[Wolfram's syndrome with spastic-type vesicosphincter dysfunction].
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Adult↗
Biomedical subjects
H Allain
Publications and source records attributed to H Allain.
Drugs used in Alzheimer's disease and neuroplasticity.
Drugs indicated for use in Alzheimer's disease (AD) must clinically improve the cognitive symptomatology of the disorder, although nonexclusively. From a neurochemical standpoint, these drugs must oppose the multiple processes recognized as stigmata of AD. In these two ways, so-called AD drugs may be considered substances modifying cerebral plasticity. Long-term evaluation of anticholinesterases and of tacrine, in particular, provides arguments in support of this initially purely biologic, theoretical approach. This concept of neuroplasticity applied to dementia may modify the traditional pharmaceutical drug development programs.
Alzheimer Disease↗
[Pharmacology of central cholinergic synapse].
Because it intervenes in normal and pathological cerebral ageing, plays a role in late dyskinesias of Parkinson's syndrome and is involved in the memorization processes, central cholinergic neurotransmission deserves to be known with precision. Its physiological approach deals with the anatomical organization of the central cholinergic system and with the mechanisms of synthesis, release and degradation of acetylcholine and its interaction with its receptors. The pharmacological changes (inhibition or stimulation) conceivable at different levels lead to therapeutic applications.
Acetylcholine↗
Effect of triethyltin chloride on the central aminergic neurotransmitters and their metabolites: relationship with pathophysiology of aging.
Triethyltin (TET) salt intoxication provokes a myelinic vacuolisation associated with a white matter cerebral edema. The central nervous system disturbances accompanying these phenomena (Na-K-ATPase activity, neurological symptoms, water and sodium cerebral content) can be counteracted by drugs used in age-related brain failure; consequently, TET intoxication could be suggested as an experimental model for studying the aging process. The aim of the present study is to follow-up the biogenic amine concentrations in different brain areas of TET treated rats, knowing that modifications of cerebral amines exist throughout the aging process. The following results are obtained: the cerebral water content of the TET treated rats is significantly increased, confirming the existence of a brain edema. Monoamine concentrations are significantly decreased, specifically noradrenaline (in hypothalamus, mesencephalon, cerebellum); serotonin (in striatum, hypothalamus, mesencephalon); dopamine only in hypothalamus; these are accompanied by an increase of the metabolites 5 HIAA (in striatum and mesencephalon) and HVA (striatum). These modifications are compared to those occurring in physiological aging, and hypothetical mechanisms are reviewed. We conclude that TET intoxication must not be considered as a pathophysiological model of brain aging, but may be considered as a useful pharmacological tool for studying experimental drugs liable to counteract brain age-induced disturbances.
3,4-Dihydroxyphenylacetic Acid↗
Procedural memory in recent-onset Parkinson's disease.
Parkinson's disease is accompanied by cognitive disorders which may affect procedural memory. Procedural memory uses a specific knowledge resource that expresses itself through pre-established acting procedures. The aim of this study was to better define the characteristics of procedural memory, first of all, by trying to determine the level of involvement of that memory in the acquisition process (during learning and/or during procedure maintenance), then by specifying the effect of the type of resource involved (verbal or motor). To achieve this, we compared the mnestic performances of 20 recent-onset parkinsonian patients with those of 20 healthy controls, using two memory tasks with a fixed rule (poetry, visuomotor tracking). Result analysis revealed that parkinsonian patients had more difficulty than controls in learning the two rules, regardless of the material involved. Their deficiencies were often associated with an impairment of executive functions, and the procedural memory problems described in parkinsonian patients are linked to the involvement of these resources in the various tasks.
Aged↗
Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease.
