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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 199 records · Page 11Linked to original sources
PubMed1996

Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist.

Although considerable progress has been made in characterising the 5-HT1A receptor using agonists, partial agonists or non-selective antagonists, further studies of 5-HT1A receptor function have been hindered by the lack of highly selective antagonists. The term 'silent' antagonist has been used for such compounds in order to distinguish them unequivocally from several 5-HT1A receptor partial agonists which were initially designated 'antagonists'. In this report we provide a comprehensive review of the biochemical, pharmacological and behavioural properties of the first potent, selective and silent 5-HT1A receptor antagonist, WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride). WAY-100635 had an IC50 (displacement of specific [3H]8-OH-DPAT binding to 5-HT1A receptors in the rat hippocampus) of 1.35 nM and was > 100-fold selective for the 5-HT1A site relative to a range of other CNS receptors. [3H]WAY-100635 was also characterised as the first 5-HT1A antagonist radioligand, displaying the same regional distribution of binding sites as [3H]8-OH-DPAT in rat brain. As would be expected for the binding of an antagonist to a G-protein-coupled receptor, the Bmax of [3H]WAY-100635 specific binding was consistently 50-60% greater than that of the agonist radioligand, [3H]8-OH-DPAT. Mn2+, but not guanine nucleotides, inhibited [3H]WAY-100635-specific binding. [3H]WAY-100635 was also shown to bind selectively to brain 5-HT1A receptors in vivo, following intravenous administration to mice. In vitro electrophysiological studies demonstrated that WAY-100635 had no 5-HT1A receptor agonist actions, but dose-dependently blocked the effects of agonists at both the postsynaptic 5-HT1A receptor in the CA1 region of the hippocampus, and the somatodendritic 5-HT1A receptor located on dorsal raphe 5-HT neurones. In vivo, WAY-100635 also dose-dependently blocked the ability of 8-OH-DPAT to inhibit the firing of dorsal raphe 5-HT neurones, and to induce the '5-HT syndrome', hypothermia, hyperphagia and to elevate plasma ACTH levels. In the mouse light/dark box anxiety model, WAY-100635 induced anxiolytic-like effects. WAY-100635 had no intrinsic effect on cognition in the delayed-matching-to-position model of short-term memory in the rat, but reversed the disruptive effects of 8-OH-DPAT on motor motivational performance. These data clearly demonstrate that WAY-100635 is the first potent, selective and silent 5-HT1A receptor antagonist. Furthermore, [3H]WAY-100635 is the first antagonist radioligand to become available for 5-HT1A receptor binding studies both in vitro and in vivo. The positive effects of WAY-100635 in an anxiety model also indicate that a postsynaptic 5-HT1A receptor antagonist action may contribute to the anxiolytic properties of 5-HT1A receptor partial agonists.

Adrenocorticotropic Hormone↗
PubMed1996

Serotonin1A receptors are expressed by a subpopulation of cholinergic neurons in the rat medial septum and diagonal band of Broca--a double immunocytochemical study.

The possible colocalization of 5-hydroxytryptamine1A receptors and choline acetyltransferase in the same neurons of the medial septum and diagonal band of Broca was investigated using double immunocytochemical techniques, either on the same section or on adjacent thin sections of the rat brain. The presence of both antigens in the same neurons was demonstrated at the light and electron microscopic levels. The proportion of cholinergic neurons that express 5-hydroxytryptamine1A receptors was similar in the different parts of the septal complex (around 25%). By contrast, the proportion of 5-hydroxytryptamine1A receptor-positive neurons also exhibiting choline acetyltransferase immunoreactivity was much higher (40-44%) in the dorsal and ventral groups of cholinergic cells, than in the intermediate group (18%). In line with the topographical distribution of cholinergic projections, this result points out the potential involvement of 5-hydroxytryptamine1A receptors in the control of the septohippocampal cholinergic projection by serotonin. This connection might be relevant to learning and memory, and in the appearance of age-dependent or neurodegenerative cognitive deficits, which have been shown to involve alterations in both the serotoninergic and the cholinergic systems.

