[Does aspirin have a place in primary cardiovascular prevention by the polypill ? Simulation study on a realistic virtual population]. / L'aspirine a-t-elle une place dans la prévention cardiovasculaire primaire par la polypill ? Étude de simulation sur une population virtuelle réaliste.

BACKGROUND: The polypill strategy could become widely accepted in cardiovascular prevention due to reduced costs and its simplicity, which promote compliance. Aspirin is often included as a component of the polypill for primary prevention, but three powerful recent trials failed to show any favorable net benefit even in high-risk subgroups. Our objective is to estimate the net benefit associated with aspirin in primary cardiovascular prevention. METHODS: We simulated the impact of different polypill compositions combining pravastatin, ramipril, hydrochlorothiazide, with or without aspirin, on a realistic French virtual population between 35 and 65 years old. We assessed how this impact on myocardial infarction and stroke varied according to gender, diabetes, and arterial hypertension. We identified the subgroup of individuals whose specific benefit from aspirin was greater than twice the risk of serious bleeding it induced. RESULTS: The absolute benefit associated with aspirin was reduced by co-prescriptions. No subgroup of women benefited from aspirin, and the subgroup of women with a clear net benefit represented 128 women out of 529,421. Men at high risk of cardiovascular death, or with diabetes and hypertension, had a benefit from aspirin exceeding the risk of bleeding induced, but this risk represented more than half of the benefit. No subgroup analyzed did show a benefit greater than twice the risk of bleeding. The proportion of men whose expected benefit from aspirin was greater than twice the risk of bleeding represented 3% of all men. An optimal polypill strategy in primary prevention between the ages of 35 and 65, combining three drugs but not aspirin, can hope to save two out of three strokes and more than one out of two myocardial infarctions. It would prevent a major cardiovascular accident every 16 to 193 individuals treated according to the subgroups considered. CONCLUSION: Until proven otherwise, aspirin has only a limited place in individuals between 35 and 65 years without a cardiovascular history. We showed how simulating therapeutic strategies on a realistic virtual population could be used for best applying available evidence.

Do drugs interact together in cardiovascular prevention? A meta-analysis of powerful or factorial randomized controlled trials.

AIM OF THE STUDY: To explore whether preventive cardiovascular drugs (antihypertensive, antiplatelet, lipid lowering and hypoglycemic agents) interact together in cardiovascular prevention. METHODS: We searched PubMed®, Web of science™, Embase and Cochrane library for powerful randomized placebo-controlled trials (>1000 patients). We explored whether drug effect on major vascular events changed according to cross-exposure to other drug classes or to cardiovascular risk factors (hypertension or type 2 diabetes), through a meta-analysis of relative odds ratio computed by trial subgroups. A significant interaction was suggested from confidence intervals of the ratio of odds ratios, when they excluded neutral value of 1. RESULTS: In total, 14 trials with 178,398 patients were included. No significant interaction was observed between co-prescribed drugs or between these medications and type 2 diabetes/hypertension status. CONCLUSIONS: Our meta-analysis is the first one to evaluate drug-drug and drug-hypertension/type 2 diabetes status interactions in terms of cardiovascular risks: we did not observe any significant interaction. This indirectly reinforces the rationale of using several contrasted mechanisms to address cardiovascular prevention; and allows the combination effect prediction by a simple multiplication of their odds ratios. The limited availability of data reported or obtained from authors is a strong argument in favor of data sharing.

Mechanisms underlying the endothelium-dependent vasodilatory effect of an aqueous extract of Elaeis Guineensis Jacq. (Arecaceae) in porcine coronary artery rings.

