Preventive Beneficial Effect of an Aqueous Extract of Phyllanthus amarus Schum. and Thonn. (Euphorbiaceae) on DOCA-Salt-Induced Hypertension, Cardiac Hypertrophy and Dysfunction, and Endothelial Dysfunction in Rats.

This study investigated the preventive effect of an aqueous extract of the whole plant of Phyllanthus amarus (AEPA) on blood pressure, cardiac, and endothelial function in the deoxycorticosterone acetate (DOCA) salt-induced hypertensive rat model. Male Wistar rats were assigned into 5 groups receiving either vehicle (control and DOCA salt), DOCA salt combined with AEPA at 100 or 300 mg/kg, or AEPA (100 mg/kg) alone for 5 weeks. In addition, DOCA salt-treated rats were allowed free access to water containing 1% NaCl. Systolic blood pressure, left ventricle parameters, vascular reactivity of primary mesenteric artery rings, the vascular level of oxidative stress, and the level of target proteins were determined, using respectively tail-cuff sphygmomanometry, echocardiography, organ chambers, dihydroethidium staining, and immunofluorescence methods. After 5 weeks, AEPA treatments (100 or 300 mg/kg per day) significantly prevented the increase in systolic blood pressure in DOCA salt-treated rats, respectively, by about 24 and 21 mm Hg, improved cardiac diastolic function, and reduced significantly the increased posterior and septum diastolic wall thickness and the left ventricle mass in hypertensive rats. Moreover, the DOCA salt-induced endothelial dysfunction and the blunted nitric oxide- and endothelium-dependent hyperpolarization-mediated relaxations in primary mesenteric artery were improved after the AEPA treatments. AEPA also reduced the level of vascular oxidative stress and the expression level of target proteins (eNOS, COX-2, NADPH oxidase subunit p22) in DOCA salt rats. Altogether, AEPA prevented hypertension, improved cardiac structure and function, and improved endothelial function in DOCA salt rats. Such beneficial effects seem to be related, at least in part, to normalization of the vascular level of oxidative stress.

Ethanol Extract of Leaves of Cassia siamea Lam Protects against Diabetes-Induced Insulin Resistance, Hepatic, and Endothelial Dysfunctions in ob/ob Mice.

Despite long traditional utilization and some reports on the antihyperglycemic and antihyperlipidemic action of Cassia siamea, the mechanisms involved have not been investigated yet. Thus, the objective of the present study was to investigate whether and how oral administration of the ethanolic extract of Cassia siamea Lam leaves (LECS) improves glucose and insulin homoeostasis, liver damage, and endothelial dysfunction in an experimental model of type 2 diabetes, the leptin-deficient ob/ob mice. Oxidative stress and protein expression of insulin-dependent and insulin -independent signaling pathways were studied. Obese ( ob/ob) vs. control (ob/+) mice were treated daily with intragastric administration of either vehicle or LECS (200 mg/kg, per day) for 4 weeks. Fasting blood glucose, body weight, food intake, glucose and insulin tolerance, oxidative stress, and liver damage as well as vascular complications with respect to endothelial dysfunction were examined. Administration of LECS in obese mice significantly reduced blood glucose and insulin levels, improved glucose tolerance and insulin sensitivity, and restored the increase of circulating AST and ALT without modification of body weight and food intake. These effects were associated with increased activity of both insulin and AMPK pathways in the liver and skeletal muscles. Of particular interest, administration of LECS in obese mice completely prevented the endothelial dysfunction resulting from an increased NO· and decreased reactive oxygen species (ROS) production in the aorta. Altogether, oral administration of LECS remarkably attenuates features of type 2 diabetes on glucose, hepatic inflammation, insulin resistance, endothelial function, and vascular oxidative stress, being as most of these effects are related to insulin-dependent and insulin-independent mechanisms. Therefore, this study points for the therapeutic potential of Cassia siamea in correcting both metabolic and vascular alterations linked to type 2 diabetes.

The acute diuretic effect of an ethanolic fraction of Phyllanthus amarus (Euphorbiaceae) in rats involves prostaglandins.

BACKGROUND: Phyllanthus amarus (Schum & Thonn), a plant belonging to the family of Euphorbiaceae is used in Ivorian traditional medicine to treat cardiovascular disorders such as hypertension. However, although this plant has been described as a diuretic agent, the underlying mechanism remains unclear. Therefore, the aim of the present study was to investigate the mechanism action of diuretic effects of an ethanolic fraction of Phyllanthus amarus (EFPA) in rats. METHODS: Effects of EFPA on urinary excretion were carried out for doses ranging from 5 to 80 mg/kg given by intraperitoneal injection (i.p.) and compared with that induced by furosemide (5 mg/kg) after 8 h. Thereafter, the diuretic activity of EFPA was also evaluated in the presence of indomethacin (5 mg/kg, i.p.) in order to determine the involvement of prostaglandins, after 24 h. RESULTS: Between 5 and 80 mg/kg, EFPA induced a significant urinary excretion. The profile of urinary excretion showed that after 2 h, the highest dose of 80 mg/kg induced a urinary volumetric excretion (UVE), which was similar to that induced by furosemide. After 24 h, EFPA at 10 mg/kg increased significantly UVE, Na+ (43 mEq) and Cl¯ (97 mEq) urinary excretions without promoting kaliuresis. In rats pretreated with indomethacin, the urinary excretion and the natriuretic response of EFPA were significantly reduced. CONCLUSION: Altogether, this study has shown that EFPA promotes a significant urinary excretion of water and Na+, confirming its diuretic activity. Moreover, the increased diuresis could be attributed, at least in part, to the involvement of prostaglandins.

