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Biomedical subjects

W E Gutteridge

Publications and source records attributed to W E Gutteridge.

At least 55 records · Page 3Linked to original sources
PubMed1982

Crithidia fasciculata: a catalase-containing trypanosomatid sensitive to nitroheterocyclic drugs.

Crithidia fasciculata, which contains high levels of a cytosolic catalase, is sensitive to inhibition by at least two nitroheterocyclic drugs, Nifurtimox and MK 436, both of which are also active against Trypanosoma cruzi. Drug sensitivity is not enhanced in organisms containing reduced levels of catalase. The ultrastructural lesions in T. cruzi produced by nitroheterocycles, especially the swelling and gross vacuolation of the mitochondria, are seen also in C. fasciculata. These results are not consistent with the hypothesis that the action of drugs such as Nifurtimox on T. cruzi involve hydrogen peroxide accumulation as a result of the absence of catalase.

Animals↗
PubMed1982

A primary screen for drugs to prevent transmission of Chagas's disease during blood transfusion.

This paper describes how Microslide tubes can be used as the basis for a quick, simple, inexpensive screen to test for compounds which might prevent the transmission of Chagas's disease as a result of blood transfusion. The test uses Trypanosoma cruzi-infected mouse blood and requires only very small amounts of compound. The screen identifies compounds known to be active against blood trypomastigotes in vitro at 4 degrees C, and is apparently free of false negative and positive results.

Animals↗
PubMed1982

Identification and drug binding capabilities of tubulin in the nematode Ascaridia galli.

Cell extracts of Ascaridia galli bind colchicine in a manner suggesting the presence of a tubulin-like protein. Column chromatography of these extracts on DEAE-Sephadex yielded only one peak with colchicine-binding activity. Single peaks of radioactivity in this same position were obtained on chromatography of extracts prelabelled with either [3H]colchicine or [3H]parbendazole. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and two dimensional gel electrophoresis of the fractions making up the peaks indicated the presence of two proteins which co-migrate with mammalian brain alpha- and beta-tubulin markers. More detailed investigation showed that the A. galli tubulin has a slightly different alpha-subunit when compared with mammalian tubulin.

Animals↗
PubMed1981

Comparison of drug sensitivities of three strains of Trypanosoma cruzi in inbred A/Jax mice.

The sensitivity to 15 drugs of the Peru, Sonya and Y strains of Trypanosoma cruzi was investigated in inbred A/Jax strain mice. Some variation was seen in the percentage of survivors and more still in the survival times of those that died. Marked variation was seen when the two sets of data were analysed together by Litchfield's rapid graphic method for evaluating time-percent effect curves. No one strain, however, was found to be especially drug-sensitive and therefore particularly useful in primary drug screening. Furthermore, the differences in sensitivity were apparently not marked and are unlikely to have clinical significance once an effective drug with a high chemotherapeutic index is discovered for Chagas's disease.

Animals↗
PubMed1980

Subcellular localization of some glycolytic enzymes in parasitic flagellated protozoa.

1. The glycolytic enzymes of Tritrichomonas foetus, unlike those of Trypanosoma brucei, are apparently not located in microbody-like organelles (glycosomes) but appear to occur in the cytosol. 2. The localization of the glycolytic enzymes in Crithidia fasciculata and in the epimastigote and trypomastigote forms of Trypanosoma cruzi is however similar to that in T. brucei. 3. No evidence was obtained for the existence of glycolytic enzyme-containing microbodies in rat liver. 4. The glycosome is probably an organelle unique to members of the Kinetoplastida.

Animals↗
PubMed1979

Conversion of dihydroorotate to orotate in parasitic protozoa.

The conversion of dihydroorotate to orotate, one of the key reactions in the de novo pyrimidine biosynthetic pathway, has been studied in a number of parasitic protozoa. Enzyme activities capable of carrying out this reaction were detected in six members of the Kinetoplastida (Trypanosoma brucei, Trypanosoma congolense, Trypanosoma vivax, Trypanosoma lewisi, Trypanosoma cruzi, Leishmania enriettii) and three members of the genus Plasmodium (P. knowlesi, P. berghei, P. gallinaceum). The mechanism of the reaction in the two groups of protozoa were quite distinct. In the Kinetoplastida, the enzyme is an hydroxylase which occurs in the soluble fraction of the cell and probably requires tetrahydrobiopterin for activity. In contrast, in Plasmodium, the enzyme is a dehydrogenase which is particulate, probably mitochondrial, and intimately connected to the electron transport chain to which it passes electrons directly, probably at the ubiquinone level. Neither activity is regulated by fully formed pyrimidines. The enzyme in Plasmodium is similar in mechanism to the isofunctional mammalian enzyme. However, since malarial ubiquinones are apparently different from those in the mammal and since menoctone, which is active in vivo in experimental malaria, is a good inhibitor of the malarial enzyme, it could represent a useful target for chemotherapeutic attack. The enzyme in the Kinetoplastida is quite distinct from that in the mammal so that it too apparently falls into this category, though none of the currently used antitrypanosomal drugs appears to block it activity at physiological concentrations.

Animals↗
PubMed1978

Ultrastructural alterations and peroxide formation induced by naphthoquinones in different stages of Trypanosoma cruzi.

Addition of beta-lapachone, an o-naphthoquinone with bactericidal, cytotoxic, and trypanocidal activities, to Trypanosoma cruzi epimastigote and amastigote stages induced the release of O2- and H2O2 from the whole cells into the suspending medium. In the presence of reduced nicotinamide adenine dinucleotide as reductant beta-lapachone was also able to stimulate O2- and H2O2 production by homogenates of these stages. Electron micrographs showed that in beta-lapachone-treated amastigotes and trypomastigotes, the chromatin is arranged in patches, clearly differing from the normal pattern of chromatin distribution. Alterations of the nuclear, mitochondrial, and cytoplasmic membranes, as well as swelling of the mitochondria were also observed.

Animals↗