Animals↗
PubMed1996

Differential addressing of 5-HT1A and 5-HT1B receptors in transfected LLC-PK1 epithelial cells: a model of receptor targeting in neurons.

Based on the finding that the mechanism of membrane protein sorting may be similar in neurons and epithelial cells, we have investigated the localization of the 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors in Eli Lilly and Company canine kidney (LLC-PK1) cells (epithelial cells from pig kidney) stably transfected with the corresponding cDNAs. Receptors were characterized by radioligand binding, measurement of coupled adenylate cyclase activity and immunofluorescene with specific antibodies. Confocal microscopy and cell surface biotinylation experiments showed that the 5-hydroxytryptamine1A receptor, which is at the somatodendritic level in neurons, was targeted to the basolateral surface whereas the 5-hydroxytryptamine1B receptor, which is localized on nerve endings, predominated intracellularly. Such a difference in the localization of these two receptors suggests that the signal for the differential addressing of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors is contained within their primary sequence and confirms that epithelial cells can be used as a suitable model to study receptor targeting in neurons.

Animals↗
PubMed1996

Autoradiographic mapping of serotonin 5-HT1A, 5-HT1D, 5-HT2A and 5-HT3 receptors in the aged human spinal cord.

Quantitative autoradiography with selective radioligands was used to establish the respective distribution of serotonin 5-HT1A, 5-HT1D, 5-HT2A and 5-HT3 receptors at the cervical, thoracic and lumbar levels of the spinal cord from subjects who died at 81-94 years. A high density of 5-HT1A receptors, labeled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT), was found in the superficial layers of the dorsal horn, with a significant enrichment ( approximately 20%) in the lumbar vs. the thoracic and cervical segments. In contrast, only very low specific labeling by [3H]8-OH-DPAT (i.e. less than 10% of that measured in the dorsal horn), was detected in the ventral horn. 5-HT1D sites labeled by [125I]serotonin-O-carboxymethyl-glycyl-iodo-tyrosinamide ([125I]GTI) were also mainly located within the superficial layers of the dorsal horn, but no difference in their relative density was noted at the three levels of the spinal cord examined. 5-HT2A sites labeled by [3H]ketanserin were found in the dorsal horn of the cervical segments but no specific binding of this radioligand could be detected at any other level of the spinal cord of such aged subjects. Finally, a high density of [3H]S-zacopride-labeled 5-HT3 receptors was noted especially in the most superficial layer (lamina I) of the dorsal horn at all segments examined. These data provide anatomical support for a role of spinal serotonin especially in nociception processing.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Functional specialization in the ruminant placenta: evidence for two populations of fetal binucleate cells of different selective synthetic capacity.

Trophoblast binucleate cells (BNC) in the ruminant placenta demonstrate a characteristic development, mature structure and migratory capacity whether situated in cotyledonary or intercotyledonary regions of the placenta. However, previous immunocytochemical studies demonstrated clear differences in gene expression in granule contents of BNC according to their anatomical location with some proteins being expressed in all BNC (e.g. ovine placental lactogen) whereas others were unique to a particular origin (e.g. SBU3 antigen in cotyledonary BNC only). We have used enriched preparations of binucleate cells and showed differences in steroid metabolic capacity in vitro which is more related to their species origin (sheep or goat) than to their anatomical location. The predominant product from [3H]pregnenolone is progesterone (sheep) and 5 beta-pregnane-3 alpha, 20 alpha-diol (goat) and the amount formed (corrected for the number of BNC) is similar irrespective of whether BNC were derived from the cotyledonary or intercotyledonary regions. These studies indicate specific forms of regional functional specialization of BNC and emphasize their multifunctional role in the ruminant placenta.

Animals↗
PubMed1996

Stress- and yohimbine-induced release of cholecystokinin in the frontal cortex of the freely moving rat: prevention by diazepam but not ondansetron.

