Effets pharmacologiques d’un extrait aqueux de Costus afer (Zingiberaceae) sur l’activité cardiaque et la pression artérielle couplée à la respiration de mammifères

Costus afer, couramment utilisée pour ses vertus médicinales, est une plante de la pharmacopée traditionnelle africaine. Elle intervient dans le traitement de nombreuses maladies telles que le paludisme, la diarrhée et l’hypertension. L’objectif de la présente étude a été d’évaluer les effets de l’extrait aqueux de cette plante sur le système cardiovasculaire et l’activité respiratoire chez les mammifères. L’étude des effets pharmacologiques de l’extrait aqueux total de Costus afer (Caf) sur l’activité cardiaque et la pression artérielle couplée à la respiration a révélé que Caf aux doses comprises entre 2,94.10-3 et 4,71.10-2 g/kg de poids corporel (PC) induit une diminution de l’amplitude des ondes P et QRS ainsi que la fréquence cardiaque du Lapin. Cet extrait aux doses comprises entre 2,94.10-3 et 3,82.10-2 g/kg de PC provoque une hypotension et une baisse de l’amplitude de l’activité respiratoire chez le lapin. En présence de l’atropine (10-6 mg/ml), l’effet inotrope négatif de Caf est aboli. La persistance de l’effet chronotrope négatif en présence de cet antagoniste des récepteurs cholinergiques de type muscarinique, suggère également la présence de substances cardioinhibitrices non cholinergiques. Pour des concentrations comprises entre 10-12 et 10-6 mg/ml, Caf induit sur le coeur isolé de rat des effets inotropes positifs qui seraient dus à la présence de substances cardiotoniques. Caf, aux concentrations supérieures à 10-6 mg/ml,  provoque des effets inotrope et chronotrope négatifs sur l’activité contractile du coeur isolé de rat. Les résultats obtenus lors de cette étude suggèrent donc que cet extrait brut contiendrait des principes actifs  cholinomimétiques et non cholinomimétiques et des principes actifsadrénomimétiques. Mots clés : Costus afer, Atropine, Propranolol, récepteur muscarinique

Evaluation de l’effet d’un extrait aqueux de Bridelia ferruginea Benth. (Euphorbiaceae) sur les activités spontanée et locomotrice chez le rat

L’objectif de ce travail est d’évaluer l’effet d’un extrait aqueux de l’écorce de tige de Bridelia ferruginea (SEA) sur le système nerveux central chez le rat. L’extrait aqueux de cette plante est administré aux animaux par la voie intrapéritonéale 30 minutes avant l’évaluation. L’actographe a permis de quantifier l’activité spontanée alors que l’activité locomotrice a été évaluée grâce à la roue d’activité et la traction. SEA, à la dose de 10 mg/kg de poids corporel réduit de manière significative l’activité spontanée de 63,26% (

From L-Dopa to Dihydroxyphenylacetaldehyde: A Toxic Biochemical Pathway Plays a Vital Physiological Function in Insects

One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD) family based on extremely high sequence homology (∼70%) with dopa decarboxylase (Ddc), was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA) directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects

A Deep Insight into the Sialotranscriptome of the Gulf Coast Tick, Amblyomma maculatum

Background: Saliva of blood sucking arthropods contains compounds that antagonize their hosts ’ hemostasis, which include platelet aggregation, vasoconstriction and blood clotting; saliva of these organisms also has anti-inflammatory and immunomodullatory properties. Perhaps because hosts mount an active immune response against these compounds, the diversity of these compounds is large even among related blood sucking species. Because of these properties, saliva helps blood feeding as well as help the establishment of pathogens that can be transmitted during blood feeding. Methodology/Principal Findings: We have obtained 1,626,969 reads by pyrosequencing a salivary gland cDNA library from adult females Amblyomma maculatum ticks at different times of feeding. Assembly of this data produced 72,441 sequences larger than 149 nucleotides from which 15,914 coding sequences were extracted. Of these, 5,353 had.75 % coverage to their best match in the non-redundant database from the National Center for Biotechnology information, allowing for the deposition of 4,850 sequences to GenBank. The annotated data sets are available as hyperlinked spreadsheets. Putative secreted proteins were classified in 133 families, most of which have no known function. Conclusions/Significance: This data set of proteins constitutes a mining platform for novel pharmacologically activ

RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response

Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying individuals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood samples collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies