Activités anticholinestérasiques des alcaloïdes totaux extraits des feuilles, fruits, écorces de racines et écorces de tronc de Guiera senegalensis, une plante médicinale Malienne

Guiera senegalensis J. F. Gmel., arbuste d’espèce soudano-sahélienne; surtout abondant en Afrique occidentale. Très connu dans le sahel où il forme des peuplements mono spécifiques qu’on trouve dans les jachères, sur sol argileux ou sableux. Il est largement utilisé en médicine traditionnelle. Dans la perspective de découvrir de nouveaux composés pouvant trouver une application notamment dans le traitement de la maladie d’Alzheimer, nous avons réalisé les tests d’activité anticholinestérase sur les alcaloïdes totaux extraits des organes des 3 sites de récolte et avec comme produit de référence la Galanthamine. L’action thérapeutique des inhibiteurs des cholinestérases est essentiellement due à l’inhibition de l’acétylcholinestérase. Les résultats obtenus semble très intéressent avec les fruits des trois sites. Ce qui pourrait être une base solide pour la recherche d’un phytomédicament contre cette affection.Mots clés : Guiera senegalensis, alcaloïdes, inhibition acétylcholinestérase

Zona planto-pédieux révélateur de l’infection à VIH

Le zona est une dermatose virale qui peut intéresser n’importe quelle partie du corps. La plus part des personnes atteintes d’un zona ont entre 50 à 70 ans. Toutefois son apparition chez le sujet jeune doit fait rechercher une immunodépression à VIH. Nous rapportons un cas atypique de zona révélant l’infection à VIH chez une patiente de 25 ans présentant une éruption vésiculeuse, douloureuse reposant sur un fond érythémateux localisé sur la plante du pied gauche. Le diagnostic du zona a été évoqué grâce aux éléments cliniques et réconforté par le cytodiagnostic et l’histologie. Cette localisation atypique nous a incités à demander une sérologie à VIH qui est revenue positive

Etude préliminaire portant sur le dépistage de la protéinurie à l’aide de bandelette urinaire chez les patients vivants avec le VIH au CHNU de Fann à Dakar.

Les glomérulopathies et autres affections rénales sont fréquentes au cours de l’histoire naturelle du VIH même si leur incidence a diminué avec la trithérapie. Elles sont pratiquement toujours responsables d’une protéinurie et/ou d’une hématurie. Nous avons fait une étude préliminaire portant sur la prévalence de la protéinurie dépistée à l’aide de bandelettes urinaires chez les PVVIH suivies à la clinique des maladies infectieuses du CHNU de Fann à Dakar. Il s’agissait d’une étude prospective allant du 1er Août au 30 Octobre 2008. Ont été inclus de façon exhaustive les patients séropositifs pour le VIH à la fois vus en ambulatoire et en hospitalisation présentant une protéinurie sans infection urinaire intercurrente. Nous avons recueilli leurs données sociodémographiques, les éléments de l’histoire naturelle, les facteurs en rapport avec la protéinurie et la néphropathie. La saisie et l’analyse des données ont été faites avec le logiciel Epi Info version 6.04. Nous avons utilisé le test de Chi2 pour comparer les variables qualitatives et p<0,05 a été retenu comme significative. Au total 100 patients ont été inclus, la moyenne d’âge était de 43± 9,8 ans chez les hommes et de 39± 10 ans pour les femmes. Les femmes étaient prédominantes (sex ratio H/F = 0,5). Tous les patients étaient infectés par le VIH1, ils avaient été dépistés à un stade tardif d’immunodépression, la moitié était sous ARV avec le plus souvent le protocole AZT +3TC+ EFV. La prévalence de la protéinurie était de 47,9%. Les facteurs significativement associés à la présence d’une protéinurie étaient : le sexe ; le taux de CD4<350/mm3 ; la charge virale > 100000copies/mm3 ; l’IMC <18,5 ; le taux d’hémoglobine<8,5 g/dl, la chimioprophylaxie au cotrimoxazole et les stades cliniques OMS 3 et 4. La fréquence de la néphropathie au cours du VIH au service des maladies infectieuses de Fann à Dakar suggère d’inclure son dépistage à la bandelette dans le bilan initial et de suivi de tout patient infecté par le VIH. Dans tous les cas il faudrait corriger tout facteur favorisant la survenue de cette néphropathie. La ponction biopsie rénale pourrait permettre des études plus approfondies

Facility and community results-based financing to improve maternal and child nutrition and health in The Gambia

In 2013, the Government of The Gambia implemented a novel results-based financing (RBF) intervention designed to improve maternal and child nutrition and health through a combination of community, facility and individual incentives. In a mixed-methods study, we used a randomized 2 x 2 study design to measure these interventions' impact on the uptake of priority maternal health services, hygiene and sanitation. Conditional cash transfers to individuals were bundled with facility results-based payments. Community groups received incentive payments conditional on completion of locally-designed health projects. Randomization occurred separately at health facility and community levels. Our model pools baseline, midline and endline exposure data to identify evidence of the interventions' impact in isolation or combination. Multivariable linear regression models were estimated. A qualitative study was embedded, with data thematically analyzed. We analyzed 5,927 household surveys: 1,939 baseline, 1,951 midline, and 2,037 endline. On average, community group interventions increased skilled deliveries by 11 percentage points, while the facility interventions package increased them by seven percentage points. No impact was found, either in the community group or facility intervention package arms on early ANC. The community group intervention led to 49, 43 and 48 percentage point increases in handwashing stations, soaps at station and water at station, respectively. No impact was found on improved sanitation facilities. The qualitative data help understand factors underlying these changes. No interaction was found between the community and facility interventions. Where demand-side barriers predominate and community governance structures exist, community group RBF interventions may be more effective than facility designs

