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S Radouco-Thomas

Publications and source records attributed to S Radouco-Thomas.

At least 19 recordsLinked to original sources
PubMed1989

Double blind study on the efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute alcohol withdrawal syndrome.

1. Efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute or Primary Alcohol Withdrawal Syndrome (PAWS) were assessed during a randomized double blind clinical trial, carried out on sixty male alcoholic in-patients. 2. The two drugs were administered four times a day in double dummy conditions, according to a fixed-flexible decreasing dosage schedule (six days basic regimen). 3. Drug efficacy was measured daily throughout the study period using a battery of standard instruments for collecting quantitative clinical, behavioral, psychopathological and laboratory data. Side effects were daily recorded. 4. Tetrabamate was found to be as efficient as chlordiazepoxide in reducing the intensity of the PAWS, improving sleep and vital signs rapidly and alleviating anxiety progressively. 5. Tetrabamate was found particularly beneficial for severe tremor. Psychomotor and mood scores consistently favored tetrabamate, suggesting psychoanaleptic properties of this compound (increased diurnal vigilance). 6. Side effects were minimal with tetrabamate and generally of weak intensity with chlordiazepoxide. 7. The results of this study indicate that tetrabamate may represent a new alternative drug of choice for the therapy of the acute alcohol withdrawal syndrome.

Adult↗
PubMed1986

On the pathogenesis and therapy of dementia of the Alzheimer type: some neuropathological, biochemical, genetic and pharmacotherapeutic considerations.

The extensive literature on dementia of Alzheimer type (DAT) testifies to the enormous progress achieved in the clinical and biochemical delineation of this disease. Newly developed laboratory and imaging techniques are also being applied to the diagnosis of DAT. Nevertheless, unequivoval diagnosis still relies primarily on morphological data from biopsy or autopsy. An overview is presented of major morphological changes occurring at different levels of organization in the central nervous system (CNS) in DAT. Currently formulated etiopathogenic hypotheses of DAT are reviewed and discussed in the context of morphological alterations. Some of the recombinant DNA methods, that are currently available for gene analysis, are described. Some approaches for studying Alzheimer specific genes using the above methods have been suggested. Finally, a critical overview of the current pharmacotherapeutic armamentarium used in DAT and senile dementia is presented. The efficacy, side effects, and the main mechanisms of action of the two categories of drug therapy -supposed etiopathogenic and symptomatic- are presented.

Aluminum↗
PubMed1986

Nosology and diagnosis of alcoholism. Issues and perspectives in subtyping (DSM III) simple alcoholism and alcoholism associated with other psychopathologies.

The presence of psychopathological syndromes in alcoholic in-patients was assessed using the NIMH-Diagnosis. The most stricking finding of this study was the high percentage of additional psychopathological syndromes associated to alcoholism. Based on this finding, a tentative classification of alcoholism is proposed. The urgent need for a comprehensive diagnostic scheme for alcoholism is underlined.

Alcoholism↗
PubMed1986

Ethanol metabolizing system in Drosophila. Aldehyde dehydrogenase: functional aspects in adult and during development.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were determined in adult flies from several Drosophila species endowed with widely different tolerance to ethanol (ETOH). Plotting ALDH against ADH activities resulted in a high correlation coefficient (r = 0.966). This finding was confirmed in developmental studies. From early larval stage up to late adult life, DH and ALDH activities demonstrated almost parallel profiles. In the highly ETOH tolerant species D. melanogaster (D.m.), ADH and ALDH profiles were U-shaped: high activities in larvae, low activities in pupae and high activities in adults. In D. simulans (D.s.), a species less tolerant to ETOH, the profiles were L-shaped: high activities in larvae but low activities in both pupae and adults. Interestingly, similar activities (ADH and ALDH) were observed in the larvae of both species. Subcellular distribution studies of larval ALDH in both species revealed that the total ALDH activity is largely contributed by a mitochondrial high affinity enzyme. ALDH activity, clearly distinguishable from aldehyde oxidase (ALDOX), was visualized through analytical isoelectric focusing of the subcellular fractions. The estimated pIs for D.m. and D.s. were 4.9 and 5.2 respectively, thus different from those of ADH. The key biological role initially attributed to Drosophila ALDH is further supported by the present data. In addition the Drosophila developmental model opens new avenues for research on the study of genetic regulation of ADH and ALDH expression.

Alcohol Oxidoreductases↗
PubMed1985

Effects of trichothecenes (T-2 toxin) on protein synthesis in vitro by brain polysomes and messenger RNA.

The effects of T-2 toxin on protein synthesis were tested in two reticulocyte lysate in vitro systems pretreated with micrococcal nuclease. One of the test systems contained purified globin mRNA and was initiation dependent. The other contained rat brain polysomes and incorporated amino acids by an elongation dependent process. T-2 toxin inhibited the translation of globin mRNA at all concentrations tested, from 10(-8) M to 10(-4) M. Rat brain polysomes were much less sensitive to T-2 toxin than globin mRNA. While high concentrations of the toxin (10(-4) M) led to partial inhibition of protein synthesis by polysomes, low concentrations (10(-8) M and 10(-6) M) stimulated protein synthesis. Comparison of the above results with those obtained by other workers suggest that the T-2 toxin may inhibit not only the initiation step of translation, but also elongation and termination, depending upon the concentration of the toxin and the nature of the translation system. A similar mechanism may operate for all the trichothecene toxins that exert their effect through binding to ribosomal peptidyl transferase.