This study was undertaken to investigate the vasodilatory effect of an aqueous extract of Elaeis guineensis Jacq (EGE) in the porcine coronary artery and elicit its possible mechanism(s) of action. Vascular effects of crude extract of dried and powdered leaves of Elaeis guineensis were evaluated on isolated coronary arteries on organ chambers. Determination of eNOS expression and the phosphorylation level of eNOS were determined by Western blot analysis. In the presence of indomethacin, EGE caused pronounced relaxations in endothelium-intact but not in endothelium-denuded coronary artery rings. Relaxations to EGE were significantly reduced by N(ω)-nitro-L-arginine (L-NA, a competitive inhibitor of NO synthase), slightly but not significantly by charybdotoxin plus apamin (two potent inhibitors of EDHF-mediated responses) and abolished by the combination of L-NA and charybdotoxin plus apamin. Relaxations to EGE were abolished by the membrane permeant, SOD mimetic, MnTMPyP, and significantly reduced by wortmannin, an inhibitor of PI3-kinase. Exposure of endothelial cells to EGE increased the phosphorylation level of eNOS at Ser1177 in a time and concentration-dependent manner. MnTMPyP abolished the EGE-induced phosphorylation of eNOS.In conclusion, the obtained data indicate that EGE induces pronounced endothelium-dependent relaxations of the porcine coronary artery, which involve predominantly NO. The stimulatory effect of EGE on eNOS involves the redox-sensitive phosphorylation of eNOS at Ser1177 most likely via the PI3-kinase pathway.

[Development of Ethylcellulose/Eudragit matrix for controlled and continuous release of insulin]. / Developpement d'une matrice ethylcellulose/eudragit pour la liberation controlee et continue de l'insuline.

PURPOSE: Diabetes Type I is a chronic disease requiring insulin repeated injections by parenteral during a lifetime. This method of administration as well as traumatic can be a problem for adherence of patients to treatment. In order to overcome these difficulties, we considered the development of therapeutic transdermal drug delivery (TTDD) of insulin. MATERIAL AND METHOD: As active ingredient we used anhydrous human insulin Actarapid HM from Novo Nordisk laboratory, the excipients are ethyl cellulose, Eudragit RS 100 and butylphtalate. We developed two matrix Ethylcellulose/Eudragit in reports 1 and 2, in which are incorporated different proportions of insulin. RESULTS: The study of the release of insulin in phosphate buffer at pH 7.4, showed a continuous release profiles strongly depending on Ethylcellulose/Eudragit report and the initial charge of insulin. CONCLUSION: This study shows that the matrix Ethylcellulose/Eudragit lends itself to the development of a controlled release of insulin. This allows us to continue this work by combining this matrix with other elements for achieving an insulin TTDD.

[Clinical trials in Dakar: survey on knowledge, attitudes and practices of key actors on the period from 2003 to 2007]. / Essais cliniques à Dakar: enquête sur les connaissances, attitudes et pratiques des principaux acteurs sur une période allant de 2003 à 2007.

AIM: The general objective of this study was to agree an inventory of fixtures of clinical trials done in Dakar, in order to make recommendations to improve the quality of clinical trials in Senegal. METHOD: We have done a survey from mars to may 2007, with investigators of the two biggest Senegalese university teaching hospitals and to the pharmacy management and the ethical committee. RESULTS: Our key results showed: 1) a small participation rate of teachers to clinical trials (11 on 37 interviewed); 2) that the principal sponsor is pharmaceutical industry; 3) that most of investigators have not degree in clinical trials; 4) that most pathologies concerned were malaria and AIDS; 5) that there are regulations related to clinical trials in Senegal. CONCLUSION: This study shows the necessity to integrate, in Senegal, clinical trials in the curricula of students training.

Medicinal plants and the treatment of diabetes in Senegal: survey with patients.

Diabetes is the most common metabolic disorder worldwide and is a major public health problem. Its frequency increases every day in all countries. However, in developing African countries, few people have access to drugs. In addition, in Africa, traditional beliefs induce people to use medicinal plants whenever they have health problems. Thus, many people in these developing countries use plants for the treatment of diabetes. Yet, few studies are focused on the knowledge and attitudes of the users on medicinal plants in Africa in general and in Senegal in particular. Hence we undertook this survey on the use of medicinal plants for the treatment of diabetes in Senegal in order to make recommendations which could contribute to the increase of the value of herbal medicines in developing countries. We did a cross-sectional survey by direct interview at a university teaching hospital, in Dakar with a representative sample of 220 patients. Forty-one plants were used by the patients and the two most frequently cited were Moringa oleifera Lam (65.90%) and Sclerocarya birrea (A. Rich) Hochst (43.20%). Patients gave several reasons for using medicinal plants (traditional treatment: 40%, efficacy: 32%, low cost: 20%). The principal suppliers of plants were tradesmen in the market (66.8%) and traditional therapists (5%). Sixty-five per cent of patients think that medicinal plants are efficient for the treatment of diabetes and 20% have reported adverse effects which could be caused by medicinal plants. In conclusion, many people in our study think that medicinal plants are efficient for the treatment of diabetes, which requires research work by scientists in developing countries in this field in order to prove their efficacy and innocuousness.

