Laboratory animal science最新文献

Background and purpose: Serologic testing for antibody to monkey B virus (BV) in macaque sera is problematic due to the biohazardous nature of BV and BV antigens. Herpesvirus papio 2 (HVP2), a herpesvirus of baboons, is more closely related genetically and antigenically to BV than is human herpes simplex virus 1 (HSV1). The potential for use of HVP2 relative to HSV1 as an alternative test antigen for detection of anti-BV antibody in macaque sera was assessed.

Methods: Standard ELISA formats were developed, using BV-, HVP2-, and HSV1-infected cell extracts. Performance of the HVP2 and HSV1 tests was assessed relative to that of the BV test.

Results: Using the BV antigen ELISA, 349 sera from 7 macaque species were tested, and results were classified as positive (253), negative (94), or suspect (2). The ELISA using HVP2 antigen detected 98.0% of BV-positive sera (248 of 253), whereas the HSV1-based ELISA detected only 96.0% (243 of 253). All three ELISAs identified the same two samples as suspect, and the HSV1 ELISA identified three additional BV-positive sera as suspect.

Conclusions: The HVP2 antigen-based ELISA was equal in sensitivity and specificity to the BV antigen-based ELISA and was superior to the HSV1 ELISA for detection of BV-positive macaque sera. In addition, the HVP2 ELISA has greater laboratory safety, compared with BV antigen use for ELISA testing.

Background and purpose: To the authors' knowledge, histopathologic changes associated with early H. pylori infection and ulceration have not been established. We examined presence of H. pylori infection in an acetic acid-induced gastric ulcer (AAU) model in Mongolian gerbils.

Methods: Sixty Mongolian gerbils were used as an AAU model, and another 60 gerbils were studied as a control (non-AAU) group. All animals were orally administered H. pylori, then were evaluated by use of histologic and bacteriologic examinations.

Results: Helicobacter pylori were scattered on the surface mucous gel layer and in the pyloric gland gastric were pits; inflammation seen at the early stages later extended to the mucosa of the fundic gland area. The organisms were predominantly observed in the AAU model, but findings were comparable to those in controls at 1, 3, 7, 14, 28, or 56 days. Evaluation with regard to viable bacterial numbers reflected the histologic aspects, that the pyloric gland area had more viable counts than did the fundic gland area. Carbohydrate composition of mucin differed between pyloric and fundic gland areas. These findings shed light on L-fucose related to the H. pylori adhesive factor abundant in mucin of the pyloric gland area.

Conclusions: Findings for this ulcer model of Helicobacter pylori infection make it useful for the study of onset of infection and screening of anti-ulcer agents.

Objective: This study was conducted to compare various strategies for insulin replacement therapy in the streptozotocin-induced diabetic rat model.

Methods: Control and diabetic Sprague Dawley rats were fed ad libitum, blood glucose concentration was measured twice daily, and outcome was assessed over the final 5 days of a 10-day treatment period, with adjustment of insulin dosage toward the goal of normal glucose values.

Results: All insulin regimens induced weight gain at least comparable to that of controls, but glucose regulation differed. It was not possible to normalize glucose values by use of protamine zinc insulin (PZI) or Ultralente insulin given once daily. In contrast, PZI and neutral protamine Hagedorn (NPH) insulin given twice daily provided glucose values comparable to those in controls, whereas glucose values were modestly higher in response to a 70% human insulin isophane suspension and 30% soluble human insulin solution (70/ 30 insulin) given twice daily. Attempted normalization of glucose values was limited by hypoglycemia, which was most common after administration of PZI once daily, and least common after 70/30 insulin given twice daily. Dosage requirements for Ultralente insulin were four- to fivefold higher than those for all other insulins.

Conclusion: In streptozotocin-diabetic rats, normal weight gain can be achieved by treatment with PZI insulin once daily, but attainment of near-normal glucose values requires administration of PZI, NPH, or 70/ 30 insulin twice daily. Ultralente insulin may have reduced bioeffectiveness in this animal model.

Background and purpose: The pig is being investigated as an organ donor for humans. Induction of immunologic tolerance to pig tissues in primates would overcome the major immunologic barriers to xenotransplantation. A proven method of inducing tolerance to allografts is by the induction of mixed hematopoietic chimerism by bone marrow transplantation. We are therefore investigating induction of mixed hematopoietic chimerism in the pig-to-baboon model.

