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Biomedical subjects

K C Carter

Publications and source records attributed to K C Carter.

At least 91 records · Page 5Linked to original sources

Visceral leishmaniasis: resistance to reinfection in the liver following chemotherapy in the BALB/c mouse.

The ability of BALB/c mice to resist reinfection with Leishmania donovani following chemotherapy was studied. BALB/c mice, infected with L. donovani, were treated on Days 7 and 8 postinfection with free, niosomal, or liposomal sodium stibogluconate. It was found that all three drug treatments caused a dramatic reduction in liver parasite burdens as measured on Days 6 and 29 post-treatment. On Day 6 postdrug treatment infection with L. donovani amastigotes, of mice from infected, drug-treated groups, along with age- and sex-matched uninfected controls, showed that at 23 days later, significantly fewer parasites were recovered from the livers of reinfected animals compared with controls given their first infection. Treatment of mice with sodium stibogluconate 6 days prior to a primary infection significantly reduced the number of parasites recovered 14 days later, especially using the carrier form of the drug. In vivo macrophage activity in the liver, as measured by the uptake of radiolabeled horseradish peroxidase immune complex, was significantly raised following stibogluconate treatment of infected but not uninfected mice. These results suggest that a state of resistance persists in the liver of infected mice following chemotherapy which may in part be due to local macrophage activation but also to an unsuspected persistance of the drug.

Animals↗

The course of infection in rats given small primary doses of Strongyloides ratti and S. venezuelensis.

Development of exact doses (less than 100) of Strongyloides venezuelensis third-stage larvae in adult Wistar rats was insignificant (mean proportion of 0.076 of the dose at day 8, n = 16) compared with a homogonic strain of S. ratti (0.538, n = 6; 0.726, n = 6) and heterogonic S. ratti (0.681, n = 6). Newly-weaned Wistars allowed development of a mean proportion of S. venezuelensis of 0.298 (n = 4) compared with 0.013 (n = 4) of the same sample of larvae in adult hosts. Experiments with 75Se-labelled larvae established that S. venezuelensis effectively failed to migrate from skin to intestine in adult animals, while mean proportions of 0.141 (n = 5) and 0.138 (n = 4) of the label was found in the intestines of newly-weaned rats 72 h after skin application. Labelled larvae of homogonic S. ratti migrated equally well in both age groups of host (0.350 and 0.358 in 12- and 3-week-olds respectively). Adult S. venezuelensis transferred surgically to the intestines of previously uninfected full-grown Wistars survived over a 21-day period to the same extent as either strain of S. ratti. Resistance of Wistar rats to S. venezuelensis therefore appears to affect the migratory stage preferentially. S. venezuelensis developed better in mature PVG inbred rats (mean = 0.301, n = 20). Studies of S. ratti showed that infections of both strains initiated by exact (less than 100) doses in Wistar rats had decayed to insignificance between days 26 and 32. The rate of loss of adults of the heterogonic strain was significantly greater than that for the homogonic. The egg content of worms declined as infection progressed and rats were idiosyncratic in their influence on parasite reproduction from the earliest time of sampling (8 d). It was established that 'autoinfection' was an unlikely feature of the biology of homogonic S. ratti following the surgical transfer of 450 first-stage larvae to the intestines of 8 adult Wistar rats. No evidence of infection appeared in the guts of these animals 8 days post-transfer. The significance of these results in terms of the biology of Strongyloides spp. naturally occurring in the rat is discussed.

Animals↗

Studies on the topical treatment of experimental cutaneous leishmaniasis: the therapeutic effect of methyl benzethonium chloride and the aminoglycosides, gentamicin and paromomycin.

BALB/c mice infected with either Leishmania major or Leishmania mexicana were treated twice a day for 10 days with an ointment containing 15% gentamicin or paromomycin, with or without 12% methylbenzethonium chloride (MBCl). It was found that topical application of either paromomycin or MBCl cured the parasite lesion, and that combined treatment with the two compounds had an additive effect. However, after four days' therapy there was a severe inflammatory response at the treatment site, and in most experiments mice relapsed and renewed lesion growth was observed. It is suggested that a non-specific inflammatory reaction may be an important component of the therapeutic response. In further experiments, L. major infected mice treated with paromomycin and MBCl which had cured but not relapsed 58 days after treatment were challenged with a similar dose of the homologous parasite. Lesions developed 16 days post-infection, and the number of parasites recovered from these lesions was similar to that recovered from lesions in control mice. Therefore no protective immunity had been induced by chemotherapy.

Administration, Topical↗

Visceral leishmaniasis: drug carrier system characteristics and the ability to clear parasites from the liver, spleen and bone marrow in Leishmania donovani infected BALB/c mice.

The efficacy of various sodium stibogluconate formulations against Leishmania donovani has been investigated using a BALB/c mouse model of visceral leishmaniasis. Only one therapy, multiple dosing with drug loaded sonicated vesicles, liposomes or niosomes, was found to be effective against parasites in the liver, spleen and bone marrow. Other treatments significantly reduced parasite liver burdens but either failed to effect spleen and bone marrow parasites, or were effective but toxic. Prophylactic treatment with sodium stibogluconate preparations, six days before infection, reduced parasite multiplication in the liver (free, niosomal and liposomal drug) and the spleen (sonicated, drug loaded niosomes only), but had no suppressive effect on bone marrow parasite burdens compared with controls. These results indicate that in-vivo sodium stibogluconate persists in some compartments at parasiticidal concentrations and that failure to reach this concentration at some sites of infection such as bone marrow, is the cause of treatment failure and relapse.

1,2-Dipalmitoylphosphatidylcholine↗

The therapeutic effect of sodium stibogluconate in BALB/c mice infected with Leishmania donovani is organ-dependent.

A study of the antileishmanial efficacy of sodium stibogluconate was carried out in BALB/c mice. The drug was administered to Leishmania donovani-infected animals on days 7 and 8 post-infection in one of three forms; free (40-50 mg Sbv Kg-1), liposomal, or niosomal (6.4-8.0 mg Sbv Kg-1) drug. On day 14 post-infection counts of the number of parasites present in the liver, spleen and bone marrow of treated and control animals showed that although all three drug preparations significantly reduced parasite numbers in the liver (approximately equal to 99% suppression) they had little effect on those residing in the spleen or bone marrow. The carrier forms of the drug were therefore significantly more effective than free drug in reducing liver parasite burdens. Increasing the concentration and the number of doses of free drug (maximum of 500 mg Sbv Kg-1), and reducing the size of the vesicles used to deliver the drug had a minimal effect on parasite numbers in the spleen and bone marrow. It is proposed that because of the resistance of spleen and bone marrow parasites to drug therapy, the BALB/c mouse infected with L. donovani provides an excellent model system for the study of drug delivery to these deeper tissue sites.

Animals↗

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Austria↗

Chromosome distribution in neuroblast metaphase cells of Lucusta migratoria L.

Chromosome distribution has been investigated at metaphase and C-metaphase in neuroblast cells of Locusta migratoria embryos. There is no evidence for generalised somatic association of homologues or nucleolus organising chromosomes at either stage. Homologous chromosomes 9 are found closer together than expected in C-metaphase but this seems to be due to their tendency to lie in the centre of the C-metaphase squash.

Animals↗