The in vivo release of cholecystokinin (CCK)-like material (CCKLM) was measured in the frontal cortex of freely moving rats using the microdialysis technique combined with a sensitive radioimmunoassay. Local perfusion of K+ (100 mM)-enriched artificial CSF resulted in a 10-fold increase in CCKLM outflow, as compared with that occurring under basal resting (K+ = 3.0 mM) conditions, and this effect could be completely prevented by removal of Ca2+ in the perfusing fluid. Chromatographic analyses demonstrated that CCK-8S contributed to 70% of CCKLM. Stressful stimuli such as a 2-min exposure to diethyl ether and a 30-min restraint produced a marked but transient increase in cortical CCKLM release. In addition, anxiety-like behavior induced by the systemic administration of yohimbine (5 mg/kg i.p.) was associated with a long-lasting enhancement in the peptide outflow. Pretreatment with the potent anxiolytic drug diazepam (5 mg/kg i.p., 5 min before each condition), which exerted no effect on its own, completely prevented CCKLM overflow due to diethyl ether, restraint, or yohimbine administration. In contrast, neither the systemic injection (0.1 mg/kg i.p.) nor the local application (100 microM through the microdialysis probe) of the serotonin 5-HT3 antagonist ondansetron affected the increased release of CCKLM in rats restrained for 30 min or treated with yohimbine. These results indicate that cortical CCKergic neurotransmission is increased during stress or anxiety-like behavior in rats. Prevention of this effect by diazepam suggests that an inhibitory influence of benzodiazepines on cortical CCKergic neurons might participate in the anxiolytic action of these drugs.

Administration, Inhalation↗
PubMed1996

Morphological changes after percutaneous transluminal coronary angioplasty of unstable plaques. Insights from serial angioscopic follow-up.

OBJECTIVE: To describe the morphological changes occurring in the months following percutaneous transluminal coronary angioplasty (PTCA) of unstable plaques. BACKGROUND: Coronary angioscopy is a relatively new technique to assess plaque morphology. Previous angioscopic studies have shown that unstable coronary lesions are characterized by complex morphology, evidence of plaque rupture, and intraluminal thrombi. No serial angioscopic studies have investigated the effects of PTCA on plaque morphology at such lesions. METHODS: We studied 15 patients who underwent successful PTCA for an unstable coronary syndrome (unstable angina: n = 5; recent myocardial infarction: n = 10). Angioscopy was performed immediately before PTCA in 14 patients, immediately after PTCA in 13 patients, and at follow-up (225 +/- 62 days after PTCA) in all patients. RESULTS: Pre-PTCA, plaque morphology was defined as complex in 18%, ulcerated in 27%; the vessel was totally occluded in 18% of cases. Plaque colour was yellow in 75% of patients. A thrombus was identified at the lesion site in 71% of patients. Immediately post-PTCA, small surface disruptions and dissections were observed in 62% of patients. Plaque colour was yellow in 85% of cases. Seventy-seven percent of patients had an angioscopically visible thrombus at the PTCA site. At follow-up, however, plaque shape was almost uniformly classified as smooth concentric (93%); plaque colour was white in 93%; no thrombus was observed. CONCLUSIONS: These results demonstrate the healing of unstable plaques in the months following PTCA. The angioscopic appearance at 6 months is that of a stable plaque (smooth concentric, white, without thrombus). Whether this stable angioscopic appearance predicts long-term clinical stability remains to be determined.

Adult↗
PubMed1996

Restenosis after coronary angioplasty for rapidly progressive coronary stenosis.