BACKGROUND: Silymarin is a well-known hepatoprotective agent. Tacrine, the first drug marketed for Alzheimer's disease (AD), induces an elevation of serum liver transaminase prohibiting an effective dosage in many patients. This 12-week randomised, double-blind, placebo-controlled study was undertaken to evaluate the ability of silymarin to antagonise or prevent the hepatotoxic effects of tacrine and to analyse its action on tacrine efficacy and tolerability. METHODS: Outpatients suffering from mild-to-moderate dementia of the Alzheimer type were randomly assigned to two treatment groups: tacrine + silymarin and tacrine + placebo. The study was double-blind for silymarin and open for tacrine and was conducted in 22 French neurology and geriatric centres. Silymarin (420 mg/day) was given first (1 week) and tacrine was added at 40 mg/day for 6 weeks, then increased to 80 mg/day (6 weeks). Serum ALAT was the main evaluation criterion (> upper limit of normal, ULN). Serum ASAT as well as adverse side effects and cognitive performance assessed by MMSE and the Syndrome Kurtz test (SKT) were secondary evaluation criteria. Null hypotheses were evaluated with Fisher's exact test. FINDINGS: 222 patients were recruited and received silymarin and tacrine (110 patients) or placebo and tacrine (112 patients). 28 patients dropped out; 217 were included in the intent-to-treat analysis. No statistical difference was observed between the two groups for serum ALAT (p = 0.39). Fewer patients had ALAT levels >5 ULN in the silymarin group (-33.3%). Side effects and notably gastrointestinal disorders were much less frequent in the silymarin group. Cognitive performance remained unchanged in both groups. INTERPRETATION: Silymarin does not prevent tacrine-induced ALAT elevation but does reduce the rate of gastrointestinal and cholinergic side effects without any impact on cognitive status. As a consequence, silymarin (420 mg/day) could be co-administered with tacrine to improve tolerability in the initial phases of AD treatment.
Aged↗
Effect of normal aging and of Alzheimer's disease on, episodic memory.
Performances of 12 patients with Alzheimer's disease (AD), 15 healthy elderly subjects and 20 young healthy volunteers were compared on two episodic memory tests. The first, a learning test of semantically related words, enabled an assessment of the effect of semantic relationships on word learning by controlling the encoding and retrieval processes. The second, a dual coding test, is about the assessment of automatic processes operating during drawings encoding. The results obtained demonstrated quantitative and qualitative differences between the population. Manifestations of episodic memory deficit in AD patients were shown not only by lower performance scores than in elderly controls, but also by the lack of any effect of semantic cues and the production of a large number of extra-list intrusions. Automatic processes underlying dual coding appear to be spared in AD, although more time is needed to process information than in young or elderly subjects. These findings confirm former data and emphasize the preservation of certain memory processes (dual coding) in AD which could be used in future therapeutic approaches.
Aged↗
Procedural memory and Parkinson's disease.
A detailed analysis of the mnestic deficits associated with Parkinson's disease (PD) contributes to explaining the cognitive disorders and their well documented consequences. This study was designed to show that, in PD declarative as well as procedural memory is severely impaired. Three tests designed to explore this aspect of mnestic functioning were proposed to a group of 16 parkinsonian patients whose motoricity was controlled: inverted reading, braille reading, sound form association. The results obtained, compared with those of young and aged controls, show that PD is associated with marked deficits in both declarative and procedural memory. Declarative memory impairment was similar to that observed in the control population (healthy elderly subjects, age-matched with the PD patients) but more marked in PD subjects. The procedural memory deficit was linked with age and pathology. Procedural memory involves a variety of processing modules dedicated to the type of information (visual, auditive, tactile codes). The deficits observed were more like a loss of automatism than procedural impairment stricto sensu ('knowing how'). It would be worth pursuing research by studying akinesia and motor disorders from the angle of automatic memory impairment.
Adult↗
Potential biological targets for anti-Alzheimer drugs.
The stunning accumulation of data on the physiopathology of Alzheimer's disease is a real hinderance to pharmacologists who have to make decisions as to what molecules should be assessed first in man. Considering the cumbersomeness and cost of clinical trials in that field, a review of potential targets for drugs that are supposed to be active against the disease has become necessary, for a true definition of the rational justifications of trials to be envisaged.