[Hepatonephritis during the treatment of malaria by the therapeutic combinations from a pharmacovigilance database]. / Hépatonéphrites au cours du traitement du paludisme par les combinaisons thérapeutiques à partir d'une base de données de pharmacovigilance.

INTRODUCTION: Prior studies have shown an association between the onset of hepatonephritis and the use of arteminisin-based combination therapy (ACT) during the treatment of uncomplicated malaria. The objective of this study was to identify the risk factors of hepatonephritis occurrence because of the uncertainty regarding the appearance and the aggravation of this syndrome. METHODS: A case-non case study was carried out on 428 notifications of pharmacovigilance extracted from the database of the clinical pharmacology department of the teaching hospital of Cocody from 2008 to 2012. Twenty-two cases of hepatonephritis were identified. Univariate analysis and multivariate logistic regression were performed to identify the risk factors and an adjusted odds ratio (AOR) was calculated for each factor. The cut-off for significant association was set at 0.05. RESULTS: The average age of cases was comparable with that of non-cases (34.04±3.68 years versus 33.94±3.92 years) with a median duration of therapy of 5 days and 6 days respectively. Male (AOR: 6.71; P<0.0001), toxic antecedents, traditherapy (AOR: 6.25; P<0.0001), consumption of CTA (AOR: 1.25; P<0.0001), betalactam (AOR: 0.46; P<0.0001), fluoroquinolone and self-medication (AOR: 2.89; P<0.0001) would be the majors risk factors associated with hepatonephritis onset. The risk increased with the number of antimalarial drugs taken. The evolution towards the offset was less frequent (AOR: 0.078; P<0.02). CONCLUSION: The risk factors of hepatonephritis were the consumption of malarial drugs and connected molecules, self-medication and misuse. The outcome was generally unfavourable. Both the general population and health professionals should be trained on the good use of the antimalarial drugs.

Pharmacotherapeutic aspect of antibiotic therapy during acute community-acquired pneumonia in adults at the University Hospital of Cocody (Abidjan).

OBJECTIVE: Acute community-acquired pneumonia in Côte d'Ivoire, mainly in the pneumology units, is the second most common cause of hospitalization after tuberculosis. This study aimed to evaluate the compliance of antibiotic therapy during bacterial acute community-acquired pneumonia with international guidelines serving as frame of reference at the University Hospital of Cocody. MATERIALS AND METHODS: We carried out a descriptive retrospective and analytic study on 62 hospitalized patients from December 1, 2008 to November 30, 2010 in the Pneumophtisiology department at the University Hospital of Cocody (Abidjan). The prescription of antibiotics was compared with the recommendations of the 15th consensus conference on anti-infectious therapy by the Société de Pathologie Infectieuse de Langue Francaise (SPILF) (French Speaking Society of Infectious Pathology) held in 2006. RESULTS: The main antibiotics prescribed were amoxicillin-clavulanic acid (42.27%), netilmicin (34.5%) and ciprofloxacin (6%). The antibiotic therapy diagrams were dominated by an antibiotic bitherapy; the association of amoxicillin-clavulanic acid+netilmicin was observed in 80.64% of the prescriptions. An antibiotic monotherapy was reported in 14.52% of the prescriptions. Apyrexia at 72 hours was obtained with 64% of the patients with nonstop antibiotic treatment, 24% of them presented a lack of apyrexia, and 12% of them died. The lack of apyrexia at 72 hours treatment correlated with concomitant administration of cotrimoxazole with prophylactic doses among HIV positive patients. The level of the compliance with the SPILF recommendations is low (3.6%). CONCLUSION: Thus, our results convey the necessity to draw up national recommendations because of the specific realities of countries with limited incomes.

Eliciting preferences for reimbursed drugs selection criteria in Côte d'Ivoire.

BACKGROUND: Côte d'Ivoire, a West African country, has decided to set up a formulary as part of its universal health insurance (UHI) program. One of its goals will be to facilitate access to safe and efficacious drugs. To guarantee transparency throughout the formulary listing process, it is important to select and value relevant decision criteria for that purpose. OBJECTIVE: To investigate the preferences of healthcare professionals (physicians) when selecting reimbursable drugs and to analyze trade-offs between criteria for formulary listing in Côte d'Ivoire. METHODS: Choice sets based on four attributes (cost effectiveness of treatments, severity of the disease for which the treatments are indicated, age of the population affected by diseases considered, and social class affected by diseases considered [poor, rich]) were presented in a self-completion questionnaire. RESULTS: Analysis of questionnaire responses showed that 'cost effectiveness', 'severity of disease', and 'social class' were significant attributes in responder's preferences for reimbursable drugs. More specifically, respondents' choices were more sensitive to drugs that are very cost effective, that target very severe disease, and that target diseases in poor people. CONCLUSION: This explorative study enabled us to elicit the preferences of a sample of healthcare professionals (physicians) for reimbursed drug selection criteria in Côte d'Ivoire using the discrete-choice experiment method. Further work is required to achieve the ultimate objective of developing a formulary for Côte d'Ivoire.

Assessment of the relative advantage of various artesunate-based combination therapies by a multi-treatment Bayesian random-effects meta-analysis.

Over the years, multiple articles on Artemisinin-based Combination Therapies (ACTs) were published, highlighting the relative advantages or drawbacks of these combinations. Many studies were comparative. Because none of the studies compare all combinations and methodology varies between studies, there is no homogeneity. A multi-treatment Bayesian random-effects meta-analysis was designed to assess the relative effect of each combination therapy to artesunate + sulfadoxine-pyrimethamine (4 mg/kg/day for 3 days). By far the most attractive result for the variable adequate clinical and parasitological response at day 28 PCR corrected is given by the combination artemether-lumefantrine. Annual follow-up on the data published is intended to reveal the changes in the relative drug efficacy values of ACTs.