Éditeur(s) : HAL CCSD American Chemical Society
Résumé : Three new monoterpene indole alkaloids (13) have been isolated from the bark of Geissospermum laeve-, together with the known alkaloids (-)-leuconolam (4), geissolosimine (5), and geissospermine (6). The structures of 1-3 were elucidated by analysis of their HRMS and NMR spectroscopic data. The absolute configuration of geissolaevine (I). was deduced from the comparison of experimental and theoretically calculated ECD spectra. The isolation workflow was guided by a molecular networking-based dereplication strategy using an in-house database of monoterpene indole alkaloids. In addition, five known compounds previously undescribed in the Geissospermum genus were dereplicated from the G. laeve alkaloid extract network and were assigned with various levels of identification confidence. The antiparasitic activities against Plasmodium falciparum and Leishmania donovani as well as the Ortotoxic activity against the MRC-5 cell line were determined for compounds 1-5.
ISSN: 0163-3864

hal-01605065
https://hal.archives-ouvertes.fr/hal-01605065
DOI : 10.1021/acs.jnatprod.6b01013
PRODINRA : 402605
PUBMED : 28282127

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
: Malaria is a public health problem in French Guiana. Plasmodium vivax is the most frequent parasite. The objective of this analysis was to estimate the proportion of relapses in the burden of vivax malaria using the statistical rule stating that any case of vivax malaria occurring less than 90 days following a first episode is a relapse.A total of 622 subjects were followed for 2,9 years with 336 first single episodes of P. vivax malaria, and a total of 1,226 episodes of vivax malaria among which 559 were relapses (45.5%). For 194 patients having had falciparum malaria followed by vivax malaria it was estimated that 19% of the vivax episodes occurred less than 90 days following the falciparum episode and thus were possibly relapses due to the activation of latent hypnozoites. Despite the number of vivax cases and the number of relapses, there were only 28 recorded primaquine prescriptions (3.4% of vivax episodes, 4.5% of subjects).The present study points out that despite the fact that nearly half of the P. vivax cases, many of which in children, are caused by latent hypnozoites, only a minority of them benefit from primaquine radical cure. The obstacles to this are discussed and suggestions are made to reduce the burden of vivax malaria in Camopi and other remote health centres in French Guiana.
ISSN: 1475-2875

inserm-00903890
http://www.hal.inserm.fr/inserm-00903890
http://www.hal.inserm.fr/inserm-00903890/document
http://www.hal.inserm.fr/inserm-00903890/file/1475-2875-12-367.pdf
DOI : 10.1186/1475-2875-12-367

Résumé : L’objectif du travail effectué était la recherche de nouvelles substances actives d’origine végétale, présentant soit une activité antiplasmodiale soit une activité antifongique. Cette étude a été menée suivant deux stratégies différentes: l’étude de remèdes traditionnels antipaludiques identifiés suite à des enquêtes ethnopharmacologiques, et la mise en évidence des propriétés antifongiques d’huiles essentielles grâce à une stratégie bioinspirée. La première partie du travail a permis de mettre en évidence le rôle d’un quassinoïde connu, la simalikalactone D, dans l’activité antipaludique d’une tisane de jeunes feuilles fraîches de Quassia amara L. (Simaroubaceae). Dans le cas de la décoction de rameaux de Psidium acutangulum DC. (Myrtaceae), c’est cette fois un mélange de flavonoïdes glycosylés qui est responsable de l’activité du remède. Dans le cadre de la recherche de nouvelles substances antifongiques, le criblage effectué a permis d’identifier de nombreuses huiles essentielles présentant des activités intéressantes, validant ainsi la démarche bioinspirée retenue dans ce cas. L’huile essentielle d’Otacanthus azureus (Linden) Ronse a en particulier démontré une activité remarquable, à la fois seule et en combinaison avec des antifongiques azolés. Enfin, l’étude métabolomique de la composition des huiles essentielles a permis de mettre au point un outil pouvant orienter la sélection des huiles en fonction des données obtenues en GC/MS dans l’optique de la recherche de nouvelles substances antifongiques. Ce travail démontre donc la validité des stratégies retenues – ethnopharmacologie et bioinspiration – dans la recherche de nouvelles substances bioactives.
The aim of this work was to search for new bioactive compounds, displaying either antiplasmodial or antifungal activity. Two strategies were developed here: the evaluation of traditional remedies identified as antimalarial through ethnopharmacological studies, and the search for antifungal essential oils, the criterium being here a bioinspired approach. Our work led to the discovery that the antimalarial activity of Quassia amara L. (Simaroubaceae) fresh young leaves was due to the presence of a known quassinoid, simalikalactone D. In the case of Psidium acutangulum DC. (Myrtaceae), a flavonol glycosides mixture explained the activity observed for the decoction. The search for antifungal essential oils from the Amazonian flora led to the identification of several interesting species, thus validating our bioinspired strategy. The essential oil of Otacanthus azureus (Linden) Ronse was among the most active ones, either alone or in combination with azole drugs. Eventually, a metabolomic study of the GC/MS composition of these oils allowed us to develop a statistical tool which could help to select interesting antifungal products. This work thus demonstrates the major interest of the two strategies – ethnopharmacology and bioinspiration – for the search of new bioactive compounds.

