Search PubMed⌕ Search

Biomedical subjects

P Ringwald

Publications and source records attributed to P Ringwald.

At least 73 records · Page 4Linked to original sources
PubMed1993

In vitro activity of cycloguanil against African isolates of Plasmodium falciparum.

The in vitro activity of cycloguanil was assessed against 86 African isolates of Plasmodium falciparum by a semi-micro assay system. A bimodal distribution of susceptibility patterns was observed, with 44% of the isolates being cycloguanil susceptible. Cycloguanil alone retains a high activity against the intraerythrocytic forms of some isolates and, together with its activity against the hepatic stages, may be useful for chemoprophylaxis when combined with chloroquine.

Animals↗
PubMed1993

Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines.

To determine virulence factors of isolates of Plasmodium falciparum and the potential role of cytokines in cerebral malaria, 46 Malagasy patients presenting with cerebral (n = 10), severe (n = 10), and uncomplicated (n = 26) malaria were enrolled in a study. The capacity of 21 of 46 P. falciparum isolates to form rosettes in vitro and to adhere to human umbilical vein endothelial cells (HUVECs) that express intercellular adhesion molecule-1 receptors and to C32 amelanotic melanoma cells that express mainly CD36 receptors was investigated together with the effects of tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-6 alone and in two-by-two combinations on the cytoadherence of infected erythrocytes to HUVECs. Plasma levels of these cytokines were also measured in the patients at admission. The percentage of rosette formation was higher for the isolates from patients with cerebral (n = 6; 19.5%) and severe (n = 6; 30.5%) malaria than for those from patients with uncomplicated malaria (n = 9; 5%) (P < 0.002). The cytoadherence properties of the isolates did not differ among the three groups whatever the target cell used, but adherence to melanoma cells was systematically higher than that to HUVECs. Adhesion to HUVECs was increased more after TNF-alpha stimulation than after GM-CSF, IL-3, or IL-6 stimulation (P < 0.01). Only the combination of TNF-alpha and IL-3 enhanced cytoadherence more than TNF-alpha used alone (P < 0.02). No difference in the modulation of cytoadherence by cytokines was found in relation to the severity of the disease. TNF-alpha and IL-6 levels in peripheral blood were higher in the patients with cerebral and severe malaria than in the patients with uncomplicated malaria (P < 0.005). Most of the patients' sera contained little or no IL-3 or GM-CSF. Our results challenge the role of intercellular adhesion molecule-1 as the principal receptor mediating the cytoadherence of P. falciparum-infected erythrocytes and contrast with data obtained in the murine model.

Adolescent↗
PubMed1993

Evolution of chloroquine resistance in central and west Africa.

The evolution of in vitro chloroquine susceptibility of clinical isolates of Plasmodium falciparum obtained from travellers returning to France was studied between 1986 and 1991 using the isotopic semi-microtest. Based on the analysis of 1,147 interpretable tests on isolates originating from Central and West Africa, the study showed that the proportion of chloroquine-resistant falciparum malaria remained stable between 1986 and 1988 and has diminished between 1989 and 1991. The diminution of chloroquine-resistant imported malaria may be associated, at least in part, with a better compliance of French travellers with the recommendation to use either mefloquine or a combination of chloroquine and proguanil since 1989 and an increasing proportion of African immigrants who tend to neglect regular chemoprophylaxis during the visit to their countries. The reason for the stabilisation of chloroquine resistance is unknown, and this phenomenon may be temporary, necessitating a continuous surveillance of drug susceptibility.

Africa, Central↗
PubMed1992

Kinetics of lymphocyte subsets from peripheral blood during a Plasmodium falciparum malaria attack.

