Search PubMed⌕ Search

Biomedical subjects

S L Croft

Publications and source records attributed to S L Croft.

At least 91 records · Page 5Linked to original sources
PubMed1989

Antileishmanial effects of clofazimine and other antimycobacterial agents.

In the search for more effective alternatives to the presently-used antileishmanial drugs, the activity of the major groups of antimycobacterial compounds has been examined, both in vitro and in animal models of infection. In vitro, clofazimine was the most active compound tested, with a mean ED50 of 2.3 mg l-1 against Leishmania mexicana amazonensis, 1.4 mg l-1 against L. donovani and 0.5 mg l-1 against L. major. Other active compounds were the thiosemicarbazone, thiambutosine, and salinazid, a derivative of isoniazid. Isoniazid itself was inactive, and rifampicin only partially active. In vivo, only clofazimine displayed significant activity, and it was most effective against the cutaneous infections. It is concluded that antimycobacterial activity is in general a poor predictor of antileishmanial potency.

Administration, Topical↗
PubMed1988

Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi. II. Partial biochemical characterization.

Culture supernatants of splenic T cells from susceptible CBA mice chronically infected with Trypanosoma cruzi contain a suppressive substance which can inhibit the induction of delayed-type hypersensitivity (DTH) to a wide range of antigens. The suppressive substance is distinct from T. cruzi antigen inasmuch as the supernatant depleted of any residual T. cruzi antigen by an affinity column still retains the suppressive activity, whereas addition of T. cruzi antigens to control supernatant did not confer suppressive function. The suppressive supernatant does not contain detectable levels of IL-1, IL-2, IL-3, or IFN-gamma but a modest level of IL-1 and IL-2 inhibitory activities. However, both these inhibitory activities elute at a different position from the DTH suppressive activity on gel filtration. The DTH suppressive activity is heat labile (1 h, 56 degrees C), cryostable, but destroyed by trypsin treatment. It binds to ricin but not to lentil lectin. Sepharose 4B gel filtration and HPLC analysis in mild chaotropic agents (urea, ethylene glycol) demonstrate that the suppressive substance has an apparent Mr of 30 to 60 kDa, but full DTH-suppressive activity is retained only in an aggregated form.

Animals↗
PubMed1988

Screening of drugs for rapid activity against Trypanosoma cruzi trypomastigotes in vitro.

Previous studies to find drugs with an existing product licence which were active at 4 degrees C within 24 hours and which would be suitable to prevent the transmission of Chagas' disease during blood transfusion were unsuccessful. As part of an alternative approach to identify drugs active at 37 degrees C or 25 degrees C within 2 hours, over 280 compounds were screened against bloodstream trypomastigotes of Trypanosoma cruzi Sonya strain in a microslide test in vitro. Although compounds from a wide range of chemical groups were tested only three polyene antibiotics showed outstanding trypanocidal activity. Amphotericin B, candicidin and trichomycin lysed all trypomastigotes at 8 X 10(-6) as determined by microscopical techniques. However, these compounds also showed toxicity to mammalian erythrocytes at the same concentration after a 24 hours incubation period. It seems unlikely that this approach will yield a candidate replacement for gentian violet.

Amphotericin B↗
PubMed1987

Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi. I. Preferential inhibition of the induction of delayed-type hypersensitivity.

Culture supernatants of spleen cells from susceptible CBA mice chronically infected with Trypanosoma cruzi were able to inhibit the induction of delayed-type hypersensitivity (DTH) to a wide range of antigens as measured by 24-hr footpad swelling, bone marrow homing, and radioactivity accumulation assays. The suppressive activity, which was also present in the serum of these chronically infected mice, appears to be specific for the induction of DTH and had no effect on the 3-hr immediate-type hypersensitivity. It also failed to modify the expression of DTH in presensitized mice. Furthermore, it did not affect the synthesis in normal recipients of specific antibody or the induction of helper T cells or cytotoxic T cells. It also failed to induce DTH tolerance as recipient mice with markedly reduced DTH were able to develop a normal DTH response after secondary immunization. The suppressive activity was produced by an Ig- macrophage-depleted splenic T cell population, whose capacity to secrete the suppressive substance was completely abrogated by treatment in vitro with anti-L3T4 antibody and complement, but not with anti-Lyt-2 antibody and complement. These results therefore demonstrate that L3T4+ T cells from mice chronically infected with T. cruzi can produce substances which interfere with the induction of DTH. This finding may help to identify the differential antigenic stimulatory requirement for the activation of the various subsets of T cells.

Animals↗
PubMed1987

The activity of alkyl phosphorylcholines and related derivatives against Leishmania donovani.

