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L K Basco

Publications and source records attributed to L K Basco.

At least 91 records · Page 5Linked to original sources
PubMed1992

In vitro activities of chloroquine in combination with chlorpromazine or prochlorperazine against isolates of Plasmodium falciparum.

The combinations of chloroquine plus chlorpromazine and chloroquine plus prochlorperazine were evaluated in vitro for potentiation against isolates of Plasmodium falciparum. Potentiation was observed against all chloroquine-resistant isolates. There was no potentiation against 8 of 10 chloroquine-susceptible isolates. The results indicated that the phenothiazines can potentiate chloroquine action against resistant parasites found in natural conditions.

Animals↗
PubMed1992

In vitro activity of halofantrine and its relationship to other standard antimalarial drugs against African isolates and clones of Plasmodium falciparum.

The in vitro activity of halofantrine was studied in chloroquine-susceptible and chloroquine-resistant African clones of Plasmodium falciparum over a period of six months. The susceptibility level remained stable in both clones. The chloroquine-susceptible clone (50% inhibitory concentration [IC50] 6.88 nM) was less susceptible to halofantrine than the chloroquine-resistant clone (IC50 2.98 nM). Using an isotopic semimicro drug susceptibility test, the in vitro activity of halofantrine was compared with the activities of chloroquine, quinine, and mefloquine to study the cross-resistance patterns against 76 African isolates of P. falciparum isolated from cases of malaria imported into France. Chloroquine-resistant isolates (n = 47) were significantly less susceptible to quinine (IC50 234 nM), but were more susceptible to both mefloquine (IC50 3.20 nM) and halofantrine (IC50 1.14 nM) compared with the chloroquine-susceptible isolates (n = 29; IC50 147 nM for quinine, 7.16 nM for mefloquine, and 2.62 nM for halofantrine). A significant positive correlation was found between the activities of chloroquine and quinine and between those of mefloquine and halofantrine, indicating cross-resistance between these drugs, while a negative correlation was observed between chloroquine and mefloquine or halofantrine. The responses to quinine and mefloquine or halofantrine showed no correlation with each other. These results reinforce the importance of a cautious use of antimalarial drugs in Africa.

Africa↗
PubMed1992

[Contribution of molecular genetics to the understanding of chemoresistance of Plasmodium falciparum].

Resistance to pyrimethamine and proguanil is due to a single point mutation in the gene that codes for dihydrofolate reductase. A single mutation gives rise to resistance to only one of the drugs. Resistance to both drugs results from several mutations. Chloroquine resistance phenotype is due to a rapid efflux of the drug from the parasite's digestive vacuole. This efflux is associated with a transmembrane permeability glycoprotein, or P-gp, which is similar to the protein implicated in the multidrug resistant phenotype of some cancer cells. However, one or several other poorly understood major gene(s) may be involved. Drugs which can inhibit the supposed affinity of P-gp for chloroquine are under study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Evaluating the efficacy of chloroquine in febrile Guinean children infected with Plasmodium falciparum by a simplified in vivo test.

A modified version of a simplified in vivo test was applied to assess the susceptibility of Plasmodium falciparum to chloroquine among semi-immune febrile children in Kouroussa, Guinea. In 27% of cases, a partial response (RI/RII) to chloroquine was observed; the remainder showed a good response (S/RI). This test is both practical and useful to assess the efficacy of chloroquine at the intermediate level of health care services.

Animals↗
PubMed1991

Plasmodium falciparum: in vitro drug interaction between chloroquine and enantiomers of amlodipine.

Both enantiomers of amlodipine, whose calcium antagonist action resides almost exclusively in the R(-) enantiomer, reversed chloroquine resistance in Plasmodium falciparum in vitro. R(-) enantiomer was slightly more effective than the S(+) enantiomer in potentiating chloroquine action against chloroquine-resistant strains of parasites. No potentiating effect was observed in chloroquine-sensitive parasites. Both enantiomers entered rapidly into parasitized erythrocytes to the same extent. Reversal of chloroquine resistance by the enantiomers of amlodipine was related to dose-dependent increase in the accumulation of chloroquine inside the erythrocytes parasitized by resistant parasites. These results suggest that the potentiating effect on chloroquine is independent of calcium metabolism of malaria parasites.

