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Biomedical subjects

A Puech

Publications and source records attributed to A Puech.

At least 19 recordsLinked to original sources
PubMed1992

11p15.5-specific libraries for identification of potential gene sequences involved in Beckwith-Wiedemann syndrome and tumorigenesis.

Constitutional and somatic chromosomal abnormalities of the chromosome 11p15 region are involved in an overgrowth malformation syndrome, the Beckwith-Wiedemann syndrome (BWS), and in several types of associated tumors. The bias in parental origin for the different etiologic forms of this syndrome and for loss of heterozygosity in the tumors suggests that a gene (or genes) mapping to this region undergoes genomic imprinting. However, the precise localization of the locus (or loci) for the BWS and associated tumors is still unknown and more markers are required. We therefore isolated 11p15 markers from two libraries: the first one obtained by microdissection of the chromosome 11p15.5 region and the second one, a phage library, constructed from a hybrid cell line containing this region as its sole human DNA. Of 19 microclones isolated from the microdissection library, 11 were evolutionarily conserved. Four phage clones were isolated; one (D11S774) detected a highly informative variable number of tandem repeats (VNTR) and another (D11S773) a biallelic polymorphism. These clones were sublocalized using a panel of somatic cell hybrids that defines eight physical intervals in 11p15.5. Twenty-one clones map to the distal interval that harbors the BWS locus.

Animals↗
PubMed1991

[Antioncogenes: models for tumors in children].

The chromosomal assignment of genes responsible for malformation syndromes associated with increased susceptibility to malignancy could be determined owing to specific constitutional chromosomal abnormalities or to family studies. For certain types of tumors, somatic chromosomal rearrangements (loss of alleles) occur at the same locus indicating the presence of a recessive suppressor gene or an antioncogène. For other types of tumors chromosomal rearrangements involving regions different from the locus for predisposition suggest genetic heterogeneity and/or implication of genes for tumor progression. These genes which are also involved in development and regulation of differentiation and cell growth, may undergo a differential genomic imprinting.

Alleles↗
PubMed1990

Beta-adrenoceptor blockade potentiates exercise-induced release of atrial natriuretic peptide.

The effect of a non selective and a cardio-selective beta-blocker on basal and exercise-stimulated plasma atrial natriuretic peptide concentrations in healthy volunteers has been studied. Nine healthy volunteers received single oral doses of 5 mg tertatolol, 100 mg atenolol or placebo, at one week intervals, in a double blind cross over trial. At rest plasma atrial natriuretic peptide, aldosterone, antidiuretic hormone and cyclic GMP concentrations and plasma renin activity were not modified by the treatments. During exercise plasma atrial natriuretic peptide concentrations were significantly increased by each treatment, the increment being significantly greater on beta-blockers than on placebo. The rise in atrial natriuretic peptide was 72% after placebo (from 24 to 42 pg/ml), 184% after atenolol (from 30 to 86 pg/ml), and 183% after tertatolol (from 34 to 95 pg/ml), respectively. Thus, the study has shown that in healthy subjects the plasma natriuretic peptide concentration is increased by exercise and that the increase is considerably and equally potentiated by selective and non selective beta-adrenoceptor blockade. The effect may be mainly due to a reduction in ventricular contractility with an increase in atrial pressure. The beta-blockers did not influence the resting plasma atrial natriuretic peptide levels, which suggests that in healthy subjects basal atrial natriuretic peptide secretion is not controlled via beta-receptors.

Adrenergic beta-Antagonists↗
PubMed1990

Desipramine induces cardiac beta-adrenergic sensitivity decrease in major depressed patients without relationship to therapeutic response.

Nineteen major depressed inpatients were treated over three weeks with desipramine. Cardiac beta-adrenergic receptor sensitivity was evaluated by an isoproterenol test before and after the three-week treatment. Desipramine induced a beta-adrenergic sensitivity decrease in most of the patients: I 20 (isoproterenol dose necessary to increase by 20 beats/min. the basal heart rate) before treatment: 89 +/- 37 ng/kg (mean +/- SD); after treatment: 170 +/- 135 ng/kg; p(t) less than 0.03. Despite a linear relationship between pretreatment beta-adrenergic sensitivity and post-treatment clinical state, there was no relation between post-treatment cardiac beta-adrenergic sensitivity and therapeutic response or even desipramine plasma levels.

Depressive Disorder↗
PubMed1990

Early clinical testing of cognition enhancers: prediction of efficacy.

The major problem in predicting clinical efficacy from animal experimental results and phase I data is the lack of resemblance between the models used and the clinical condition. This problem is complicated by the diversity of the potential mechanisms of action of new compounds. A further question is whether Phase I studies should be used as predictors of clinical efficacy at all. Should they be used simply for determining pharmacologically active dose ranges and tolerance? If used as predictors should drug development stop if negative results are obtained? These questions were not resolved. It was nonetheless suggested that some human models (e.g. scopolamine-induced amnesia, hypoxia-induced performance deficits) were indeed potential predictors of clinical response and, in addition, were analogous to similar models in animals. On the other hand characterisation of quantified EEG (QEEG) profiles remained controversial.

