Showing papers in "Therapie in 1998"

[Free radicals and antioxidants: physiology, human pathology and therapeutic aspects (part II)].

Abstract: Although they are considered as destructive agents, free radicals can sometimes become useful. Their presence is intimately coupled with the activity of certain hemal oxydases which insert an atom of oxygen into their substrate by a stereospecific radical mecanism. The cytochromes P450 and the enzymes of the eicosanoide metabolism are some examples. The free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract or to infer a myorelaxation. They can even play the role of neurotransmitters such as azote monoxyde. The activation of phagocytes, which is an essential event in the inflammatory reaction, integrates these notions at several levels: in the mechanisms of bacterial death, in the spread of the inflammatory reaction and in the alteration of the extra-cellular matrix. The inflammatory reaction is initiated by interactions between vascular endothelium, platelets and leukocytes including signal exchanges, adhesion molecule expression and secretion of chimiotactic mediators. Activation of vascular endothelium is a key event in the initiation of the phenomenon. The cells intervening in the precocious inflammatory phase were tissular mastocytes and platelet-liberating mediators (histamine) and neutrophile cells responsible for vascular injuries induced by oxygen free radicals and nitric oxide. Reactive oxygen intermediates play a critical role, primarily to limit tissue damage and prevent or inhibit infection, secondary to enhancing and prolonging reaction. The monocytes and platelets liberate cytokines early, which appears to be important in activation and production of an inflammatory response. In fact, cytokines, especially TNF alpha and IL-1, induce synthesis and secretion endothelial adhesion molecules such as ICAM-1, VCAM-1 and E-selectin, which have been demonstrated to mediate leukocyte recruitment to sites of inflammation. The cytokines also activate the fibroblasts and endothelial cells that produce, among others, free radicals and other chimiotactic cytokines of which some (IL-8 and related) can induce neutrophil degranulation and stimulate oxidative stress and formation of free radicals. Furthermore, endothelial cells have been shown to make use of a broad repertoire of cytokines including IL-1, IL-6, IL-8, MCP-1 and gro/MGSA, which may be secreted during an inflammatory response and exercise pro-inflammatory functions. Under the influence of the inflammatory mediators, other enzymes are also activated. The inducible isoforms of cyclo-oxygenase (COX-2) and nitric oxide synthase (iNOS) play an important role in inflammatory reactions via the production respectively of prostaglandins and nitric oxide. The induction of cell adhesion molecules (ICAM-1, VCAM-1 and E-selectin), cytokines, acute phase proteins, growth factors, COX-2 and iNOS expression is mediated by the activation of transcriptional factors, especially the nuclear factor kappa B (NF-kappa B). The NF-kappa B system is essentially involved in immediate early expression of various immunoregulatory genes and has been demonstrated to represent an important regulatory system of endothelial activation. The target genes for NF-kappa B comprise a growing list of genes intrinsically linked to a coordinated inflammatory response. The NF-kappa B is a heterodimer composed of two subunits (p65 and p50). In non-stimulated cells, NF-kappa B resides in the cytoplasm as an inactive complex bound to its inhibitor, I kappa B. Upon stimulation with various agents including cytokines, mitogenes, viruses and reactive oxygen intermediates, I kappa B dissociates from the NF-kappa B-I kappa B complex and translocates to the nucleus, binding with high affinity to specific sites in the promoter regions of target genes and stimulating their transcription. In the case of any weakness of this anti-oxidizing defence or any over-production of radical species, a state of oxidative stress occurs. (ABSTRACT TRUNC

[Interaction between the sympathetic and renin-angiotensin system]

