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Biomedical subjects

R A Neal

Publications and source records attributed to R A Neal.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Reversal of drug resistance in Trypanosoma cruzi and Leishmania donovani by verapamil.

Following previous studies of verapamil reversal of chloroquine resistance in malaria and multi-drug resistance in cancer cells, the effect of verapamil was investigated on nifurtimox-resistant Trypanosoma cruzi in vitro and antimony-resistant Leishmania donovani in vitro and in vivo. Verapamil alone was not active against either parasite, but in combination with nifurtimox it reversed the drug resistance of T. cruzi and in combination with sodium stibogluconate reversed the drug resistance of L. donovani.

Animals↗
PubMedDate not supplied

Leishmania infecting man and wild animals in Saudi Arabia. 8. The influence of prior infection with Leishmania arabica on challenge with L. major in man.

A clinical trial is described of an attempt to protect against Leishmania major by prior vaccination with live L. arabica. After a single, previously leishmanin-negative, adult male volunteer was bitten by 8 Phlebotomus papatasi infected with L. arabica, no infected lesions were observed. He remained leishmanin-negative and his lymphocytes reacted weakly to antigens of L. arabica or L. major. Subsequently he and 3 other leishmanin-negative adult male volunteers were vaccinated with cultures containing 4 x 10(6) promastigotes of L. arabica. All remained leishmanin-negative but their lymphocytes showed some response to both L. arabica and L. major antigens. 96 d after vaccination these 4, and another, non-vaccinated, volunteer were challenged with 2 x 10(6) promastigotes of L. major. Active cutaneous, ulcerated lesions developed in all 5 volunteers. The lesions in 3 vaccinated volunteers were associated with marked lymphadenitis and beading, but the lesions started to heal spontaneously within 120-250 d after challenge. The lesion in the fourth vaccinated volunteer was less severe and lymphadenitis was not observed. The lesion in the unvaccinated subject developed more slowly and was smaller, but more chronic, than those in the vaccinated individuals. Marked cross-reactivity in terms of lymphocyte proliferation and interferon-gamma production was observed between L. major and L. arabica in both directions in subjects exposed first to one or the other organism. Although the procedure followed in this trial failed to give protection against L. major, further studies in volunteers should be considered.

Adolescent↗
PubMedDate not supplied

Leishmania infecting man and wild animals in Saudi Arabia. 7. Partial protection of mice against Leishmania major by prior infection with L. arabica.

A survey of inbred mouse strains showed that strain C3H/he was the most comparable to man in respect of its susceptibility to Leishmania major and the subsequent healing of lesions produced by this organism. L. arabica proved to have a lower virulence than L. major and prior inoculation with the former resulted in a decrease of the lesion sizes following subsequent L. major challenge. Moreover, L. major lesions that did develop in mice previously inoculated with L. arabica generally healed faster.

Animals↗
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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↗
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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

Comparison of the metabolism of parathion by a rat liver reconstituted mixed-function oxidase enzyme system and by a system containing cumene hydroperoxide and purified rat liver cytochrome P-450.

The metabolism of parathion by a reconstituted mixed-function oxidase enzyme system (rat liver cytochrome P-450, NADPH-cytochrome c reductase, dilauroyl phosphatidylcholine, deoxycholate, and NADPH) or a cumene hydroperoxide system (cytochrome P-450, dilauroyl phosphatidylcholine, and cumene hydroperoxide) have been compared. The products formed on incubation of parathion with both systems were paraoxon, diethyl phosphorothioic acid, diethyl phosphoric acid, p-nitrophenol, and atomic sulfur. The apparent KM values for parathion for formation of paraoxon and diethyl phosphorothioic acid with the cumene hydroperoxide system were 55 and 39 X 10(-6) M, respectively. These KM values are not significantly different. When the reconstituted system was used, apparent KM values of 2.8 x 10(-6) M for formation of paraoxon and 3.9 x 10(-6) M for The formation of diethyl phosphorothioic acid and diethyl phosphoric acid were determined. These KM values are also not significantly different. covalent binding of the sulfur atom, released in the metabolism of parathion to paraoxon, to the proteins of the reconstituted system and to cytochrome P-450 of the cumene hydroperoxide system was also examined. With both the reconstituted system and the cumene hydroperoxide system approximately 65% of the sulfur released became bound to the proteins of these enzyme systems. The binding of the sulfur atome resulted in a progressive inhibition of the metabolism of parathion by these two systems.

Animals↗
PubMedDate not supplied

Metabolism of methimazole by rat liver cytochrome P-450-containing monoxygenases.

The incubation of methimazole (1-methyl-2-thioimidazole, MMI) with rat hepatic microsomes led to the formation of 3-methyl-2-thiohydantoin and N-methylimidazole. In addition, an NADPH-stimulated binding of 14C and 35S from [14C]- and [35s]MMI to microsomal macromolecules was seen. Both the NADPH-stimulated N-methylimidazole formation and binding of radioactivity from [14C]- and [35S]MMI to microsomal macromolecules appeared to be catalyzed largely by the cytocrhome P-450 to monoxygenase systems of rat hepatic microsomes. A portion of the radioactivity bound to microsomes incubated with [14C]- and [35S]MMI was released as unchanged MMI on prolonged incubation under acid conditions; this suggests that strong binding of MMI to microsomes occurred. A portion of the 35S bound to microsomes incubated with [35S]MMI can be released as 35SCN- on incubation of the 35S-labeled microsomes with CN-. These data suggest that a portion of the sulfur released in the metabolism of MMI to N-methylimidazole is in the form of atomic sulfur (S), which binds to cysteine sulfhydryl groups (R-S-H) in microsomal proteins to form a hydrodisulfide (R-S-S-H).

Animals↗