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Biomedical subjects

R Tissot

Publications and source records attributed to R Tissot.

At least 19 recordsLinked to original sources

Platelet membrane alpha 2-adrenergic receptors in depression.

The platelet membrane was used as a model system to examine alpha 2-adrenergic receptors in 30 depressed patients and 30 healthy control subjects. The number of binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were assayed in the same sample. A decreased agonist-receptor affinity was found in depressed patients, whereas receptor density was not significantly altered compared with that in control subjects. In bipolar depressed and dysthymic patients, there was a tendency toward a higher density of alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent depressed subjects. Moreover, a positive correlation between Bmax and Kd values was observed in patients but not in control subjects--a finding that suggests that a compensatory phenomenon occurs in depression. After the patients were treated with antidepressant drugs, an increased affinity (decrease in Kd) was observed, together with a decrease in binding sites. Plasma magnesium concentrations were higher in drug-free depressed patients than in control subjects. In addition, magnesium concentrations were negatively correlated with the density of alpha 2-adrenergic receptor binding sites in depressed patients, both before and during treatment. Lastly, a trend toward a negative correlation between plasma MHPG concentration and the number of binding sites was also observed. These results suggest a complex multifactorial regulation of alpha 2-adrenergic receptors, which are probably hyposensitive in depressive syndromes.

Adrenergic alpha-Agonists

Decrease in epinephrine-induced attenuation of platelet adenylate cyclase activity in depressed patients: relation with plasma electrolytes.

We have measured the alpha 2-adrenoceptor-mediated inhibition of platelet membrane adenylate cyclase in depressed patients and control subjects. The results showed a decrease in the forskolin-stimulated adenylate cyclase inhibition of depressed patients compared to the healthy subjects. This suggests a subsensitivity of alpha 2-adrenoceptor in depression. However, this subsensitivity was not correlated to the severity of depression as both severely and moderately depressed patients exhibited the same percent of adenylate cyclase inhibition. The antidepressant drugs treatment induced an increase in the percent of adenylate cyclase inhibition with a trend towards the control values. However, this increase did not equal control value, and moreover both remitted and unremitted patients presented a similar change in their alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. This result raises the question about a simple and direct relation between the clinical status of depression and the power of alpha 2-adrenoceptor-mediated adenylate cyclase inhibition. Plasma magnesium and sodium yielded correlations to this alpha 2-adrenoceptor-mediated adenylate cyclase inhibition suggesting a relation between the platelet adrenergic function and plasma electrolytes.

Adenylyl Cyclase Inhibitors

Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months.

No consensus has been obtained about blood electrolyte status, especially about magnesium, in affective disorders. This is mainly due to the lack of information about the distribution of the patients in clinical subgroups, sex, type of treatment and about the severity of their illnesses. Most of these studies concerned treated patients. We confirmed in this study that drug-free depressed patients have higher erythrocyte and plasma magnesium than controls, as shown in previous reports. Significant differences are observed in as shown in previous reports. Significant differences are observed in patients for sex and between clinical subgroups. Low plasma potassium levels are described in both male and female depressed patients. The erythrocyte magnesium level tends to normalize in parallel with clinical improvement, depending on sex and clinical subgroup, and seems then to be related to the intensity of the depression. Plasma magnesium in male and female patients, except for female unipolars, remains higher than controls in all conditions and might be related to the diagnosis of affective disorders.

Adult

Inherited congenital adrenal hyperplasia in the rabbit: absent cholesterol side-chain cleavage cytochrome P450 gene expression.