Abstract: The renin-angiotensin system is involved in the control of sodium and water balance, mitogenesis and the regulation of vascular tone as well as of the activity of the sympathetic nervous system. Many of these effects may be regulated at a local level by independent tissue renin-angiotensin systems. The renin-angiotensin and adrenergic nervous systems are cross-regulated by interactive compensatory mechanisms. Therefore, the activation of one of these systems induces the activation or induction of the other leading to a co-amplification of cellular mechanisms, for instance resulting in the facilitation of sympathetic neurotransmission. This paper describes the interactions between these systems in the central nervous system and at pre- and postsynaptic sites of the nerve endings in cardiovascular tissues. Since these systems are cross-regulated, the inhibition of one would attenuate the activity of the other. The drugs that inhibit specifically the various components of the renin-angiotensin system have proved powerful tools for studies of the physiology of this system as well as for the treatment of hypertension and heart failure.

Putative roles of melatonin in glucose regulation.

Abstract: Le role eventuel de la melatonine dans la regulation glucidique chez l'homme a ete peu explore. Dans des conditions normales, la tolerance au glucose est modulee par la rythmicite circadienne et par le sommeil, deux processus du systeme nerveux central qui peuvent etre influences par la melatonine. En presence d'un stimulus constant (par ex. perfusion intraveineuse de glucose a debit constant), les taux sanguins de glucose augmentent progressivement tout au long de la journee et culminent au milieu de la periode de sommeil. Ce rythme de tolerance au glucose resulte de modifications de l'utilisation (insulino-dependante et non insulino-dependante) du glucose ainsi que d'alterations de la sensibilite a l'insuline et de la secretion insulinique. Le rythme circadien du cortisol et la secretion d'hormone de croissance liee au sommeil sont impliques dans les mecanismes sous-jacents. Des variations de la balance sympatho-vagale au niveau du pancreas pourraient egalement etre impliquees mais n'ont pas encore ete explorees chez l'homme. Il est probable que la melatonine influence le metabolisme glucidique de l'homme par l'intermediaire de ses effets sur les noyaux suprachiasmatiques et sur la regulation du sommeil.

Complex effects of melatonin.

Abstract: The primary function of melatonin in mammals is to transmit information concerning light-dark cycles for the organization of day length dependent on seasonal functions. There is little evidence for an essential role in circadian organization in mammals, in contrast with lower vertebates. It does, however, appear to reinforce physiological functions associated with darkness. Free-running blind and indeed sighted subjects show a close correlation between maximum sleepiness, minimum temperature and peak melatonin secretion. In humans exogenous melatonin will lower core body temperature and induce transient sleepiness in suitable doses and conditions. Similarly it will shift circadian phase, as assessed by a number of marker rhythms. These phase-shifting properties may not be sufficient to synchronize all circadian rhythms in the absence of other time cues. In most normal sighted subjects and a number of blind subjects the sleep-wake cycle can be 'stabilized' to a 24 h period by daily melatonin administration in free-running conditions. However, anomalous results have also been obtained. Daily administration of melatonin (5 mg) appears to fragment sleep in some subjects treated in dim light conditions. This observation requires further investigation since it may compromise the therapeutic potential of both melatonin and its agonists.

[Assessment of preventable iatrogenic drug therapy: methodology. Round Table No 2 at Giens XIII]

Abstract: The concept of preventable iatrogenesis has a high priority for the Conference Nationale de Sante. Its implementation could result in the identification of the main relevant actions to be taken to prevent drug related iatrogenesis. Based on a critical analysis of pharmacovigilance experiences, we propose, a scheme to evaluate the degree of avoidability of adverse drug effects. This scheme contains three group of items concerning the drug, the patient and the prescription. It assesses the prescription and the therapeutic approach used for a specific patient within the context of medical knowledge as well as the risk factors presented by the patient.

[Investigation on self-medication: from disease to performance].

