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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 343 records · Page 19Linked to original sources
PubMed1990

Subcutaneous formalin induces a segmental release of Met-enkephalin-like material from the rat spinal cord.

The possible influence of a noxious chemical stimulus on the activity of spinal enkephalinergic neurones was examined by measuring the outflow of Met-enkephalin-like material (MELM) in CSF perifusates from the lumbar and cervico-trigeminal zones in halothane-anaesthetized rats. Following subcutaneous injection of 50 microliters of a 10% formalin solution in saline into the muzzle, MELM outflow increased at the cervico-trigeminal level but not at the lumbar level. Conversely, a significant enhancement in MELM outflow occurred at the lumbar but not at the cervico-trigeminal level when formalin was injected into a hind paw. In both cases, the increase in MELM release took place 5-10 min after the treatment and was of short duration (5-10 min). It is concluded that noxious chemical stimuli can induce a transient activation of enkephalinergic neurones within spinal zones receiving the nociceptive inputs. The marked differences in the characteristics of spinal MELM overflow due to noxious chemical, thermal and mechanical stimuli further support the notion that each type of nociceptive stimulus probably activates spinal enkephalinergic systems by triggering distinct neuronal mechanisms.

Animals↗
PubMed1990

Biochemical models for cognition enhancers.

Although the etiology of Alzheimer's disease includes a wide range of dysfunction, the most essential dysfunction is probably in the mesolimbic acetylcholine (ACh) system. Three novel approaches to modulating ACh function were considered, somatostatin, serotonin (5-HT) and modulation of cortical ACh tone through angiotension II. Concerning somatostatin there is no correlation between the decrease in somatostatin binding sites in brain and choline-acetyl-transferase activity suggesting that modulating somatostatin is not a promising therapeutic approach to Alzheimer's disease. With 5-HT, evidence suggests that 5-HT receptors (in particular 5HT1A) are located on cholinergic projections and behavioral evidence suggests 5-HT modulation of memory function. This area could therefore develop rapidly, particularly in view of the recent discovery of numerous subtypes of 5-HT receptor. Concerning the third approach, recent evidence has shown that angiotensin converting enzyme (ACE) inhibitors can facilitate ACh release and also possess cognition enhancing activity. The possibility was also evoked that drugs such as piracetam might prevent age-related decreases in ACh receptor density. Concerning trophic factors (e.g. glutamate-induced neuronal sprouting) most approaches have induced amnesia but the search for partial glutamate agonists may have potential. Finally, a neuronal transplant approach was considered but was thought to be very difficult in view of the global brain shrinkage associated with aging and Alzheimer's disease.

Alzheimer Disease↗
PubMed1990

Regional distribution of calcitonin gene-related peptide-, substance P-, cholecystokinin-, Met5-enkephalin-, and dynorphin A (1-8)-like materials in the spinal cord and dorsal root ganglia of adult rats: effects of dorsal rhizotomy and neonatal capsaicin.

Biochemical mapping of five different peptide-like materials--calcitonin gene-related peptide (CGRP), substance P (SP), Met5-enkephalin (ME), cholecystokinin (CCK), and dynorphin A (1-8) (DYN)--was conducted in the dorsal and ventral zones of the spinal cord at the cervical, thoracic, and lumbar levels in 3-month-old rats 10 days after unilateral dorsal rhizotomy at the cervical level (C4-T2) or after neonatal administration of capsaicin (50 mg/kg s.c.). In control rats, all peptide-like materials were more abundant in the dorsal than in the ventral zone all along the spinal cord. However, in both zones, absolute concentrations of CGRP, SP, ME, and CCK were significantly higher at the lumbar than at the cervical level. Rhizotomy-induced CGRP depletion (-85%) within the ipsilateral dorsal zone of the cervical cord was more pronounced than that due to neonatal capsaicin (-60%), a finding suggesting that this peptide is contained in both capsaicin-sensitive (mostly unmyelinated) and -insensitive (myelinated) primary afferent fibers. In contrast, similar depletions of SP (-50%) were observed after dorsal rhizotomy and neonatal capsaicin treatment, as expected from the presence of SP only in the capsaicin-sensitive small-diameter primary afferent fibers. Although the other three peptides remained unaffected all along the cord by either intervention, evidence for the existence of capsaicin-insensitive CCKergic primary afferent fibers could be inferred from the increased accumulation of CCK (together with SP and CGRP) in dorsal root ganglia ipsilateral to dorsal root sections.

