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Biomedical subjects

R Jeanningros

Publications and source records attributed to R Jeanningros.

At least 37 records · Page 2Linked to original sources

L-tyrosine and L-tryptophan membrane transport in erythrocytes and antidepressant drug choice.

In the treatment of depression, when antidepressant drug choice is made according to alterations of erythrocyte membrane transport of L-tyrosine and L-tryptophan in the individual patient, the clinical results are superior to those obtained when drugs are prescribed according to the physician's judgment. This is demonstrated by comparing three experimental groups: I, 100 patients treated in relation to their L-tyrosine and L-tryptophan transport; II, 30 patients treated according to the clinician's experience; III, 38 subjects treated against the L-tyrosine and L-tryptophan transport indications. In these groups, the frequency of patients improved by more than 70% is 77%, 47%, and 16%, respectively.

Adult↗

A multivariate analysis of red blood cell membrane transports and plasma levels of L-tyrosine and L-tryptophan in depressed patients before treatment and after clinical improvement.

The purpose of this study was to examine whether biological variables, such as erythrocyte membrane transports and plasma levels of monoamine precursor amino acids (tyrosine, tryptophan and phenylalanine), exhibit a particular pattern relatively to DSM-III depressive subgroups (dysthymic disorders, major recurrent depression and biopolar depression), when they are treated synthetically by a stepwise discriminant analysis. We conducted two tests in 97 subjects (64 depressed patients vs. 33 controls): the first before any antidepressant treatment, and the second after pharmacotherapy and clinical improvement. Our results clearly indicate a satisfying homogeneity for the controls and bipolar depressed patients as opposed to dysthymic disorders and major recurrent depression in both tests. The most informative biological variables are the erythrocyte membrane transports before treatment, tryptophan parameters after clinical improvement. Evidence is provided that multivariate analysis constitutes an interesting approach in biological psychiatry.

Adult↗

Platelet [3H]-imipramine binding according to DSM-III subtypes of depression.

The question of the previously reported changes in the density of high-affinity binding sites for [3H]-imipramine (IMI) in platelets from depressed patients was reexamined among the different diagnostic subtypes of depression according to the DSM-III classification and taking into account the possible influence of the low-affinity binding site. Using a least-square computer-assisted analysis, a precise determination of the [3H]-IMI binding parameters exclusively in relationship to the high-affinity site was performed in 46 untreated depressed patients and compared to 35 healthy controls. The results revealed a clear and highly significant 22% decrease in the maximal density (Bmax) of [3H]-IMI binding in all of the depressed patients compared to controls with no change in affinity values. Considering the diagnostic subgroups, we found that all the bipolar patients, the depressed as well as the euthymic or manic ones, had very low Bmax values and that some of them also exhibited an unusual low-affinity binding. Mean Bmax of the unipolar and dysthymic patients significantly decreased when compared to controls, although the Bmax values showed a large variability. Only dysthymic patients presented Bmax values which were significantly associated to symptom severity as assessed by the Hamilton Depression Rating Scale scores. Our results confirm the lower density of platelet [3H]-IMI binding in affective disorders, particularly in bipolar patients, and also suggest that this biological parameter is a trait marker in bipolar depression and a state marker in dysthmic disorder.

Adolescent↗

Modulation of lateral hypothalamic single unit activity by gastric and intestinal distension.

Single unit discharges in the lateral hypothalamic area (LH) were extracellularly recorded in chloralose anesthetized cats, while gastric or intestinal distension was performed. 47 out of 95 units were sensitive to gastric distension. Both phasic or tonic increases and decreases in firing rate were observed. Out of 41 units sensitive to gastric filling, 7 were also responsive to gastric emptying, exhibiting changes in the same direction to positive and negative variation in gastric pressure. Intestinal distension elicited changes in firing rate in 15 out of 34 units tested. As during gastric distension, units decreased or increased in firing rate while distension of the lumen was performed. The latencies of responses to gastric and intestinal distension were very short (less than one second) and were consistent with the functional properties of gastrointestinal mechanoreceptors previously described. In addition, 5 out of 25 units sensitive to gastric or intestinal distension, were responsive to both gastric and intestinal distensions exhibiting changes in the same direction. In this case, vagus nerve stimulation produced the same effect as the gastro-intestinal distensions. The results are discussed in terms of convergence of gastric and intestinal mechanoreceptor inputs on lateral hypothalamic neurons, in relation to the propagation of ingested food throughout the digestive tract.

Action Potentials↗

Effect of intestinal amino acid infusions on hypothalamic single unit activity in the anesthetized cat.