Amlodipine↗
PubMed1991

Chloroquine-potentiating action of antihistaminics in Plasmodium falciparum in vitro.

Tricyclic antihistaminics have relatively few side-effects compared to other agents that enhance the susceptibility to chloroquine of chloroquine-resistant strains of Plasmodium falciparum. Their efficacy was tested in vitro against resistant and sensitive culture-adapted strains of P. falciparum. Isobologram analysis showed that both cyproheptadine and azatadine exert a marked synergistic action on chloroquine against chloroquine-resistant, but not against chloroquine-sensitive, strains of parasites. Cyproheptadine was about twice as effective as azatadine in reversing chloroquine resistance. Loratadine had no effect on chloroquine against both resistant and sensitive strains of parasites. Our in vitro study showed that cyproheptadine and azatadine may be promising candidates for potentiating chloroquine against resistant malaria parasites.

Animals↗
PubMed1991

In vitro and in vivo potentiation of chloroquine against malaria parasites by an enantiomer of amlodipine.

A combination of chloroquine and amlodipine, a derivative of 1,4-dihydropyridine calcium channel blocker, was tested against Plasmodium falciparum in vitro and P. yoelii in mice. The dextrorotary enantiomer of amlodipine, practically devoid of calcium channel blocking action, increased chloroquine accumulation inside the infected mouse erythrocytes and potentiated chloroquine action against the resistant strains of P. falciparum in vitro and P. yoelii in mice. Unlike the racemate, the dextrorotary amlodipine was not toxic to the host animal, even at the highest dose of 250 mg/kg. No potentiating effect was noted in the chloroquine-susceptible strains of P. falciparum. The results of this study indicate that chloroquine potentiation of amlodipine is probably independent of calcium channels and that a combination therapy of the dextrorotary enantiomer of amlodipine and chloroquine might be a potentially useful therapeutic strategy against chloroquine-resistant falciparum malaria.

Amlodipine↗
PubMed1991

Type RI resistance to halofantrine in West Africa.

A case of recrudescent falciparum malaria after halofantrine treatment is described. The patient contracted Plasmodium falciparum in Ivory Coast and was treated with halofantrine. Plasma levels of halofantrine and its metabolite were adequate. Thirty-one days after treatment, the patient was rehospitalized with symptoms of malaria. Recrudescence was confirmed by microscopic examination, indicating a type RI resistance to halofantrine. Mefloquine was given to treat recrudescent malaria. The parasite was susceptible to chloroquine and quinine in vitro but displayed elevated values of 50% inhibitory concentration for mefloquine and halofantrine. The case reminds us that chloroquine still has an important therapeutic role against African strains of P. falciparum and that mefloquine and halofantrine should be reserved for multi drug-resistant P. falciparum.

Animals↗
PubMedDate not supplied

Reversal of chloroquine resistance with desipramine in isolates of Plasmodium falciparum from Central and West Africa.

Twenty freshly isolated strains of Plasmodium falciparum from non-immune and semi-immune patients infected in Central and West Africa were tested for in vitro drug sensitivity to chloroquine alone and to a combination of chloroquine and desipramine without prior adaptation to continuous culture. Combination of desipramine at 625 nmol/litre and chloroquine reversed resistance totally (IC50 less than 100 nmol/litre) in all 14 chloroquine-resistant isolates. No effect on chloroquine sensitivity was noted in the 6 chloroquine-sensitive isolates. These observations provide additional evidence that reversal of chloroquine resistance in the presence of desipramine is not a phenomenon unique to culture-adapted strains and that desipramine may exert the same potentiating effect in vivo, provided that effective plasma concentration can be attained without serious side-effects.

Animals↗