Abstract: Cette etude a pour but de determiner le profil des usagers de l'automedication et leurs attitudes face au medicament. Une enquete est menee aupres de 600 personnes residant en Meurthe et Moselle. Les sujets sont repartis en 312 fennes (52 pour cent) et 288 hommes (48 pour cent). L'âge moyen est de 42.7 ± 18.4 ans (moyenne ± ecart-type): 313 sujets recourent a l'automedication (52.2 pour cent), contre 247 qui n'y recourent pas (41.2 pour cent). Cette pratique concerne surtout les cephalees (46.9 pour cent des citations), les rhinites et etats grippaux (22.1 pour cent), les douleurs abdominales (7.3 pour cent). Les medicaments utilises proviennent surtout du reliquat de traitements prescrits anterieurement par un medecine generaliste (76 pour cent des cas) ou achete sans aucun conseil, a la seule initiative du sujet (28 pour cent). Les personnes qui recourent a l'automedication sont surtout cells qui ne prennet aucun medicament ou un seul medicament par jour. L'usater de l'automedication serait plutot une femme, âgee de 20 a 39 ans, vivant maritalement, habitant en zone urbaine et exercant une profession intermediaire ou commercante. L'analyse typologique fait apparaitre cinq sous-groupes de consommateurs et suggere donc autant d'attitude differentes fface a cette pratique. Ce constat pourrait impliquer des mesures d'education pour la sante adaptees a chaque categorie. En particulier pour le sous-groupe D, sujets qui recourent a l'automedication non pas pour une pathologie mais pour rester 'performant'.

Melatonin and the gastrointestinal tract

Abstract: Melatonin has been detected in the digestive tract of several species and appears to be synthesized by the enterochromaffin cells of the gut. Although a diurnal rhythm of melatonin release has been observed in gastrointestinal tissues of birds, in other species it seems to depend on the presence of nutritional elements. Melatonin binding sites have been identified in the digestive tract of several species and it has been suggested that melatonin could act as a protecting agent of the gastrointestinal mucosa. Moreover, the potential role of melatonin as a local regulator of gastrointestinal motility has been investigated. It seems that at least some effects of melatonin on gut activity depend on an antagonistic relationship between serotonin and melatonin. The effects of melatonin on segmental gut transit both in the fasting and in the fed state, as well as on the electromyographic pattern of the small intestine in rats, are described.

[Genetic polymorphisms in the renin-angiotensin system]

Abstract: Gene coding for the main components of the renin-angiotensin system have been characterized and localized: angiotensinogen (AGT, chromosome 1q42), renin (REN, chromosome 1), angiotensin I-converting enzyme (ACE, chromosome 17), angiotensin II receptors (AT1R, chromosome 3 and AT2R, chromosome X). A positive linkage and association have been found between AGT and essential hypertension. M235T is also associated with plasma AGT concentration. In vitro studies suggest that a polymorphism (G-6A) which is in complete linkage disequilibrium with M235T and which is located in the promoter close to the start of transcription might explain this association with high blood pressure. The ACE I/D polymorphism explains about 30 to 40 per cent of the variance of plasma ACE levels. Although the ACE gene itself does not seem to play a role in blood pressure level, the corresponding chromosomal region has been linked to blood pressure in both spontaneously hypertensive rats and humans. In tissues, an increased ACE activity may explain the association between the ACE I/D polymorphism and coronary heart disease, left ventricular hypertrophy, neointimal proliferation in vessels and progression of diabetic and IgA nephropathy.

[Cutaneous side effects of ketoprofen gels: results of a study based on 337 cases].

Abstract: Ketoprofen gels, since their introduction on the French market (1989), have been responsible for various cutaneous side-effects (essentially photosensitization and contact eczemas). A study conducted by the French drug surveillance system detected 337 cases. Analysis showed that the frequency of cutaneous adverse events was from 0.008/1000 to 0.023/1000 according to the commercial gel. The sex ratio was well distributed, and the population was young (30-40 years) and athletic. Treatment lasted about 7 days, and the appearance of the side-effect was sometimes quite delayed relative to discontinuance of treatment. Reactions were severe in 40 per cent of cases. The factors favourable to side-effects were essentially exposure to the sun (one-third of cases) and occlusive dressing. No particular predisposing conditions were noted, although 2.6 per cent and 8.5 per cent of cases respectively involved earlier sensitization by a topical NSAID. The side-effect lasted about 16 days. The course was usually favourable but hospitalization was required in about 10 per cent of cases. Photoallergological testing indicated photosensitization to ketoprofen. These results led the National Commission of the French drug surveillance system to request a modification in the indications for the prescription of the ketoprofen gels.