OBJECTIVES: We hypothesized that percutaneous transluminal coronary angioplasty performed on coronary stenoses that have demonstrated rapid angiographic progression would be associated with a high risk of restenosis. BACKGROUND: High rates of restenosis have been documented after percutaneous transluminal coronary angioplasty of unstable lesions and of lesions that recur rapidly after a successful initial angioplasty. This suggests that the "activity' of the plaque at the time of angioplasty may be an important factor determining the risk of restenosis. METHODS: In our institution we recommend angiographic follow-up for all patients with successful percutaneous transluminal coronary angioplasty. In this way we identified 86 consecutive patients who, at the time of angiographic follow-up had not developed restenosis at the dilated site, but required a further percutaneous transluminal coronary angioplasty at a different site. (which was successful). Based on quantitative angiographic measurements, 45 of these lesions (rapidly progressive lesions) had significantly increased in severity in the interval between the two angiograms (7.7 +/- 3.3 months) while 41 (stable lesions) had not. Rapid progression was defined as a > 0.4 mm decrease in minimal lumen diameter between initial angiography and percutaneous transluminal coronary angioplasty. All 86 patients had further angiographic follow-up 6 months later. RESULTS: Baseline clinical and angiographic variables were similar in both groups except that a higher proportion of patients in the rapid progression group had unstable angina (20% vs 5%; P < 0.05). Late loss during follow-up did not differ statistically between groups (0.31 mm) and minimal lumen diameter at follow-up was also similar (stable lesion group = 1.40 +/- 0.48 mm; rapidly progressive lesion group = 1.30 +/- 0.59 mm). The loss index (late loss divided by acute gain) was also similar in both groups (0.45 +/- 0.52 in the stable lesion group, 0.37 +/- 0.76 in the rapidly progressive lesion group). A strong correlation between acute gain and late loss was observed in the stable lesion group (r = 0.61; P < 0.0001); by contrast, there was no relationship between these two variables in the rapidly progressive lesion group (r = 0.20; P = 0.19). CONCLUSIONS: Percutaneous transluminal coronary angioplasty in patients with unstable angina or with early recurrence after a first percutaneous transluminal coronary angioplasty is associated with an increased risk of restenosis. By contrast, this study shows that angiographic instability, as evidenced by rapid stenosis progression, has no deleterious effect on the occurrence of restenosis. Percutaneous transluminal coronary angioplasty thus appears as a reasonable therapeutic option for coronary stenoses that have demonstrated rapid angiographic progression in the months prior to the procedure.

Age Factors↗
PubMed1996

Hypersensitivity of human coronary segments to ergonovine 6 months after injury by coronary angioplasty: a quantitative angiographic study in consecutive patients undergoing single-vessel angioplasty.

OBJECTIVE: Multiple studies have been designed to analyse restenosis angiographically but few have studied the vasoreactivity of coronary segments subjected to angioplasty a few months before. In the present study we analysed, with use of quantitative angiography, the vasoreactivity of previously dilated segments to graded doses of ergonovine and of isosorbide dinitrate. PATIENTS: Fifty consecutive patients undergoing follow-up angiography 6 months after a single coronary angioplasty procedure were studied. RESULTS: The vasoconstrictor response at dilated segments (-19.3 +/- 3.0%) was significantly greater than at control proximal and distal sites in dilated (-7.3 +/- 1.1%, -11.0 +/- 2.9%) and non-dilated (-9.1 +/- 1.3%, -8.3 +/- 2.2%) vessels for the lowest dose of ergonovine (100 micrograms). The constrictor response to 100 micrograms ergonovine (-20.2 +/- 5.3%) at restenosed segments (> 50% stenosis, n = 18) was similar to that (-18.8 +/- 3.8%) at non-restenosed sites (n = 32). In contrast, the degree of constrictor response was similar in all segments including dilated segments for the highest dose of ergonovine used. All segments dilated significantly after intracoronary injection of isosorbide dinitrate. CONCLUSION: Our results demonstrate hypersensitivity of the dilated site to ergonovine 6 months after angioplasty at both restenosed and non-restenosed sites. This response may reflect partial dysfunction of endothelium that has regenerated after injury or hypersensitivity of vascular smooth muscle cells at the site of arterial injury.

Aged↗
PubMed1996

Sleep deprivation reduces the citalopram-induced inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis of the rat.

