Browsing by Author "Muregi, Francis Wamakima"

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    Antiplasmodial Activity Assay of 3-Chloro-4-(4-chlorophenoxy) Aniline Combinations with Artesunate or Chloroquine In Vitro and in a Mouse Model
    (BioMed Research International, 2019-10-17) Muregi, Francis Wamakima; Kimani,Francis Thuo; Kariuki,Daniel Wainaina; Sifuna , Martin Wekesa; Nganga,Joseph Kang’ethe; Wambui ,Milka
    Malaria is the eighth highest contributor to global disease burden with 212 million cases and 429,000 deaths reported in 2015. *ere is an urgent need to develop multiple target drug to curb growing resistance by Plasmodia due to use of single target drugs and lack of vaccines. Based on a previous study, 3-chloro-4-(4-chlorophenoxy) aniline (ANI) inhibits Plasmodia enoyl acyl carrier protein reductase. *is study aimed at evaluating the antiplasmodial activity of ANI combinations with artesunate (AS) or chloroquine (CQ) against P. falciparum in vitro based on the semiautomated microdilution assay and P. berghei in vivo based on Peters’ 4-day test. Data were analysed by linear regression using version 5.5 of Statistica, 2000. From the results, on the one hand, a combination of 1.1 ng/ml AS and 3.3 μg/ml of ANI inhibited 50% growth of W2 , while a combination of 0.8 ng/ml of AS and 2.6 μg/ml of ANI inhibited 50% growth of 3D7 . On the other hand, a combination of 22 ng/ml CQ and 3.7 μg/ml of ANI inhibited 50% growth of W 2 , while a combination of 4.6 ng/ml CQ and 3.1 μg/ml of ANI inhibited 50% growth of 3D7 . In in vivo assays, a combination of ED50 concentrations of AS and ANI cleared all parasites, while 1/2 and 1/4 ED50 combinations inhibited 67.0% and 35.4% parasite growth, respectively. ED50 combinations of CQ and ANI inhibited 81.0% growth of parasites, while 1/2 and 1/4 ED 50 combinations inhibited 27.3% and 10.2% parasite growth. Assuming a linear relationship between percentage chemo- suppression and combination ratios, only 0.88 mg/kg of AS combined with 1.68 mg/kg of ANI or 1.78 mg/kg of CQ with 3.15 mg/ kg of ANI inhibited 50% parasite growth in vivo. ANI combinations with AS or CQ are thus potential antimalarial drug combinations if their clinical efficacy and safety are ascertained
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    Chromosomal mapping of host resistance loci to Trichinella spiralis nematode infection in rats
    (Springer Nature, 2006-02-08) Muregi, Francis Wamakima; Takabayashi, Shuji; Terada, Mamoru; Takagi, Hisayoshi; Suzuki, Tohru; Ishih, Akira; Kino, Hideto; Nishikawa, Tetsu
    The differences in host response among strains of rats to intestinal nematode parasite Trichinella spiralis infection could provide a powerful benefit for further elucidation of molecular interactions between the host and the parasite. Using several strains of rats, we previously observed that DA strain is a strong responder and F344 strain is a weak responder with respect to expulsion of the adult worm. To identify the host resistance loci, quantitative trait loci (QTLs) analysis in F2 population from crosses between DA and F344 strains was performed. One significant QTL (designated as Tspe) was mapped to the middle region of chromosome 9. In addition, the effect of DA allele at Tspe locus could act recessively and lead to the rejection of more adult worms from the gut. The results from the present study provide more insights on host–parasite interactions, which may be useful in facilitating the development of novel approaches for treatment and control of intestinal parasites in human and domestic livestock.