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Biomedical subjects

W L Chapman

Publications and source records attributed to W L Chapman.

17 recordsLinked to original sources
PubMed1992

Activity of amphotericin B cholesterol dispersion (Amphocil) in experimental visceral leishmaniasis.

Standard therapy of human visceral leishmaniasis with parenteral pentavalent antimonial agents is generally curative but has the disadvantages of a 28-day treatment course, occasional treatment failures, and toxicity. The antifungal and antileishmanial agent amphotericin B has been complexed with lipids to develop a less toxic formulation of amphotericin B. Because lipid particles are phagocytized by the reticuloendothelial system, lipid-associated amphotericin B should be concentrated in infected macrophages and be very effective against visceral leishmaniasis. One formulation, amphotericin B cholesterol dispersion (ABCD) (Amphocil), was tested for antileishmanial activity in Leishmania donovani-infected hamsters. In the first experiment, hamsters were infected, administered with the drug 3 days later, and then sacrificed after a further 4 days. ABCD (dose needed to suppress 99% of hepatic parasites compared with controls [SD (99)], 0.4 mg/kg of body weight) was 15 times as effective as conventional amphotericin B [SD (99), 6.0 mg/kg]. Pentavalent antimony in the form of meglumine antimonate had an SD (84) of 416 mg/kg. In a second experiment in which animals were allowed to become more heavily infected, the drug was administered 10 days after infection and the animals were sacrificed after a further 2, 7, or 11 days. ABCD was approximately four times as active as conventional amphotericin B. These experiments suggest that ABCD is at least four times as active as conventional amphotericin B against visceral leishmaniasis and that clinical trials are warranted.

Amphotericin B↗
PubMed1992

Canine leishmaniasis caused by Leishmania leishmania infantum in two Labrador retrievers.

Canine leishmaniasis, a generally fatal parasitic disease, was diagnosed in 2 dogs with a medical history of foreign travel, lymphadenopathy, emaciation, anorexia, intermittent fever, and cutaneous lesions. Clinically, hyperproteinemia, proteinuria, azotemia, and glomerulopathy were evident. Isolation of Leishmania species was done using Schneider's Drosophila medium. Syrian hamsters were used for infectivity studies. Clear taxonomic identification was done biochemically by isoenzyme analysis and comparison of zymogram banding patterns with 6 World Health Organization reference strains. Based on the geographic origin of affected dogs, clinicopathologic presentation, visceralization with hepatosplenomegaly in hamsters, and isoenzyme analysis, a diagnosis of Leishmania leishmania infantum was made. This study, representing the first taxonomic identification of an isolate from canine leishmaniasis, demonstrates the zoonotic and epidemiologic implications of this disease.

Animals↗
PubMed1991

Development of Leishmania (Viannia) panamensis lesions and relationship of numbers of amastigotes to lesion area on antimony-treated and untreated hamsters.

Young adult (60-70-g) male golden hamsters (Mesocricetus auratus) each were injected intradermally at the dorsal base of the tail with 15 x 10(6) promastigotes of Leishmania (Viannia) panamensis (MHOM/PA/83/WR539), and progression and regression of subsequent lesions were evaluated for up to 17 wk postinfection (PI) as to area, weight, and number of amastigotes within lesions in untreated hamsters and in hamsters treated with meglumine antimoniate (Glucantime). In untreated hamsters total area of lesion, weight, and numbers of amastigotes generally increased rapidly and concomitantly up to 3-4 wk PI. Amastigote numbers tended to decrease from 4 to 11 wk PI and subsequently the numbers of amastigotes within the lesions decreased rapidly, whereas relatively little change occurred in the area and weight of the lesions. Meglumine antimoniate treatment of cutaneous hamster lesions resulted in marked concomitant decrease in size of the lesions and numbers of amastigotes within the lesions examined 1 wk after treatment. Measurement of the area of cutaneous leishmanial lesions thus would appear to be a valid method of evaluating the efficacy of promising compounds against L. panamensis in hamsters when measurements are taken 3-5 wk after experimental infection and reflects the number of amastigotes present in the lesion.

Animals↗
PubMed1978

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↗
PubMed1978

Influence of iron on Corynebacterium renale-induced pyelonephritis in a rat experimental model.

Growth of Corynebacterium renale in vitro on low-iron medium (1.34 micron) was only slightly less than that on high-iron media (7.16 and 9.85 micron). However, studies on C. renale-induced pyelonephritis using the rat as an experimental model revealed that C. renale cultivated in high-iron media was capable of producing pyelonephritis, but when grown on low-iron medium, these bacteria were noninfective. This apparent avirulence of the bacteria cultivated on low levels of iron could be reversed by injecting the rats intramuscularly with ferric ammonium citrate.

Animals↗
PubMed1978

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↗
PubMed1977

Amyloidosis in rhesus monkeys with rheumatoid arthritis and enterocolitis.

Generalized amyloidosis was diagnosed by light and electron microscopy in 4 of 5 monkeys (Macaca mulatta) that had a history of chronic arthritis or chronic intermittent diarrhea, or both. Clinical signs and lesions of arthritis in the monkeys were compatible with diagnostic criteria for rheumatoid arthritis. Shigella sp was cultured from 1 monkey, and 2 other monkeys had colonic lesions characteristic of shigellosis. At necropsy, gross changes attributed to amyloid were seen only in the liver. Amyloid deposits in the liver, spleen, mesenteric lymph nodes, kidney, heart, adrenal glands, and other organs were determined by staining reactions and fine structural characteristics.

Amyloidosis↗
PubMed1977

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↗
PubMed1977

Experimental Rat model for Corynebacterium renale-induced pyelonephritis.

The laboratory rat was able to serve as a model for ascending pyelonephritis after implantation of a zinc disk coated with Corynebacterium renale into the urinary bladder because it satisfied three different criteria for infection. The production of an alkaline urine and the presence of significant numbers of C. renale in the kidneys, as well as distinct pyelonephritic lesions as revealed by histological examination, were observed in all rats infected with C. renale. Control rats that harbored sterile disks in their urinary bladders exhibited none of the above effects.

Animals↗
PubMed1977

Influence of acetohydroxamic acid on experimental Corynebacterium renale pyelonephritis.

The role of Corynebacterium renale urease in the establishment of pyelonephritis was studied by the oral administration of acetohydroxamic acid (AHA), a urease inhibitor, to experimentally infected rats. The bacteria were introduced by surgical insertion of a zinc disc containing 1 X 10(6) colony-forming units of C-renale into the urinary bladder whereas sterile discs were implanted in the bladders of the control animals. Daily administration of AHA via the drinking water did not halt the development of pyelonephritis. Larger doses, given by gavage, did accomplish this goal; that is, the pH of the urine was lowered, the number of colony-forming units of C. renale in the kidney was reduced drastically, and pyelonephritic lesions were observed in the kidney by light-microscopic examination. All experimental rats developed cystitis in varying degrees of severity. About 70% of the intact AHA given by gavage was excreted in the urine 24 h after administration of this compound. Rats implanted with a urease-negative mutant of C. renale displayed no signs of pyelonephritis but did develop cystitis.

Animals↗
PubMed1975

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↗