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Biomedical subjects

D C Warhurst

Publications and source records attributed to D C Warhurst.

At least 91 records · Page 5Linked to original sources
PubMed1990

In vitro cultivation of Cryptosporidium parvum and screening for anticryptosporidial drugs.

Sporozoites of Cryptosporidium parvum which were excysted in vitro from oocysts isolated from calves or patients with acquired immune deficiency syndrome underwent development in monolayers of the mouse fibroblast cell line L929. Asexual multiplication occurred, with the maximum numbers of parasites usually being observed between 24 and 48 h after infection. Gametocytes were also found, but their numbers were relatively small compared with those of the asexual stages. A study was made of the effect on parasite development of 20 antimicrobial agents, most of which were anticoccidial or antimalarial agents. The majority of the drugs had a limited inhibitory effect on parasite development, but usually only at high concentrations. The two most active drugs were monensin and halofuginone, which reduced parasite multiplication by more than 90% at high concentrations. In the case of monensin, however, inhibition of parasite development at higher concentrations was due, at least in part, to a toxic effect of the drug on the host cells.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Efficient diagnosis of giardiasis among nursery and primary school children in Santiago, Chile by capture ELISA for the detection of fecal Giardia antigens.

Fecal samples were obtained from 722 of 820 children attending 7 nursery schools and 1 primary school in the city of Santiago, Chile. Microscopy of formol-ether concentrates showed that 33% of the children were infected with Giardia lamblia. Prevalences among primary school students (5-10 years of age) of G. lamblia (38%), Endolimax nana (43%), and Entamoeba coli (25%) were overall higher than among nursery school students (3 months-5 years of age; prevalences 29%, 21%, and 16%, respectively). There was no apparent association between socio-economic intake and levels of G. lamblia infection: the private nursery school had the highest recorded level of infection (40%). One hundred sixty-two triplicate stool specimens were used to compare microscopy with an enzyme-linked immunosorbent assay (ELISA) for the detection of Giardia fecal antigens. The ELISA was highly sensitive and specific either visually (95% and 97%, respectively) or by optical density determination (99% and 96%, respectively). Incorporation of non-immune rabbit immunoglobulin-coated control wells did not enhance sensitivity and specificity. The antigen detection ELISA is an extremely effective tool for the epidemiological investigation of giardiasis.

Animals↗
PubMed1989

In vitro studies on the mode of action of quassinoids with activity against chloroquine-resistant Plasmodium falciparum.

Using the incorporation of [3H]isoleucine or [3H]hypoxanthine into acid-insoluble products as indices of protein- and nucleic acid-synthetic activity, respectively, it was shown that seven plant-derived quassinoids with differing chemical substitutions all inhibited protein synthesis more rapidly than nucleic acid synthesis in human erythrocytes infected with Plasmodium falciparum, in vitro. Five quassinoids (ailanthinone, bruceantin, bruceine B, glaucarubinone and holacanthone) were effective within 30 min at doses 10 times their 48 hr in vitro IC50 values. Chaparrin and glaucarubol differed in that they did not inhibit protein synthesis during the time course of these experiments when applied at 10 times their in vitro IC50 values. When these compounds were used at 209 and 114 times their respective IC50 values, their observed effects were identical to those of the other quassinoids studied. The time (t50) at which nucleic acid synthesis was reduced to 50% of control was directly proportional to the t50 for protein synthesis, suggesting that failure of nucleic acid synthesis is a consequence of inhibition of protein synthesis. It is concluded that in the malaria parasite, as in eukaryote models, quassinoids are rapid and potent inhibitors of protein synthesis, and that this is most likely due to effects upon the ribosome, rather than upon nucleic acid metabolism.

Animals↗
PubMed1989

The chemotherapy of rodent malaria. XLIV. Studies on the mode of action of CM 6606, an indolo (3,2-c) quinoline N-oxide.

CM 6606 differs in its mode of action from chloroquine but studies on its activity against parasites resistant to other antimalarials suggest that it may have some features in common with aminoalcohols. Similarities in drug-induced pigment changes are especially striking. Only halofantrine shows a reduced activity, however, against parasites that are highly resistant to CM 6606, while such parasites are slightly hypersensitive to sulfadoxine and clindamycin. Evidence suggesting that CM 6606 may function through an active metabolite, possibly CM 6609 in which the N-oxide is reduced, is discussed.

Animals↗
PubMed1988

Use of microdilution to assess in vitro antiamoebic activities of Brucea javanica fruits, Simarouba amara stem, and a number of quassinoids.

