The problem of educative charge of the asthmatic patient has mobilised general physicians, specialists and kinesitherapists for many years. The first mutual aid associations for asthmatic patients, created at the initiative of pneumologists and allergists or their patients date back for a score or so of years and their principal objectives are the adaption of educational measures, in transmission of clear information and in the loan of surveillance equipment, to ensure that inhalation equipment is adapted appropriately to the case. Since, the mediatisation has reinforced this action in all directions, in the interests of and for the great benefit of asthmatic patients; and so the role of the pharmacist has also become essential not only in the field of information but also in that of control of the self-evaluation of the patient; three inseparable aspects are thus emphasized: information aspect, technical aspect, initiation of surveillance of the illness.

The synthesis of 54 3-phenacyl-5-benzylidene-thiazolidine -2,4-diones is reported. Eight of them were tested for anti-oedema, analgesic and anticonvulsant activity. Only one compound showed significant anti-oedematous and analgesic activity. Three compounds protected against tonic seizures and death.

OBJECTIVEThe aim was to compare the effects of two diuretics, indapamide and hydrochlorothiazide, on cardiac hypertrophy in stroke prone spontaneously hypertensive rats (SHR-SP).METHODSSix week old SHR-SP, on a 1% sodium chloride water intake, were treated with oral indapamide (3 mg.kg-1 x d-1) or hydrochlorothiazide (20 mg.kg-1 x d-1) over a 44 d period. The hypertrophic process was evaluated by classical indices and by the morphological analysis of myocyte cross sectional area, coronary artery thickness, and immunohistochemical analysis of interstitial fibrosis.RESULTSIn the untreated SHR-SP on 1% sodium chloride, all animals developed severe hypertension and cardiac hypertrophy when compared to normotensive salt loaded WKY by 13 weeks of age. In salt loaded SHR-SP treated with indapamide or hydrochlorothiazide, systolic blood pressure was moderately decreased by the end of the treatment when compared with untreated SHR-SP, at 259(7) and 245(7) mm Hg respectively, v 300(11) mm Hg, p < or = 0.05. Myocyte enlargement appears to be the main feature involved in the development of cardiac hypertrophy in the SHR-SP. By the end of treatment both indapamide and hydrochlorothiazide prevented the development of cardiac hypertrophy evaluated by heart weight to body weight ratio [4.69(0.07) and 4.61(0.08) respectively, v 5.39(0.13), p < or = 0.001] and myocyte hypertrophy (-33% and -21% of the SHR-SP values, p < or = 0.001). Myocardial interstitial fibrosis and perivascular fibrosis were practically absent in the two treated groups.CONCLUSIONSOur results allow the characterisation of SHR-SP cardiac hypertrophy and indicate that the two types of chronic diuretic treatment prevent SHR-SP cardiac hypertrophy with a drug specific efficiency.

Ethanol naive alcohol preferring rodents have low serotonin transmission. Both pharmacological, biochemical and behavioral studies show that increased serotonin transmission influence reduces ethanol consumption in animals. This paper develops the role of serotonin in different lines of ethanol preferring rats and mice, and shows a regulation of 5-HT1A receptors in alcoholised dependent mice. Different sensitivities to ethanol observed between ethanol-preferring and non-preferring rats or mice seems to be at the root of the maintenance of alcohol intake.

We studied platelet 3H-serotonin uptake in 32 former alcoholics, withdrawn for from 1 month to 22 years, in their descendants ( 21.7+/-1.6 years old, n=17; 10.9 0.7 years old; n=19), and in respective control groups, paired in age and sex. All of the alcoholics presented high 3H-serotonin uptake (Vmax=10.88+/-4.23 pmoles/10(8)pl/30sec.,vs. 0.93+/-0.15pmole/10(8)pl/30sec. Their descendants also showed high platelet serotonin uptake: 3.94+/-1.44 pmoles/10(8)pl/30sec., vs. 0.93+/-0.15 pmoles/10(8)pl/30sec. for adult descendants, and 5.99+/-2.23 vs. 0.84+/-0.15 pmole/10(8)pl/30 sec. for young descendants. All subjects were free of alcoholisation ( biological parameters studied were blood ethanol concentration, gamma glutamyl transferase and mean corpuscular volume), and dependence of former alcoholics was evaluate by using, a posteriori, the CAGE test. In descendants, 28% of the subjects have Vmax values higher than the highest of the control group. Alcohol, in vitro, (54 mM) did not affect serotonin uptake in any group. These results indicate that in descendants of alcoholics, platelet serotonin uptake is altered, without modification of sensitivity to ethanol. The genetic basis of alcohol dependence could be linked with the platelet serotonin transport.

