Search

A non-radioactive, thymidine analogue-bromodeoxyuridine (Brdu), derivative of uridine has been used for incorporation in DNA in culture of P. falciparum at various dosages and at different time period. Parasite growth rate and effect of chloroquine in culture were monitored by microscopic observation of stained smears and incorporation of Brdu molecules were visualized by immunofluorescence and measured by enzyme immuno assay using anti-Brdu. Uptaking of Brdu in parasite is slower unlike tumour cells. A positive correlation between parasite growth and Brdu uptake measurement by ELISA has been observed.

Kerosene lamps containing one per cent neem oil were used for mosquito repellent action in a village near Delhi. The safety aspects of this personal protection method developed by Malaria Research Centre were evaluated by animal studies and clinical examination of population before and after exposure. Single application of neem oil (1%) did not produce skin irritation in rabbits and adverse effect on guinea pigs after exposure to aerosol. Clinical examination of 156 adults and 110 children did not reveal any major adverse effects after one year of exposure to 1% neem oil.

Twenty-two cases (nineteen Plasmodium falciparum and three P. vivax) of severe malaria among 200 pregnant women from District Jabalpur, M.P. were studied for malaria parasite density. Almost all of them were found anaemic. The patients were treated with quinine/chloroquine intravenously but seventeen Pf cases died within 96 h of admission in hospital. Out of twenty-two, thirteen were primigravidae.

Synthetic analogues of a monoterpenic fragment of aplasmomycin were tested for their antimalarial activity in Plasmodium falciparum culture in vitro. The antimalarial activities of these agents were evaluated in chloroquine sensitive strains. Parasite growth was inhibited in a dose dependent manner in the presence of the synthetic compounds (3-9).

Fifteen patients of uncomplicated falciparum malaria from Delhi were treated with norfloxacin (10 with 400 mg, 5 with 800 mg, both twice daily) for 3 days and the response was measured according to the WHO extended in vivo test criteria. The lower dose produced S response in two, RII response in five and RIII response in three patients, while the higher dose produced S response in four and RI response in one patient. In patients with S or RI response, the parasite clearance time was 68.6 +/- 9.1 h the defervescence time being 48 h. Thus, norfloxacin did reveal in vivo activity in falciparum malaria, but a dose of 400 mg twice daily proved to be curative only in a small percentage of cases and not consistently. Nausea and bitter taste were the only side effects noted in two patients.

The in vitro activity of three fluoroquinolones--ciprofloxacin, norfloxacin and ofloxacin--was studied on four laboratory-adapted strains (one chloroquine-resistant) and one fresh isolate of P. falciparum from Delhi by the schizont maturation inhibition microtest. The IC50 concentrations (mean +/- SD) were found to be as: ciprofloxacin 6.38 +/- 1.34 micrograms/ml, norfloxacin 11.24 +/- 1.27 micrograms/ml, and ofloxacin 22.3 +/- 3.11 micrograms/ml, while the MIC values were 32 micrograms/ml, 64 micrograms/ml and 128 micrograms/ml for the three drugs in the same order. The IC50 and MIC values for chloroquine-resistant strain were not significantly different from those for the chloroquine-sensitive strains. We conclude that there is little interstrain variability in the in vitro susceptibility of P. falciparum to fluoroquinolones, and that there is no cross resistance between them and chloroquine. The reported variability in clinical response of falciparum malaria to fluoroquinolones is not likely to be due to variation in parasite sensitivity.

The effects of verapamil on the parasite susceptibility to chloroquine were examined in mice infected with chloroquine-sensitive and chloroquine-resistant lines of Plasmodium berghei. Verapamil in a dose of 10-50 mg/kg daily s.c. for 4 days did not affect the growth of both sensitive and resistant parasites. When verapamil in the same dose range was combined with 1.5 mg/kg chloroquine diphosphate, the chloroquine-sensitive parasites became more susceptible to chloroquine. Similarly, verapamil severely suppressed the growth of chloroquine-resistant parasites in combination with 3 mg/kg (base) of chloroquine, but the reversal of resistance was not complete. Thus, still higher doses of verapamil, which are not tolerated by the host, are required for the complete reversal of resistance.

Pharmacokinetics of lithium was studied in 60 manic-depressive patients after an initial dose of 900 mg, in serial blood samples for 24 h. The values (mean +/- SD) obtained were peak serum Li concentration 0.81 +/- 0.18 mEq/l; time to peak 2.57 +/- 0.87 h; total Li clearance 33.2 +/- 15.5 ml/min; volume of distribution 0.62 +/- 0.26 l/kg; elimination rate constant 0.0514 +/- 0.02 h; area under serum concentration-time curve 16.41 +/- 11.41 mEq/1 h; serum half life 15.34 +/- 6.06 h. Thereafter, the applicability of various dose prediction methods was evaluated vis-a-vis the actual doses needed to attain steady state serum lithium concentration of 0.6-1.2 mEq/l in 46 patients. The method based on body weight was not found suitable. A nomographic method predicted higher doses in 27 patients, while Zetin's mathematical model predicted dose was in the range of +/- 150 mg of the actual dose in 21 patients. A method for predicting maintenance dose based on 24 h serum lithium level and body weight is suggested.

The effect of pretreatment with clonidine, methyldopa and propranolol, and of atropine was studied in mice on acute toxicity of fenitrothion, the active ingredient of TIK-20. Atropine significantly decreased and propranolol somewhat decreased the fenitrothion induced death in mice. Clonidine and methyldopa somewhat increased the percentage mortality due to fenitrothion.