A microdilution technique for the assessment of in vitro activity against Entamoeba histolytica was devised and validated with metronidazole. The test was used to detect the antiamoebic activities of plant extracts prepared from the traditional remedies Brucea javanica fruits and Simarouba amara stems. The activity was associated with quassinoid-containing fractions. The 50% inhibitory concentrations for some quassinoids against amoebae were determined by using the microdilution method. These concentrations ranged from 0.019 micrograms.ml-1 for bruceantin, the most active quassinoid, to greater than 5 micrograms.ml-1 for glaucarubol, the least active compound tested. These results are discussed with reference to the known activities of these compounds against Plasmodium falciparum. Overall, the activities of the quassinoids against both protozoa are similar. The microdilution technique will be useful in the search for novel antiamoebic drugs.

Amebicides↗
PubMed1987

The effect of combinations of qinghaosu (artemisinin) with standard antimalarial drugs in the suppressive treatment of malaria in mice.

Artemisinin is a novel antimalarial drug isolated in China from the wormwood plant Artemisia annua L. Studies with rodent malaria were carried out to detect antagonism and synergism with a variety of antimalarial drugs. Isobolograms of drug interaction were plotted at the ED90 level. With a normally susceptible strain of Plasmodium berghei, marked potentiative synergism was found with mefloquine, tetracycline and spiramycin. There was some synergism also with primaquine. Combinations of artemisinin with dapsone, sulfadiazine, sulfadoxine, pyrimethamine, pyrimethamine/sulfadoxine and cycloguanil showed antagonism. A high degree of potentiation was shown between artemisinin and primaquine with a primaquine-resistant strain, whilst the combination with mefloquine showed enhanced potentiation with a mefloquine-resistant strain. Combinations of artemisinin with mefloquine, primaquine, tetracycline or clindamycin showed marked potentiation with an artemisinin-resistant strain. The mechanisms underlying the drug interactions observed are discussed.

Animals↗
PubMed1987

Amoebae and humidifier fever.

One hundred and nineteen sera from workers at four different work sites exposed to different contaminated humidifiers were examined by the immunofluorescent antibody (IFA) technique for antibodies to the amoebae Acanthamoeba polyphaga and Naegleria gruberi. Twenty-five of the sera were from workers with humidifier fever (HF) and six from workers with work related asthma (WRA) shown to be due to the contaminated humidifiers. A positive IFA test was found to correlate precipitin reaction to humidifier antigen, but did not correlate with smoking habit, work related symptoms (detected by standard questionnaire) or with HF or WRA. Amoebae were identified in all humidifiers studied.

Amoeba↗
PubMed1987

Acanthamoeba keratitis.

We report on four patients seen during the past two years who had acanthamoeba keratitis. One is described in detail. We believe that acanthamoebic eye infection is not rare. An immunofluorescent technique for localisation of amoebae and cysts is described. Our patients' response to propamidine and dibromopropamidine therapy was complicated by problems of toxicity.

Acanthamoeba↗
PubMed1987

Antimalarial drugs. An update.

Over the last decade, chloroquine-resistant falciparum malaria has spread to other areas from its original foci in Southeast Asia and South America. Additionally, new knowledge about the life-cycle of the malaria parasite, and about the pharmacokinetic properties of antimalarial drugs, has emerged. It is appropriate to reassess our approach to prevention and management of malaria with these factors in mind. Antimalarial drugs can be classified in two ways: biologically as tissue schizontocides, hypnozoitocides, blood schizontocides, gametocytocides or sporontocides; or by a mixed chemical/biological classification as 8-aminoquinolines, antimetabolites and (again) blood schizontocides. Chloroquine resistance in P. falciparum can now be found in most areas where malaria occurs. Malarial strains moderately resistant to the chloroquine group of drugs (chloroquine and mepacrine) are generally susceptible to the aryl amino alcohols such as quinine. Indeed, quinine is the most widely used drug for treating malaria due to chloroquine-resistant strains, followed by a 7-day course of tetracycline where some resistance to quinine is also found. Alternatively, the course of quinine may be followed by sulfadoxine/pyrimethamine or the newer quinoline derivative, mefloquine. Quinidine has also shown activity against quinine-resistant strains. Prophylaxis of chloroquine-resistant strains is best undertaken with daily proguanil (chloroguanide), and weekly chloroquine. In severe malaria, including cerebral malaria, an intravenous loading dose of quinine should be considered, and plasma concentration monitoring may be advisable to assist with dosage adjustment. In patients with severe renal insufficiency, there is evidence that the elimination of chloroquine is prolonged, and dosage adjustments may be necessary. Other recent findings on the pharmacodynamic properties, mechanisms of action and toxicity of antimalarial drugs are also discussed.

Antimalarials↗