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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., (Copyright © 2023 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2022 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Semi-structured focus group discussions were employed to capture rural Senegalese attitudes and perceptions of their behavior to changes in the climate and their land use and livelihood strategies. Seven focus groups stratified by gender, ethnicity (Wolof and Peulh) and dominant production system (cultivators and pastoralists) in five villages in semi-arid northern Senegal revealed seven main themes. Rural livelihoods remain predominantly based on rainfall dependant practices, and although cultivators and pastoralists had a clear appreciation of changes in natural resources compared to a perceived more favorable past, few adaptive coping strategies beyond established ones were advocated. The seven themes are discussed in detail and their implications for rural livelihoods under future long term climate predictions discussed with the implications of this study for the development of scenarios of future land cover land use.

Context: The long term treatment of VIH/SIDA puts down majors risks among which the happening of virological failure or resistance to the anti-retroviral treatment at the patient., Objective: To study the cases of resistance to antiretroviral to a cohort of 70 patients of the social hygiene of Dakar., Method: This is a retrospective study of the medical records of 70 patients followed in the social hygiene of Dakar during 24 mouths. Data were gathered with the help of form having following variables: The period of meadow inclusion; The period of inclusion; The period of rebound virological; The rate of CD4 count; The viral load and weight of patients., Results: Average of age in inclusion is of 47.5 years with a sex ratio of the women HIV 1 was dominant. Two cases of virological failure were found or (2.8%). The patient 1 was the stade II of the classification of the with as therapeutic class 2INTI + 2 INNTI. It was in stage asymptomatic with as therapeutic protocol DDI + 3TC + NVP. The patient 2 was at the stade III of the whom that is to say at the stade in AIDS with as therapeutic class: 2INTI + 1IP with the protocol of treatment DDI + 3TC +IND., Conclusion: The virological failure to the newly infected persons noticed more and more in the world poses a problem of public health because it constitutes a threat for the success of the programs of treatment of the HIV/AIDS.

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.

Introduction: This study aimed to investigate the mechanism of action of acetonic and hexanic extracts of the leaves of Vernonia colorata on blood glucose regulation., Materials and Methods: Experiments were performed in normoglycaemic, type 1 and 2 diabetic rats. The effects of acetonic and hexanic extracts on blood glucose were evaluated. The antagonism effect of hexanic extract on the decrease of blood glucose induced with glibenclamide and metformin was also tested., Results: The hexanic extract of the leaves of V. colorata (HELVC) dose dependently increased the blood glucose in normoglycaemic rats. At the dose of 30 and 100 mg/kg, the glycaemia varied from 0.84 +/- 0.02 to 1.11 +/- 0.10 g/l and 0.68 +/- 0.02 to 1.31 +/- 0.30 g/l (p<0.05, n = 5). Such glibenclamide, the acetonic extract of the leaves of V. colorata (AELVC) induced hypoglycaemia in normoglycaemic rats. The HELVC prevents significantly the AELVC and glibenclamide induced hypoglycaemia. The chronic administration of the AELVC and HELVC as well as glibenclamide in type 1 diabetic rats did not change significantly the level of blood glucose. In type 2 diabetic rats, the single dose administration of metformin (300 mg/kg, per os) decreased the glycaemia which is completely prevented by a HELVC pretreatment., Conclusion: These results suggest that: i) The respective hypo- and hyperglycaemic effects of AELVC and HELVC require the presence of the pancreatic beta cells. ii) The AELVC would act by a sulfonylurea-like mechanism as glibenclamide to induce an hypoglycaemic effect.

Spathodea campanulata Beauv. (Bignoniaceae) is widely distributed through Africa and found in particular in Cameroon and Senegal. It is used in traditional herbal medicine for the treatment of ulcers, filaria, gonorrhea, diarrhea and fever. S. campanulata was also known in Cameroon traditional medicine to have a healing activity in burn wounds. The aim of the present study was to assess the burn healing effectiveness of the methanolic extract of the barks of S. campanulata ointment (MEBSCO) in comparison to those of Centella asiatica and Peru's balm in experimental burn model in rats. Experimental burn was made in rat under chloral anaesthesia with electric iron (200 degrees C) on the right and left side of the medianus line. Topical applications of MEBSCO (2%, 10% and 49%) dose-dependently decreased the score damage of the burn site. Treatment with 10% and 49% of MEBSCO varied the score damage from 5 to 1 +/- 0.4 and 5 to 0.2 +/- 0.5 (p < 0.05, n = 5) respectively, at day 15 after experimental burn. As well as C. asiatica (1%) and Peru's balm (1%) ointments, MEBSCO (10% and 49%) induced a complete burn healing on the 19-20th post burn day. This study shows for the first time, the burn healing effectiveness of MEBSCO in experimental burn model. It also provides a rational use of the S. campanulata barks in traditional medicine to promote burn healing.

Lyophilised aqueous extract and alcaloidic totum (basic form) from roots of Tinospora bakis (Miers) have been tested with hyperthermic rabbits by sub-cutaneous administration of Saccharomyces cerevisiae mixture at 2g/kg. Total aqueous extract had been orally administrated at three doses: 150, 300 and 600 mg/kg and we obtained significant antipyretic effects at 300 and 600 mg/kg. With the alcaloidic totum at 2.5 mg/kg and 10 mg/kg (per os) corresponding to 150 and 600 mg/kg of the aqueous extract, we have observed significant antipyretic effects as compared with those of Aspirin used as reference product. These results show that aqueous extract of Tinospora bakis (Miers) has an antipyretic effect and total alcaloids could account for this activity.

The World Health Organization has proposed the syndromic approach for management of sexually transmissible diseases (STD) in countries where diagnostic laboratory tests are not consistently available. The purpose of this study was to evaluate the effectiveness of this approach for treatment of ureteral discharge in Senegal. Twenty seven men presenting ureteral discharge underwent two-week treatment using a combination of cotrimoxazole plus tetracycline for suspected gonococcal and a chlamydial infections. Ureteral samples were collected before and after treatment to detect Neisseria gonorrhoeae by culture and Chlamydia trachomatis by direct immunofluorescence and ELISA. Results demonstrated successful treatment of all patients presenting gonococcal and chlamydial infections i.e. 84.6% of cases. Neither germ was detected in 15.4% of cases. Before treatment, Neisseria gonorrhoeae, Chlamydia trachomatis or both were found respectively in 53.9%, 5.1% and 25.6% of samples respectively. Based on these findings we conclude that the syndromic approach was effective in 84.6% of cases but treatment was in adequation with STD biologically documented only with 25.6% of cases.

Moringa oleifera is a bush of African savannah, used in folk Medicine for the treatment of rheumatic and articulary pain. We have tested the anti-inflammatory action of an aqueous extract of root in rats with weight between 120 and 160 g. We administered per os either distilled water (control group), the aqueous root extract (750 mg/kg or 1000 mg/kg) or indomethacin (10 mg/kg) 30 min before an oedema was induced in the rat-paw by subcutaneous injection of carrageenin. The rat-paw volume was measured 1, 3 and 5 hours after injection of carrageenin. At a dose of 750 mg/kg the Moringa oleifera treatment significantly inhibited the development of oedema at 1, 3 and 5 hours (reduction by 53.5, 44.6 and 51.1% respectively). Increasing the dose of Moringa oleifera to 1000 mg/kg did not increase the inhibitory effect on oedema development at 1 and 3 hours, whereas this dose potentiated the oedema at 5 hours. Treatment with indomethacin significantly inhibited the development of oedema 1, 3 and 5 hours (49.1, 82.1 and 46.9% respectively). These findings indicate that an aqueous root extract of Moringa oleifera at 750 mg/kg reduces the carrageenin induced oedema to similar extent as the potent anti-inflammatory drug indomethacin. Moreover, these results provide further evidence that the roots of Moringa oleifera contain anti-inflammatory principle that may be useful in the treatment of the acute inflammatory conditions.

Basal tension for optimal contraction either for a maximal contraction in pregnant Wistar rat is not well know. Our study aims to determinate the optimal basal tension for the study of aortic contraction in pregnant Wistar rat. The stability of vessels tone depending on basal tension was also determinate. Aortic rings with endothelial cells from non-pregnant and 20-day pregnant Wistar rats were used. Rings with different basal tensions of 1 g, 1.5 g, 2 g or 2.5 g were contracted with KCl at 100 mmol/l or norepinephrine in a cumulative manner (10-9M à 3.10-5M). Our results show, at least, one hour of stability for all basal tensions. On the other hand, contractions raise in a significant manner depending in basal tension either with KCl or norepinephrine. However, There is no significant difference in contractions with the basal tensions of 2 g and 2.5 g except in pregnant rats where vessels were contracted with norepinephrine. These results suggest that basal tension of 2 g would be used for the study of aortic reactivity in pregnant Wistar rat because it allows a good stability, the tension is practically optimal in pregnant and non-pregnant rats with any contracting agent and this tension is most commonly used.

Some authors usually described an enhanced vascular reactivity to vasodilatoragents during pregancy. We would like toverifythis hypothesis with acetylcholin which is the vasodilator agent habitually used in animal experimentation. Young adult Wistar rats, pregnant and nonpregnant, were used. Rats received either a control diet, or this control diet supplemented with nitroargininin (0.063 % i.e. 30 mg/kg for7 days [treated group], from day 13th to day 20th for pregnants. Relaxation of rings thoracic aorta, with or without endothelium, in the presence of acetylcholin in cumulative was studied after contraction induced by depolarisation with KCl or after noradrenalin addition. The results show that relaxation in the presence of acetylcholin needs functional endothelial cells and that the nitric oxide plays a key role in this relaxation. So, there is no difference in vascular reactivity in late pregnant rats compared to nonpregnant rats. In addition, chronic inhibition of nitric oxide synthesis in pregnant rats do not modify pregnancy reactivity to nitric oxide because relaxation to S-nitroso-N acetyl penicillamin, which is a nitric oxide donor, is not different in control pregnant rats compared to treated pregnant rats. A judicious observation of work conditions with a particular attention with calcium concentration in organ bath solutions would certainly explain contradictory results obtained by different authors on vascular reactivity in vitro during gestation.