Melatonin and biological rhythms

Abstract: La melatonine est une hormone secretee rythmiquement la nuit par la glande pineale. Chez les mammiferes, ce rythme est genere par les noyaux suprachiasmatiques (NSC) de l'hypothlamus (siege de l'horloge circadienne) et est entraine a 24 h par le cycle jour/nuit. Le rythme de melatonine est donc un signal hormonal efferent de l'horloge circadienne et l'un de ses roles pourrait etre d'imposer la rythmicite circadienne a des organes cibles de la melatonine. Il a par exemple ete observe que la melatonine est capable d'entrainer les rythmes en libre-cours (conditions constantes) d'activite locomotrice des rongeurs et de veille-sommeil chez certains aveugles. Le rythme de melatonine est genere par les NSC mais la duree de secretion nocturne est proportionnelle a la duree de la nuit. Ce sont les variations de la duree de secretion nocturne de melatonine qui permettent au cerveau de 'lire' l'information photoperiodique. Les resultats ont deja des applications directes en agriculture ou la melatonine est regulierement utilisee pour 'manipuler' certains rythmes saisonniers (fourrure chez le vison, laine et reproduction chez le mouton, etc.). La secretion nocturne de melatonine, de par son expression rythmique, est donc a la fois une message circadien et saisonnier qui permet a l'organisme de s'organiser temporellement. Les effets de la melatonine les plus documentes concernent son role sur la regulation des fonctions saisonnieres, mais son role dans l'organisation circadienne des fonctions apparait etre fondamental meme si aujourd'hui nos connaissances sont encore tres fragmentaires. En fait, le front actuel de nos connaissances se situe au niveau de l'etude des sites et mecanismes d'action de la melatonine. L'hormone agit classiquement par l'intermediaire des recepteurs membranaires (2 sous-types Mella et Mellb clones a ce jour chez les mammiferes) couples a une proteine G et peut-etre par l'intermediaire de recepteurs nucleaires. Les potentialites therapeutiques et utilitaires de la melatonine sont tres importantes puisque toutes nos fonctions (e.g. systeme immunitaire, cardiovasculaire...) sont organisees temporellement et que de nombreux troubles resultent d'un dereglement de cette organisation temporelle (e.g. durant le vieillissement). Ces potentialites therapeutiques n'en sont toutefois qu'au premier stade d'evaluation.

Melatonin and regulation of the cardiovascular system

Abstract: Evidence from the last 10 years suggests that melatonin may influence the cardiovascular system. Vascular melatoninergic receptors/sites have been demonstrated and are functionally linked with vasoconstrictor or vasodilatory effects of low (10(-9)-10(-7) M) and high (10(-6)-10(-3) M) melatonin concentrations respectively. Furthermore several other properties of the neurohormone (e.g. sympathetic inhibition) could contribute to cardioprotection. In vivo melatonin beneficially affects the rat cerebrovascular circulation and protects the rat heart following myocardial ischaemia. In this regard, preliminary clinical data report some alteration of the melatoninergic system in human stroke and coronary heart disease. Finally, the suprachiasmatic nucleus and possibly the melatoninergic system may modulate cardiovascular rhythmicity. Clinical cardiovascular data on melatonin treatment are very scarce; the effects of a therapy modulating the melatoninergic system on cardiovascular haemodynamics and rhythmicity under several physiopathological conditions need to be further explored together with the possible impact on cardiovascular morbidity and mortality.

