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Biomedical subjects

F Verdier

Publications and source records attributed to F Verdier.

At least 73 records · Page 4Linked to original sources

Chloroquine uptake by Plasmodium falciparum-infected human erythrocytes during in vitro culture and its relationship to chloroquine resistance.

Chloroquine uptake by Plasmodium falciparum-infected human erythrocytes (RBC) was studied in vitro before and during culture by measuring the chloroquine gradient between the cells and medium (C/M) by high-pressure liquid chromatography. The C/M values were 5.9 +/- 2.7 (n = 23) for uninfected RBC, 13 to 34 for six chloroquine-susceptible isolates (concentration required to inhibit 50% of parasite growth, less than 100 nmol/liter) in partially infected RBC (parasitemia from 0.3 to 5%) (n = 28), and 8.4 to 4.9 for four chloroquine-resistant isolates (concentration required to inhibit 50% of parasite growth, 320 to 1,500 nmol/liter) in partially infected RBC (parasitemia from 0.4 to 5%) (n = 26). Two isolates were studied before and after adaptation to continuous culture. C/M was found to decrease (34.2 to 2.1 and 19.3 to 4.9), whereas the concentration required to inhibit 50% of parasite growth increased (35 to 1,400 and 54 to 1,500 nmol/liter), thus indicating the acquisition of chloroquine resistance. These results demonstrate that chloroquine uptake decreased in RBC in which the infective strain, initially susceptible, became resistant in culture and imply that the drug is bound to ferriprotoporphyrin IX to a lesser extent or that a parasite protein competes with ferriprotoporphyrin IX to a greater extent. We suggest that genotypic modifications in the mechanism of chloroquine uptake might occur in the parasite.

Chloroquine↗

[Pharmacokinetics of amodiaquine and prevention of Plasmodium falciparum malaria].

Amodiaquine might appear as an alternative in prophylaxis of chloroquine-resistant P. falciparum malaria. In an attempt to explain the discrepancy between its in vivo-in vitro activity, a pharmacokinetic study was conducted in healthy subjects with HPLC assays. The results showed that: amodiaquine was no more detected in the blood, a main metabolite (monodesethyl derivative) appeared as the active form of the drug in vivo, metabolite's half-life had a mean value of 15.6 +/- 5.4 days. This study shows that monodesethylamodiaquine (and not amodiaquine) must be monitored in vitro. Furthermore the high individual variations of blood levels and half-life's values suggest that the weekly prophylactic schedule must be eventually re-evaluated.

Adult↗

[Biotransformation of amiodaquine and prophylaxis of Plasmodium falciparum malaria].

The authors have devised a specific HPLC method for amodiaquine assay which demonstrated that the drug disappeared rapidly from the blood of subjects under prophylaxis for malaria (10 mg/kg/week in a single oral dose). The main metabolite was identified as the monodesethyl derivative which is the only active form of the drug. The low erythrocytic levels of the metabolite, observed at day +7, might account for the failure in the prophylaxis of P. falciparum malaria with amodiaquine in a few cases. The in vitro activity of monodesethyl amodiaquine should be evaluated during the chemosensitivity tests and the chemoprophylaxis schedule, re-evaluated.

Amodiaquine↗

[Distribution of chloroquine and desethylchloroquine in blood, plasma and erythrocytes of healthy subjects and malaria patients. Assay using HPLC].

Chloroquine (Cq) and desethyl-chloroquine ( CqM ) levels were measured by HPLC in the blood, plasma, and erythrocytes of 9 healthy subjects under standard prophylactic treatment (100 mg/day for 10 days) and 8 malarial patients given a therapeutic regimen (10 or 25 mg/kg). Chloroquine levels in various fractions of the healthy subjects were as follows: whole blood: 1 265 +/- 598 nmol/l; plasma: 145 +/- 63 nmol/l of whole blood; erythrocytes: 827 +/- 460 nmol/l of whole blood. The CqM /Cq ratio in malarial patients varied from 0.4 to 0.8. These results show that Cq levels and Cq metabolization varied significantly from one individual to the next. Above all, they demonstrate the presence of Cq in other types of blood cells. This underlines the practical importance of the conditions of chloroquine assay in blood.

Chloroquine↗

[Effect of a histamine aerosol in 20 subjects with histamine hyperreactivity. Application to a study of the protective properties of pipoxizine].

The authors made a study of the antihistaminic properties of Pipoxizine in 20 subjects with proven histaminic hyperreactivity. The design of the trial consisted in comparing the changes of VC, FEC1, expiratory airway resistance and V50 produced by a histamine aerosol given before and after administration of Pipoxizine. Pipoxizine was given by mouth to 10 patients and intravenously to the other 10 of the group. The statistical analysis of the results demonstrated an antagonist effect of Pipoxizine on the histamine induced bronchoconstriction. The data of this trial are confirmative of the results of other experimenters. It seems therefore reasonable to take into consideration the use of Pipoxizine in the preventive treatment of the paroxystic attacks of the asthmatic disease.

