Use of topical selamectin for the treatment of Syphacia muris infection in laboratory rats

Efficacy of selamectin was studied in naturally acquired S. muris infections in rats. Fourty-eight S. muris-positive rats were divided into six treated and two control groups. Selamectin (6 mg/kg) was applied topically to the skin in a single spot at the base of the neck in the treatment group. The rats of treated and control groups were necropsied on the 24th day after the treatment. Topical selamectin was found to be 40.7-63.3% effective (based on egg per gram method) in eliminating S. muris infection in rats. The efficacy of the treatment against S. muris (based on adult worm counts) in male and female rats was 35.14-58.88%, respectively (mean 48.39%).     

Characterization of a Cryptosporidium muris infection and reinfection in CF-1 mice

To establish control values for circulating cells and immune associated organs over the course of a self-limiting Cryptosporidium muris infection and rechallenge infection, mice were sacrificed at intervals starting before oral inoculation and ending after oocyst shedding had ceased. These values were used in other experiments to evaluate changes in these parameters induced by a single dose glucocorticoid immunosuppression model and in other immunosuppression studies. Flow cytometry counts of circulating T-lymphocytes and neutrophils, differential leukocyte counts, leukocyte morphology, spleen and thymus changes, and oocyst shedding were evaluated. Immediately after C. muris oocyst inoculation and up to the start of oocyst production (day 0 to day 7), the circulating blood profile showed a 50% drop in all leukocytes, including both large and small lymphocytes and CD3, CD4 and CD8 T-lymphocytes. There was an initial slight rise in circulating mature neutrophils after oocyst inoculation but numbers promptly dropped below normal and remaineded below normal. In the differential cell counts, monocytes with a fat, oval morphology increased by 60% at 24 h and remained high through oocyst shedding and beyond (day 8 through day 36). During oocyst shedding and continuing past the end of shedding, T-lymphocytes increased 100%. Monocytes with a flat, angular morphology increased in a similar manner. Immediately after oocyst inoculation the spleen contracted by 29%, but became 92% larger than its pre-inoculation size by day 14 when heavy oocyst shedding began. It remained enlarged through the end of oocyst shedding (day 29) and beyond (day 36). Spleen volume decreased and increased similar to changes in T-cell numbers. Throughout the C. muris infection the thymus remained largely unchanged. The transit of an oocyst bolus was followed from the stomach through the gut to the colon. No oocysts could be found in the stomach, caecum or feces of mice one half hour after oocyst inoculation. Likewise, an oral bolus of India ink passed from the stomach entirely into the colon after 3 h; therefore, no oocysts from the inoculum passed completely through the intestine and out into the feces. Recovered mice rechallenged with C. muris showed increased B-lymphocyte numbers; however, T-lymphocyte numbers remained level. The large lymphocytes increased after rechallenge, peaking on day 3, then decreased through day 10. B-cell numbers followed a pattern similar to the large lymphocytes. On day 10 of infection monocytes with a fat oval morphology rose sharply while B-cells fell in number. In both the initial infection and the rechallenge there was no unique blood profile which could definitely indicate a protozoal disease or identify a specific point during the course of the disease. There was no increase in the number of either small or large lymphocytes prior to increases in fat or flat monocytes.     

Infectivity and oocyst excretion patterns of Cryptosporidium muris in slightly infected mice

To determine the infectivity of Cryptosporidium to hosts in slight infections, we examined the infectivity and oocyst output patterns of Cryptosporidium muris in mice inoculated with small numbers of oocysts. One of the 25 ICR mice inoculated with 2.4 x 10(1) oocysts and 19 of the 25 mice inoculated with 2.4 x 10(2) oocysts shed oocysts in the feces after inoculation. Four of the 50 mice inoculated with 2.4 x 10(1) oocysts for 10 consecutive days also shed oocysts and their OPG values were similar to that of the mice which received 2.4 x 10(2) oocysts. Consequently, it is clear that less than 10% of the mice which received 2.4 x 10(1) C. muris oocysts for 10 consecutive days.     

Parasite infections in laboratory mice colonies

Problems dealing with common parasites--oxyurids, which affect laboratory mice colonies are discussed and reviewed. Their life histories, pathogenicity and immunity are examined. The attention is paid to the influence of age, sex, strain and status of the host in the infection. It is agreed that helminth infections are usually more severe in male than in female vertebrate hosts.     

