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Biomedical subjects

W L Chapman

Publications and source records attributed to W L Chapman.

At least 55 records · Page 3Linked to original sources

Evaluation of penicillin in conjunction with acetohydroxamic acid in treatment of experimental Corynebacterium renale pyelonephritis.

The therapeutic efficacies of procaine penicillin G and acetohydroxamic acid, when administered alone or in combination, were evaluated in rats with experimentally induced pyelonephritis at 24 h and 4 days after intrabladder inoculation with Corynebacterium renale. Penicillin alone prevented the development of pyelonephritis when administered in a once daily dose of 50,000 units for 5 days beginning within 24 h of infection challenge. However, if therapy was not initiated until the 4th day after induction of infection, pyelonephritis ensued which could not be differentiated from untreated rat pyelonephritis. Acetohydroxamic acid, when administered by itself in a once daily dose of 100 mg for 5 days, was completely ineffective whether therapy was started at 24 h or 4 days after initiation of infection. On the other hand, the combination of penicillin and acetohydroxamic acid prevented progression of pyelonephritic infection and facilitated healing when rat kidneys were examined at 14 and 30 days after initiation of infection. The kidneys of those rats sacrificed at 30 days after cessation of treatment revealed the presence of increased interstitial fibrous connective tissue in the renal medulla suggesting prior damage followed by recovery and repair. In vitro studies on the action of penicillin and acetohydroxamic acid against C. renale revealed no signs of synergism or antagonism.

Animals↗

Occurrence of antibody to Trypanosoma cruzi in dogs in the southeastern United States.

Seven of 365 dogs from Georgia and other southeastern states were seropositive for antibody to Trypanosoma cruzi by the complement-fixation (CF) test. Sera from 24 dogs, including the 7 dogs seropositive by CF test, were reactive at dilutions of 1:128 or 1:256 by the direct-agglutination (DA) test. Dogs with positive CF titers were significantly (P less than 0.05) younger than were the dogs in the total population surveyed. The occurrence of antibody to T cruzi was similar, regardless of the dogs' origin, sex, or length of hair. Dogs with specific antibody to T cruzi did not have clinical signs of disease related to the cardiovascular or gastrointestinal systems, the systems most frequently affected in American trypanosomiasis (Chagas' disease). Sera from an additional 20 dogs from Minnesota were examined by the DA test. One of these sera had a reaction at a dilution of 1:2, and 19 sera had no reaction in the DA test for antibody to T cruzi.

Animals↗

Light and electron microscopic evaluation of thymuses from feline leukemia virus-infected kittens.

Light microscopic and electron microscopic findings in thymuses from 4-week old feline leukemia virus-infected and 4- and 9-week old noninfected kittens were evaluated and found to be morphologically similar to each other. Thymuses from 9-week old feline leukemia virusinfected kittens were markedly atrophied and individual lobules within each thymus varied in the severity of atrophy. Loubules having the least severe atrophy had a moderate thinning of the cortex and a heterogeneous thymuses included intense eosinopoiesis at the corticomedullary junction, increased prominence of vasculature, and enlarged Hassal's corpuscles. In addition to these changes lobules of thymus having the most severe atrophy had a marked cortical thymocyte depletion, lobule collapse, and increased numbers of mast cells. Degeneration of epithelial cells in most lobules was indicated by electronlucency of the cytoplasmic matrix and often greatly dilated rough endoplasmic reticulum.

Animals↗

Leishmaniasis: in search of new chemotherapeutic agents.

Members of a class of compounds designated lepidines (8-amino-6-methoxy-4-methylquinoline derivatives) were tested in a hamster-Leishmania donovani model and found to have activity many-fold that of a reference drug meglumine antimoniate. One of them, 8-(7-isopropylaminoheptylamino)-6-methoxy-4-methylquinoline, was found to be 138 times as effective as the standard antimonial drug used.

Aminoquinolines↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