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Biomedical subjects

R Jeanningros

Publications and source records attributed to R Jeanningros.

13 recordsLinked to original sources

Rapid changes in 3H-imipramine platelet binding after chronic treatment with amineptine, a selective dopamine uptake blocker, in major depressed patients.

The effect of chronic treatment with amineptine (200 mg daily), a tricyclic antidepressant drug selectively blocking dopamine uptake, on 3H-imipramine binding, was investigated in platelets of major depressed patients in conjunction with changes in clinical state. Before treatment, depressed patients had a significantly lower Bmax (P less than 0.01) than age- and gender-matched healthy controls. After only 1 week of amineptine administration, Bmax values increased significantly (P less than 0.01) and reached the control value concomitantly with a large and significant clinical improvement (P less than 0.01). After 1 month, Bmax was still significantly different from the pretreatment value (P less than 0.05), and not significantly different from the control value, while the improvement in clinical status persisted. No significant changes in Kd values were observed during treatment. We also verified that amineptine did not displace 3H-imipramine binding from platelets either in depressed or in control subjects. The results show that the successful treatment with amineptine, an antidepressant drug devoid of affinity for the tritiated imipramine platelet binding site, can rapidly lead to its density normalization.

Adult

Beta-adrenoceptor density of intact mononuclear leukocytes in subgroups of depressive disorders.

Binding parameters of (-)-iodopindolol to beta 2-adrenoceptors were determined on intact mononuclear cells in 41 untreated patients with different DSM-III subtypes of depression. Both maximal beta-receptor density (Bmax) and dissociation constant (Kd) were not significantly different between control and all depressed subjects. However, Bmax was significantly decreased in unipolar patients as compared to controls (p less than 0.001) whereas no significant difference was found in bipolar or dysthymic patients. In unipolar patients, a very strong association was found between Bmax values and the severity of the depression as assessed by the Hamilton Depression Rating Scale score (r = -0.75; p less than 0.005). This correlation was also highly significant in the entire depressed population (r = -0.58; p less than 0.0009). These results suggest that the lower number of beta-adrenoceptors in intact leukocyte cells of depressed patients is related to the depression severity.

Adrenergic beta-Antagonists

Early decrease in density of mononuclear leukocyte beta-adrenoceptors in depressed patients following amineptine treatment: possible relation to clinical efficiency.

1. The effect of chronic amineptine treatment (200mg/day) on beta-adrenoceptor density of intact mononuclear leukocytes (MNL) was examined in unmedicated major unipolar depressed patients. 2. Pretreatment parameters of (-)-[125I]-iodopindolol specific binding did not differ significantly from age- and sex-matched healthy controls as the patients were only moderately depressed. 3. All patients showed a highly significant clinical improvement as assessed by the AMDP-depression scale after one week of amineptine (D7), while 2 patients relapsed after one month of treatment (D28) and were considered to be non-responders. 4. The maximal density of beta-adrenoceptors (Bmax) was significantly decreased at D7 (by 33%) compared to pretreatment level (D0) in the treatment responders and remained lower at D28, although the difference was no longer significant. No alteration in beta-receptor affinity (Kd) was detected during the treatment. 5. These results indicate that treatment with amineptine, an antidepressant drug known to selectively inhibit the dopamine uptake system, can rapidly affect MNL beta-adrenoceptors. 6. Moreover, the present findings show that the reduction in MNL beta-adrenoceptor density, which is associated with a stable clinical improvement, may provide a predictive index for successful antidepressant treatment.

Adult

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

[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

[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

[Changes in the kinetics of erythrocyte membrane transport of tryptophan in depression].

The initial rate of L-tryptophan uptake into human red cells as a function of its concentration in the medium was measured in a group of 8 depressed patients hospitalized included 2 bipolar disorders (296.5x, DSM III), 3 major depressions, single episode or recurrent (296.3x and 296.2x, DSM III) and 3 dysthymic disorders (300.40x, DSM III), which were out of antidepressive treatment, with age ranging from 34 to 64 years compared to a group of 11 healthy volunteers with age ranging from 23 to 54 ans. Kinetic constants were measured at 37 degrees C on red cells incubated with tritiated L-tryptophan and cold L-tryptophan over the concentration range 0.1 to 10 mM. The maximum velocity (Vmax) of the saturable transport is severely lowered in a significant manner in the patients compared to controls (mean +/- s.e.m. = 48.9 +/- 5.5 mumol/l cells/min and 92.0 +/- 14 which represents 47% in decrease). In return, the Michaelis constant is unaffected. The linear component of tryptophan transport, which corresponds to the participation of nonspecific transport systems, is not modified. The possible incidence of such a deficit in the plasmatic reserve of tryptophan in depressed patients on the central availability of serotonin synthesis precursor is postulated.

Adult