Sleep deprivation (SD) for one night induces mood improvement in depressed patients. However, relapse often occurs on the day after deprivation subsequently to a sleep episode. In light of the possible involvement of central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission in both depression and sleep mechanisms, we presently investigated, in the rat, the effects of SD and recovery sleep on the electrophysiological response of 5-HT neurons in the nucleus raphe dorsalis (NRD) to an acute challenge with the 5-HT reuptake blocker citalopram. In all rats, citalopram induced a dose-dependent inhibition of the firing of NRD neurons recorded under chloral hydrate anaesthesia. After SD, achieved by placing rats in a slowly rotating cylinder for 24 h, the inhibitory action of citalopram was significantly reduced (with a concomitant 53% increase in its ED50 value). After a recovery period of 4 h, a normal susceptibility of the firing to citalopram was restored. The decreased sensitivity of 5-HT neuronal firing to the inhibitory effect of citalopram after SD probably results in an enhancement of 5-HT neurotransmission. Such an adaptive phenomenon (similar to that reported after chronic antidepressant treatment), and its normalization after recovery sleep, parallel the mood improvement effect of SD and the subsequent relapse observed in depressed patients. These data suggest that the associated changes in 5-HT autocontrol of the firing of NRD serotoninergic neurons are relevant to the antidepressant action of SD.

Animals↗
PubMed1996

NO synthesis is involved in structural and functional effects of ACE inhibitors in injured arteries.

Angiotensin-converting enzyme (ACE) inhibitors reduce intimal hyperplasia after balloon injury. A role for nitric oxide (NO) has been suggested in this effect. Because recent data suggest that NO may modulate some features of endothelial cells and because endothelial cells are involved in the control of intimal hyperplasia, we investigated the role of NO synthesis in the effect of an ACE inhibitor, perindopril, on neoendothelial dysfunction and intimal hyperplasia in a rabbit model of unilateral iliac balloon injury. New Zealand White male rabbits received placebo, perindopril, or cotreatment with perindopril and NG-nitro-L-arginine methyl ester (L-NAME) and were evaluated 4 wk after the injury. Fifteen rabbits (5 in each group) were used to assess in vitro vasoreactivity and twenty-four (8 in each group) for morphometric analysis. In injured vessels, neoendothelium-dependent relaxation in ACE inhibitor-treated animals was improved compared with placebo (P < 0.05) and restored to the level of noninjured vessels (NS). The improvement observed with ACE inhibitor was abolished by cotreatment with L-NAME (P < 0.05). In the same vessels, no effect was observed on neoendothelium-independent vasoreactivity. The improved neoendothelial dysfunction with ACE inhibitor was associated with a 66% reduction in intimal thickening (P < 0.01). The effect was also reversed by cotreatment with L-NAME (P < 0.01). In noninjured vessels, treatment did not alter vasoreactivity or morphology of the vessel wall. These results suggest that NO synthesis may play a key role in the improvement of vascular function seen with ACE inhibitor in balloon-injured vessels.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Stimulation of 5-HT3 receptors in the NTS inhibits the cardiac Bezold-Jarisch reflex response.

Intra-atrial administration of phenylbiguanide has been shown to trigger, through the stimulation of vagal afferent C-fibers, reflex bradycardia, hypotension, and sympathoinhibition classically known as the Bezold-Jarisch (B-J) reflex (O. Krayer. Naunyn-Schmiedeberg's Arch. Exp. Pathol. Pharmacol. 240: 361-368, 1961). The effects of microinjections, into the nucleus tractus solitarius (NTS), of serotonin (5-HT) and 1-(m-chlorophenyl)-biguanide (CPBG), a potent 5-HT3 receptor agonist, on these reflex responses were studied in urethananesthetized rats. 5-HT (600 and 900 pmol) and CPBG (10-150 pmol) produced a dose-dependent inhibition of the atropine-sensitive bradycardiac component of the B-J reflex. The effect of both agonists was reversed by prior local microinjection of the 5-HT3 receptor antagonists zacopride (100 pmol) and ondansetron (100 pmol), but not by that of the 5-HT2 receptor antagonist ketanserin (10 pmol) or the mixed 5-HT1/5-HT2 receptor antagonist methysergide (100 pmol). In contrast, CPBG (150 pmol) did not affect the B-J reflex inhibition of lumbar sympathetic nerve discharge. These results show that stimulation of NTS 5-HT3 receptors produced an inhibition of the cardiovagal component of the B-J reflex without affecting its sympathetic component. Because the stimulation of these receptors also inhibits the cardiac component of the baroreflex, the present data suggest the participation of NTS 5-HT3 receptors in the mechanisms that modulate cardiac reflex responses elicited by messages from different vagal afferents.