Alzheimer Disease↗
[Adverse effects and drugs for Alzheimer's disease].
Molecules currently available or in late phases of development for the treatment of Alzheimer's disease have modest and apparently equivalent efficacies. Thus, the choice will depend on the safety profile of these drugs and on the patient characteristics. The aim of this review is to undertake an inventory of adverse effects and interactions reported in the literature for anticholinesterasics (the only ones approved by authorities). As most of the molecules described in this article are still in early phases of development, data reported here mainly issued from clinical trials carried out on specific populations. Most of these reported adverse effects have not been attributed according to the rules of pharmacovigilance. Nevertheless, we believe that the data presented in this review will be of great interest to clinicians and pharmacovigilance specialists as the compounds concerned become available on the market.
Alzheimer Disease↗
[An experience in teaching pharmacology on the internet].
Internet and Intranet are omnipresent in the University world. We developed an easy-access website (www.med.univ-rennes1.fr/etud/pharmaco) devoted to teaching pharmacology and report here our experience after 4 years of use. Our objective was to determine the value of this new teaching tool in the medical coursus. The site is entirely free and presents approximately 50 topics and diaporamas discussing various themes: the cell, the receptor, general pharmacology, clinical research, population research, drug classes, etc. Harbored by the Medical Informatics Laboratory of the University of Rennes Medical School, this site serves as a reference for medical students and others. More than 100 visits are recorded daily, approximately half from visitors outside France. The advantages of this new teaching tool, which operates within the framework of a Virtual Medical University project, are evident for students and professors alike. Its impact on the quality of drug therapy by future doctors remains to be determined.
Curriculum↗
[Acting out and psychoactive substances: alcohol, drugs, illicit substances].
In humans, some psychotropic agents (alcohol, drugs, illicit substances) have been suggested to play a role in the occurrence of major behavioural disorders, mainly due to the suppression of psychomotor inhibition. Behavioural disinhibition is a physiological mechanism which allows humans to behave appropriately according to a given environmental situation. The behavioural disinhibition induced by either therapeutic dosage or misuse involves the loss of restraint over certain types of social behaviour and may increase the risk of auto or hetero-aggression and acting out. The increased use of psychotropic agents in recent years and the occurrence of unwanted effects are worrying and must be detected and evaluated. The objective of the present study was to establish a causal relationship between psychoactive substance use and occurrence of major behavioural disorders, such as paradoxical rage reactions and suicidal behaviour, based on a literature analysis. It consisted of reviewing reports of drug-induced violent reactions in healthy volunteers and demonstrating, where possible, a cause-effect relationship. Patients with schizophrenia and psychopathic personalities were not included in our study since psychiatric comorbidity could influence behavioural responses. Psychotropic agents included drugs, licit and illicit substances already associated with violence in the past. Many reports used the "Go/No Go test" to evaluate the disinhibiting effect of psychotropic substances; this allows the "cognitive mapping" of drugs. The results suggest that only alcohol, antidepressants, benzodiazepines and cocaïne are related to aggressive behaviour. The best known precipitant of behavioural disinhibition is alcohol, which induces aggressive behaviour. However, there are large differences between individuals, and attentional mechanisms are now recognised as being important in mediating the effects of alcohol. Suicidal tendency as an adverse antidepressant reaction is rare, especially with atypical antidepressants. However, the risk of acting out exists and the responsibility of antidepressant agents in the genesis of suicidal tendencies is now established. The disinhibiting effects of benzodiazepines are well-known and proven by clinical trials. It's a "model" of acting out, and the causal relationship is undeniable. That cocaïne is related to violent behaviour is demonstrated by its pharmacological actions on CNS. The chronic use of cocaïne induces "a limbic dyscontrol syndrome" based on the altered activity of limbic structures. On the contrary, we could not demonstrate a causal relationship between aggression and either cannabis, ecstasy or phencyclidine. Cannabis abusers look particularly for