Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a well-known target for pyrimethamine and cycloguanil. The low amounts of enzyme obtainable from parasites or the currently available heterologous expression systems have thus far hindered studies of this enzyme. The 1912-base pair P. falciparum DHFR-TS gene was designed based on E. coli codon preference with unique...

BACKGROUND Atovaquone-proguanil (AP) is the most commonly used treatment for uncomplicated Plasmodium falciparum malaria in the United States. Apparent AP treatment failures were reported 7 months apart in 2 American travelers who stayed in the same compound for foreign workers in Rivers State, Nigeria. METHODS We analyzed pretreatment (day 0) and day of failure samples from both travelers fo...

Plasmodium falciparum strains bearing quadruple mutations of dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) at codons 51, 59, 108, and 164 are highly resistant to pyrimethamine (PYR), a diaminopyrimidine, but sensitive to WR99210 (WR), a cycloguanil analog, suggesting different enzyme-inhibitor binding interactions. A combination of these inhibitors to delay the onset of antifolate re...

A combination of atovaquone and proguanil has been found to be quite effective in treating malaria, with little evidence of the emergence of resistance when atovaquone was used as a single agent. We have examined possible mechanisms for the synergy between these two drugs. While proguanil by itself had no effect on electron transport or mitochondrial membrane potential (DeltaPsim), it significa...

A rapid, sensitive and selective gas chromatographic method with flame ionization detection was developed for the determination of paraldehyde in small blood samples taken from children. Whole blood samples (300 microl) collected in a 3 ml Wheaton glass sample vial were spiked with acetone (internal standard: 15 ng) followed by addition of concentrated hydrochloric acid. The mixture was heated ...

Detailed information on the mode of action of antimalarial drugs can be used to improve existing drugs, identify new drug targets, and understand the basis of drug resistance. In this study we describe the use of a time-resolved, mass spectrometry (MS)-based metabolite profiling approach to map the metabolic perturbations induced by a panel of clinical antimalarial drugs and inhibitors on Plasm...

Abstract. Widiyono I, Rusmihayati, Purnamaningsih H, Sahara A. 2023. Zoonotic gastrointestinal nematodes in pet cats Yogyakarta (Indonesia) and their susceptibility to anthelmintics. Biodiversitas 24: 3332-3337. Domestic (Felis catus Linnaeus, 1758), which live close humans, can host some zoonotic nematodes. Therefore, a study on domestic anthelmintic resistance is essential for controlling pre...

The dissemination of mutant and resistant strains of Plasmodium falciparum makes a considerable contribution to the spread of drug-resistant malaria. Populations around harbours and airports could be particularly exposed to Plasmodium isolates introduced with imported cases of malaria. The use of chloroquine as well as the use of and sulfadoxine/pyrimethamine is currently an effective method fo...