Animals↗
PubMed1996

[Relation between progression of atherosclerosis and the phenomenon of restenosis after coronary angioplasty].

The authors undertook a retrospective study of medium-term coronary angiographic controls of a group (Gr) of patients (pts) who had undergone coronary angioplasty for rapidly progressive lesions, to determine whether the rate of progression of a coronary stenosis before angioplasty affected the risk of restenosis. 89 pts underwent primary angioplasty with absence of restenosis at 6 months, but required another angioplasty for another lesion. Angiographic follow-up after the 2nd procedure was performed in 86 pts (96%). The coronary lesion dilated at the 2nd angioplasty procedure was analysed quantitatively with four measurements: one immediately before angioplasty, one after, one at the 6 months control, and finally, one measurement 6 months before the angioplasty during the procedure on the 1st site. Multivariate statistical analysis showed that the only predictive factor of post-angioplasty loss in the general population was the immediate gain (F = 11.82; p < 0.005). On the other hand, no correlation was found between progression of the lesion before angioplasty and loss. The rapidly progressive nature of the lesion was defined with a threshold of 0.4 mm, corresponding to the variability of the quantitative angiographic system. Analysis of the procedure parameters showed a lower inflation pressure in the Gr with rapidly progressive lesions (6.58 +/- 21 atm vs 7.63 +/- 1.96 atm; p < 0.05). The immediate gain was significantly greater in the rapidly progressive lesion Gr (0.82 +/- 0.34 vs 0.67 +/- 0.29 mm; p = 0.05). The loss at the 6 months control was identical in the two Gr (0.31 +/- 0.50 vs 0.31 +/- 0.42 mm; p < 0.05). The loss/gain ratio was also comparable (0.37 +/- 0.76 vs 0.45 +/- 0.52; p > 0.05). These results show that rapidly progressive atherosclerosis does not increase the risk of post-angioplasty restenosis.

Aged↗
PubMed1996

Electrophysiological effects of N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635) on dorsal raphe serotonergic neurons and CA1 hippocampal pyramidal cells in vitro.

The aim of the present study was to examine the effects of N-(2-(4-2-methoxphenyl)-1-piperazinyl)ethyl)-N-(2-pyridnyl) cyclohexane carboxamide (WAY 100635) on 5-HT1A receptor-mediated responses in the dorsal raphe nucleus (DRN) and the CA1 hippocampal region. In DRN slices superfused with WAY 100635 (10 nM), the majority of putative 5-HT neurons increased their firing rate (13 +/- 2% of baseline rate). In addition, WAY 100635 completely prevented the decrease in firing rate produced by 5-HT (3-15 microM), 8-OH-DPAT (10 nM), 5-carboxamidotryptamine (20 nM) and lesopitron (100 nM). The antagonism exerted by WAY 100635 (IC50 = 0.95 +/- 0.12 nM against 15 microM 5-HT) was fully surmounted by increasing the concentration of 5-HT to 300 microM. In hippocampal slices, WAY 100635 (0.5-10 nM) did not alter the resting membrane potential or the membrane input resistance of intracellularly recorded CA1 pyramidal cells. However, WAY 100635 completely prevented (IC50 = 0.9-1.7 nM) the hyperpolarization and the decrease in membrane input resistance produced by 5-HT (15-30 microM) and by 5-carboxamidotryptamine (50-300 nM). In contrast, WAY 100635 affected neither the block of action potential frequency adaptation and slow afterhyperpolarization produced by 5-HT (15 microM) nor the hyperpolarization and decrease in membrane input resistance evoked by bath application of GABA(B) receptor agonist baclofen (10 microM). The cumulative concentration-hyperpolarization curve for 5-carboxamidotryptamine (3 nM-10 microM) was shifted to the right by WAY 100635 (apparent Kb = 0.23 +/- 0.07 nM), and the latter drug also reduced the maximal response to the agonist. These data show the WAY 100635 is a potent antagonist at 5-HT1A receptors, both in the DRN and in the CA1 region of the hippocampus. The antagonism is apparently competitive in the DRN and partly noncompetitive in the hippocampus. Kinetic characteristics of the antagonist-receptor interactions might account for these regional differences.