We investigated adrenal steroidogenic enzymes, their activity and mRNA expression, and in vitro biosynthesis of an enzyme in rabbits with congenital adrenal hyperplasia (CAH; weight: CAH, 19 +/- 5 mg/adrenal; normal, 2.7 +/- 1.0 mg/adrenal). Serum pregnenolone (delta 5-P) levels in CAH newborn rabbits (12-36 h) were normal (mean/range, 438/51-2191 ng/dl), but corticosterone levels were low [0.05 +/- 0.05 microgram/dl; P less than 0.001 vs. normal (0.66 +/- 0.57)]. Serum Na+ levels in CAH newborn rabbits were in the normal range (143 +/- 30 meq/liter), but K+ levels were elevated [7 +/- 1.1 meq/liter; P less than 0.05 vs. normal (5.9 +/- 0.6 meq/liter)]. Minced normal adrenal tissue incubated with [3H] cholesterol (30-100 pmol/flask) and ACTH (100 mU/flask) produced [3H]delta 5-P (newborn, 21 and 45 fmol/100 mg; adult, 3 and 5 fmol/100 mg) and [3H]corticosterone (newborn, 23 fmol/100 mg; adult, 11.3 fmol/100 mg), but CAH adrenals produced no product (less than 1.3 fmol/100 mg). Adrenal mitochondria from normal newborn rabbits produced delta 5-P (4.4-7 nmol/mg protein), but CAH adrenals did not, while CAH adrenal mitochondria demonstrated over 4 times greater 11 beta-hydroxylase activity. A Western blot of adrenal homogenate from normal newborn rabbits revealed a cholesterol side-chain cleavage cytochrome P450 (P450scc)-immunoreactive species (mol wt, 53 x 10(3), but this species was absent in CAH adrenals; CAH adrenals had a normal adrenodoxin and intensified 17 alpha-hydroxylase cytochrome P450 (P450(17)alpha) band compared to normal adrenals. In vitro translation of RNA in a cell-free rabbit reticulocyte lysate system containing [35S] methionine yielded a precursor P450scc protein (mol wt, 58.5 x 10(3)) with normal adrenal RNA, but not with CAH adrenal RNA. P450scc mRNA was detected in all normal adrenals, but was not detected in all CAH adrenals. 21-Hydroxylase cytochrome P450 mRNA expression was detected at a similar level in both normal and CAH adrenals. We conclude that CAH in the rabbit is caused by inherited absent P450scc gene expression. The clinical, pathological, and biochemical manifestations of P450scc deficiency in the rabbit are nearly identical to the human disorder. Increased 11 beta-hydroxylase activity and increased P450(17)alpha on Western blot of CAH adrenals indicate altered gene expression of other steroidogenic enzymes due to CAH. Further molecular analysis of the P450scc gene in this animal CAH model will facilitate understanding of P450scc deficiency CAH.

Adrenal Glands

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

Inositol monophosphate esterase inhibition by lithium in normal human studies using neuroendocrine tests. Part I. PRL and TSH responses to TRH.

1. Many neuroendocrine events are mediated by intracellularly second messengers, among which are the breakdown of phosphatidylinositol 4,5-biphosphate (PIP2). 2. Lithium (Li) was shown in therapeutic doses to be a specific inhibitor of the enzyme inositol monophosphate esterase Li reduces the turnover of PIP2 and diminishes the cell responses. 3. In order to investigate this new mode of action of Li the authors studied the influence of acute dose of Li on the response of prolactin (PRL) and thyrotropin (TSH) to thyrotropin stimulating hormone (TRH), a stimulation mainly mediated through the activation of the turnover of PIP2. 4. In seven normal subjects a single dose of 19.80 meq of Li reduced the response of PRL in 4, and augmented it in 3 subjects: Li decreased the TSH response in 4 subjects, it was increased in 1 and remained unchanged in 2. 5. These results are discussed in the light of the different interactions between hormone secretion, and the fact that adenopituitary is located out of the brain blood barrier.

Adult

Inositol monophosphate esterase inhibition by lithium in normal human studies using neuroendocrine tests. Part II. HGH, PRL and TSH responses to clonidine.

1. Recent preclinical researches gave evidence that the actions of many neurotransmitters and drugs are mediated through the activation of the turnover of phosphatidylinositol 4,5 biphosphate (PIP2). Lithium (Li) a specific inhibitor of the enzyme inositol monophosphate esterase reduces the turn over of PIP2 and decreases the cell responses mediated via the cleavage of PIP2. 2. The authors studied the influence of a therapeutic single dose of Li on the response of human growth hormone (HGH) prolactin (PRL) and thyrotropin (TSH) to clonidine (C), an alpha adrenergic agonist which stimulates the turn over of PIP2. 3. Li reduces the HGH response to C in 3, increases in 1 and provokes no change in 2 subjects. The basal secretion of PRL and TSH were not modified. 4. These findings could support the hypothesis that some of the action of Li in humans is mediated through the inhibition of the enzyme inositol monophosphate esterase. Further studies are needed in order to determine the importance of this action.

Adult

Plasma 3-methoxy-4-hydroxyphenylglycol in manic patients: relationships with clinical variables.

Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were found to be significantly higher in manic patients than in age- and sex-matched normal controls (n = 22). In 18 manic patients plasma MHPG correlated with manic symptoms but not with anxiety, depression, motor behaviour, acute psychosis, schizophrenia and severity of illness. A positive correlation between MHPG and grandiosity items on rating scales suggests a link with cognitive contents and therefore a relationship with central factors.