Afferent Pathways↗
PubMed1990

Physicochemical properties of serotonin 5-HT3 binding sites solubilized from membranes of NG 108-15 neuroblastoma-glioma cells.

Specific binding sites with pharmacological properties typical of serotonin 5-HT3 receptors were identified in membranes of the murine hybridoma cell line NG 108-15, using [3H]zacopride as a ligand. Optimal solubilization of these sites (yield, 50%) could be achieved using the detergent 3-[3-(cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) at 24 mM plus 0.5 M NaCl in 25 mM Tris-HCl, pH 7.4. Specific [3H]zacopride binding to soluble sites in the 100,000-g CHAPS extract was saturable and showed characteristics (Bmax = 425 +/- 81 fmol/mg of protein; KD = 0.19 +/- 0.02 nM) closely related to those of membrane-bound sites (Bmax = 932 +/- 183 fmol/mg of protein; KD = 0.60 +/- 0.03 nM). Determination of association (k+1 = 0.17 nM min-1) and dissociation (k-1 = 0.02 min-1) rate constants for the soluble sites gave a KD value of 0.12 nM, a result consistent with that calculated from saturation studies. As assessed from the displacement potencies (IC50) of 10 different drugs, the pharmacological profile of [3H]zacopride specific binding sites was essentially the same (r = 0.99) in the CHAPS-soluble extract and in cell membranes, although some increase in the affinity for 5-HT3 antagonists (zacopride, ICS 205-930, and MDL 72222) and decrease in the affinity for 5-HT3 agonists (2-methyl-5-hydroxytryptamine and phenylbiguanide) were noted for the soluble sites. Sucrose density gradient sedimentation of the CHAPS-soluble extract gave a Svedberg coefficient of 12S for the material with [3H]zacopride specific binding capacity. Chromatographic analyses using Sephacryl S-400 and wheat germ agglutinin-agarose columns indicated marked enrichment (by 2.5- and 10-fold, respectively) in [3H]zacopride specific binding activity in the corresponding eluates compared with the starting soluble extract, a finding suggesting that both steps are of potential interest for the partial purification of solubilized 5-HT3 receptors. Two soluble materials with apparent molecular masses of approximately 600 and approximately 36 kDa were found to bind [3H]zacopride specifically in the Sephacryl S-400 eluate. Interestingly, molecular mass determination by radiation inactivation of [3H]zacopride binding sites in frozen NG 108-15 cells gave a value of approximately 35 kDa.

Animals↗
PubMed1990

Alterations of central serotoninergic and dopaminergic neurotransmission in rats chronically treated with ipsapirone: biochemical and electrophysiological studies.

Inasmuch as sustained treatment with the 5-hydroxytryptamine1A (5-HT1A) agonist, ipsapirone, is necessary for inducing anxiolytic and antidepressant effects in the clinic, investigations were performed for assessing the possible changes in serotoninergic and dopaminergic neurotransmission in the brain of rats 24 hr after a 2-week treatment with this drug. Receptor binding assays with membranes and quantiative autoradiography indicated that the twice-daily administration of ipsapirone (5 mg/kg i.p.) for 14 days did not alter the characteristics of 5-HT1A sites in the hippocampus, septum and dorsal raphe nucleus. In contrast, significant decreases in the Bmax values for 5-HT2 sites (-24%) and 5-HT3 sites (-19%) were found in the frontal and posterior cortex, respectively. As expected from unchanged postsynaptic 5-HT1A receptors, inhibition of forskolin-stimulated adenylate cyclase by 5-HT1A agonists (8-hydroxy-2-(di-n-propylamino)tetralin, ipsapirone) exhibited the same characteristics in hippocampal homogenates from both control and ipsapirone-treated animals. An acute administration of 8-hydroxy-2-(di-n-propylamino)tetralin (0.5 mg/kg i.p.) or ipsapirone (1 or 5 mg/kg i.p.) 24 hr after the last injection for the chronic treatment produced a similar decrease in the rate of 5-HT turnover in various brain areas in rats treated for 2 weeks with saline or ipsapirone. At the highest dose (5 mg/kg i.p.), acute ipsapirone also increased the rate of dopamine turnover in the striatum and cerebral cortex approximately to the same extent in both treatment groups. In vitro recording of the firing of serotoninergic neurons in brain stem slices revealed a desensitization of the somatodendritic 5-HT1A receptors, which might be responsible for the increased 5-HT turnover in the brain stem and striatum of rats chronically treated with ipsapirone as compared with controls. These data demonstrated that chronically administered ipsapirone produces adaptive changes in central serotoninergic neurotransmission which might account for the anxiolytic and antidepressant properties of this drug after sustained treatment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

