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Biomedical subjects

S L Croft

Publications and source records attributed to S L Croft.

107 records · Page 6Linked to original sources
PubMed1985

Oxygen radical release by adherent cell populations during the initial stages of a lethal rodent malarial infection.

A series of experiments was carried out to assess the levels of reactive oxygen intermediates (ROI) released by macrophages and monocytes during an acute malarial infection, and to consider the importance of oxidant-induced parasite killing in host protection. Adherent cell populations were removed from the peritoneum and spleen of BALB/c and B10/D2/n mice between Days 0-5 of a Plasmodium yoelii nigeriensis infection. These cell populations were quantified, characterized and their ROI-releasing capacity was measured by following ferricytochrome c reduction upon stimulation with phorbol myristate acetate (PMA). Both strains of mice displayed higher numbers of macrophages and macrophage precursors as the infection progressed; this rise was more marked and accompanied by splenomegaly in BALB/c mice. A concurrent decrease in peritoneal cell numbers was observed. Splenic adherent cell populations released much lower levels of ROI than peritoneal macrophages upon triggering. The levels of ROI released from BALB/c splenic adherent cells rose gradually until Day 3, when the parasitaemia was slightly decreased. In contrast, splenic populations from B10 mice had a decreased capacity to release ROI, particularly after Day 3, when the parasitaemia rose sharply. In further studies, electron microscopy was used to detect H2O2 release during the in vitro interaction of peritoneal macrophages and parasitized erythrocytes. Cerium chloride staining techniques demonstrated that H2O production was not dependent on phagocytosis or the presence of immune serum, although levels were increased by the presence of the latter.

Animals↗
PubMed1984

An in-vitro system for determining the activity of compounds against the intracellular amastigote form of Leishmania donovani.

A method has been defined for infecting primary mouse peritoneal macrophages with amastigotes of Leishmania donovani in vitro, and analysing the response of the infected macrophages to treatment with drugs. The growth of intracellular amastigotes was inhibited by all clinically used antileishmanial drugs. Toxic effects on macrophages were observed with some drugs. Other experimental antileishmanial compounds were active in this system. This test is proposed as an initial screening test for the discovery of novel antileishmanial compounds.

Animals↗
PubMed1984

Trypanosome infection rates of Glossina spp. (Diptera: Glossinidae) in transitional forest-savanna near Bouaflé, Ivory Coast.

Tsetse, caught in biconical traps near Bouaflé, Ivory Coast in 1980-81, were examined for trypanosome infections. In a sample of 1138 non teneral Glossina palpalis s.l. there were infection rates of 12.2% (all infections) and 5.3% (mature infections). Female flies had a significantly higher infection rate than males. In G. palpalis only 3 (0.26%) salivary gland infections were detected, 62.3% of the mature infections were T. vivax-like and 71.4% of all infections were restricted to the midgut. The infection rate in forest/plantation caught G. palpalis was twice that of village caught flies. The infection rate increased with fly age and is correlated in female flies. In smaller samples of G.p. pallicera and G. fusca group flies the trypanosome infection rates were 37% and 46% respectively. In both these groups of flies 64.7% of infections were mature and were predominantly T. vivax-like and in females.

Animals↗
PubMed1982

Anti-trypanosomal factor in the haemolymph of Glossina.

The motility of cultured procyclic forms of Trypanosoma brucei brucei ANTat serodeme derived from EATRO 1125 was greatly reduced when incubated in vitro with the haemolymph of Glossina morsitans morsitans at dilutions as low as 1:512 after incubation periods of 1-2 h at 27 degrees C. This effect was demonstrated in the haemolymph of male and female, teneral and non-teneral G.m. morsitans but was abolished by heat inactivation. A significant reduction in the motility of cultured forms of Trypanosoma (S.) dionisii was also observed when incubated in G.m. morsitans haemolymph but little effect was seen on culture forms of Crithidia fasciculata and Leishmania hertigi. An anti-trypanosomal factor was also demonstrated in the haemolymph of Glossina austeni, G. palpalis gambiensis and G. tachinoides.

Animals↗
PubMed1979

Studies on the ultrastructure, virus-like particles and infectivity of Leishmania hertigi.

Five strains of Leishmania hertigi hertigi isolated in Panama and three strains of L. hertigi deanei isolated in Brazil were studied. Ultrastructural examination of promastigotes grown in culture showed virus-like particles (VLPs), 55--60 nm diameter, in the cytoplasm of all strains. The VLPs were normally either organized in paracrystalline clusters or associated with induced tubules. In some cases the VLPs were associated with dense vesicular bodies. Mitochondria with which the VLPs were associated had enlarged elongate or circular cristae. Elongate 'microbodies' containing rod-like structures were observed in promastigotes grown in culture. Poor infections of promastigotes developed in the midguts of 10% of laboratory-bred Lu. longipalpis following experimental feeding on cultures of L. h. hertigi. VLPs were seen in a promastigote in the midgut of a sandfly five days after feeding. Laboratory mammals proved poor hosts for L. hertigi. Cryptic infections in the visceral organs of immunosuppressed hamsters and immunodeficient 'nude' mice were detectable only by culture. Infections of DS cell and mouse peritoneal macrophage cultures showed amastigotes with a high ribosomal density and deep invaginations of the pellicular layer. VLPs were rarely seen in these amastigotes.