Variations of lymphocyte subsets were followed longitudinally in 16 patients during an acute falciparum malaria attack. Before treatment, lymphocyte numbers were highly reduced, but the subset distribution was similar to that of healthy individuals. After parasite clearance, lymphocyte counts were normalized and the subset distribution was unchanged. This led to a normalization of all the absolute counts of lymphocyte subsets, except CD8+. The fast normalization of lymphocyte counts suggests that the initial decrease in lymphocyte numbers may reflect sequestration. Magnitude and kinetics of this variation were not related to parasite density or to severity of the attack. Activated T cells (CD3+HLA-DR+) were fewer in African than in European patients, suggesting the importance of the past exposure to malaria parasites in reallocation phenomena. These variations in lymphocyte numbers must be taken into account in the design and the analysis of cellular investigations in patients experiencing a falciparum malaria attack.

Adult↗
PubMed1992

[Stability and chemosensitivity of Plasmodium falciparum to chloroquine in 1990 and 1991 in Ankazobe, a village in high plateau Madagascar].

The in vivo and in vitro response of Plasmodium falciparum to chloroquine was conducted in Ankazobe, a village located in the high plateau area. These studies confirmed the low level of chloroquine-resistance. The in vivo data indicate the absence of increase resistance during the 2 years study. Chloroquine is still the drug of choice for the treatment of malaria attack in this area.

Animals↗
PubMed1992

[Stability of P. Falciparum resistance to chloroquine between 1987 and 1989 in Mounana, Gabon].

Between 1987 and 1989 the trend in the chloroquine resistance of Plasmodium falciparum in the mining town of Mounana in south-eastern Gabon was studied in vivo and in vitro in 58 and 158 subjects, respectively, aged from 1 to 15 years. The tests used were a simplified variant of the standard WHO 7-day test for the in vivo study and the isotopic semi-microtest of chemosensitivity for the in vitro study. The health situation in 1989 showed no change from the 1987 situation, but an increase in febrile symptoms suggestive of malaria was observed in 1989. This observation may be linked to a decrease in the distribution of chloroquine since 1987, accompanied by the use of other antimalarials following the appearance of chloroquine-resistant strains. While the parasitological efficacy in vivo remained the same in 1989, there was a decrease in the proportion of strains resistant to chloroquine in vitro compared to 1987; likewise, the therapeutic efficacy as estimated from temperature readings was better in 1989 than in 1987: the modification of the prophylactic strategy since 1986 and the drop in chloroquine consumption since 1987 could be responsible for a stabilization of chloroquine resistance at Mounana. The authors consider it appropriate in this region to continue treating malaria in children with chloroquine (in a dosage of 25 mg/kg) and to use a second-line treatment in the event of the recurrence of malaria symptoms within the next two weeks.

Adolescent↗
PubMed1992

Susceptibility of African isolates of Plasmodium falciparum to artemisinin (qinghaosu).

We studied in vitro susceptibility of 79 African strains of Plasmodium falciparum to artemisinin, chloroquine, quinine, mefloquine and halofantrine and the potential cross-resistance among the drugs. Most strains presented an 50% inhibitory concentration (IC50) of artemisinin below 26 nmol/liter. A positive correlation between IC50S of artemisinin and those of quinine, mefloquine and halofantrine was observed. Cross resistance between artemisinin and other antimalarials may limit its use as a replacement drug.

Animals↗
PubMed1992

[Participation of cytokines and immune sera to the cytoadherence of erythrocytes infected by Plasmodium falciparum on the endothelial cells in culture].

In vitro binding capacity of erythrocytes infected with P. falciparum and the modulation of cytoadherence on human endothelial cells by cytokines and sera from semi immune subjects in relation to cytoadherence were studied. Tumor necrosis factor and interleukin-3, alone or in combination with granulocyte macrophage-colony stimulating factor, enhanced in vitro cytoadherence. Contrary to pooled immune sera, patients' sera obtained during acute or convalescent phase did not reverse nor inhibit in vitro cytoadherence.

Animals↗
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

Levels of cytokines in plasma during Plasmodium falciparum malaria attacks.

The variation of levels of tumor necrosis factor, granulocyte-macrophage colony-stimulating factor, gamma interferon, neopterin, and interleukin-2 receptors in plasma were monitored in 16 patients presenting with an acute Plasmodium falciparum malaria attack. Relations among cytokine levels and between cytokine levels and hematological and parasitological data were assessed.

Adult↗
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↗