Fenbendazole treatment without environmental decontamination eradicates Syphacia muris from all rats in a large, complex research institution.

Syphacia muris parasitism was eliminated from rats and voles by feeding fenbendazole-medicated chow (150 ppm) for five 7-day periods; treatment periods were separated by 7-day periods of feeding non-medicated chow, yielding atotal treatment course of 9 weeks. No other manipulations to facilitate eradication, including the use of filter tops, autoclaved cages, environmental decontamination, colony depopulation, breeding cessation, and research restriction, were done. The examination of 3143 cellophane-tape impressions of the anus and 160 cecal examinations from euthanized rats and voles during the treatment period and for 7 months afterwards confirmed the efficacy of treatment. Treatment was rapidly effective in voles. In rats, pinworm eggs persisted at high levels for 2 weeks after the start of treatment, but no eggs were found after 22 days.

Pathogenicity of Mycoplasma volis in mice and rats.

A new species of Mycoplasma, M. volis, was isolated from the respiratory tract of clinically normal field-trapped prairie voles (Microtus ochrogaster) that were to be housed in close proximity to other rodents. To determine the pathogenic potential of the new mycoplasmal isolate, three groups of rodents (Sprague Dawley rats, BALB/c mice, and severe combined immunodeficient [SCID] mice) were intranasally inoculated with 2 x 10(8) color-changing units (CCU) of M. volis and were observed for 4 to 6 weeks. Experimental animals did not manifest clinical signs of disease; however, one experimental SCID mouse was euthanized 5 days after inoculation because of a severe circling disorder. Lung lesions in experimental SD rats ranged from mild to severe bronchial-associated lymphoid tissue (BALT) hyperplasia. Lung lesions in BALB/c and SCID mice ranged from no lesions to mild pneumonia. We were able to isolate M. volis from some control mice, none of which had lung lesions. All mice were seronegative for Sendai virus, mouse hepatitis virus, and M. pulmonis. All immunocompetent experimental animals (BALB/c mice and Sprague Dawley rats) were seropositive for M. volis. All immunocompetent control animals and SCID mice were seronegative for M. volis. Our data suggest that M. volis is capable of causing microscopic lesions and seroconversion in rats and mice, and therefore these rodents should not be housed in close proximity to voles.

Sphingomyelin consumption suppresses aberrant colonic crypt foci and increases the proportion of adenomas versus adenocarcinomas in CF1 mice treated with 1,2-dimethylhydrazine: implications for dietary sphingolipids and colon carcinogenesis.

Sphingolipids are hydrolyzed in the gastrointestinal tract to ceramide, sphingosine, and other metabolites that can modulate cell growth, differentiation, and apoptosis. To characterize the effects of dietary sphingolipids on colon carcinogenesis, female CF1 mice were administered 1,2-dimethylhydrazine and then fed an essentially sphingolipid-free diet supplemented with 0 to 0.1% (w/w) sphingomyelin (SM) purified from milk. As was found in a previous pilot study (D. L. Dillehay et al., J. Nutr., 124: 615-620, 1994), SM (@ 0.1%) reduced the number of aberrant colonic crypt foci (by 70%, P < 0.001) and aberrant crypts per focus (by 30%, P < 0.003), which are early indicators of colon carcinogenesis. In longer term studies, SM had no effect on colon tumor incidence or multiplicity; however, up to 31% of the tumors of mice fed SM were adenomas, whereas all of the tumors of mice fed the diet without SM were adenocarcinomas. These findings demonstrate that milk SM suppresses the appearance of more advanced, malignant tumors as well as early markers of colon carcinogenesis. Although the sphingolipid content of foods has not been widely studied, several foods (e.g., milk and soybeans) contain the sphingolipid levels used in these investigations; therefore, this class of compounds could be significant contributors to the cancer preventive effects of some foods.

Pulmonary alveolar proteinosis in SCID mice.

Pulmonary alveolar proteinosis (PAP) is an uncommon disorder of unknown origin in which the alveoli are filled with lipoproteinaceous material, including surfactant. We have characterized a spontaneously occurring lesion in the lungs of CB.17 scid/scid mice which resembles PAP in humans. Lungs from 45 severe combined immunodeficient (SCID) mice were evaluated by light and electron microscopy and immunohistochemistry. Lung lavage fluid was evaluated biochemically and for the presence of surfactant protein A (SP-A) and B (SP-B) by enzyme-linked immunosorbent assay and Western blot. Light microscopy showed varying amounts of a homogeneous to granular proteinaceous material in alveolar spaces. This material was eosinophilic by hematoxylin and eosin stain and was periodic acid-Schiff (PAS) positive. Ultrastructurally, the material was predominantly homogeneous with areas of a lamellated pattern that resembled surfactant. Biochemical analysis revealed 2.7- and 3.6-fold increases in the surfactant-associated phospholipids phosphatidylcholine and disaturated phosphatidylcholine respectively, when affected SCID mice were compared with control mice. Immunohistochemical staining of lung tissue and Western blot and enzyme-linked immunosorbent assay of lavage fluid showed marked increases in SP-A and SP-B in comparison with controls. These results suggest that SCID mice have a defect in surfactant homeostasis that resembles PAP in humans and may serve as an animal model in further elucidating the pathogenesis of this disease.

Dietary sphingomyelin inhibits 1,2-dimethylhydrazine-induced colon cancer in CF1 mice.

Sphingolipids are in all eukaryotic cells and modulate cell growth, differentiation, and transformation; however, little is known about the physiological effects of their consumption. Mice were fed diets supplemented with milk sphingomyelin to determine effects on colon carcinogenesis. Cancer was initiated in CF1 mice by 1,2-dimethylhydrazine. Mice were then fed AIN76A diets supplemented with 0.025 to 0.1 g sphingomyelin/100 g for 28 wk until the supply of sphingomyelin was depleted and then fed unsupplemented diet for 24 wk. Sphingomyelin did not affect weight gain. Mice fed sphingomyelin had a 20% incidence of colon tumors compared with 47% in controls (P = 0.08 for all sphingomyelin-fed mice vs. controls). Tumors were adenomas or adenocarcinomas and located in the distal third of the colon. In shorter-term studies, colonic epithelial cell proliferation was significantly greater than controls in mice fed 0.025 g sphingomyelin/100 g diet, but not in those fed higher amounts of sphingomyelin. The number of aberrant crypts was significantly lower in 1,2-dimethylhydrazine-treated mice fed 0.05 g sphingomyelin/100 g diet than in controls. These results demonstrate that consumption of sphingomyelin affects the behavior of colonic cells. Because sphingolipids are present in food, the reduction in 1,2-dimethylhydrazine-induced premalignant lesions and the incidence of colon tumors in CF1 mice implies that these compounds may be another important class of nutritional modulators of carcinogenesis.