Animals↗
PubMed1984

Biological markers in major psychosis and alcoholism: phenotypic and genotypic markers.

Some basic concepts and trends which appear to be essential in the search for biological markers in mental disorders are discussed. Comments related to major psychosis and alcoholism are presented under three headings: (i) heterogeneity of disorders (ii) multifactoriality of disorders and (iii) mental disorders as genetically influenced disorders. Tentative classification and terminology of biological markers are given. Various types of phenotypic markers are discussed and alcoholism is taken as a model for a more detailed discussion of available putative phenotypic markers and of research strategies to be used, namely the pharmacological challenge in high risk subjects (e.g. ethanol and TRH challenge). Some highlights from the field of DNA markers are described, mainly the basic procedures which may be used to investigate genetic aspects of mental disorders by recombinant DNA technology.

Alcoholism↗
PubMed1982

Importance of subtyping in psychopharmacogenetic studies.

Research on the importance of genetic and environmental risk factors (multifactorial) in the etiology of mental disorders and substance use disorders (alcoholism) is now growing rapidly. Biological and psychological studies in this field should include basic concepts of medical genetics and take heterogeneity (multidimensionality) of mental disorders into account. One of the best means to cope with heterogeneity is to redefine the diagnostic phenotype at different levels: biochemical, behavioral, familial. Data are presented where the introduction of different quantitative definitions of the phenotype and their analysis by multivariate technics are used for better understanding of alcoholic disorders.

Alcoholism↗
PubMed1980

Biochemical correlates of tolerance in rodents and in Drosophila. Possible role of alcohol dehydrogenase, aldehyde dehydrogenase and superoxide dismutase.

In the rat, prolonged exposure to ethanol (ETOH) vapor induced an acquired increase in tolerance. After a single ETOH administration, the duration of recovery was decreased by 20% as compared to control animals and the rate of ETOH elimination from blood was increased by 27%. From the data obtained on liver enzymes--alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and superoxide dismutase (SOD)--it is suggested that the increased ALDH activity would be the consequence of an increased formation of the product of ETOH oxidation, the acetaldehyde. This over-production would not be accounted for by ADH. It is assumed that among others, the coupled reaction SOD-catalase would represent a possible alternate pathway. Data on Drosophila demonstrate that initial tolerance to ETOH is well correlated with ADH activity. It is suggested that ETOH metabolites (mainly acetaldehyde) would act also as determinant of this initial tolerance. The value of Drosophila as animal model for the study of behavioral and biochemical correlates of initial tolerance is discussed.

Alcohol Oxidoreductases↗
PubMed1979

Primary and secondary prevention of alcoholism: emerging trends and research strategy.

1. The theoretical and empirical value of a "level conceptualization in prevention" as proposed by the classical 'public health' model is challenged. 2. Although prevention should be related only to reduction of incidence of the disease (new cases), for various reasons the authors also include secondary prevention in the prevention of alcoholism. 3. Two main strategies are proposed in the prevention of alcoholism: (a) the global prevention directed to the population at large, and (b) the oriented or selective prevention directed to specific target groups (high risk groups). 4. In primary prevention a theoretical model, based on system theory "the ecogenetic wheel model" is proposed which tries to integrate the multidimensional (dependent variables), multifactorial and family approaches (independent variables) involved in alcoholic-related problems. 5. The biological predictors (chromosomal and biochemical markers) and psychological predictors to be used in the early detection of alcoholism are discussed. 6. Two theories are suggested for detection of biochemical markers: direct detection in naive subjects and indirect detection (activating theory) in subjects exposed to ethanol. 7. Secondary prevention could presently benefit from a "constellation" of clearly identified biological markers which would allow for the early detection of initial alcoholics. Screening programs could be implemented for selected target groups such as (a) occupational alcoholism programs, (b) programs for alcoholics' families, (c) programs for specific hospitalized patients and (d) alcohol programs related to traffic accidents.

Alcoholism↗
PubMed1979

Genetic epidemiology and the prevention of functional mental disorders and alcoholism: family study and biological predictors.

1. This review intends to present some theoretical and practical considerations which appear essential for the development of rational research strategies in the field of primary and secondary prevention of mental disorders and alcoholism. 2. The various advances and trends regarding the nosology and diagnosis of these disorders are discussed. Integrative epidemiological models for relating the multifactorial causation and the heterogeneity (multidimensionality) of these disorders are presented. 3. It is emphasized that alcoholism and the functional mental disorders occur in families as shown by (i) the increased incidence of these disorders among relatives and (ii) the existence of various clinical categories genetically associated. 4. Current methodology in clinical diagnosis and genetic epidemiology represent powerful procedures for typing and subtyping of these disorders. Family studies could identify more homogeneous subgroups and generate hypotheses as to the mode of transmission of mental disorders and alcoholism. 5. Real progress could be made in prevention only if the search for predictors is carried out in homogeneous subgroups. 6. There is a lack of knowledge regarding biological predictors. An urgent need for association studies and linkage analysis should be carried out in order to identify genetic markers (causal relationship) and chromosomal markers. These could provide for the specification of a constellation of markers and the development of appropriate tests to identify subjects at risk likely to develop alcoholism and mental disorders. 7. The immediate issues in secondary prevention and the later outcomes in primary prevention are outlined.

Alcoholism↗