[Not Available]. / Essais cliniques à Dakar : enquête sur les connaissances, attitudes et pratiques des principaux acteurs sur une période allant de 2003 à 2007.

AIM: The general objective of this study was to agree an inventory of fixtures of clinical trials done in Dakar, in order to make recommendations to improve the quality of clinical trials in Senegal. METHOD: We have done a survey from mars to may 2007, with investigators of the two biggest Senegalese university teaching hospitals and to the pharmacy management and the ethical committee. RESULTS: Our key results showed: 1) a small participation rate of teachers to clinical trials (11 on 37 interviewed); 2) that the principal sponsor is pharmaceutical industry; 3) that most of investigators have not degree in clinical trials; 4) that most pathologies concerned were malaria and AIDS; 5) that there are regulations related to clinical trials in Senegal. CONCLUSION: This study shows the necessity to integrate, in Senegal, clinical trials in the curricula of students training.

[Prescription of benzodiazepines by general practitioners in the private sector of Dakar: survey on knowledge and attitudes]. / Prescription des benzodiazépines par les médecins généralistes du privé à Dakar: Enquête sur les connaissances et les attitudes.

OBJECTIVE: The objective of this study was to evaluate knowledge and attitudes of general practitioners of the private sector, in Dakar, concerning prescription of benzodiazepines, in order to make, possibly, recommendations for their rational use. METHOD: A survey was done in 2005 with a representative sample of 55 medical doctors. Medical doctors filled in the questionnaire which focused on the main benzodiazepines' indications, those prescribed and their rules of prescription. RESULTS: The main indications were anxiety, convulsions, epilepsy and insomnia and the benzodiazepines prescribed in first intention were prazepam against anxiety and insomnia and diazepam against convulsions and epilepsy. Practically 17% of medical doctors ignored the existence of limited period of benzodiazepine use and 70.9% of medical doctors considered their training on benzodiazepines insufficient. CONCLUSION: These results show the necessity to base continuous training for these general practitioners on the pharmacology of benzodiazepines.

Benzodiazepines prescription in Dakar: a study about prescribing habits and knowledge in general practitioners, neurologists and psychiatrists.

Benzodiazepines are relatively well-tolerated medicines but can induce serious problems of addiction and that is why their use is regulated. However, in developing countries like Senegal, these products are used without clear indications on their prescription, their dispensation or their use. This work focuses on the prescription of these medicines with a view to make recommendations for their rational use. Benzodiazepine prescription was studied with psychiatrists or neurologists and generalists in 2003. Specialist doctors work in two Dakar university hospitals and generalists in the 11 health centres in Dakar. We did a survey by direct interview with 29 of 35 specialists and 23 of 25 generalists. All doctors were interviewed in their office. The questionnaire focused on benzodiazepine indications, their pharmacological properties, benzodiazepines prescribed in first intention against a given disease and the level of training in benzodiazepines by doctors. Comparisons between specialists and generalists were made by chi-square test. Benzodiazepines were essentially used for anxiety, insomnia and epilepsy. With these diseases, the most benzodiazepines prescribed are prazepam against anxiety and insomnia and diazepam against epilepsy. About 10% of doctors do not know that there is a limitation for the period of benzodiazepine use. The principal reasons of drugs choice are knowledge of the drugs, habit and low side effects of drugs. All generalists (100%) said that their training on benzodiazepines is poor vs. 62.1% of specialists, and doctors suggest seminars, journals adhesions and conferences to complete their training in this field. There are not many differences between specialists and generalists except the fact that specialists prefer prazepam in first intention in the insomnia treatment where generalists choose bromazepam. In addition, our survey showed that specialists' training in benzodiazepines is better than that of generalists. Overall, benzodiazepine prescription poses problems particularly in training, and national authorities must take urgent measures for rational use of these drugs.