Aerosols↗

[Statistical study of the correlations between spirometric data and arterial blood gas tensions. II. During a 40-watt exercise (author's transl)].

PaO2 and PaCO2, after 5 min of a 40-Watt exercise, and spirometric data have been statistically evaluated in 152 patients with chronic obstructive bronchitis. In these patients, the hypoventilation syndrome increases during exercise. The correlation between age and PaO2 is identical during rest and exercise, but the correlation between PaO2 or PaCO2 and FEV1 (% predicted) is closer during exercise than during rest. The value 50 of the FEV1 (% predicted) divides the patients into two groups: the patients who stay normocapnic and those who become hypercapnic or increase their hypercapnemia. These data show the interest of the FEV1 (% predicted) values and allow to explain the evolution of the arterial blood gas tensions during exercise.

Adult↗

Changes of P50 in hypoxaemia, hypercapnia and polycythaemia: multivariate analysis.

Multivariate analysis of P50 changes in hypoxia, hypercapnia and polycythaemia was performed in an heterogeneous group of forty three patients: hypoxic subjects with or without hypercapnia, with or without polycythaemia and polycythaemic subjects without hypoxia. A statistical analysis was undertaken using comparison of the means, study of the correlations, principal component analysis, multiple regression and correspondence analysis. In the patients studied, P50 changes were not wholly explained by those of 2-3 DPG and pH; PaCO2, per se, did not play an important part. Haemoglobin concentration and P50 value would represent an adaptative mechanism to hypoxia: when hypoxia is moderate (80 greater than PaO2 greater than or equal to 65 torr) and isolated, oxygen haemoglobin affinity decreases (P50 increases); when hypoxia is severe (PaO2 less than 65 torr) and combined with hypercapnia and disturbed acid-base equilibrium, P50 comes back to normal range but haemoglobin increases, restoring thus, the normal blood oxygen content.

Adult↗

[Measurement of the oxygen affinity of hemoglobin. Application to patients with angina pectoris with normal coronography. Study of 10 cases].

A study of 2-3 D.P.C. (diphosphoglycerate) and of P50 (PO2 of half-saturation of blood at pH 7.40, PCO2 40 torr and temperature 37 degrees C) was carried out in ten subjects: eight women and two men suffering from angina pectoris with no evidence of obstruction on their coronary arteriograms. The study was made with the subjects at rest, in the absence of any acute coronary episode. The results show that these patients have a normal affinity of haemoglobin for oxygen: the 2-3 D.P.G. was 13.05 +/- 2.2 muM.g-1 Hb; P50 was 26.7 +/- 1.3 torr; Hill's "n" was 2.65 +/- 0.29. Deviation to the right of the oxyhaemoglobin curve may be seen, after effort or during a provoked attack, but this movement to the right seems to be the result rather than the cause of the myocardial ischaemia.

Adult↗

[Statistical study on correlations between spirometric data and arterial blood gas tensions. I. Under testing conditions].

Spirometric data, resting Pao2 and Paco2 have been statistically evaluated in 152 patients with chronic obstructive bronchitis. Spirographic studies show a restrictive and obstructive syndrome, associated with hypoxaemia and hypercapnia. Partial correlations show that Pao2 is positively correlated with age and negatively with VC (predicted percentage) and with FEV1 (predicted percentage); Paco2 is only correlated with FEV1 (predicted percentage). FEV1 (predicted percentage) divides the patients into two groups, the hypercapnic and normocapnic. These data show the interest of the FEV1 (predicted percentage) values.

Age Factors↗

Efficacy of a 3-day oral regimen of a quinine-quinidine-cinchonine association (Quinimax) for treatment of falciparum malaria in Madagascar.

In the search for an effective, safe and field-adapted alternative to chloroquine for therapy of chloroquine-resistant Plasmodium falciparum infections in Africa, a 3-d oral regimen of Quinimax (an association of quinine, quinidine and cinchonine) was evaluated in 35 individuals with P. falciparum in Madagascar, an area with chloroquine resistance. 63% of the parasite strains isolated were resistant in vitro to chloroquine, and 59% of the infections were present despite previous chloroquine intake. Three daily oral doses of 10 mg/kg Quinimax for 3 d cleared parasitaemia and improved clinical status in all subjects. Mean parasite and fever clearance times were 51.7 and 37.4 h, respectively. All patients were aparasitaemic at the end of the 7-d follow-up. When formulating therapy guidelines, the 3-d Quinimax regimen should be considered as a valuable alternative to chloroquine for treating falciparum malaria in African areas with clinical resistance to chloroquine.

Animals↗