[Degradation of diazepam in aqueous solution. Simulation essay by action of diluted hydrogen peroxide].

The mild oxidation of diazepam by hydrogen peroxide in neutral medium at room temperature in daylight is reported. The oxidation product has been isolated and purified and its purity determined by thin layer chromatography. It has been identified by spectroscopy, chiefly by infrared and mass spectroscopy. Finally it has been compared, by high pressure liquid chromatography, to the product from an aqueous diazepam solution placed 6 months at room temperature in daylight.

Chromatography, Thin Layer↗
PubMed1990

[(125I)iodo-zacopride: new ligand for the study by autoradiography of central 5-HT3 receptors].

This paper describes the synthesis and the pharmacological characteristics of the first radioiodinated ligand of central 5-HT3 receptors: [125I]iodo-zacopride. Specific sites having a high affinity (Kd = 4.3 nM) for [125I]iodo-zacopride have been found in membranes from the rat entorhinal cortex. In addition, a highly significant correlation (r = 0.995) existed between the Ki of several 5-HT-related drugs for displacing both [125I]iodo-zacopride from its specific binding sites, and [3H]zacopride from 5-HT3 receptors. Finally, [125I]iodo-zacopride was successfully used for the autoradiographic mapping of 5-HT3 receptors in the rat central nervous system.

Animals↗
PubMed1990

[Assessment of the content of small peptides in enzymatic proteolysates using a cuprimetric method: value in nutritional medicine].

The nutritional interest of dipeptides and tripeptides is more and more recognized nowadays. Directly absorbed by enterocyte, they enable to improve the transfer of amino acids not easily absorbable. The quality of proteins hydrolysates mainly depends on the importance of their concentration. But official methods of analysis of protein hydrolysates (total nitrogen, alpha amino-nitrogen) are inept to estimate their concentrations. It is possible to realize this estimation by grounding on reactivity with Cu II. Indeed like free amino acids they can give complexes with this ion. The proposed cuprimetric method loads to a more sensible estimation, and especially it's possible to differentiate homogeneous hydrolysates from mixtures which have been added with amino acids. Theirs it enables the nutritional physician to have a better knowledge of the biodisponibility of this preparation.

Copper↗
PubMed1989

Determination of the molecular size of the 5-HT3 receptor binding site by radiation inactivation.

The radiation inactivation technique has been used to estimate the molecular size of the 5-HT3 receptor binding site labelled by [3H]zacopride, in comparison with that of the 5-HT1A receptor binding site labelled by [3H]8-OH-DPAT, in rat cortical membranes. The calculated molecular weight of the 5-HT3 site: 35.4 +/- 2.2 kDa (mean +/- S.E.M., n = 4) was significantly less than that of the 5-HT1A site: 62.9 +/- 1.8 kDa (mean +/- S.E.M., n = 4) and of other 5-HT1 and 5-HT2 receptors of the G-protein coupled family. These data further support that the 5-HT3 receptor is not coupled to G-proteins in the rat brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma.