The effects of two diuretics, indapamide (3 mg/kg/day) and hydrochlorothiazide (20 mg/kg/day), were analyzed over a 44-day period on the cardiovascular hypertrophy of stroke-prone spontaneously hypertensive rats (SHR-SP). Untreated SHR-SP developed severe hypertension and cardiac hypertrophy when compared to normotensive Wistar-Kyoto (WKY) rats after 8 weeks on 1% sodium chloride. In diuretic-treated animals, systolic blood pressure was moderately decreased by the end of the treatment when compared with untreated SHR-SP (- 13 and - 18%. respectively, p < 0.05). Morphometric analysis of myocyte cross-sectional areas evidenced that indapamide was the most effective in preventing myocyte hypertrophy ( −33%, p < 0.0001). Small coronary artery wall thickness was efficiently prevented in the two treated groups, but medial hypertrophy was prevented by hydrochlorothiazide only. Among markers of smooth-muscle cell phenotype (contractile or extracellular matrix proteins) EIIIA-fibronectin (FN), one FN cellular isoform, was shown to be the most sensitive marker by an immunohistochemical technic. Medial expression of EIIIA-FN, which was characteristic of SHR-SP coronary arteries, was prevented by the two treatments. The two diuretic treatments, despite similar effects on blood pressure and smooth-muscle phenotype, prevent SHR-SP cardiovascular hypertrophy with a drug-specific efficiency.

There is considerable evidence from animal and human studies that serotonin plays a role in the modulation of alcohol intake and/or alcohol dependance. Biochemical, behavioral and pharmacological studies both in animal and man had verified this hypothesis. Central and peripheral levels of serotonin and of its metabolite 5-hydroxyindolacetic acid (5-HIAA) are modified by alcoholisation. Moreover, the use of pharmacological drugs modifying specifically serotonin transmission decreases ethanol intake. Our own studies suggest that a disfunctioning of serotonin uptake system could be implicated in the individual risk of alcohol dependence. Even if other systems, e.g. amino acids, are involved in the regulation of alcohol behavior, all data are favor of a modulation of alcohol intake by serotonin transmission.

Triptosine is a new L-5-hydroxytryptophan derivative whose effect has been studied in the Long-Evans alcohol-preferring rat. At an oral dose of 100 mg/kg once daily, triptosine reduced alcohol consumption by 42% in the second week of treatment and increased that of water by 80%. The results suggest that this precursor of serotonin might play an important role in diminishing preference for alcohol and reaccustoming the animal to water, without exerting an anorexic effect.

Fourteen fluoro pyrimidine-4-ones, four fluoro bispyrimidine-4-ones and two fluoro pyrimidine-4-ones with fused ring have been prepared. The reactivity of the carbonyl group of two pyrimidine-4-ones phosphorus oxychloride was studied. The 4-chloro pyrimidines reacted with ammonia or morpholine giving 4-substituted pyrimidines. Eight compounds are evaluated for their anti-inflammatory and anti-convulsivant properties: they were found to be weakly active against oedema and three of them protected rats form tonic convulsions.

There is considerable evidence from animal and human studies that serotonin plays a role in the modulation of alcohol intake and/or alcohol dependence. Biochemical, behavioral and pharmacological studies both in animal and man had verified this hypothesis. Central and peripheral levels of serotonin and of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) are modified by alcoholisation. Moreover, the use of pharmacological drugs modifying specifically serotonin transmission decreases ethanol intake. Our own studies suggest that a dysfunctioning of serotonin uptake system could be implicated in the individual risk of alcohol dependence. Even if other systems, e.g. amino acids, are involved in the regulation of alcohol behavior, all data are in favor of a modulation of alcohol intake by serotonin transmission.

