-mRNA was the most abundant in the nucleus accumbens, followed by the olfactory tubercle and the striatum. High levels of 5-HT6-mRNA were also found in the hypothalamus and the hippocampus, whereas the cerebral cortex, the substantia nigra, and the spinal cord contained moderate levels of the transcript. Low but easily quantifiable levels of 5-HT6-mRNA were measured in the ventral tegmental area, the anterior raphe area, and the cerebellum. In addition, moderate to low levels of this mRNA were also found in dorsal root ganglia and the pituitary gland. Three weeks after the microinfusion of 5,7-dihydroxytryptamine into the anteroventral vicinity of the dorsal raphe nucleus in nomifensine-pretreated rats, the levels of serotonin transporter-mRNA were reduced by 90% in the anterior raphe area, as expected of the extensive lesion of serotoninergic neurons. In contrast, quantitative determinations of the 5-HT6-mRNA in this area as well as in the nucleus accumbens, the striatum, and the hippocampus indicated that its levels were not significantly different in 5,7-dihydroxytryptamine-treated rats and in controls. These data showed that the 5-HT6 receptor: 1) is not an autoreceptor, and 2) exhibits probably no up regulation in postsynaptic target cells after the selective degeneration of serotoninergic projections.

5,7-Dihydroxytryptamine↗

PubMed1996

White matter magnetic resonance imaging hyperintensity in Alzheimer's disease: correlations with corpus callosum atrophy.

We have previously demonstrated with MRI that as well as marked white matter involvement in late-onset Alzheimer's disease (AD), atrophy of the corpus callosum may also be present. This finding prompted us to study possible correlations between atrophy of the corpus callosum and white matter hyperintensity (WMH) and between white matter lesions and the severity of the disease. We compared the corpus callosum and white matter lesions on MRI from 15 AD patients and 15 controls. The white matter lesions were scored according to the Scheltens' rating scale. We found a significant reduction of the area of the corpus callosum and more severe white matter lesions in AD patients than in controls. Both atrophy of the corpus callosum and the severity of lesions depended mainly on the diagnosis of senile dementia of the Alzheimer type and on age but not on the diagnosis of presenile AD. We demonstrated a negative correlation between white matter lesions scores and areas of corpus callosum in AD patients and no correlation between the white matter lesions and the severity of the disease. We demonstrated that white matter lesions including WMH and atrophy of the corpus callosum are more frequent in AD than in controls. The predominance of white matter lesions in senile AD may be explained by the combination of aging and disease processes.

Aged↗

PubMed1996

Effects of chronic treatment with zimelidine and REM sleep deprivation on the regulation of raphe neuronal activity in a rat model of depression.

Electrophysiological investigations on the mechanism of action of antidepressants have shown that both deprivation of rapid eye movement (REM) sleep and chronic treatment with antidepressants render serotoninergic (5-HT) neurons less sensitive to the inhibitory effect of 5-HT reuptake blockers in the rat. It was of interest to test whether the same mechanisms could be evidenced in a possible experimental model of depression. The latter consisted of rats which had been treated neonatally with clomipramine and exhibited at adult age behavioural and sleep alterations which resemble the human disorder. Recording the electrophysiological activity of 5-HT neurons in the nucleus raphe dorsalis (NRD) revealed that both chronic treatment with zimelidine and REM sleep deprivation induced a hyporeactivity of these neurons to the inhibitory effect of citalopram in "normal" rats. However, in rats which had been treated neonatally with clomipramine, 5-HT neurons were hyporeactive to the effect of this 5-HT reuptake blocker already under baseline conditions, and no further modification could be induced by chronic zimelidine administration or REM sleep deprivation. It can be hypothesized that adaptive phenomena at the serotoninergic NRD level are not a relevant element to explain the mechanism of action of anti-depressants in the present model of depression, while they have been considered as a crucial event in "normal" rats.

Animals↗