In pregnant rats during hypertension induced by NO synthase inhibition, endothelin (ET) plasma levels are increased as in some preeclamptic women. Previously, the enhanced vasodepressor effect of endothelin-1 (ET-1) has been observed in this model, thus we decided to study the relaxation induced by ET-1 on the aorta. Non-pregnant or pregnant Wistar rats (n = 7 by group) were fed for 7 days (day 13-day 20) on a nitroarginine-enriched diet (L-NNA, 0.063% i.e. 30 mg/kg/day) or a control diet. Systolic blood pressure, measured by the tail cuff method on conscious rats at day 20 of gestation, was raised by the chronic L-NNA treatment (mean +/- s.e.m., mmHg, p < 0.001: pregnant L-NNA treated, 145 +/- 1.84 vs. pregnant control, 101 +/- 2.00 and non-pregnant L-NNA treated, 148 +/- 3.11 vs. non-pregnant control, 119 +/- 1.80). On day 20 ex vivo aortic ring relaxation was produced by ET-1 in vessels previously precontracted with norepinephrine only when endothelium was present. In control rats, ET-1 (10(-8) to 5 x 10(-8) M) produced a short but significant relaxation (mean value between 4 to 19%) followed by a long-lasting contracting phase, and a higher ET-1 concentration (10(-7) M) only produced contraction. Chronic L-NNA treatment decreased the level of relaxation (at least p < 0.05, in non-pregnant and pregnant rats) and with a 30 min L-NAME (10(-4) M) preincubation, relaxation was completely inhibited in non-pregnant and pregnant rats. BQ-123, an ETA receptor antagonist, did not produce any effect on ET-1 induced relaxation. BQ-788, an ETB receptor antagonist, significantly decreased it. In conclusion, in female rats, as in male rats, ET-1 induces a transient relaxation in the preconstricted aorta which involves endothelial ETB receptors. Despite a decrease in the systemic vascular reactivity during late gestation, the vasodilating and vasoconstricting properties of ET-1 on the aorta are not changed.

Hypertensive pregnant rats with inhibition of NO synthase are frequently considered as model of pre-eclampsia with proteinuria, hypertension and elevated endothelin (ET-1) blood levels. We describe here the cardiovascular in vivo effects of ET-1 in this rat model since ET-1 and NO are both important vasoactive mediators in uteroplacental circulation. From day 13 of gestation 2 groups of Wistar female rats were fed control (C) or nitroarginine enriched diet (0.063%, Treated: T). On gestational day 20 mean arterial pressure (MAP, mmHg) was measured via a carotid catheter in pentobarbital (60 mg/kg) anesthetized rats. After chronic NO synthase inhibition hypertension develops; MAP on day 20: 158 +/- 2.2 in T and 113 +/- 2.2 in C, p < 0.001. ET-1 bolus injection (0.1 nmol/kg) is rapidly followed by a decrease in blood pressure significantly more important in T: -46 +/- 5.1 than in C: -30 +/- 2.2. In vivo depressor effect is blocked by the specific antagonist BQ-788. After inhibition of cycloxygenase with acetylsalicylic acid (27 mumol/kg, 30 min before) the hypotension is not modified. Since NO and PGI2 productions are not expected in our conditions, vasodepressor effect can be explained by an endothelial hyperpolarazing factor (EDHF). In conclusion in vivo ET-1 hypotensive effects in pregnant rats are mediated by ETB receptors and more pronounced in hypertensive NO-deprived animals.

During gestation endothelium induces decreases in vascular responses to vasopressor agents but endothelium disease is followed by hypertension and enhanced vascular reactivity during preeclampsia. In a rat model of preeclampsia induced by NO synthase inhibition we study here isolated aortic contractions. From day 13 of gestation 2 groups of Wistar female rats were fed control (C) or nitro-arginine enriched diets (0.063%, i.e. 30 mg/kg/d) (treated) (T). On gestational day 20 systolic blood pressure (SBP, mmHg) is measured by tail cuff method and isolated thoracic ring aorta contractions are studied after depolarisation (KCl 60 mM) or norepinephrine (cumulative concentrations 10-9 M-10-5 M). After chronic NOS inhibition, hypertension develops: SBP is 154 +/- 2.17 in T and 116 +/- 3.75 in C, p < 0.01 and significant proteinuria (mg/d) appears: T, 63.4 +/- 21.6 versus C 3.08 +/- 0.48, p < 0.01. NO synthase inhibition in treated rats impairs the depressed contractile response obtained in the presence of endothelium in control rats but addition of L-arginine suppresses the effect of nitroarginine. Taking in account our results and those described in literature it appears that L-arginine treatment could ameliorate some pathologic pregnancies.

We confirmed the innocuity of different extracts (leaves and stem bark) of Calotropis procera (Asclepiadaceae), a plant widely used in Asian and West African traditional therapy in dermatological and bronchal affections. We proved the against cough activity of the aqueous stem bark extract after administration, per os, upon bronchal irritation by ammoniac on Guinea Pig.