Single unit discharges in the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LH) were recorded extracellularly in anesthetized cats, while amino acid solutions were perfused through the small intestine via implanted cannulae. Test infusions consisted of 5 amino acid mixtures (arginine, leucine, phenylalanine, tryptophan, alanine: 50 mM each), 5.0% casein hydrolysate; arginine 125 mM (2.2%); leucine 125 mM (1.6%). Sixty-six units were recorded in 30 cats. Of 52 tested in the LH, 19 or 37% were affected: 14 increased and 5 decreased in firing rate in response to amino acid intestinal perfusions with a very short latency consistent with activation of intestinal amino acid receptors. Of 14 neurons tested in VMH, only 3 or 21% were activated by amino acid infusions but with a long latency of several minutes which cannot exclude the involvement of a postabsorptive signal. Results are discussed in terms of intestinal afferent control over hypothalamic neuronal activity related to amino acid induced satiety.

Amino Acids↗

Vagal unitary responses to intestinal amino acid infusions in the anesthetized cat: a putative signal for protein induced satiety.

Single unitary discharges in the nodose ganglia were recorded extracellularly in chloralose anesthetized cats while amino acid solutions were being perfused through the small intestine via implanted cannulae. Test infusions consisted of either amino acid mixtures (12 amino acids; 120 mM in all) or individual amino acids (50 mM each) dissolved in Krebs Henseleit buffer. Units which were activated by amino acid infusions were also tested with 10% glucose infusions performed in the same way. Control infusions consisted of either buffer alone or a physiological saline solution isotonic to the test solution. All perfusions were performed at 38 degrees C, pH 7.4 by means of a syringe over a 10 second period. Out of 1250 vagal units activated by electrical vagal stimulation, 92 units showed an increased firing rate in response to amino acid intestinal perfusions. Of these, only 1/7 were also responsive to glucose perfusions. Osmotic, thermal or mechanical stimuli associated with infusions did not modify vagal responses to the amino acids. Among vagal units responding only to amino acid but not to glucose infusion, some were activated in a specific manner, depending on the specific amino acid infused intraduodenally. These neurons illustrated a very strict specificity regarding the nature of chemical stimuli. The very short latency, mean of 9 sec +/- 0.7 (SE) of these vagal neurons to amino acid infusions unequivocally indicates that chemoreceptors are located at the preabsorptive level. The corresponding fibers were non-myelinated (conduction velocities: 0.8/1.4 m/sec.) and were of the C type. The functional characteristics of these vagal amino acid receptors are discussed in terms of the role of intestinal signals in short term protein satiety.

Animals↗

Vagal and splanchnic effects at the level of the ventromedian nucleus of the hypothalamus (VMH) in the cat.

A systematic study of vagal and splanchnic projections to the VMH area was undertaken in anaesthetized cats by means of macroelectrodes and microelectrodes. Responses elicited by vagal and splanchnic nerve stimulation were recorded from the VMH nucleus and the region situated above it. The fact that they are identical, whatever the nerve stimulated, indicates that the afferences follow a common central pathway. From the response latency and the stimulation parameters, it is assumed that the small vagal and splanchnic fibres (A delta, B and C) are involved. Evoked potentials are generally constituted of two parts: the earlier implies certainly the VPL nucleus (since it disappears definitively after VPL coagulation), whereas the later concerns a different relay probably located in the neighbouring and associative structure (since it persists after VPL coagulation). Similar late responses were simultaneously recorded in VPL nucleus, suggesting that this structure was the same for both nuclei. Its exact location was discussed. On the other hand, effects of gastric distension on the evoked potentials produced by vagal and splanchnic nerve stimulation were studied. The results obtained (decrease or increase in the responses, occurrence of an additional potential) indicated clearly that the gastric afferences projected to the VMH region. This simple method could be used to determine the importance of the sensory innervation of the different parts of the digestive tract.

Afferent Pathways↗

[Role of vagal intestinal glucoreceptors in insulin regulation].

This paper summarizes recent data on the existence of insulin nervous regulation by duodenal glucoreceptors which are connected to non-medullated fibres included in the vagal nerves. These glucoreceptors respond to intestinal perfusion of glucose or other carbohydrates, but other conventional mechanical stimuli are unable to activate them; therefore, they must be considered as true specific glucoreceptors. Their activation produces an immediate increase of insulin which precedes changes in glycemia. From bivagotomy experiments and from experiments which pharmacologically exclude the efferent parasympathetic or sympathetic fibres, it has been shown that this regulation is chiefly mediated by the vagal nerves. On the other hand, it was found that glucoreceptor afferents project on the hypothalamic nuclei (VMH and LHA) like the whole splanchnic and vagal afferents. The physiological importance and the role of insulin nervous regulation are discussed.

Afferent Pathways↗

[Preliminary data on intestinal chemoreceptor responses to amino acids].

