Some dihydropyridines (DHPs), such as amlodipine and cilnidipine, have been shown to block not only L-type but also N-type Ca(2+) channels; therefore, DHPs are no longer considered as L-type-specific Ca(2+) channel blockers. However, selectivity of DHPs for Ca(2+) channel subtypes including N-, P/Q-, and R-types are poorly understood. To address this issue at the molecular level, blocking effec...

BACKGROUND Monitoring the prevalence of drug resistant Plasmodium falciparum is essential for effective malaria control. Resistance to pyrimethamine and sulfadoxine increases as mutations accumulate in the parasite genes encoding dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps), respectively. Although parasites are exposed to these antifolate drugs simultaneously, it remains v...

BACKGROUND Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) is a major cause of mortality in human immunodeficiency virus (HIV)-infected infants in Africa, but the prevalence of mutations in the gene encoding dihydropteroate synthase (DHPS) in isolates from Africa has not been reported. METHODS This study investigated the prevalence of DHPS mutations in P. jiroveci isolat...

Plasmodium falciparum causes the most severe form of malaria in humans. An important class of drugs in malaria treatment is the sulfone/sulfonamide group, of which sulfadoxine is the most commonly used. The target of sulfadoxine is the enzyme dihydropteroate synthase (DHPS), and sequencing of the DHPS gene has identified amino acid differences that may be involved in the mechanism of resistance...

Failure of sulfa or sulfone prophylaxis is associated with mutations in Pneumocystis carinii gene coding for dihydropteroate synthase (DHPS). The DHPS genotype was analyzed in AIDS patients who had two separate episodes of P. carinii pneumonia. The results suggest that DHPS mutations can be selected de novo within patients by the pressure of a sulfa or sulfone drug.

Dihydropteroate synthase (DHPS) gene mutations have raised concerns about emerging sulfonamide resistance in Pneumocystis jirovecii. DHPS and dihydrofolate reductase (DHFR) gene products were amplified in clinical specimens from South African patients. One of 53 DHPS genes sequenced contained the double mutation Thr55Ala Pro57Ser. DHFR gene mutations detected were Ala67Val and the new mutations...

We examined mutations in the dihydropteroate synthase (DHPS) genes of Pneumocystis carinii f. sp. hominis (P. carinii) strains isolated from 24 patients with P. carinii pneumonia (PCP) in Japan. DHPS mutations were identified at amino acid positions 55 and/or 57 in isolates from 6 (25.0%) of 24 patients. The underlying diseases for these six patients were human immunodeficiency virus type 1 inf...

OBJECTIVES To assess the relationship between the presence of DHFR and DHPS mutations in Plasmodium falciparum, parasite in vitro resistance, and in vivo efficacy of sulfadoxine-pyrimethamine (SP) treatment. PATIENTS AND METHODS Measurement of SP treatment efficacy in malaria-infected children in Gabon was combined with in vitro tests of susceptibility to pyrimethamine and cycloguanil, and mo...

The effects of eleven 1,4-dihydropyridine derivatives (DHPs) used alone or together with prooxidant anticancer drug doxorubicin were examined on two cancer (HOS, HeLa) and two nonmalignant cell lines (HMEC, L929). Their effects on the cell growth (3H-thymidine incorporation) were compared with their antiradical activities (DPPH assay), using well-known DHP antioxidant diludine as a reference. T...

Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive benefits of sulfadoxine/pyrimethamine, and might exacerbate placental malaria. We explored emerging lineages of dhps mutant haplotypes in Malaw...