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Biomedical subjects

W L Hanson

Publications and source records attributed to W L Hanson.

At least 91 records · Page 5Linked to original sources

Susceptibility of five strains of mice to Babesia microti of human origin.

One outbred (CF1) and four inbred (BALB/c, C57, CBA and C3H) strains of mice were tested for susceptibility to Babesia microti of human origin. Of these, intact C3H mice developed higher parasitemia than all other intact mice, while BALB/c mice developed the highest parasitemia among splenectomized mice. Susceptibility was not related to H-2 haplotype in any obvious way. Because C3H and BALB/c mice developed relatively high initial peak parasitemias, the parasite was serially passaged in both of these mouse strains in an attempt to increase parasite virulence. After 30 passages in BALB/c and 49 passages in C3H mice over a period of 12 months, maximum parasitemias were 50 times higher than those observed initially. After the peak parasitemias of these two mouse-adapted parasites had stabilized, the relationship between onset and level of maximum parasitemia and number of parasites inoculated was determined. With both C3H- and BALB/c-adapted parasites, as inoculum size increased, the time required to reach maximum parasitemia decreased and the level of maximum parasitemia increased. Studies involving infection of either mouse strain with parasites adapted to the heterologous mouse strain indicated that C3H mice were more susceptible than BALB/c mice to homologous or heterologous parasites. These data suggest that the virulence of B. microti to the mouse can be increased by prolonged passage in this host. Once adaptation to this host species has occurred, virulence appears to be more dependent on the innate susceptibility of the mouse strain than on adaptation of the parasites to a particular strain of mouse.

Animals↗

Hematotropic parasites of translocated raccoons in the southeast.

Ninety-four raccoons (Procyon lotor) from 6 southeastern states were examined for hematotropic parasites, to evaluate the carrier potential of these animals as they relate to translocation and release for hunting purposes. Four species of hematotropic parasites were identified, viz, Babesia procyonis, Haemobartonella procyoni, Hepatozoon procyonis, and Trypanosoma cruzi. Lesions in infected raccoons were associated only with H procyonis. Babesia procyonis was enzootic in populations of raccoons used as sources for exportation and in raccoons resident in typical release areas. Haemobartonella procyoni, H procyonis, and T cruzi were prevalent only in locales of raccoon origin. Due to the potential pathogenicity of H procyonis and T cruzi in raccoons or other hosts, the practice of translocating raccoons from enzootic to nonenzootic areas was considered biologically hazardous.

Anaplasmataceae↗

Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs.

Liposomes containing antimonial compounds trapped in the aqueous phase were tested in the treatment of experimental leishmaniasis. The rationale of this approach was based on the hypothesis that the liposomes and the parasite are taken up by the same cell, the reticuloendothelial cell, and we present electron microscopic evidence that supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When two antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to either of the free (unencapsulated) drugs. After infection, if untreated, all of the hamsters eventually would die from the disease. Liposome-encapsulated meglumine antimoniate was about 330-640 times more effective in causing a drop in the death rate than was the free antimonial. The efficacy of treatment was influenced by the lipid composition and charge of the liposomes. For example, positively charged liposomes containing egg phosphatidylcholine were much less effective than negatively charged ones. In contrast, positively and negatively charged sphingomyelin liposomes were equally effective. Liposomes containing phosphatidylserine (which were negatively charged, but also had a much higher charge density) were among the less-effective preparations. Among those tested, the most consistently efficacious liposomes contained highly saturated long-chain phospholipids (eg., dipalmitoyl phosphatidylcholine), cholesterol, and a negative charge. We conclude that liposomes may be useful as carriers of drugs to treat infectious diseases involving the reticuloendothelial system. The toxicities of antimony are very similar to those of arsenic. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis.

Animals↗

The antileishmanial activity of lepidines.

A series of lepidines (6-methoxy-4-methyl-8-aminoquinoline derivatives) was studied in a hamster-Leishmania donovani model. Members of this class were found to have activity many-fold that of the standard, meglumine antimoniate (Glucantime). One of them, 8-(6-diethylamino-hexylamino)-6-methoxy-4-methylquinoline, designated WR 6026, when given orally was over 700 times as effective as the standard antimonial drug.

Aminoquinolines↗

In search of anti-Trypanosoma cruzi drugs: new leads from a mouse model.

Nine of 25 carefully selected compounds (from a stock of more than 200 000 chemical species amassed principally as a result of testing against other parasitic diseases) were found to have significant suppressive activity against the parasites in the blood of a Trypanosoma cruzi mouse model. Eight of these compounds evaluated in this model had suppressive activity equal to or greater than the reference compound, nifurtimox. For the first time, suppressive activity against T. cruzi is reported for a 7-aminoquinoline, a phosphonium salt, and TAC pamoate; The biological model is believed to be able to serve as a means of identifying other new "leads* in seeking drugs broadly effective against T=ruzi infections in man.

5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazol↗

The influence of gonadectomy of host on parasitemia and mortality of mice infected with Trypanosoma cruzi.

Male CF1 mice were more susceptible to acute infections of Trypanosoma cruzi than female mice as evidenced by significantly greater maximum mean parasitemia of approximately 8.9 times 10-6 per ml in males as compared to 1.5 times 10-6 per ml in females. Mortality was also greater in males (80 to 90% as compared to 28% in females). Ovariectomy of female mice made them more susceptible than unoperated female of similar age and stock to the Brazil strain of T. cruzi as indicated by maximum mean parasitemia of 10.9 times 10-6 per ml in the former and 7.5 times 10-6 in the latter. Mortality of the ovariectomized mice was as great as 90% in some experiments while that of unoperated controls nerve exceeded 30%. Parasitemia and mortality is castrated male mice were not significantly different from unoperated male mice infected with T. cruzi.

Animals↗