Animals↗
PubMed1979

The Noguchi-Adler phenomenon: an ultrastructural study of the effects of homologous antiserum on the growth of promastigotes of Leishmania braziliensis braziliensis and Leishmania hertigi hertigi.

A light and electron microscope study was made of the agglutinated bodies formed on growing promastigotes of a Leishmania b braziliensis and a L. h. hertigi strain in their homologous antisera to determine the role of leishmanial excreted factor (EF) in the Noguchi-Adler phenomenon, since the L. b. braziliensis strain produced a demonstrable EF, whereas the L. h. hertigi strain did not. Promastigotes of L. b. braziliensis, when grown in high concentrations of homologous antiserum, formed Noguchi-Adler (N-A) bodies, in which the cells were embedded in an extensive amorphous matrix. The cells of L. b. braziliensis in the embedding matrix often appeared unhealthy or dead, with swollen flagellar pockets and distorted flagella, with which small visicles were associated. Even though promastigotes of L. h. hertigi do not produce an EF that precipitates with homologous antibody, N-A bodies containing agglutinated cells separated by a thin structured layer of precipitate were formed during growth in homologous antiserum. In high concentrations of antiserum, some of the agglutinated cells of L. h. hertigi were enlarged and showed syncytial characters that included up to five nuclei, two dividing nuclei and five basal bodies associated with a single kinetoplast. Small vesicles and membranous folds were also observed between cells. The complexity of the Noguchi-Adler phenomenon and significance of the morphological changes seen are discussed.

Agglutination↗
PubMedDate not supplied

Antileishmanial activity of the ether phospholipid ilmofosine.

The ether phospholipid ilmofosine (BM 41.440) was active in vitro against amastigotes of Leishmania donovani and an antimony-resistant line of L. infantum in mouse peritoneal macrophages with ED50 values of 3.7 microM and 3.5 microM respectively. Ilmofosine was also active against L. donovani in BALB/c mice following oral and subcutaneous dosing, with an ED50 value of 10.5 mg/kg x 5 by the oral route.

Administration, Oral↗
PubMedDate not supplied

Aminosidine ointments for the treatment of experimental cutaneous leishmaniasis.

A 15% aminosidine sulphate (AS)/10% urea/white soft paraffin (WSP) ointment cured all Leishmania major lesions on Balb/C mice following topical application for 10 d. Some relapses were observed 10 weeks after treatment. AS alone in WSP ointment was also highly effective. The ointment containing urea was non-irritant to mice, whereas ointments containing quaternary ammonium compounds were irritant. The 15% AS/10% urea/WSP ointment was not effective in the treatment of L. mexicana or L. panamensis lesions on Balb/C mice, no cure being observed.

Animals↗
PubMedDate not supplied

A topical nitric oxide-generating therapy for cutaneous leishmaniasis.

Nitric oxide (NO) synthesized by macrophages is cidal to Leishmania. Since NO diffuses into tissues, we reasoned that NO-generating creams applied topically to lesions might be an effective and inexpensive treatment for cutaneous leishmaniasis (CL). NO was generated non-enzymatically by the acidification of nitrite (KNO2) by ascorbic acid (ASC) or salicylic acid (SAL). Experiments in vitro showed that the combinations of KNO2 and SAL, ASC, or KC1 all killed promastigotes and amastigotes of L. major in a dose- and time-dependent manner, but were toxic to macrophages at higher concentrations. Experiments in vivo showed modest efficacy of the combinations applied topically to L. major CL lesions of BALB/c mice. Forty patients with parasitologically proven L. tropica CL from Aleppo, Syria, were treated for 4 weeks with KNO2 in aqueous cream combined with KC1, ASC, or SAL. Only 11 (28%) of 40 patients showed improvement and only 5 (12%) of 40 were cured at 2 months. Further development of NO-generating creams is warranted.

Administration, Topical↗
PubMedDate not supplied

Pharmacological approaches to antitrypanosomal chemotherapy.

There is an urgent need for new drugs for the chemotherapy of human African trypanosomiasis, Chagas disease and leishmaniasis. Progress has been made in the identification and characterization of novel drug targets for rational chemotherapy and inhibitors of trypanosomatid glycosomal enzymes, trypanothione reductase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, cysteine proteases and of the purine and sterol biosynthetic pathways. However, less attention has been paid to the pharmacological aspects of drug design or to the use of drug delivery systems in the chemotherapy of African trypanosomiasis and Chagas disease. A review of research on pharmacology and drug delivery systems shows that there are new opportunities for improving the chemotherapy of these diseases.

Animals↗