Animals↗
PubMed1996

[Diabetes insipidus revealing pituitary metastasis of bronchial carcinoma].

Pituitary metastasis are rare but represent an important differential diagnosis of intrasellar tumorous syndromes. We report one case of intrasellar metastasis of a bronchial adenocarcinoma in a 50 year old woman. Clinical syndrome associated a tumorous syndrome (cephalalgia, bitemporal hemianopsia) and an anterior and posterior hypopituitarism biologically proven. A large intra and suprasellar mass which compressed the optic chiasma and highly enhanced after gadolinium injection was found by nuclear magnetic resonance imaging. The surgical biopsy displayed a pituitary metastasis of a right inferior lobar bronchial adenocarcinoma with bone secondary localizations. Cerebral radiotherapy and corticotherapy allowed recovery of visual loss but did not prevent rapid death. The clinical and radiological features which may evoke an intrasellar metastasis were: the tumorous syndrome associated with or revealed by diabetes insipidus, loss of spontaneous hypersignal of the neurohypophysis in nuclear magnetic resonance imaging, bulking pituitary stalk, bilobar character of the mass which is in favour of rapid cell proliferation, postero-superior extension, lowering of the V3 floor and very strong and homogeneous signal after gadolinium injection.

Carcinoma, Bronchogenic↗
PubMed1996

The two orphan Na+/Cl(-)-dependent transporters Rxt1 and V-7-3-2 have an overlapping expression pattern in the rat central nervous system.

The messenger RNA expression patterns of two orphan Na+/Cl(-)-dependent transporters, Rxt1 and V-7-3-2, were compared in the adult rat CNS by in situ hybridization histochemistry. The sites of synthesis of both orphan transporters were found to largely overlap. The highest concentrations of Rxt1 and V-7-3-2 mRNAs were present in the olfactory bulb, cerebral cortex, hippocampus, habenular and pontine nuclei, and cerebellum. Low levels of orphan transporters mRNAs were observed in the basal ganglia (caudate-putamen, nucleus accumbens, globus pallidus), septum nuclei, substantia nigra, colliculi and brainstem. Only few regions were found to express only one of these two orphan transporters: Rxt1 mRNA in the thalamic area and the hilus of the dentate gyrus. V-7-3-2 mRNA in motoneurons of the most ventral zone of the spinal cord. Rxt1 mRNA was generally more abundant than V-7-3-2 mRNA, except in few areas (piriform cortex, horizontal limb of the diagonal band, medial habenular nucleus, pyramidal and granular cell layers in the hippocampus) where the levels of both mRNAs were similar. The overall parallelism between both distributions was further confirmed at the cellular level on emulsion-coated sections, especially in the hippocampus where pyramidal and granular neurons very probably synthesize both Rxt1 and V-7-3-2. These data provide a further demonstration of the synthesis of the orphan transporters Rxt1 and V-7-3-2 exclusively in neurons whose locations suggest that they might correspond to glutamatergic neurons and subsets of GABAergic neurons.

Amino Acid Sequence↗