Combining indoor residual spraying with chlorfenapyr and long-lasting insecticidal bed nets for improved control of pyrethroid-resistant Anopheles gambiae: an experimental hut trial in Benin.

BACKGROUND: Neither indoor residual spraying (IRS) nor long-lasting insecticidal nets (LLINs) are able to fully interrupt transmission in holoendemic Africa as single interventions. The combining of IRS and LLINs presents an opportunity for improved control and management of pyrethroid resistance through the simultaneous presentation of unrelated insecticides. METHOD: Chlorfenapyr IRS and a pyrethroid-impregnated polyester LLIN (WHO approved) were tested separately and together in experimental huts in southern Benin against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus. The bed nets were deliberately holed with either six or 80 holes to examine the effect of increasing wear and tear on protectiveness. Anopheles gambiae were genotyped for the kdr gene to assess the combination's potential to prevent the selection of pyrethroid resistance. RESULTS: The frequency of kdr was 84%. The overall mortality rates of An. gambiae were 37% and 49% with the six-hole and 80-hole LLINs, respectively, and reached 57% with chlorfenapyr IRS. Overall mortality rates were significantly higher with the combination treatments (82-83%) than with the LLIN or IRS individual treatments. Blood feeding (mosquito biting) rates were lowest with the 6-hole LLIN (12%), intermediate with the 80-hole LLIN (32%) and highest with untreated nets (56% with the 6-hole and 54% with the 80-hole nets). Blood feeding (biting) rates and repellency of mosquitoes with the combination of LLIN and chlorfenapyr IRS showed significant improvement compared to the IRS treatment but did not differ from the LLIN treatments indicating that the LLINs were the primary agents of personal protection. The combination killed significantly higher proportions of Cx. quinquefasciatus (51%, 41%) than the LLIN (15%, 13%) or IRS (32%) treatments. CONCLUSION: The chlorfenapyr IRS component was largely responsible for controlling pyrethroid-resistant mosquitoes and the LLIN component was largely responsible for blood feeding inhibition and personal protection. Together, the combination shows potential to provide additional levels of transmission control and personal protection against pyrethroid-resistant mosquitoes, thereby justifying the additional resources required. Chlorfenapyr has potential to manage pyrethroid resistance in the context of an expanding LLIN/IRS strategy

Isolement par partition bio guidé du principe actif myostimulant de l’extrait aqueux de Mareya micrantha (Benth) Mull. Arg. (Euphorbiaceae)

Objectif: Isoler le principe actif myostimulant de l’extrait aqueux de Mareya micrantha (MAR) lors de sa partition dans différents solvants (70 % éthanol / eau ; 50 % cyclohexane / eau et 50 % acétate d’éthyle / eau), en utilisant le duodénum isolé de lapin comme marqueur de l’activité pharmacologique, afin d’identifier la fraction possédant la meilleure activité myostimulante.Méthodologie et résultats: le dispositif d’enregistrement de l’activité mécanique du duodénum isolé de lapin, a permis d’évaluer les propriétés pharmacologiques de MAR, des fractions ((hydro-alcoolique) F1, (cyclohexanique) F2, (aqueuse) F3, (acétate d’éthyle) F4 et (aqueuse) F5) et précipité (P) obtenus par partition de MAR dans différents solvants (70 % éthanol / eau ; 50 % cyclohexane / eau et 50 % acétate d’éthyle / eau). Les effets myostimulants de MAR diminuent fortement en milieu physiologique sans calcium et contenant de l’EDTA. Les fractions, hydro-alcoolique (F1), aqueuses (F3 ; F5), et le précipité (P) obtenus par partition de MAR, stimulent l’activité contractile du duodénum de lapin. La fraction acétate d’éthyle (F4) est myorelaxante, La F2 (cyclo-hexanique) est sans effet. L’étude dose réponse de F5 à des concentrations allant de 20 à 240 Ig. mL-1, montre qu’elle est 120 % plus spasmogène que MAR. Ces effets inotropes positifs de F5 sont inhibés par l’atropine.Conclusion et application: Les principes actifs myostimulants de MAR augmenteraient l’amplitude des contractions du duodénum isolé de lapin en mobilisant principalement le calcium extracellulaire puis intracellulaire comme en témoigne le résultat de l’expérience avec l’EDTA. La forte activité spasmogène de la F5 et l’expérience avec l’atropine, suggèrent que la partition de MAR a enrichi la F5 en principe actifs myostimulants de nature cholinergique. Ces données indiquent que la partition peut contribuer à isoler de manière significative les principes actifs des plantes médicinales, y compris ceux de MAR aux propriétés myostimulantes, justifiant son utilisation comme laxatif.Mots clés: Mareya micrantha, fractions, myostimulant, AtropineEnglish AbstractObjective: To isolate the myostimulant active principle in Mareya micrantha (MAR) aqueous extract during its partition in different solvents (70% aqueous-ethanol, 50% aqueous-cyclohexane and 50% aqueous ethylacetate), while using the isolated rabbit duodenum as a pharmacological activity marker in order to identify the fraction having the best myostimulant activity.Methodology and results: The mechanical activity recording device of the isolated rabbit duodenum, allowed the assessment of the pharmacological properties of MAR, ((Hydro-alcoholic) F1, (cyclohexane) F2, (aqueous) F3, (ethylacetate) F4, (aqueous) F5) fractions and the precipitate (P) obtained by MAR partition in different solvents (70% aqueous-ethanol, 50% aqueous-cyclohexane and 50% aqueous-ethylacetate). The myostimulant effects of MAR decrease strongly in physiological environment without calcium and in presence of the EDTA. The Hydro-alcoholic (F1) and aqueous fractions (F3; F5), and the precipitate (P) stimulate the rabbit duodenum contractile activity. The ethylacetate fraction (F4) is myorelaxant; the cyclohexane fraction (F2) has no effect. The Dose-response study of F5 with concentrations ranging from 20 to 240-Ig. ml -1, shows that it is 120% more spasmogen than MAR. These inotropic positive effects of aqueous fraction (F5) are inhibited by atropine.Conclusion and application: The myostimulant active principles of MAR increased the amplitude of the contractions of the isolated rabbit duodenum by mainly mobilizing the extracellular calcium then the intracellular calcium as with EDTA. The high spasmogen activity of the aqueous fraction (F5) and the experiences with atropine suggest that this partition of MAR enriched the F5 in myostimulant active principles of cholinergic nature. These data indicate that the partition can significantly contribute to isolate the active principles from MAR with myostimulant properties, justifying its use as laxative.Keywords: Mareya micrantha, fractions, myostimulant, Atropin

Polymorphism of the testis-specific serine/threonine kinase 2 gene and risk of asthenozoospermia in Côte d'Ivoire

Background: The testis-specific serine/threonine protein kinase (TSSK2) is an indispensable protein responsible for the mobility of spermatozoa expressed specifically in the germ cells during spermatogenesis and present in the mature spermatozoa. Its gene mutation could constitute a risk of infertility. The aim of this study is to investigate the polymorphism of this TSSK2 gene in men with asthenozoospermia.Methods: The ejaculates were obtained from patients attending the reproductive biology unit of Institut Pasteur of Côte d’Ivoire for their spermiological evaluations. The semen analyses are performed with the automatic sperm analyzer SQA-Vision. 30 sperms, including 20 asthenozoosperms and 10 normosperms, were selected from their spermiological results and the spermatozoa DNA was extracted by the phenol/chloroform method. Direct Sequencing of the spermatozoa DNA fragments was done using the Sanger method. The frequencies of mutation were analysis with the Fisher and Mann-Whitney tests.   Results: It was revealed 17 mutations in 22 ejaculates. The frequent mutations are c.839C>T (T280M), c.816G>C (L372L), c.1026G>A (R342R), c.785A>C (H262P) and c.80A>G (K27R) with respectively frequencies of 50.0%, 26.67%, 16.67%, 13.33% and 10.0%. The analysis of these mutations indicated a significant difference in the frequency of occurrence of mutations between normosperms and asthenozoosperms (p-value = 0.01).Conclusions: This study shows that mutations in the TSSK2 gene are more common in asthenozoosperm ejaculates than normosperm ejaculates. This fact suggests the probable association of mutations in the TSSK2 gene with asthenozoospermia

Effects of short-term treatment with atorvastatin in smokers with asthma - a randomized controlled trial

<b>Background</b> The immune modulating properties of statins may benefit smokers with asthma. We tested the hypothesis that short-term treatment with atorvastatin improves lung function or indices of asthma control in smokers with asthma.<p></p> <b>Methods</b> Seventy one smokers with mild to moderate asthma were recruited to a randomized double-blind parallel group trial comparing treatment with atorvastatin (40 mg per day) versus placebo for 4 weeks. After 4 weeks treatment inhaled beclometasone (400 ug per day) was added to both treatment arms for a further 4 weeks. The primary outcome was morning peak expiratory flow after 4 weeks treatment. Secondary outcome measures included indices of asthma control and airway inflammation.<p></p> <b>Results</b> At 4 weeks, there was no improvement in the atorvastatin group compared to the placebo group in morning peak expiratory flow [-10.67 L/min, 95% CI -38.70 to 17.37, p=0.449], but there was an improvement with atorvastatin in asthma quality of life score [0.52, 95% CI 0.17 to 0.87 p=0.005]. There was no significant improvement with atorvastatin and inhaled beclometasone compared to inhaled beclometasone alone in outcome measures at 8 weeks.<p></p> <b>Conclusions</b> Short-term treatment with atorvastatin does not alter lung function but may improve asthma quality of life in smokers with mild to moderate asthma. Clinicaltrials.gov identifier: NCT0046382