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Biomedical subjects

R E Howells

Publications and source records attributed to R E Howells.

At least 73 records · Page 4Linked to original sources
PubMed1984

Combination of the antibiotics erythromycin and tetracycline with three standard antimalarials against Plasmodium falciparum in vitro.

Combinations of antibiotics and standard antimalarials have been assayed against P. falciparum in vitro, using incorporation of 14C isoleucine as an indicator of drug action. Chloroquine and erythromycin have been shown to act synergistically against a chloroquine-resistant strain and additively towards a chloroquine-sensitive strain, confirming their action against sensitive and resistant P. berghei in vivo, described elsewhere. Combinations of erythromycin with mefloquine or quinine acted anergically in 24 hour assays in which unphysiologically high concentrations of quinolinemethanol were necessary for demonstrable drug effect. In 48 hour assays, an additive effect was obtained with these combinations. Tetracycline is additive in combination with each of the standard antimalarials used in this study. The relevance of results obtained in vitro to parasite drug sensitivities in vivo is discussed.

Animals↗
PubMed1984

The microfilaricidal activity of ivermectin in vitro and in vivo.

Ivermectin has been tested against the microfilariae of Onchocerca lienalis, Brugia pahangi and Dirofilaria immitis in vitro and in vivo. All in vitro tests were performed on larvae incubated for 48 hours at 37 degrees C in Hepes buffered medium 199 containing 20% serum, benzylpenicillin and streptomycin. In vivo tests were performed on larvae in female BALB/C mice dosed with ivermectin, 5 mg/kg, orally. The microfilariae of B. pahangi in vitro were insensitive to ivermectin at concentrations to 30 ng/ml. In vivo, an 87% reduction in the level of microfilaraemia was obtained by 24 hours after drugging but no reduction was observed in the numbers of peritoneal microfilariae. O. lienalis microfilariae in vitro were killed by ivermectin at 3 ng/ml and the larvae of this species within the subcutaneous and cutaneous tissues of the mouse were also eliminated by ivermectin at 5 mg/kg. D. immitis larvae within the bloodstream of the mouse were also sensitive to ivermectin at the dosage employed but were unaffected by ivermectin in vitro at concentrations up to 30 ng/ml.

Animals↗
PubMed1983

The mechanisms of amino acid uptake by Brugia pahangi in vitro.

The transcuticular uptake of L-glycine and L-arginine by adult female Brugia pahangi has been shown to involve both a saturable carrier transport system and diffusion. The uptake of L-glycine was competitive with regard to L-methionine, L-valine, and L-phenylalanine but noncompetitive with L-arginine. It is suggested that at least two distinct loci are involved in the transcuticular movement of amino acids in this filarial nematode.

Animals↗
PubMed1983

The mode of action of suramin on the filarial worm Brugia pahangi.

The mode of action of suramin upon Brugia pahangi has been investigated in vivo and in vitro. The drug was without effect on the glycolytic activity of worms in vitro at 2 X 10(-4) M. The lack of effect was correlated with the failure of [14C]suramin to penetrate the worms in vitro. Suramin bound to the surface of worms in vitro presumably by virtue of its polyanionic nature. B. pahangi adults ingested [14C]suramin in vivo but no reduction in the rate of lactate production, of glucose utilization or in the rates of uptake of [14C]glucose, [14C]leucine or [14C]adenosine was observed in worms recovered from jirds between weeks 1 and 5 following 4 daily doses of suramin at 50 mg/kg given intraperitoneally. Worm death occurred between weeks 5 and 7 but this delayed drug effect was not the result of a progressive accumulation of suramin in the worms. Ultrastructural changes were observed in the intestinal epithelium of worms from suramin-treated jirds and parallel observations on worms exposed to Trypan blue in vivo suggest that both polyanionic compounds are restricted to the intestinal lumen of the worms. The evidence presented is consistent with the concept that, in B. pahangi, suramin acts at the surface of the intestinal epithelium and not by primarily inhibiting glucose catabolism or inhibiting phagosome and lysosome fusion as previously demonstrated for bloodstream trypanosomes and mammalian macrophages, respectively.

Adenosine↗
PubMed1983

The moulting process and the phenomenon of intermoult growth in the filarial nematode Brugia pahangi.

The larvae of Brugia pahangi recovered from the jird have been shown to grow continuously between moults, their length increasing at least 5-fold during the 4th instar. This intermoult growth is achieved without an increase in the surface area of larvae. The cuticle of very early 4th and 5th-stage worms is highly folded and intermoult growth is accommodated by an expansion of surface annular folds. The major increases in the surface area of larvae occur only through ecdysis, with an 8-fold increase in the surface area being achieved at the 3rd moult. The growth curve of these worms is therefore sigmoidal but the surface area curve is stepped. The relationship between the cuticles of nematodes and insects is discussed.

Animals↗
PubMed1983

The susceptibility of BALB/C and other inbred mouse strains to Brugia pahangi.

The susceptibility of several strains of inbred mice to infection with the filarial worm Brugia pahangi has been examined. BALB/C, C57BL/10, C3H/He, 101, CBA/Ca mice, congenitally asplenic (DH/+) mice and their normal litter-mates (+/+) were each challenged by the intraperitoneal inoculation of 50 infective larvae. During the first four weeks of infection high (19-42%) larval recoveries were obtained from the CBA/Ca, BALB/C and Dh/+ mice but fewer than 10% of inoculated larvae were recovered from C3H/He, 101; C57BL/10 and +/+ mice. Larval growth rates in all mice were similar. BALB/C and Dh/+ mice only were examined later than four weeks after infection. The yield of adult worms from BALB/C was 7.5% at 16 weeks and from Dh/+ 4.2% at 21 weeks. Microfilariae were present in the peritoneal fluids but not the blood of some mice harbouring both adult male and female worms.

Animals↗
PubMed1981

The effect of 5-fluorouracil and 5-fluorocytosine on the development of the filarial nematodes Brugia pahangi and Dirofilaria immitis.

5-fluorouracil and 5-fluorodeoxyuridine at 30 mg/kg body weight daily for four days inhibit microfilarial production in Brugia pahangi in the jird. Disruption of intrauterine embryogenesis was observed in treated female worms but the compounds were not macrofilaricidal or microfilaricidal under the conditions employed. 5-fluorocytosine possessed no filaricidal or embryostatic activity. The inhibition of microfilaria production by 5-fluorouracil was temporary and larval production was resumed within nine weeks. The compound also inhibited the development of B. pahangi and Dirofilaria immitis larvae in the mosquito Aedes aegypti, when administered to cages of mosquitoes as a 0.01 or 0.001% solution in a 10% aqueous sucrose solution on cotton wool wicks. The development of infective larvae of B. pahangi in the jird was inhibited by 5-fluorouracil.

Animals↗