Acidophilic macrophage pneumonia in laboratory mice

Acidophilic macrophage pneumonia, characterized by an accumulation of characteristic crystalloid-laden alveolar macrophages, was seen in 30/7,500 NMRI, 7/600 T x HT, 2/100 C57BL and in no cases of 1,500 CBA and 1,100 BALB/c mice. Histologically, there was a focal accumulation of large numbers of eosinophilic macrophages, generally associated with granulocytes. Macrophages could be mononucleate or multinucleate and had a crystalline cytoplasm. Free-lying crystals were sometimes observed. Ultrastructurally, macrophages had a cytoplasmic accumulation of needle-shaped and rhomboidal crystals, often showing a clear lattice structure with a repeat of 3-5 nm. The crystalloid inclusions may be derived from the breakdown products of granulocytes and appear similar to inclusions in macrophages in other parts of the hematopoietic system. That these inclusions are probably derived from eosinophils is based on the appearance within macrophages of structures resembling eosinophil granules at various stages of degradation and the similarity between the lattice repeat of the crystalloids and that of the crystalline core of the eosinophil granule. The crystalloid inclusions may be related to the Charcot-Leyden crystals found in human beings.     

Myoepitheliomas in inbred laboratory mice.

Myoepitheliomas are subcutaneous tumors that arise from myoepithelial cells of various exocrine glands. In a retrospective study of 142 tumors observed over a period of 3 years, myoepitheliomas occurred spontaneously in A/HeJ, A/J, BALB/cJ, BALB/cByJ, LLC.A/Ckc, and NOD/Lt inbred strains of mice. Tumors presented primarily in the subcutaneous tissues of the ventral neck (74% of the myoepitheliomas evaluated) but were observed in several other subcutaneous locations, including the head, perineum, and ventral abdomen. These areas were adjacent to salivary, mammary, clitoral, preputial, and Harderian glands. Forty myoepitheliomas were tested by the avidin-biotin complex technique with a panel of antisera specific for mouse keratins, intermediate filaments, and other cytoskeletal proteins to determine the cell type from which this neoplasm originated. Antibodies directed against the specific mouse keratins K5, K6, and K14, and a broadly cross-reactive cytokeratin antibody stained acinar and ductal myoepithelial cells in normal mammary, salivary, and Harderian glands, and neoplastic cells in all cases. Antisera directed against a smooth muscle actin (anti-alpha-sm-1) stained acinar myoepithelial cells of the glands and vascular smooth muscle but neither ductular myoepithelial cells nor tumor cells. This supports the notion that these tumors originate from extraglandular ductular myoepithelial cells. Southern blots, prepared from DNA extracted from nine myoepitheliomas, did not show restriction fragment length polymorphisms when mouse mammary tumor virus (MMTV) cDNA or Int-1 genomic DNA probes were used; this implies that a retrovirus is not the etiologic agent.     

Chemically and genetically immunocompromised mice are not more susceptible than immunocompetent mice to infection with Cryptosporidium muris

The prevailing paradigm is that immunosuppressed individuals are more susceptible to infection and are at higher risk of infection from Cryptosporidium oocysts if present in drinking water. To test this hypothesis, three immune conditions were examined: genetically immunocompromised T cell deficient CD-1 nude mice, B and T cell deficient Fox Chase CB-17/IcrClB SCID mice, and chemically immunosuppressed C57Bl/6 mice. Chemical immunosuppression was induced with a single subcutaneous injection of methylprednisolone acetate (MPA) at 600 mg/kg. The MPA immunosuppressed C57Bl/6 mice were characterized by a sustained decrease in circulating CD3, CD4 and CD8 T-lymphocytes of greater than 80% and a similar decrease in B-lymphocytes. A sharp rise in circulating mature segmented neutrophils followed MPA injection, dropping sharply after 10-14 days, mirroring the decrease in lymphocytes. The cessation of oocyst production after MPA was not accompanied by a radical rise in circulating CD3 or CD4 T-lymphocytes, but rather a rise in CD8 T-lymphocytes. The ID50 for the MPA immunosuppressed C57Bl/6 mice was 122 oocysts, whereas the ID50 for the C57Bl/6 immunocompetent group was 44. The genetically immunocompromised mice showed similar differences. The ID50 for CD-1 nude mice was 166 oocysts compared to 64 in CD-1 immunocompetent mice. For Fox Chase CB-17/IcrClB SCID and the immunocompetent CB-17 mice, the ID50's were 83 and 60 oocysts, respectively. These results suggest that the lack of an immune response does not increase the ability of C. muris to establish a productive infection and produce oocysts.     