[Doctors belonging to the Senegalese Association of Sport Medicine and doping in sports: survey on knowledge and attitudes]. / Médecins de l'Association sénégalaise de médecine du sport et dopage sportif: enquête sur les connaissances et attitudes.

Doping in sports is as old as sports, but it grew considerably during the 20th century with the arrival in stadiums during the 1990s of amphetamines and anabolic steroids as well as such peptide hormones as erythropoietin. The international fight against doping took a giant step forward in 1999 with the creation of the world antidoping agency (WADA). This study is part of that fight. It follows an earlier survey of retail pharmacists in Senegal and aims to evaluate the knowledge about doping of doctors belonging to the Senegalese Association of Sports Medicine and to assess their attitude towards this phenomenon. Its goal is to determine how best to involve them in preventive actions. We conducted a survey in 2001 and randomly selected and interviewed 60 of the 92 doctors in the association. The questionnaire focused on three areas: their knowledge of doping, their attitudes to it, and the means of prevention that they proposed. The results showed that only 11 of the 60 doctors knew the definition of doping and 15% of doctors could not cite any family of doping products. They were aware mainly of testosterone and other anabolic steroids (84.3%), then amphetamines and other stimulants (64.7%), and finally peptide hormones (58.8%). The subjects mentioned blood doping and pharmacological manipulations as forbidden methods. They considered that the four groups of drugs most often used by athletes for doping were, in descending order, anabolic steroids, stimulants, peptide hormones and corticoids. Eighty per cent of doctors think that Senegalese athletes use doping products and that the sports most involved are football, wrestling, track and field and basketball. They also think that doping is a form of drug addiction and a public health problem. Eleven doctors (18%) said they had been contacted for information on use of doping products. The interviewees consider that the three best methods of prevention include information about side effects, unannounced urine and blood tests, and sanctions. This work shows that Senegalese athletes may use doping; it contains no direct proofs but many indirect indicators. Success against doping requires preventive activities that should be conducted jointly for trainers, sports federations and doctors of the Senegalese Association of Sports Medicine and then by all of them for athletes, who are the primary targets of any prevention campaign.

Myorelaxant and antispasmodic effects of the aqueous extract of Mitragyna inermis barks on Wistar rat ileum.

Mitragyna inermis is used in the Senegal traditional medicine for treating stomach and intestinal disorders. At concentrations of 0.5, 0.75 and 1 mg/ml, the aqueous extract of M. inermis bark (AEMIB) significantly induced a decrease of the ileal basal tonus, respectively, from 37+/-1, 51+/-1 and 75+/-2% (P<0.05; n=5), compared to the baseline values. As well as atropine, AEMIB inhibited submaximal contractions induced by 0.01 mg/ml ACh with IC(50) value of approximately 0.75 mg/ml (n=5). These results show that AEMIB possesses both myorelaxant and antispasmodic actions in the ileum. This may justify the pharmacological basis for the popular use of Mitragyna for the treatment of gastrointestinal disorders.

Extracellular calcium level is crucial for aortic contractile response in pregnant rat.

Studies of vascular reactivity during late pregnancy were performed to investigate the previously described hyporeactivity to vasopressors. Two groups of seven control (nonpregnant) and seven late pregnant (day 20) Wistar rats were used. Rubbed (E-) segments from thoracic aorta were studied for contractile studies in a Krebs solution containing either 1.25 or 2.50 mmol/L Ca concentration. Norepinephrine (NE; 10-9-3 x 10-5) or depolarization induced (KCl, 100 mmol/L) contractions are given as mN/mm2. With 2.50 mmol/L Ca, the maximal contraction to NE in E-segments is decreased in late pregnant rats compared with nonpregnant rats. However, this difference disappears when calcium concentration is set to 1.25 mmol/L Ca, the physiological value for free calcium concentration in extracellular fluid. For the contraction induced by opening of voltage operated calcium channels (KCl depolarization), a decreased maximal tension is also obtained in the pregnant rats compared with nonpregnant only with 2.50 mmol/L Ca concentration. It appears that aortic response to vasoconstrictors is modulated by extracellular calcium concentration in a different way between pregnant and nonpregnant rats.