DNA immunization as a technology platform for monoclonal antibody induction

To combat the threat of many emerging infectious diseases, DNA immunization offers a unique and powerful approach to the production of high-quality monoclonal antibodies (mAbs) against various pathogens. Compared with traditional protein-based immunization approaches, DNA immunization is efficient for testing novel immunogen designs, does not require the production or purification of proteins from a pathogen or the use of recombinant protein technology and is effective at generating mAbs against conformation-sensitive targets. Although significant progress in the use of DNA immunization to generate mAbs has been made over the last two decades, the literature does not contain an updated summary of this experience. The current review provides a comprehensive analysis of the literature, including our own work, describing the use of DNA immunization to produce highly functional mAbs, in particular, those against emerging infectious diseases. Critical factors such as immunogen design, delivery approach, immunization schedule, use of immune modulators and the role of final boost immunization are discussed in detail

Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second most frequent cause of cancer-related mortality worldwide. The multikinase inhibitor sorafenib is the only treatment option for advanced HCC. Due to tumor heterogeneity, its efficacy greatly varies between patients and is limited due to adverse effects and drug resistance. Current in vitro models fail to recapitulate key features of HCCs. We report the generation of long-term organoid cultures from tumor needle biopsies of HCC patients with various etiologies and tumor stages. HCC organoids retain the morphology as well as the expression pattern of HCC tumor markers and preserve the genetic heterogeneity of the originating tumors. In a proof-of-principle study, we show that liver cancer organoids can be used to test sensitivity to sorafenib. In conclusion, organoid models can be derived from needle biopsies of liver cancers and provide a tool for developing tailored therapies

Differential Plasmodium falciparum infection of Anopheles gambiae s.s. molecular and chromosomal forms in Mali

BACKGROUND: Anopheles gambiae sensu stricto (s.s.) is a primary vector of Plasmodium falciparum in sub-Saharan Africa. Although some physiological differences among molecular and chromosomal forms of this species have been demonstrated, the relative susceptibility to malaria parasite infection among them has not been unequivocally shown. The objective of this study was to investigate P. falciparum circumsporozoite protein infection (CSP) positivity among An. gambiae s.s. chromosomal and molecular forms. METHODS: Wild An. gambiae from two sites Kela (n = 464) and Sidarebougou (n = 266) in Mali were screened for the presence of P. falciparum CSP using an enzyme-linked immunosorbent assay (ELISA). Samples were then identified to molecular form using multiple PCR diagnostics (n = 713) and chromosomal form using chromosomal karyotyping (n = 419). RESULTS: Of 730 An. gambiae sensu lato (s.l.) mosquitoes, 89 (12.2%) were CSP ELISA positive. The percentage of positive mosquitoes varied by site: 52 (11.2%) in Kela and 37 (13.9%) in Sidarebougou. Eighty-seven of the positive mosquitoes were identified to molecular form and they consisted of nine Anopheles arabiensis (21.4%), 46 S (10.9%), 31 M (12.8%), and one MS hybrid (14.3%). Sixty of the positive mosquitoes were identified to chromosomal form and they consisted of five An. arabiensis (20.0%), 21 Savanna (15.1%), 21 Mopti (30.4%), 11 Bamako (9.2%), and two hybrids (20.0%). DISCUSSION: In this collection, the prevalence of P. falciparum infection in the M form was equivalent to infection in the S form (no molecular form differential infection). There was a significant differential infection by chromosomal form such that, P. falciparum infection was more prevalent in the Mopti chromosomal forms than in the Bamako or Savanna forms; the Mopti form was also the most underrepresented in the collection. Continued research on the differential P. falciparum infection of An. gambiae s.s. chromosomal and molecular forms may suggest that Plasmodium – An. gambiae interactions play a role in malaria transmission

Ecological and genetic relationships of the Forest-M form among chromosomal and molecular forms of the malaria vector Anopheles gambiae sensu stricto

<p>Abstract</p> <p>Background</p> <p><it>Anopheles gambiae sensu stricto</it>, one of the principal vectors of malaria, has been divided into two subspecific groups, known as the M and S molecular forms. Recent studies suggest that the M form found in Cameroon is genetically distinct from the M form found in Mali and elsewhere in West Africa, suggesting further subdivision within that form.</p> <p>Methods</p> <p>Chromosomal, microsatellite and geographic/ecological evidence are synthesized to identify sources of genetic polymorphism among chromosomal and molecular forms of the malaria vector <it>Anopheles gambiae s.s</it>.</p> <p>Results</p> <p>Cytogenetically the Forest M form is characterized as carrying the standard chromosome arrangement for six major chromosomal inversions, namely 2La, 2Rj, 2Rb, 2Rc, 2Rd, and 2Ru. Bayesian clustering analysis based on molecular form and chromosome inversion polymorphisms as well as microsatellites describe the Forest M form as a distinct population relative to the West African M form (Mopti-M form) and the S form. The Forest-M form was the most highly diverged of the <it>An. gambiae s.s</it>. groups based on microsatellite markers. The prevalence of the Forest M form was highly correlated with precipitation, suggesting that this form prefers much wetter environments than the Mopti-M form.</p> <p>Conclusion</p> <p>Chromosome inversions, microsatellite allele frequencies and habitat preference all indicate that the Forest M form of <it>An. gambiae </it>is genetically distinct from the other recognized forms within the taxon <it>Anopheles gambiae sensu stricto</it>. Since this study covers limited regions of Cameroon, the possibility of gene flow between the Forest-M form and Mopti-M form cannot be rejected. However, association studies of important phenotypes, such as insecticide resistance and refractoriness against malaria parasites, should take into consideration this complex population structure.</p