Skeletal muscle rhabdomyosarcomas in inbred laboratory mice.

A total of 14 well differentiated rhabdomyosarcomas were diagnosed at necropsy in 10,000 mice. Of the 14 affected mice, ten were BALB/cJ, and there was one case each of A/HeJ, BALB/cByJ, C58/J, and C.B-17-scid/scid strains. Most often (10/14) tumors originated in the quadriceps muscles and metastases occurred in six cases. When submitted, affected mice were 2 to 8 months of age, with a mean age of 4 months. Tumor frequency for BALB/cJ mice was calculated to be 2.4/100,000 mice retained as breeders. No sexual dimorphisms were determined when data were correlated to actual numbers of each sex in the colony. All 14 primary tumors and metastases were positive by immunohistochemistry for the proteins pan myosin, sarcomeric actin, desmin, actin, and myosin, but were negative for smooth muscle actin, thus confirming the diagnosis. Using cell free homogenates of primary tumors, inoculated by intraperitoneal or intramuscular injection, tumors were not induced in either BALB/cJ or C58/J mice observed over a 22-week period. Southern blot analysis of DNA prepared from tumors and hybridized with a murine leukemia virus probe that recognizes both ecotropic and dualtropic viruses did not demonstrate viral genomic fragments in addition to those known to occur in each strain.     

The pathogenesis of experimental infections of Cryptosporidium muris (strain RN 66) in outbred nude mice.

Three groups of six-week-old nude outbred mice were orally infected with 400, 20,000 and 1,000,000 oocysts of Cryptosporidium muris (strain RN 66) per mouse, respectively. Oocysts were detected in the faeces from 10-18 days post-infection (p.i.) and continued to be shed in large numbers in all groups until the termination of the trial on day 89 p.i. Clinical signs were not observed in any of the infected mice and there was no significant effect on weight gain compared to uninfected controls. Histological examination revealed the presence of parasites confined to the glandular stomach. Parasitised gastric glands were dilated, hypertrophied and filled with numerous parasites. The glands had lost their normal cellular architecture and were lined with many undifferentiated cells. In some mice receiving the largest innoculum, the glandular mucosa was congested and the lamina propria infiltrated with eosinophils, polymorphs and lymphocytes.     

Immune response to Encephalitozoon cuniculi infection in laboratory mice.

The study was performed to determine the immune response to Encephalitozoon cuniculi infection in immunocompetent mice during 120 days of experiment. Mice infected with E. cuniculi had an increased number of CD4+ T cells up to Day 20 post infection (p.i.), but counts of CD8+ T lymphocytes were significantly lower up to Day 90 p.i. in peripheral blood. Blood monocytes were significantly increased on the Day 60 and Day 120 of infection. A lack of significant decrease of CD4+ T cells may be considered as an important event in the immune response to E. cuniculi infection in immunocompetent mice.     

"Lipomatous" hamartomas and choristomas in inbred laboratory mice

In a retrospective study, 37 male and 19 female inbred laboratory mice, from 1 to 36 weeks of age, were diagnosed with "lipomatous" hamartomas or choristomas from nearly 10,000 mice examined at necropsy over a 24-month period. Hamartomas and choristomas were found to be rare, noninherited tumor-like conditions that occurred spontaneously in 18 inbred strains of mice with a predominance of the conditions in the C3H/HeJ and C57BL/6J strains. Prevalence between strains ranged from 0.6 to 6.2 cases per hundred thousand mice. The 56 cases studied had soft, raised masses that arose on the dorsal midline, primarily above the sutures of the skull. The lesions were prominent on gross examination due to abnormally long hair, change in direction of the hairs, and a change in hair color compared to the normal pelage. Microscopically, the masses consisted of normal adipose tissue in the reticular dermis and subcutis that sometimes extended through the cranial sutures, entering the brain, or expanding into the ventricles. Large masses occasionally contained normal appearing thyroid, intestine, respiratory epithelium lined cysts, squamous epithelial cysts, bone and marrow, cartilage, glands, and angiomatous anomalies. In all cases, the epidermis was intact. Hair follicles were larger in the affected areas of many cases compared to those in adjacent skin. Breeding studies did not yield affected offspring, indicating this is a congenital, noninherited abnormality. This condition resembles "lipomatous" hamartomas, a congenital defect in human beings.