Adolescent

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

Plasma levels of 3-methoxy-4-hydroxyphenylglycol in depressed patients compared with normal controls.

Plasma levels of total 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in a group of 104 hospitalized depressed patients and a group of 104 age- and sex-matched normal controls. Plasma MHPG levels were found to be normally distributed in both groups and significantly lower in depressives than in controls. However, this difference could be related to an increase in plasma MHPG levels with age found in controls (r = 0.601, d.f. = 102, p less than 0.01) but not in depressives (r = 0.013, d.f. = 102, NS). Men had significantly higher levels than women in both groups. There was no significant difference in plasma MHPG levels among any DSM-III-R diagnostic subgroups of depressives or between patients who were suppressors on the dexamethasone suppression test and those who were nonsuppressors. Significant correlations were found between AMDP Depression Rating Scale item and total scores and levels of plasma MHPG. Age, sex and clinical symptoms appeared to be main sources of variance in studying depressed patients and comparing them with normal controls.

Adult

[Different aspects of the cognitive activities of patients with schizophrenia. IV. Imbalance between assertions and negations].

Not being able to equilibrate affirmations and negations, the schizophrenic patient accedes only exceptionally to the majoring equilibrations of the second and third levels. In the logico-mathematic field, he does not approach the constructive synthetizing generalisations of reasoning. Lacking reflective abstraction, he cannot balance his logico-mathematic reasoning and differentiate what is structurally possible from what is materially possible, thus explaining his inaccessibility to perceive logic necessities, contrasting with the certainties of his delirium. In the logico-experimental domain, he reaches only rarely clause reasoning generalisation, and relapses regularly to the level of inappropriate generalisations of the extended inductive type. It is useless to try to find the "primum movens" of his difficulties, either in his imbalance assimilation/accommodation, or in his impossibility to see his contradictions, or even in his incapacity to equilibrate affirmations and negations. The majoring equilibrations, of which he is unable, are the functional expression of structures which do not follow the linear causality of Laplace's determinism but the circular causality characteristic of teleonomic processes. After a month of neuroleptic treatment, the decompensated schizophrenic's balance between assimilation and accommodation is partially restored.

Adult

Guidelines for the dosage of neuroleptics. I: Chlorpromazine equivalents of orally administered neuroleptics.

Chlorpromazine (CPZ) equivalents are often used as a relative measure of the antipsychotic potency of neuroleptics. We review the CPZ equivalents of 33 neuroleptics and illustrate why imprecisions or discrepancies will be difficult to eliminate from these values. We nevertheless underline that CPZ equivalents can be clinically useful, since they facilitate the choice of doses of different neuroleptics that should induce comparable antipsychotic effects.

Antipsychotic Agents

Guidelines for the dosage of neuroleptics. II: Changing from daily oral to long acting injectable neuroleptics.

When changing from daily oral to long acting injectable neuroleptic therapy, it is essential to choose a dose that will maintain clinical efficacy without increased adverse reactions. Information on pharmacokinetics is needed to achieve this. The authors present guidelines based on this information and observe that previous recommendations sometimes differ substantially from these guidelines. Whether these guidelines will improve the results of long term treatment of psychotic patients remains to be determined.

Administration, Oral

The heterogeneity of 3-methoxy-4-hydroxyphenylglycol levels among depressed patients.

A previous report by our group and results published by other research groups have indicated a dichotomy in MHPG levels in depressed patients. This study attempted to characterize phenomena associated with this dichotomy in plasma MHPG levels. First, we have noted, at least in female patients, that homogeneity of MHPG levels, as tested by fitting with a normal curve, can be ruled out. In contrast, in the total population, a dichotomy was less evident in this study; the 2 subgroups, high and low levels of MHPG, partially overlap, and this results in a gaussian distribution. However, based on the hypothesis of a bimodal distribution, as shown by others and not excluded here, it was possible to find some factors associated with heterogeneity. Thus, polarity of depression, sex and age of the patients, age of disease onset and depression score affect MHPG levels. On the other hand, other elements suspected to modify MHPG values, such as the different lengths of the washout period (minimum 10 days), or some medication (chloralhydrate or levomepromazine) required during the washout period, did not show any effect. The aim of this study was to better characterize this peripheral index for its possible use in clinical application.

Adult