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Columbia, MO, United States

Cook M.T.,University of Missouri | Mafuvadze B.,University of Missouri | Besch-Williford C.,IDEXX BioResearch | Ellersieck M.R.,University of Missouri | And 2 more authors.
Oncology Reports | Year: 2016

Postmenopausal women undergoing hormonereplacement therapy containing both progestins and estrogens are at an increased risk of developing breast cancer compared with women taking estrogen alone. We recently demonstrated that medroxyprogesterone acetate, a progestin commonly used for hormone-replacement therapy, accelerates development of mammary carcinogenesis in 7,12-dimethylbenz(a) anthracene treated Sprague-Dawley rats. Synthetic antiprogestins used to block the deleterious effects of progestins are themselves associated with toxic side-effects. In order to circumvent this, we used the aforementioned model to identify less toxic natural compounds that may prevent the development of progestin-accelerated tumors. Luteolin, a naturally-occurring flavonoid commonly found in fruits and vegetables, has previously been shown to possess anticancer properties. In our studies, both low (1 mg/kg) and high (25 mg/kg) doses of luteolin significantly suppressed progestin-dependent increases in tumor incidence, while increasing tumor latency and reducing the occurrence of large (>300 mm3) mammary tumors. However, an intermediate dose of luteolin (10 mg/kg) while suppressing the development of large tumors, did not affect either tumor incidence or latency. Immunohistochemical analysis of tumor tissues revealed that all concentrations of luteolin (1, 10, and 25 mg/kg) significantly reduced levels of VEGF within tumors. The suppressive effects of luteolin on tumor incidence and volume, together with its ability to reduce VEGF and blood vessels, persisted even after treatment was terminated. This suggests that luteolin possesses anti angiogenic properties which could mechanistically explain its capacity to control tumor progression. Thus luteolin may be a valuable, non-toxic, naturally-occurring anticancer compound which may potentially be used to combat progestin-accelerated mammary tumors.

Philips B.H.,University Laboratory Animal Resources | Crim M.J.,IDEXX BioResearch | Crim M.J.,University of Missouri | Claire Hankenson F.,Michigan State University | And 4 more authors.
Journal of the American Association for Laboratory Animal Science | Year: 2015

Despite the routine collection of oocytes from African clawed frogs (Xenopus laevis) for use in research, few studies have evaluated methods for preparing their skin for surgery. We evaluated 3 skin preparatory agents by examining their antibacterial efficacy and the gross and microscopic appearance of Xenopus skin after exposure. Frogs (n = 14) were sedated and treated (contact time, 10 min) with 0.9% sterile NaCl on one-half of the ventrum and with 0.5% povidone-iodine or 0.75% chlorhexidine on the other half. Bacterial cultures were obtained before and after skin treatment; bacteria were identified by mass spectrometry. To assess inflammation and degenerative changes, the incision sites were photographed and biopsied at 0, 1, and 7 d after surgery. We isolated at least 22 genera of bacteria from the skin of our frog population (mean ± SE, 5.21 ± 0.82 genera per frog). Iodine (2.00 ± 0.44 genera) and chlorhexidine (0.29 ± 0.76 genera) both had greater antimicrobial activity than did saline. Skin erythema did not correlate with treatment group. Histologic evidence of epidermal degeneration and necrosis was greater on days 1 and 7 after chlorhexidine treatment than after iodine or saline. In addition, frogs treated with chlorhexidine had a higher incidence of clinical illness associated with the exposure site. In summary, although chlorhexidine has adequate antimicrobial activity against organisms on X. laevis skin, it leads to skin damage and subsequent clinical complications. We therefore do not recommend chlorhexidine as a preoperative preparation agent in Xenopus.

Collymore C.,Kings College | Crim M.J.,IDEXX BioResearch | Lieggi C.,Sloan Kettering Cancer Center
Zebrafish | Year: 2016

The presence of subclinical infection or clinical disease in laboratory zebrafish may have a significant impact on research results, animal health and welfare, and transfer of animals between institutions. As use of zebrafish as a model of disease increases, a harmonized method for monitoring and reporting the health status of animals will facilitate the transfer of animals, allow institutions to exclude diseases that may negatively impact their research programs, and improve animal health and welfare. All zebrafish facilities should implement a health monitoring program. In this study, we review important aspects of a health monitoring program, including choice of agents, samples for testing, available testing methodologies, housing and husbandry, cost, test subjects, and a harmonized method for reporting results. Facilities may use these recommendations to implement their own health monitoring program. © 2016 Mary Ann Liebert, Inc.

Alvarado C.G.,University of Missouri | Kocsis A.G.,University of Missouri | Hart M.L.,University of Missouri | Crim M.J.,IDEXX BioResearch | And 2 more authors.
Comparative Medicine | Year: 2015

Helicobacter spp. are some of the most prevalent bacterial contaminants of laboratory mice. Although abundant data regarding the diseases associated with H. hepaticus infection are available, little is known about the pathogenicity of H. ganmani, which was first isolated in 2001 from the intestines of laboratory mice. The objective of this study was to evaluate the host response to H. ganmani colonization in H. hepaticus disease-resistant C57BL/6 and disease-susceptible A/J and IL10-deficient mice. Mice were inoculated with H. ganmani, H. hepaticus, or Brucella broth. Cecal lesion scores, cecal gene expression, and Helicobacter load were measured at 4 and 90 d after inoculation. At both time points, mice inoculated with H. ganmani had similar or significantly more copies of cecum-associated Helicobacter DNA than did mice inoculated with H. hepaticus. When compared with those of sham-inoculated control mice, cecal lesion scores at 4 and 90 d after inoculation were not significantly greater in H. ganmani-inoculated A/J, C57BL/6, or IL10-deficient mice. Analysis of cecal gene expression demonstrated that H. ganmani infection failed to cause significant elevations of IFNγ in A/J, C57BL/6, or IL10-deficient mice. However, in IL10-deficient mice, H. ganmani infection was associated with a significant increase in the expression of the proinflammatory cytokine IL12/23p40. Although H. ganmani infection in this study failed to induce the typhlitis that is the hallmark of H. hepaticus infection, infection with H. ganmani was associated with alterations in inflammatory cytokines in IL10-deficient mice. Copyright 2015 by the American Association for Laboratory Animal Science.

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