Several alkyl phosphorylcholines and related derivatives were tested against Leishmania donovani amastigotes in mouse peritoneal macrophages in vitro and ED50 values were determined in the range of 1-12 microM. The three alkyl phosphorylcholines tested against L. donovani in BALB/c mice were active, an ED50 of 12.8 mg/kg/day X 5 was ascertained for one compound, but an alkyl phosphorylethanolamine was inactive.

Alkylation↗
PubMed1986

In vitro screens in the experimental chemotherapy of leishmaniasis and trypanosomiasis.

The search for more effective drugs for the treatment of leishmaniasis and trypanosomiasis has increasingly involved the use of in vitro screens. These possess the immediate advantages of requiring only a few mg of compound for tests, providing for a large through-put of compounds with rapid results at lower costs, and requiring fewer animals. Models for the cultivation or maintenance in vitro of 'mammalian stages' of Leishmania and Trypanosoma cruzi have been available for many years but only in the last decade have satisfactory techniques for the cultivation of bloodstream forms of T. brucei been developed.

Journal Article↗
PubMed1986

Morphological changes of Trypanosoma vivax in mice.

Morphological changes were observed in the blood forms of Trypanosoma vivax strain Y486 in mice on Days 12-13 of infection, following the peak parasitaemia. During this period elongate trypomastigotes, 25-40 micron long, were observed, most showing an anterior movement of the kinetoplast towards the nucleus and some having a blunt posterior end. In a few parasites a complete transformation to the epimastigote form, 40-42 micron long, was observed. Small sphaeromastigotes were also present, especially in the fine capillaries of various organs. Smears and electron microscopy suggested the presence of extra-vascular forms in the spleen.

Animals↗
PubMed1986

A strategy for the prevention of the transmission of Chagas' disease during blood transfusion.

Our strategy for preventing the transmission of Chagas' disease during blood transfusion is discussed. In addition, the possibility that the Peru, Sonya, Tulahuen and Y strains of Trypanosoma cruzi show varying sensitivities to a series of amphiphilic cationic drugs in vitro at 4 degrees C was investigated using a microscope lysis test. All 21 drugs tested at a concentration of 10(-3) M lysed Sonya bloodstream trypomastigotes, but Peru, Tulahuen and Y strains were affected by 17, 17 and 11 drugs, respectively. All four strains were most sensitive to the acridines; acranil, aminacrine and mepacrine. Although some variation was seen in their responses to certain drugs, no one strain was particularly insensitive to the series as a whole. The effects of gentian violet, maprotiline and mepacrine on the infectivity of Sonya trypomastigotes following incubation at 4 degrees C for 24 h were evaluated. Mepacrine, at a concentration of 2.5 X 10(-4) M greatly decreased the viability of trypomastigotes, while 10(-3) M concentrations of both maprotiline, mepacrine, and gentian violet (at low parasite densities only) apparently abolished all infectivity. Although the compounds we tested did not show a significant improvement over gentian violet, the compound currently used in some blood banks, other existing amphiphilic cationic drugs could be of use in preventing the transmission of Chagas' disease during blood transfusion.

Chagas Disease↗
PubMed1985

The effect of allopurinol ribonucleoside and formycin B on Trypanosoma cruzi infections in mice.

The anti-Trypanosoma cruzi effect of allopurinol ribonucleoside and formycin B was examined against infections of the sensitive Y and Peru strains in inbred mice, strain DBA/1. Allopurinol ribonucleoside given in the drinking water at doses calculated to be 239, 511 and 929 mg/kg/day for 28 days, prevented the death of the mice but did not eradicate the infection. Formycin B given orally at 100 and 10 mg/kg/day X 5 days, showed a similar effect.

Allopurinol↗
PubMed1985

Anti-leishmanial effect of allopurinol ribonucleoside and the related compounds, allopurinol, thiopurinol, thiopurinol ribonucleoside, and of formycin B, sinefungin and the lepidine WR6026.

Allopurinol and allopurinol ribonucleoside tested in vitro and in vivo for activity against Leishmania donovani. Activity in vitro was low against the amastigote form of this parasite with ED50 values of the order of 54 and 96 microM and 86 and 213 microM respectively for the two compounds. In vivo inhibition of up to 47% was achieved with allopurinol ribonucleoside given in the drinking water. However, low blood levels were found in the mouse relative to those in man. Low in vivo activity was also seen with allopurinol ribonucleoside against L. major and other species of Leishmania causing cutaneous lesions. The metabolism of allopurinol ribonucleoside in aldehyde oxidase deficient mice (inbred strains DBA/1, DBA/2) resembled that of man, but the antileishmanial activity remained low. Other compounds, formycin B, sinefungin and the lepidine WR6026 were highly active against mice infected with L. donovani or L. major.

Adenosine↗