Michael S. Thibodeau

Distribution of Soluble Epoxide Hydrolase and of Cytochrome P450 2C8, 2C9, and 2J2 in Human Tissues

Soluble epoxide hydrolase (sEH) hydrolyzes a wide variety of endogenous and exogenous epoxides. Many of these epoxides are believed to be formed by cytochrome P450 epoxygenases. Here we report the distribution of sEH and cytochrome P450 epoxygenases 2C8, 2C9, and 2J2 by immunohistochemistry. A large number of different tissues from different organs were evaluated using high-throughput tissue microarrays. sEH was found in the liver, kidney, and in many other organs, including adrenals, pancreatic islets, pituitary gland, lymphoid tissues, muscles, certain vascular smooth muscles, and epithelial cells in the skin, prostatic ducts, and the gastrointestinal tract. Immunolabeling for sEH was highly specific for particular tissues and individual cell types. CYP2C9 was also found in almost all of these organs and tissues, suggesting that 2C9 and sEH are very similar in their tissue-specific patterns of expression. CYP2C8 and 2J2 were also widely distributed in human tissues but were less frequently associated with sEH. The results suggest potentially distinct pathways of endogenous fatty acid epoxide production and hydrolysis in a variety of human tissues.

p53 and its co-activator p300 are inversely regulated in the mouse colon in response to carcinogen.

We examined the p53 response following acute exposure of mice to the colon-specific carcinogen azoxymethane (AOM). No overall induction of p53-regulated genes was observed in the mouse colon, and only a small subpopulation of apoptotic colonocytes showed increased Bax staining. In contrast, the liver showed dramatic increases in p53-regulated gene expression. Subdued p53 gene activation in the colon did not appear to result from a lack of p53 stabilization, but did correspond to a drop in the expression of its transcriptional co-activator, p300. We propose that inefficient gene activation by p53 in the colon contributes to the organotrophic effects of AOM.

Effect of nitrogen dioxide on ovalbumin-induced allergic airway disease in a murine model.

The effect of exposure to irritant air pollutants on the development of allergic airway disease is poorly understood. This study examines the effects of the lower respiratory tract irritant, NO 2 , on the outcome of ovalbumin (OVA)-induced allergic airway disease. Male and female C57Bl/6 mice were sensitized by weekly intraperitoneal (ip) OVA injections for 3 wk followed by daily 1-h OVA aerosol inhalation challenge for 3 or 10 d. Initially, mice were exposed daily for 3 d to air or 0.7 or 5 ppm NO 2 for 2 h following each OVA aerosol challenge. OVA exposure resulted in pronounced lower airway inflammation, as evidenced by a significant increase in bronchoalveolar lavage (BAL) total cellularity and eosinophil levels. BAL eosinophil levels were significantly lower in OVA-NO 2 compared to OVA-air animals. The reduction was similar at both NO 2 exposure concentrations. In a subsequent study, sensitized animals were exposed for 3 or 10 d to aerosolized OVA followed by air or 0.7 ppm NO 2 . BAL eosinophils were again reduced at 3 d by OVA-NO 2 exposure compared to OVA-air mice. At 10 d the eosinophilia was virtually abolished. This reduction in OVA-induced cellular inflammation by NO 2 was confirmed by histopathological analysis. Contrary to expectations, exposure to NO 2 during the aerosol challenge to OVA dramatically diminished the outcome of allergic disease in lungs as measured by airway cellular inflammation.

Silica-Induced Inflammatory Mediators and Pulmonary Fibrosis

Silicosis continues to be a lung disease with significant morbidity and mortality. Although silica-induced lung injury and cell activation and/or death have been investigated over the past several years, basic research continues to reveal the cell: cell and cell: mediator interactions critical to these events. This chapter will emphasize the production and participation of several inflammatory cytokines, mediators and cell processes in the development of silica-induced lung injury and fibrosis. Mediators to be discussed will include TNFα, IFNγ, IL-1β, IL-12, IL-18, IL-9, TGFβ, MMPs/TIMPs, ROS/RNS, caspases and Fas/FasL in the processes of cell activation, cell proliferation and cell death. The mediator networks and apoptotic pathways elicited by this inorganic particle are complex, driven by many cell types and affect numerous cell functions. Understanding these interactions will help in developing strategies for therapeutic intervention at different stages of the disease.

Health and production aspects of feeding sweetpotato to cattle

If certain guidelines are followed when feeding sweetpotatoes to livestock it is possible to minimize health hazards. Careful herd management and the recognition of specific biomarkers such as excessive dental deterioration could aid in the early identification of feed problems. Where these tubers are produced locally in abundance there can be an economic and environmental incentive to divert waste sweetpotato by-products toward livestock feed. The feeding of culled sweetpotatoes and processed sweetpotato waste by-products can have three major benefits. First, expensive disposal costs are reduced. Second, negative environmental impacts from landfill dumping and crop spreading are limited. Third, the culled sweetpotatoes and SPCW offer an inexpensive and nutritious alternative feed ration for livestock that may increase economic returns.