32 previously untreated patients with multiple myeloma received vincristine, doxorubicin ('Adriamycin'), and dexamethasone (VAD) as first-line therapy. The overall response rate was 84%, with 28% of all patients entering complete remission. Response was rapid, with near-maximum response occurring after two courses of treatment and rapid improvement in bone-marrow function. Median response duration was 18 months and this seemed to be unaffected by initial prognostic criteria or by degree of remission achieved. The projected median survival was 44 months, with 75% of all patients and 83% of responders being alive at 2 years. Side-effects due to steroids were common, but there was only 1 treatment-related death. The high response rate and lack of toxicity offer an advantage over other forms of initial treatment, although other strategies will be necessary to prolong the duration of response.

Administration, Oral↗
PubMed1989

Intrathecal porcine calcitonin enhances the release of [Met5]enkephalin-like material from the rat spinal cord.

Perfusion of the intrathecal space of halothane-anaesthetized rats with artificial cerebro-spinal fluid supplemented with porcine calcitonin (1-10 microM) produced a significant increase (+67-110%) in the spinal release of [Met5]enkephalin-like material. The effect of porcine calcitonin was markedly enhanced (+100%) in animals receiving a continuous i.v. infusion of the opioid antagonist naloxone (65 micrograms/kg per min). These data strongly suggest that the antinociceptive effect of intrathecal porcine calcitonin might involve a stimulatory action of the hormone on spinal enkephalinergic interneurones. In addition, presynaptic opioid autoreceptors probably control the activity of these neurones in the rat.

Animals↗
PubMed1989

Chronic phenytoin treatment decreases GABAA but not beta-adrenoceptors in the cerebellum of young rats.

The effects of chronic treatment with phenytoin (50 mg/kg p.o. daily, for the first 30 days after birth) on GABAA and beta-adrenoceptors in the rat cerebellum were investigated by using in vitro quantitative autoradiography and binding assays with membranes. A significant decrease in [3H]muscimol binding to GABAA sites and, to a lesser extent, [3H]flunitrazepam binding to benzodiazepine sites was observed in the granular and molecular layers of the cerebellar cortex at the end of the treatment. Scatchard analyses demonstrated that these effects were associated with a decreased Bmax for the respective binding sites in cerebellar membranes the (Kd was not changed). In contrast, [125I]cyanopindolol binding remained unaffected. These data provide further support for the involvement of GABAergic synapses in the anticonvulsant action of phenytoin.

Adrenergic beta-Antagonists↗
PubMed1989

5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord.

Specific binding sites for [3H]zacopride were found in the dorsal part of the rat spinal cord, particularly in the superficial layers of the dorsal horn. These binding sites had the same pharmacological profile as 5-HT3 receptors in membranes from the rat entorhinal cortex or from NG 108-15 neuroblastoma-glioma cells. Administration of capsaicin (50 mg/kg s.c.) to neonatal rats to induce degeneration of unmyelinated primary sensory fibres resulted in a significant decrease in [3H]zacopride specific binding (-50%) in the dorsal zone of the spinal cord of 4 month-old rats. This decrease was as pronounced as the decrease in [3H]bremazocine and [3H]naloxone binding to opiate receptors. These data support the presynaptic location of 5-HT3 receptors, at least in part, on capsaicin-sensitive primary afferent fibres in the rat spinal cord.

Animals↗
PubMed1989

Segmental release of Met-enkephalin-like material from the spinal cord of rats, elicited by noxious thermal stimuli.

In order to investigate possible changes induced by noxious thermal stimuli in the activity of enkephalinergic neurones at various levels of the spinal cord, either the whole cord, the cervicotrigeminal area or the lumbar area were perifused with artificial CSF at a rate of 0.1 ml/min in halothane anaesthetized rats, and Met-enkephalin-like material (MELM) was measured in 0.5 ml fractions collected from the perifusates. Immersing the muzzle of intact rats in water at 52 degrees C produced a significant enhancement of MELM content in perifusates from both the whole spinal cord and the cervicotrigeminal area but not from the lumbar area. Heating the tail resulted in an increase in MELM release from the whole spinal cord of intact as well as of cervically transected rats. It is concluded that noxious thermal stimuli can induce a segmental release of MELM, i.e., only within spinal zones receiving the nociceptive inputs.

Animals↗