Intestinal chemoreceptor responses to amino acids in the small intestine were investigated in anaesthetized cats with a microelectrophysiological technique, i.e. vagal units in the nodose ganglion were recorded by extracellular glass microelectrodes. About 400 neurons were tested by infusing the small intestine with a mixture of several amino acids at 38 degrees C. Fifty neurons, which were generally silent before the first infusion, were activated by amino acid solutions with a short latency of a few seconds. Their discharge frequency was always low (less than 10 Hz). The corresponding fibres were non-medullated (conduction velocity: 0.8-1.4 m/s). These receptors did not respond to osmotic or mechanical stimuli. Moreover, some of them were not activated by glucose infusion and must thus be considered as specific amino acid receptors. The others which responded to both amino acids and glucose infusions were non-specific receptors. The properties of these two types of amino receptors and their roles in the nervous regulations of feeding behaviour, in particular protein satiety, are discussed.

Amino Acids↗

[Visceral, vagal, and splanchnic projections in the region of the ventro-medial nucleus of the hypothalamus in cats].

In anaesthetized cats, evoked or unitary potentials were produced in the hypothalamus by electrical stimulation of splanchnic and vagus nerves. Responses were recorded bilaterally in an area corresponding to the median nucleus. They were greater for the splanchnic stimulation than for the vagal one. The stimulation parameters and the response latencies suggested that the afferent fibres involved belonged chiefly to B and C nerve components. From this preliminary study, it will be possible to analyze the effects of different splanchnic and vagal afferents on the unitary activity of the ventro-median nucleus.

Afferent Pathways↗

Purification and properties of a debranching enzyme from Escherichia coli.

The debranching enzyme (EC 3.2.1.-) from Escherichia coli K12 was purified 312-fold with a 21% yield, DEAE-cellulose and DEAE-Sephadex chromatography were used for purification. The preparation was homogeneous and showed only a single band of protein and activity upon polyacrylamide gel electrophoresis. The enzyme hydrolyzed 1,6-alpha-glucosidic linkages in phosphorylase and beta-amylase limit dextrins prepared from glycogen and amylopectin. Small branched oligosaccharides were also hydrolyzed. Amylopectin was also completely hydrolyzed but the enzyme showed only a very low activity with glycogen as the substrate. The enzyme cannot be classified as a pullulanase because it has practically no activity with pullulan. But it also differs from the bacterial isoamylases described in other studies because of its inability to hydrolyze glycogen. The optimal pH is about 5.6. The optimal growth conditions for the synthesis of the enzyme by E. coli were also examined in the present studies.

Amylopectin↗

Lateral hypothalamic responses to pre-absorptive and post-absorptive signals related to amino acid ingestion.

This paper reports an investigation of the comparative effects of pre-absorptive and post-absorptive stimuli associated with amino acid ingestion on cat and rat lateral hypothalamic neuronal activity. Pre-absorptive signals, conveyed by the vagus nerve and originating from the small intestine while the amino acids are about to be absorbed, have been previously identified electrophysiologically in our laboratory [3]. They were found to selectively modulate the neuronal activity of some lateral hypothalamic (LHA) cells [4]. The effects of both pre-absorptive and post-absorptive signals associated with amino acid ingestion were analyzed with regard to their degree of convergence at the lateral hypothalamic level. The pre-absorptive signals consisted of either chemospecific information arising from intestinal chemoreceptors and related to the chemical nature of the ingested nutrient, or mechanical information arising from intestinal mechanoreceptors and related to distension. The post-absorptive signal consisted of a microiontophoretic application of amino acids known to selectively affect the neuronal activity of LHA amino acid-sensitive cells [15]. The convergence on these cells of the intestinal afferent amino acid-sensitive units was postulated in this study.

Amino Acids↗

Lack of CCK-like pancreatic stimulation by intraduodenal amino acids in the anesthetized cat.

We have attempted to demonstrate a pancreatic secretory response to intraduodenal amino acids in the anesthetized cat. In four cats stimulated with supramaximal doses of secretin, protein concentrations in pancreatic juice were measured after intraduodenal bolus injection of various amino acids, IV CCK, or electrical stimulation of the vagus nerve. In addition, the duodenum was perfused with phenylalanine (50 mM) for 30 min in two cats, and the vagus nerve stimulated electrically for 15 min in one. In no case did amino acids produce pancreatic protein secretion, whereas CCK and vagal stimulation always did so. We conclude that this insensitivity to amino acids in the cat is a species difference from the dog and man.

Amino Acids↗

[Brain structural abnormalities of bipolar disorder].