Methods: To obtain large numbers of pig hematopoietic cells, leukapheresis was used to collect blood cell products in miniature swine (n = 5) after progenitor cell mobilization by use of a course of hematopoietic growth factors (cytokines), consisting of porcine interleukin 3, porcine stem cell factor, and human granulocyte colony-stimulating factor.

Results: Cytokine therapy and leukapheresis were well tolerated. Cytokine therapy increased the total white blood cell count and allowed large numbers of leukocytes (60 x 10(10)) to be obtained by apheresis, of which approximately 0.1% were granulocyte-erythrocyte-monocyte-megakaryocyte colony-forming units (CFU-GEMMs), which are considered to be representative of hematopoietic progenitors with multi-lineage potential.

Conclusions: The combination of cytokine therapy and leukapheresis enables hematopoietic progenitor cells to be obtained safely from miniature swine.

Background and purpose: The existence of guinea pig adenovirus (GPAdV) has been suspected on the basis of histopathologic findings, but the virus has not yet been isolated. In susceptible animals, it may cause severe bronchopneumonia and death. Adenovirus-like inclusion bodies have been observed in the lungs of animals with clinical disease. Prevalence of the infection is unknown. Recently, a polymerase chain reaction (PCR) assay was described that was able to selectively detect GPAdV.

Methods: To investigate the pathogenesis of GPAdV, we inoculated eight guinea pigs with GPAdV; eight control animals were sham inoculated. The PCR assay was used to trace the infection. In a second experiment, transmission of GPAdV from an experimentally infected animal to five immune-naive cohorts was examined.

Results: None of the infected animals developed clinical disease. The GPAdV could be detected by PCR analysis of nasal-swab specimens on days 6 through 15 after infection. Infective virus could be recovered from the nasal mucosa during this period (as determined by inoculation of immune-naive animals). The virus was transmitted from an experimentally infected animal to two of five immune-naive cage mates.

Conclusion: The GPAdV may cause transient subclinical upper respiratory tract infection that may descend to the lungs.

Background and purpose: Phytoestrogens exert estrogenic effects on the central nervous system, induce estrus, and stimulate growth of the genital tract of female animals. Over 300 plants and plant products, including some used in laboratory animal diets, contain phytoestrogens. Therefore, the source and concentration of phytoestrogens in rodent diets were determined.

Methods: Twelve rodent diets and six major dietary ingredients were assayed for phytoestrogens (daidzein, genistein, formononetin, biochanin A, and coumestrol), using high-performance liquid chromatography. Three rodent diets recently formulated to reduce phytoestrogen content also were assayed.

Results: Formononetin, biochanin A, and coumestrol were not detected. Soybean meal was the major source of daidzein and genistein; their concentrations were directly correlated to the percentage of soybean meal in each diet.

Conclusions: High, variable concentrations of daidzein and genistein are present in some rodent diets, and dietary phytoestrogens have the potential to alter results of studies of estrogenicity. Careful attention should be given to diet phytoestrogen content, and their concentration should be reported. A standardized, open-formula diet in which estrogenic substances have been reduced to levels that do not alter results of studies that are influenced by exogenous estrogens is recommended.

Motor neuron disease is a general term applied to a broad class of neurodegenerative diseases that are characterized by fatally progressive muscular weakness, atrophy, and paralysis attributable to loss of motor neurons. At present, there is no cure for most motor neuron diseases, including amyotrophic lateral sclerosis (ALS), the most common human motor neuron disease--the cause of which remains largely unknown. Animal models of motor neuron disease (MND) have significantly contributed to the remarkable recent progress in understanding the cause, genetic factors, and pathologic mechanisms proposed for this class of human neurodegenerative disorders. Largely driven by ALS research, animal models of MND have proven their usefulness in elucidating potential causes and specific pathogenic mechanisms, and have helped to advance promising new treatments from "benchside to bedside." This review summarizes important features of selected established animal models of MND: genetically engineered mice and inherited or spontaneously occurring MND in the murine, canine, and equine species.