http://www.theses.fr/2011AGUY0415/document

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : PURPOSE OF REVIEW: Malaria represents one of the most important selective factors affecting human populations. Several inherited diseases of red blood cells lead to resistance at the erythrocytic stage. Among patients who experience hereditary elliptocytosis related to mutations of erythrocyte membrane proteins, molecular studies have shown the prevalence of particular spectrin mutations in patients from black ethnic extraction, leading one to question the selection of new malaria-resistant genes. RECENT FINDINGS: Prospective epidemiological and molecular studies in West Africa have confirmed the prevalence (between 0.6 and 1.6%) of particular spectrin mutations related to hereditary elliptocytosis. These studies have also revealed the frequency of alpha-spectrin chain polymorphisms, associated in cis with elliptocytogenic spectrin mutations and defining particular spectrin allele haplotypes. Culture studies of Plasmodium falciparum in elliptocytes bearing such elliptocytogenic alleles of spectrin showed that these alleles are supplementary genetic factors of malaria resistance in vitro. SUMMARY: Certain instances of spectrin mutations or polymorphisms have not yet been shown to constitute new factors of innate resistance to malaria in vivo. Epidemiological surveys of hereditary elliptocytosis and parasite culture studies, however, have argued that the relationships between parasite and spectrin-based skeleton should be examined more closely and the molecular interactions between parasite ligands and particular spectrin chain domains should be characterized.
ISSN: 1065-6251

inserm-00128119
http://www.hal.inserm.fr/inserm-00128119
http://www.hal.inserm.fr/inserm-00128119/document
http://www.hal.inserm.fr/inserm-00128119/file/Dhermy_et_al_figures.pdf
DOI : 10.1097/MOH.0b013e3280d21afd

Éditeur(s) : HAL CCSD
Résumé : International audience
Some of the immunologic mechanisms involved in malaria physiopathology remain unclear. In animals, the spleen seems to play a key role in protecting the host against malaria. However, little is known about the effect of spleen dysfunction on human malaria. We report two severe cases of Plasmodium falciparum infection with unusual clinical and parasitologic features in two splenectomized men living in French Guiana. The peripheral blood of these cases showed hyperparasitemia, with a high proportion of mature parasites and leukocytes with malaria pigment. Despite appropriate treatment and adequate absorption, hyperparasitemia persisted. Parasite clearance was delayed and one patient died. Only the patient who died had the merozoite surface protein 1 allele B-K1 and the varD gene genotype, which is considered to be a probable parasite virulence factor. These uncommon cases differ from most of those described in the literature, illustrating the complexity of the mechanisms underlying the protective function of the spleen in human malaria.
The American journal of tropical medicine and hygiene

pasteur-00590993
https://hal-riip.archives-ouvertes.fr/pasteur-00590993
PUBMED : 15381808

Éditeur(s) : HAL CCSD
Résumé : International audience
In this paper we present a microfluidic architecture dedicated to the study of Red Blood Cells (RBCs) deformability in microchannel smaller than the cell shape (biconcave disc of 7-8 μm in diameter) and cell capability to pass through slits separated by a gap value down to 2 μm, acting as a filter. This device is use in the context of RBCs disorders affecting their deformability, which is analysed versus number of cells trapped in the filter. This device can be seen as mimicking the human spleen. Microfabrication of the chip is based on polydimethylsiloxane (PDMS) associated to a two level thick photoresist mould (SU8). One level is used for microfluidic access with a 25 μm thickness towards the studied zone. The second level concerns the mimicking zones where RBCs flow through 5 μm down to 2 μm-wide slits acting like a mechanical filter. This level has a thickness of 5 μm. Devices have been tested on RBCs having specific disorder on their mechanical elasticity in order to validate the design principle. Two cases are presented in this paper: a.) Sickle RBCs inducing cell rigidity at two levels b.) Parasitized RBCs by Plasmodium falciparum. On both cases, we clearly show that deformability of RBCs influences the capability to pass through small slits (down to 2um) and thus is in relation with the pathology stage. This spleen-like microfluidic chip mimicking the RBCs filtering function is a promising tool for the exploration of RBC disorders combined with mechanical alterations.
4th European Conference on Microfluidics
Limerick, Ireland