Melatonin and aging

Abstract: La melatonine est une hormone secretee principalement par la glande pineale ou epiphyse et secondairement par la retine. Synthetisee a partir du tryptophane, son rythme circadien caracteristique est sous le controle de la lumiere via les deux enzymes cles de sa synthese, la N-acetyl-transferase et l'hydroxyindole-O-methyl-transferase. Chez l'homme, comme chez toutes les especes etudiees, son maximum plasmatique est nocturne, aussi est-elle consideree comme le transducteur du jour solaire fournissant a l'organisme le cadre temporel sur lequel se construisent les sequences metaboliques. Ses taux circulants diminuant pendant le vieillissement, la question se pose de l'origine et/ou des effets de cette diminution ainsi que de l'eventuel benefice que l'on peut envisager de son administration chez le sujet âge.

Evaluation of the risk of venous thromboembolism in the medical patients

Abstract: The venous thromboembolic risk seems to be demonstrated in medical patients since the incidence of symptomatic and asymptomatic deep vein thrombosis (DVT) without any prophylactic methods is respectively about 50 per cent in stroke, 25 per cent in acute myocardial infarction (AMI) and 15 per cent in internal medicine. A synthesis of clinical trials performed in medical patients shows that prophylactic doses of heparins (unfractionated heparin or low molecular weight heparins) reduce the incidence of DVT by 40 to 60 per cent compared with the lack of any antithrombotic agents but without any significant effect on total mortality. Other antithrombotic agents such as antiplatelet agents seem to reduce the incidence of DVT by about 40 per cent associated with a significant decrease in total mortality of stroke or AMI. But the recommendations made on the basis of these results have to be extremely cautious since the number of medical patients included in clinical trials is quite limited compared with the surgical area. Moreover, each of these recommendations is not sufficiently proven. Thus more clinical trials have to be carried out with a placebo control group in internal medicine and an aspirin control group for stroke and AMI.

[Melatonin, a pertinent prototype for therapeutic innovation].

Abstract: La melatonine constitue un prototype ideal pour la conception rationnelle de nouveaux medicaments. La pharmacomodulation de chacun de ses elements structuraux nous a permis de preciser les relations structure-activite et d'acceder a des ligands agonistes et antagonistes utilisables comme outils pharmacologiques et/ou comme medicaments. Des etudes de modelisation moleculaire nous permettent de proposer un modele de pharmacophore ainsi qu'un modele 3D-QSAR. Le bioisostere naphtalenique de la melatonine (agomelatine) se trouve actuellement en phase Il des essais cliniques et deux autres composes ont ete selectionnes pour un developpement.

Genotoxic and clastogenic effects of doxorubicin

Abstract: La doxorubicine (Adriblastine®) est une anthracycline largement utilisee en oncologie medicale. L'objet de ce travail est de mettre en evidence la genotoxicite et plus precisement le pouvoir clastogene de cette molecule grâce au test des micronoyaux. L'utilisation de ce test de mutagenese a court terme, de realisation aisee et d'interpretation rapide, a permis de mettre en evidence, apres exposition des cellules a la doxorubicine. une augmentation significative du taux de micronoyaux (moyenne = 10.8 ± 5.7 micronoyaux versus 31.9 ± 11.5 apres exposition, difference significative, p<0.0001) et du taux des aberrations chromosomiques (1 aberration pour la culture controle contre 17 des le premier point de gamme, p<0.001). A l'issue de cette etude, le test des micronoyaux apparait aussi comme un test fiable et reproductible pour etudier et evaluer le pouvoir genotoxique de certaines substances.