Drugs most commonly used in the treatment of alcoholic withdrawal are antianxiety agents, namely benzodiazepines. Some similarities may be found between the mechanism of action of such active principles and that of alcohol at the GABAergic transmission level. In mice with physical dependence, in vivo binding of [3H]-RO 15-1788 to central benzodiazepine receptors increases during the initial period, but then tends to taper down to its basal value in the course of withdrawal. Neurochemical treatment with alpha-adrenergic drugs or with agents than can stimulate serotonergic transmission, as opposed to meprobamate therapy, promotes faster recovery of basal levels. In man, these data may be referred to decreased benzodiazepine consumption in the course of alcohol withdrawal. The results suggest that both noradrenergic and serotonergic treatments may be associated with significantly lower risks for newly induced benzodiazepine dependence.

Des thiéno[2,3-d]pyrimidin-4-one 2-thiones diversement substituées ont été synthétisées. Elles ont été essayées, ainsi que leurs intermédiaires de synthèse, les thiénylthiourées, comme analgésiques et anti-inflammatoires. Tous ces composés (sauf un) sont dépourvus de toxicité à 1000 mg/kg par voie ip. Certains possèdent des activités anti-cedémateuse et analgésique comparables à celles de l'acide acétylsalicylique pris comme produit de référence.

This paper describes a kinetic comparative study of plasma concentrations of isosorbide dinitrate (ISDN) and its mononitrate derivatives (2-ISMN or 5-ISMN) after oral administration of a sustained release form of ISDN or a (non) sustained release form of 5-ISMN. The blood extracts determinations were performed by electron capture gas chromatography which is an accurate and sensitive method suitable for the quantitation of concentrations in the nanogram per ml range. The results are in good agreement with those of the literature. The standard form of 5-ISMN is rapidly absorbed. The Tmax value is approximately 1H with a corresponding Cmax value close to 400 ng/ml. For the sustained release drugs, the Tmax increases to 6H and Cmax is nearly half the 5-ISMN standard form value. Considering the administered dose, it seems better to use 5-ISMN than ISDN. For a long lasting treatment of angina pectoris and ischaemic cardiac diseases, both forms can be used.

AbstractThe title compounds (IVb), (IVc) and (IXa) show analgesic activity, while (IVd) and (VIb) exhibit antiinflammatory activity.

Deux séries de thiéno[2,3-d]pyrimidones-4 substituées sont synthétisées et essayées pour leurs propriétés analgésiques et anti-inflammatoires. La plupart des 18 composés synthétisés sont très peu toxiques. Quelques-uns possèdent des activités analgésique et anti-inflammatoire voisines de celles de l'acide acétylsalicylique.

The uptake and release of mIBG, a tracer of the monoamine uptake and storage function, were studied on superfused rat cerebral cortex sections. mIBG was taken up and released by a mechanism comparable to that of norepinephrine (NE), but this storage appeared to be less specific for mIBG than for NE. This implies that when mIBG is used as a scintigraphic tracer of monoaminergic synaptic vesicles, imaging should be delayed long enough to ensure release of the molecule from its nonspecific binding sites.

The properties of [3H]dihydropyridine (DHP), nitrendipine and (+)-PN 200-110, binding to rat cerebral membranes were investigated. In normotensive Wistar-Kyoto (WKY) adult rats, the highest densities of [3H]DHP binding sites were found in the hippocampus. Frontal cerebral cortex and hypothalamus had intermediate levels and no specific binding of [3H]DHP and [125I]iodipine could be detected in the brainstem membranes and more precisely in the nucleus tractus solitarius and in the locus coeruleus. Changes in the maximal number of DHP binding sites (Bmax) were observed in spontaneously hypertensive rats (SHR) and in old Sprague-Dawley rats. In adult SHR, there was a significant increase in the Bmax values of [3H](+)-PN 200-110 binding in the hippocampus when compared to the values obtained in WKY. There was no difference in the Bmax values between young (3 weeks) prehypertensive SHR and age-matched WKY. In senescent (26 months) Sprague-Dawley rats, the Bmax values of [3H](+)-PN 200-110 binding were significantly reduced (30%) in the frontal cerebral cortex and the hippocampus, as compared with the number of DHP binding sites found in mature Sprague-Dawley rats (15 weeks).