hal-01113061
https://hal.archives-ouvertes.fr/hal-01113061

Éditeur(s) : HAL CCSD
Résumé : The aim of this work was to search for new bioactive compounds, displaying either antiplasmodial or antifungal activity. Two strategies were developed here: the evaluation of traditional remedies identified as antimalarial through ethnopharmacological study, and the search for antifungal essential oils, the criterium being here a bioinspired approach. Our work led to the discovery that the antimalarial activity of Quassia amara L. (Simaroubaceae) fresh young leaves was due to the presence of a known quassinoid, simalikalactone D. In the case of Psidium acutangulum DC. (Myrtaceae), a flavonol glycosides mixture explained the activity observed for the decoction. The search for antifungal essential oils from the Amazonian flora lead to the identification of several interesting species, thus validating our bioinspired strategy. The essential oil of Otacanthus azureus (Linden) Ronse was among the most active ones, either alone or in combination with azole drugs. Eventually, a metabolomic study of the GC/MS composition of these oils allowed us to develop a statistical tool which could help to select interesting antifungal products. This work thus demonstrate the major interest of the two strategies - ethnopharmacology and bioinspiration - for the search of new bioactive compounds.
L'objectif du travail effectué était la recherche de nouvelles substances actives d'origine végétale, présentant soit une activité antiplasmodiale soit une activité antifongique. Cette étude a été menée suivant deux stratégies différentes: l'étude de remèdes traditionnels antipaludiques identifiés suite à des enquêtes ethnopharmacologiques, et la mise en évidence des propriétés antifongiques d'huiles essentielles grâce à une stratégie bioinspirée. La première partie du travail a permis de mettre en évidence le rôle d'un quassinoïde connu, la simalikalactone D, dans l'activité antipaludique d'une tisane de jeunes feuilles fraîches de Quassia amara L. (Simaroubaceae). Dans le cas de la décoction de rameaux de Psidium acutangulum DC. (Myrtaceae), c'est cette fois un mélange de flavonoïdes glycosylés qui est responsable de l'activité du remède. Dans le cadre de la recherche de nouvelles substances antifongiques, le criblage effectué a permis d'identifier de nombreuses huiles essentielles présentant des activités intéressantes, validant ainsi la démarche bioinspirée retenue dans ce cas. L'huile essentielle d'Otacanthus azureus (Linden) Ronse a en particulier démontré une activité remarquable, à la fois seule et en combinaison avec des antifongiques azolés. Enfin, l'étude métabolomique de la composition des huiles essentielles a permis de mettre au point un outil pouvant orienter la sélection des huiles en fonction des données obtenues en GC/MS dans l'optique de la recherche de nouvelles substances antifongiques. Ce travail démontre donc la validité des stratégies retenues - ethnopharmacologie et bioinspiration - dans la recherche de nouvelles substances bioactives.
https://tel.archives-ouvertes.fr/tel-00718910

tel-00718910
https://tel.archives-ouvertes.fr/tel-00718910
https://tel.archives-ouvertes.fr/tel-00718910/document
https://tel.archives-ouvertes.fr/tel-00718910/file/TheseEH2011_SUBST_BIOACTIVES.pdf

Éditeur(s) : HAL CCSD
Résumé : Anopheles darlingi, one of the main malaria vectors in the Neotropics, is widely distributed in French Guiana, where malaria remains a major public-health problem. Elucidation of the relationships between the population dynamics of An. darlingi and local environmental factors would appear to be an essential factor in the epidemiology of human malaria in French Guiana and the design of effective vector-control strategies. In a recent investigation, longitudinal entomological surveys were carried out for 2-4 years in one village in each of three distinct endemic areas of French Guiana. Anopheles darlingi was always the anopheline mosquito that was most frequently caught on human bait, although its relative abundance (as a proportion of all the anophelines collected) and human biting rate (in bites/person-year) differed with the study site. Seasonality in the abundance of human-landing An. darlingi (with peaks at the end of the rainy season) was observed in only two of the three study sites. Just three An. darlingi were found positive for Plasmodium (either P. falciparum or P. vivax) circumsporozoite protein, giving entomological inoculation rates of 0*0-8*7 infectious bites/person-year. Curiously, no infected An. darlingi were collected in the village with the highest incidence of human malaria. Relationships between malaria incidence, An. darlingi densities, rainfall and water levels in the nearest rivers were found to be variable and apparently dependent on land-cover specificities that reflected the diversity and availability of habitats suitable for the development and reproduction of An. darlingi.
Annals of Tropical Medicine and Parasitology / Annals of Tropical Medicine & Parasitology

pasteur-00583507
https://hal-riip.archives-ouvertes.fr/pasteur-00583507
DOI : 10.1179/136485911X12899838683322
PUBMED : 21396247