Melatonin and reproduction in domestic farm animals

Abstract: Melatonin, synthetized by the pineal gland, is the chemical messenger which allows seasonally reproductive animals to perceive day length changes. In the ewe, the neural message, transformed into a hormonal one, triggers pulsatile activity of the LHRH neurons. About 40 days are necessary for melatonin to centrally stimulate the pulsatile LHRH activity. Its sites and mode of action are not yet known completely, but a precise hypothalamic zone has been defined in which radioactive melatonin binds specifically and where cold melatonin delivered locally stimulates LHRH activity. In the veterinary clinic, the most frequent mode of distribution is a sub-cutaneous implant, which induces an advancement of the cyclical ovulatory activity of ewes and goats. The date of fertilization is advanced and fecundity of females is improved. It can be used alone, or in association with other hormonal treatments, or after an artificial photoperiodic treatment. Under these conditions, it allows a quantitative and qualitative increase in out-of-season sperm production in rams and billy-goats. Such an implant is registered and marketed in France, the UK, Greece, Australia and New Zealand.

[Maintenance treatment with high-dose buprenorphine: are the recommendations being followed?].

Abstract: Depuis fevrier 1996, la buprenorphine haut-dosage beneficie d'une autorisation de mise sur le marche dans l'indication de traitement substitutif des pharmacodependances aux opiaces. La mise a disposition de cette specialite a ete accompagnee de recommandations destinees aux medecins et pharmaciens relatives aux indications du produit, au choix des patients, aux modalites de prescription et de delivrance. De la date de mise sur le marche a la fin de l'annee 1996, 149 patients toxicomanes, assures sociaux residant dans le departement des Vosges et places sous buprenorphine haut-dosage, ont ete suivis par le service du controle medical de l'assurance-maladie. Les recommandations ne sont globalement pas suivies par les prescripteurs, qu'il s'agisse du recours a un avis specialise, de la mise en oeuvre d'un suivi psychosocial, de certaines modalites posologiques. Les co-prescriptions de psychotropes, principalement de benzodiazepines, restent frequentes, et posent question, a l'heure ou plusieurs cas d'intoxications mortelles par buprenorphine haut-dosage viennent d'etre rapportees.

Drug prescription and utilization in Morocco

Abstract: La prescription et l'utilisation des medicaments au Maroc et la place des medicaments essentiels dans ces prescriptions ont ete apprehendees a partir d'une etude d'ordonnances (600), d'un questionnaire aupres de 111 prescripteurs tires au sort et d'une serie prospective de consultations medicales (305), au sein de centres de soins de differents niveaux (CHU, centre de sante primaire...), auxquelles l'investigateur assistait en observateur neutre. Le nombre moyen de medicaments prescrits par ordonnance est de 3.27 ce qui correspond a l'impression d'une majorite de medecins (62.9 pour cent) pour qtti le nombre de medicaments necessaires pour un patient est de 3. Dans les structures de sante publique ce nombre de medicaments est plus faible (2.0±0.14 dans les differents niveaux: hopital ou centre de soin primaire). Parmi l'ensemble des medicaments 15.48 pour cent sont des specialites appartenant a la liste nationale des medicament essentiels, ce qui est a mettre en rapport avec les 16.2 pour cent de medecins qui declarent avoir eu connaissance du Programme d'Action pour les Medicaments Essentiels (PAME). Dans les structures publiques les prescriptions contiennent de 29.8 pour cent a 82.4 pour cent de medicaments essentiels (selon la liste generale de l'OMS). Le temps moyen de consultation varie de 3.27±0.96 min a 4.87±1.04 min selon les centres de sante. Les prescriptions comportent au moins un antibiotique dans 47.5 pour cent des cas (variation de 25 pour cent a 64 pour cent), l'etude d'ordonnances aboutissait a la valeur de 44.3 pour cent des cas, tandis que la presence de produit injectable etait notee dans 17.3 pour cent des ordonnances. Le cout moyen d'une ordonnance est de 146.25 dirhams (variant de 4 a 1200 dirhams, soit environ 100 francs). Les prescripteurs estiment pour 68.6 pour cent d'entre eux que les patients font une relation entre le cout d'une specialite et son efficacite. Parmi les elements qui motivent leur prescription, le cout vient juste apres l'efficacite et avant la disponibilite du medicament dans les centres.