The number of structural neuroimaging studies of bipolar disorder have increased during recent years, expanding the literature on the nature of cerebral abnormalities underlying this disorder. The purpose of this paper is to provide a selective review on the main issues concerning this literature. Consistent findings are higher rate of periventricular and deep subcortical white matter hyperintensites seen on MRI. Although there is strong evidence for links between hyper-intense lesions and age or cardio-vascular risk factors, some authors have observed the presence of these abnormalities early in the course of the illness. There are also frequent reports on ventricular enlargement, which has been described as mild and predominant in the right lateral ventricle. Total cerebral volume appears to be preserved. Whereas changes in total grey matter volume are uncertain, evidence suggests that reduced white matter volume reflects genetic factors predisposing to the disorder. Recent studies have reported volume changes in several cortical areas including the subgenual cingular, frontal and temporal cortices. Additionally, a number of reports described morphometric abnormalities in various subcortical structures, such as amygdala, basal ganglia and thalamus. Part of the variability in the morphometric abnormalities might be attributable to differences in clinical status and demographic characteristics of patient groups. Despite some inconsistencies across the studies, it emerges that abnormalities are asymmetrically distributed throughout the two cerebral hemispheres. When increase in volume is reported, it is preferentially localised in the left cerebral hemi-sphere and more specifically in prefrontal and temporal cortices and in amygdala. By contrast, when structural abnormalities concern the right cerebral hemisphere, they are identified as deficits. These latter results are in direct line with those of studies of mania following brain injuries, which report that these secondary mania result mainly from right cerebral lesions. It is also important to notice that most of the abnormalities concern both the cortical and subcortical level, ie frontal, striatal, thalamic and limbic regions. These abnormalities highlight the role in the pathophysiology of bipolar disorder of the loops involved in emotional information processing. The particular role of fronto-limbic loops in the phenomenology of bipolar disorder have been emphasised by recent data from functional neuroimaging studies.

Amygdala↗

[Erythrocyte membrane transport of amino acid precursors of monoamines in schizophrenic patients. Comparison with depressive patients].

The study concerned 72 schizophrenic and 200 depressed patients hospitalised between 1983 and 1990. The erythrocyte membrane transports (EMT) of L-tyrosine and L-tryptophan (at 37 degrees, 0 degrees and 37-0 degrees) of schizophrenics without treatment nor depression were different compared to controls and depressed patients. The schizophrenics under neuroleptic treatment and/or depressed showed same means of EMT values as depressed patients. The slopes of the correlations between EMT of tyrosine or tryptophan at 37 degrees, 0 degrees and 37-0 degrees, as well as that between plasma levels of these amino acids, were parallel. However the slopes of the correlations between EMT of tyrosine and tryptophan were different according to the subgroups of patients: the perturbations of EMT were related to the clinical characteristics. In depressed patients and in schizophrenic patients under neuroleptic treatment and/or depressed, little changes in EMT of tyrosine were related to high changes of EMT of tryptophan.

Antipsychotic Agents↗

[Erythrocyte membrane transports of monoamine precursor amino acids in schizophrenia].

We have determined the erythrocyte membrane uptake of the monoamine precursors L-tyrosine (L-TYR) and L-tryptophane (L-TRYP) in 72 patients with schizophrenia: 21 without neuroleptic treatment and not depressed, 15 with neuroleptic treatment and depressed, 33 without neuroleptic treatment, 27 depressed, compared to: 59 control subjects, and 54 depressed patients. We found that the ratio of L-TYR facilitated membrane diffusion to that of L-TRYP is: decreased when the patients are depressed, increased when they are untreated. When untreated patients receive neuroleptics and are depressed, the ratio tends to equal that of depressed patients'. The meaning of these anomalies is analysed, using our up-to-date knowledge of the erythrocytes's role in uptaking and dispatching the human body amino-acids, and of the role of these uptakes in regulating the functional monoamine balance. We postulate that in depressions, Parkinson's disease and schizophrenia, a change of membrane fluidity occurs, being decreased in depressions and Parkinsons's disease, and increased in schizophrenia.

Adult↗

[Erythrocyte membrane transport of tyrosine and tryptophan and plasma level of MHPG in depressive disorders].

Both plasma MHPG level and red blood cell membrane transports (TM) of L-tyrosine (L-TYR) and L-tryptophan (L-TRY) were evaluated in 29 depressed patients and compared to 16 control subjects. On the basis of MHPG plasmatic levels, we were able to define two subgroups in the depressed population showing a biological homogeneity: in the first one, both MHPG level and TYR TM decreased, while in the second one neither of these indices were disturbed. These biological features were not related to the nosographic subgroups. Bipolar depressed subjects showed a decrease in both MHPG and TYR TM; unipolar depressed subjects exhibited a decrease in both MHPG and TYR TM associated to an increase in TRY TM, whereas no change was found in dysthymic disorders. The time course of MHPG and MT were desynchronized if followed during the antidepressant treatment. At day 7, MHPG level increased significantly, while clinical improvement showed a normalisation of MHPG and TYR TM.

Adult↗