Alzheimer Disease↗
PubMed1990

Biochemical and pharmacological evaluation of the novel antidepressant and serotonin uptake inhibitor 2-(3,4-Dichlorobenzyl)-2-dimethylamino-1-propanol hydrochloride.

2-(3,4-Dichlorobenzyl)-2-dimethylamino-1-propanol, hydrochloride (JO 1017) is a novel antidepressant drug. Its biochemical and pharmacological properties were investigated in mice, rats, dogs, rabbits and guinea pigs. In vitro, it selectively inhibited serotonin uptake and had a high affinity for the 3H-paroxetine and 3H-imipramine binding sites. Biochemical studies demonstrated the lack of MAO-A and MAO-B inhibition and the absence of marked affinity for muscarinic, histaminic or other conventional brain receptors. Chronic treatment with JO 1017 induced a decrease in the Bmax values for imipramine sites but did not modify the Bmax for beta-adrenergic and 5-HT2 receptors. The neuropsychopharmacological profile of JO 1017 is characterized by a decrease of the immobility times in behavioural despair tests with mice, a decrease of the escape failures in the rat learned helplessness test, a strong potentiation of L-5-HT P-induced head-twitches in mice and an antagonism of reserpine-induced ptosis in rabbits. It weakly antagonized oxotremorine-induced hypothermia and did not influence the hypothermia induced by apomorphine. In contrast to most other antidepressants, a high dose of JO 1017 induced hypermotility in mice placed in an activity meter without producing stereotyped behaviour and group toxicity. Unlike tricyclic antidepressants, JO 1017 was devoid of severe cardiotoxicity in guinea pigs and had no central anticholinergic nor antihistaminic properties. These results suggest that JO 1017 is a selective serotonin uptake inhibitor with a high safety margin. JO 1017 may have a potential clinical utility both in the treatment of depression and for indications where serotonin transmission is involved, e.g., anxiety, panic attack, obsessive compulsive disorder, obesity and alcohol consumption.

Animals↗
PubMed1989

Cardiac beta-adrenergic sensitivity in depression: relation with endogenous subtype and desipramine response.

The authors studied the responsiveness of cardiac beta-receptors to isoproterenol, a noradrenergic agonist, in 29 depressed patients and 13 control subjects. They showed a significantly lower sensitivity in depressed patients as compared with the control subjects. Focussing on the group of depressed patients without antidepressant treatment in the month preceding the study (n = 15) in order to avoid a bias, the following significant results were obtained: cardiac beta-adrenergic receptor sensitivity was lower in patients suffering from endogenous depression than in those suffering from reactive depression (as classified by Newcastle Scale). There was a negative linear relation between cardiac beta-adrenergic sensitivity and the posttreatment clinical state (as expressed by the MADRS score) for the 9 patients who ended a 3-week desipramine treatment period.

Adjustment Disorders↗
PubMed1989

[Adsorbed plant extracts, use of extracts of dried seeds of Orthosiphon stamineus benth].

The work presented is related to the elaboration and the control of spray dried vegetable extracts of Orthosiphon Stamineus Benth. From these studies, it feasibility of the spray dried extracts. The best result concerning a pulverulent structure and the stability under moisture conditions is obtained using Aerosil 200. Pharmacological studies on rats have shown a diuretic activity under our experimental conditions with alcoholic and water extracts.

Diuretics↗
PubMed1988

Antidepressant-like effects of triiodothyroacetic acid in mice.

Triiodothyroacetic acid (TA3) is a natural thyroid analogue which possesses some of the properties of triiodothyronine (T3). In particular, it has an inhibitory effect on the thyreotropic axis, but its peripheral effects are reduced. Given the activity of T3 on psychopharmacological models of depression in rodents, we investigated the effects of TA3 on some pharmacological and behavioral tests in mice. TA3 antagonized apomorphine- and oxotremorine-induced hypothermia, potentiated yohimbine-induced toxicity and L-5-hydroxy-tryptophan-induced head twitches, but did not affect forced swimming-induced immobility or reserpine-induced hypothermia. Thus, TA3 was effective on the same psychopharmacological tests which have previously been used to demonstrate the antidepressant-like effects of T3. Moreover, TA3 under the same experimental conditions as T3 has little effect on the metabolic clearance rate parameters, and might, therefore, be preferable to T3 for clinical use in depression.

Animals↗
PubMed1987

Lack of sleep-inducing properties of propranolol (80 mg) in chronic insomniacs previously treated by common hypnotic medications.

In a double-blind, placebo-controlled crossover trial, propranolol 80 mg did not show any hypnotic properties and even increased the insomnia in a sample of 37 patients previously treated chronically with hypnotic medication (mostly benzodiazepines). This worsening of the insomnia is consistent with the observations of sleep disturbance at the beginning of treatment with beta-blocking drugs. This lack of efficacy suggests that the anti-stress or anxiolytic properties of propranolol do not apply to the rebound insomnia seen when stopping treatment with hypnotic drugs.

Adult↗