[Toxicology of reproduction: predictive value of experimental models. Round Table No 1 at Giens XIII].

Abstract: La realisation des essais cliniques destines a la commercialisation des produits pharmaceutiques a usage humain, depend directement des resultats d'un certain nombre d'etudes chez l'animal. Cette table ronde a evalue la qualite et l'interet de ces modeles experimentaux en toxicologie de la reproduction. Les protocoles des etudes toxicologiques sont raisonnables et adaptes. En terme d'extrapolation de l'animal a l'homme, le pouvoir predictif des essais precliniques va decroissant de l'evaluation des pouvoirs foetotoxique puis teratogene qui sont de reels outils predictifs, puis des effets sur la fertilite des deux sexes, a l'evaluation du risque postnatal. A l'issue de cette table ronde, nous proposons les points d'amelioration suivants: (1) standardiser et generaliser la pratique des tests d'evaluation de la fertilite (en particulier le spermogramme) afin de renforcer les correlations animal/homme; (2) developper la connaissance et la standardisation du suivi du cycle oestral; (3) favoriser la standardisation, l'harmonisation et la diffusion des tests postnatals s'averant pertinents chez l'animal; (4) multiplier les initiatives visant a une meilleure comprehension mutuelle des partenaires du medicament; (5) ouvrir des registres de suivi des effets des nouveaux medicaments sur l'ensemble de la reproduction des que possible dans les essais cliniques; (6) recommander la creation d'une ligne directrice ICH permettant la mise en place d'une hierarchisation des effets observes dans les modeles experimentaux. Ceci permettrait d'adapter au cas par cas (et pour eventnellement chaque phase du cycle de reproduction) les recommandations, precautions d'emploi et/ou contre-indications portees sur les resumes des caracteristiques des produits.

[Angiotensin II AT1 receptor antagonists: clinical development and future perspectives].

Abstract: Le blocage du systeme renine-angiotensine par les inhibiteurs de l'enzyme de conversion de l'angiotensine II est aujourd'hui reconnu comme une approche efficace pour le traitement de l'hypertension arterielle et de l'insuffisance cardiaque. En outre, ces inhibiteurs se sont reveles tres utiles dans la prevention de l'insuffisance renale chronique. Il est maintenant possible d'inhiber le systeme renine-angiotensine de maniere plus specifique en bloquant directement les recepteurs AT 1 de l'angiotensine II. Plusieurs antagonistes non-peptidiques des recepteurs de l'angiotensine, actifs par voie orale, ont recemment ete developpes et mis sur le marche pour le traitement de l'hypertension arterielle. Les etudes cliniques ont demontre que ces nouveaux composes sont aussi efficaces que les inhibiteurs de l'enzyme de conversion, les antagonistes du calcium ou les beta-bloquants. De plus, ils semblent avoir les memes effets benefiques sur la fonction ventriculaire de l'insuffisance cardiaque et sur la fonction renale que les inhibiteurs de l'enzyme de conversion. De grandes etudes cliniques telles que LIFE, RENAAL ou ELITE Il sont en cours pour demontrer les benefices a long terme de l'une de ces molecules dans l'hypertension arterielle, l'insuffisance cardiaque et la nephropathie diabetique.

Why has menopause become a public health problem

Abstract: Menopause is a very important public health problem for many reasons. DEMOGRAPHIC: In 1990 there were 467 million women aged 50 years or more; worldwide, they will number 1200 million in 2030. SOCIOLOGICAL: The expectation of life in the Occident for a 50-year-old woman is a further 33 years, thus at this point, a menopausal women is still in active employment. PHYSIOLOGICAL: Menopause is not a disease, but gives rise to many problems which involve the entire body. MEDICAL: The only available treatment for this phase of the woman's life is oestrogens. These drugs induce many beneficial effects but the large-scale treatment of women who are not ill brings into question the harmlessness of this approach. ECONOMIC: The cost of medical treatment and regular review have to be considered in addition to the increased cost of pensions for these women. HUMAN: The improved quality of life observed with the medical treatment of such women could be an added dimension of the classical evaluation of the benefit/risk ratio.