euphoria and relaxing effects. Aggression as an adverse cannabis reaction is very rare and occurs in most cases in association with other drugs and in predisposed individuals. Ecstasy use may lead to long-term alterations of neuronal function in the human CNS and cause psychiatric disorders. However, there is insufficient information about long-term use of ecstasy to estimate its role in the occurrence of behavioural disorders. Clinical and forensic assumptions about phencyclidine and violence were not warranted. However, the substance-effect relationships can be criticized in the case of alcohol, antidepressants, benzodiazepines and cocaïne. In fact, individual, social and psychiatric factors exert an influence on behaviour that is superior to the pharmacological effect of psychotropic agents. The most important parameter in drug-induced behavioural disinhibition is dosage, but mode of administration is also important. In addition, polysubstance abuse is very common. Substances may be taken simultaneously and alcohol is frequently combined with drugs. The combinations of substances result in multiple interactions, and very little is known about the effects of these interactions on violence in humans. Co-occurrence of substance abuse and other mental disorders is also very frequent. Multiple substance abuse should be avoided, because potential interactions between two or more drugs are more likely to cause violent behaviour. In the future, a specific treatment of these deleterious phenomena will have to be considered in order to reduce drug-induced iatrogenic behavioural disorders.
Alcoholism↗
[Drug distribution systems in hospitals].
Any drug generally made and marketed by drug companies must respect the quality standards conferred by New Drug Approval regarding both safety and efficacy. Once prescribed by a doctor, inside a hospital, the drug, or more precisely the decision of its prescription will follow a complex circuit, involving numerous intermediates (human and technical) leading to drug dispensation and follow-up. Regulatory guidelines and rules harmonise and standardise this drug pathway in hospitals. Any weakness in this distribution system will be the source of nosocomial drug iatrogeny. The present review aims at describing the different steps and stages from the prescription to an individual patient to drug administration and follow-up. The evaluation of this system will be mentioned in the perspective of optimisation. The computerised system is essential allowing tracking of a drug, and providing help for decision-making (by confrontation with data bases) and a research tool (i.e, pharmacoepidemiology). Different experiences of assessment of the performance of such a drug distribution system inside hospitals will be presented, trying to check the quality reference: the right drug, the right patient, the right moment, in good conditions. The challenge is to optimise and secure all steps of the process. This goal needs assessment and quality control of the different phases, opening the discussion between hospital policy and regulatory and technical considerations.
Device Approval↗
Consensus statement on dementia of Alzheimer type in the severe stage.
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Activities of Daily Living↗
[Comparative study of effect of 4 furochromone derivatives on isoprenaline induced plasma renin activity increase in anesthetized dogs. Relationship of beta-adrenolytic effect and inhibition of plasma renin increase].
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Adrenergic beta-Antagonists↗
[Proposition for a new imputation approach in pharmacovigilance related to the use of topical agents].
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Administration, Topical↗
[Therapeutical approach to involuntary movements (author's transl)].
Thirty-three patients presenting an extra-pyramidal pathology with important involuntary movements have been treated with tiapride. The main beneficial results have been obtained in Huntington's chorea and in certain types of myoclony. The association with L-dopa, must be discussed. Only some L-dopa induced dyskinesias are improved; moreover tiaprid may antagonize L-dopa. The essential familial tremor is never improved.
Administration, Oral↗
Choosing a target for cognitive enhancers.
The development of drugs to improve cognitive functions (cognitive enhancers) has been hampered by the failure to define pharmacologic targets. The justifications for the development of cognitive enhancers for medicine, the pharmaceutical industry, and society are outlined. The procedures required for the development of these drugs and their therapeutic objectives are discussed. It is concluded that a better definition of the direct targets of cognitive enhancers can guarantee cost and time savings for the industry and produce a therapeutically effective agent.
Animals↗