The prevention of venous thromboembolism: a statewide evaluation of practices in Massachusetts.

Abstract: The objective of this study was to determine the proportion of Massachusetts Medicare patients who received prophylaxis for venous thromboembolism following colectomy, hysterectomy or total hip arthroplasty. The sample frame was all 90 Massachusetts acute care hospitals, and the time frame was 1 April to 30 September 1994. The patients discharged with an International Classification of Disease (ICD-9-CM) discharge diagnostic code (recorded in the Massachusetts Medicare Claims Database) for colectomy, hysterectomy or total hip arthroplasty were used to identify the target patient population. The sample population comprised 1397 patients randomly selected from the target population, including 467 total hip arthroplasties, 474 colectomies, and 456 hysterectomies. Medical records were reviewed by trained nurse abstractors who collected information on the use of prophylaxis for venous thromboembolism. Prophylaxis for venous thromboembolism was employed by surgeons practicing in Massachusetts hospitals in 93 per cent of total hip arthroplasty cases (regional variation 85-98 per cent), 84 per cent of colectomies (regional variation 57-93 per cent), 66 per cent of hysterectomies (regional variation 35-71 per cent), and in 87 per cent of the subset of 111 hysterectomies with malignancy (regional variation 25-100 per cent). The results of this statewide study demonstrated significant regional and hospital-to-hospital variation in use of prophylaxis for venous thromboembolism following major surgery. A lower rate of prophylaxis use was observed in hospitals with fewer than 200 beds and in hospitals that did not have teaching programmes. Hospitals with below-average rates of prophylaxis were targeted for intensive quality improvement interventions.

Signaling by melatonin receptors

Abstract: Melatonin is a hormone involved in various physiological processes such as the circadian cycle, hormone release and immune response. High-affinity melatonin receptors are classified in two pharmacologically distinct groups: Mel1 and Mel2. These receptors have first been localized in different organs and brain structures and some subtypes have since been cloned. Inhibition of adenylyl cyclase by Mel1 receptors is the best investigated signalling pathway but cannot be entirely responsible for the diversity of melatonin-induced phenomena. Phospholipase C, potassium ion channels and guanylyl cyclases have also been reported to be modulated by melatonin. This review updates present knowledge of the characterization and signalization of melatonin receptors.

[Prophylaxis of venous thromboembolism in medical patients: from medical decision tools to the use of low molecular weight heparin].

Abstract: In France, low molecular weight heparins are largely used for prophylaxis of venous thromboembolic disease in medical patients. Although clinical trials show their efficacy in some particular clinical situations, there is no consensus about their use in non-surgical patients. A consequence is a wide disparity of prophylaxis of venous thromboembolic disease regimens: such a situation was observed during a practice survey in two medical units of the general hospital of Luneville. So, prior assessment for pharmacists and physicians was carried out to determine tools which guide decision-making. These comprise clinical practice guidelines, a record card which allows the scoring of risk for venous thromboembolic disease and a clinical algorithm leading to the appropriate prescription according to the risk and the haematological results. A second concomitant practice survey was organized in the same two units in order to measure the appropriateness of the decision-making tools in medical practice. The four-month study included 108 medical patients. The process was successful because: (1) validated practices are improved, particularly in respect of biological monitoring during treatment, and (2) the disparity of therapeutic strategies is highly reduced, the clinical practice guidelines being followed in 81 per cent of all cases. Despite the lack of consensus, heightened awareness of the attendant risk in many medical conditions allows appropriate prophylactic measures to be taken. These measures need decision-making tools that are easy to use and that improve heparin prescribing and thus healthcare quality.