Mast cells are multifunctional, tissue-dwelling cells capable of secreting a wide variety of mediators. They develop from bone marrow-derived progenitor cells, primed with stem cell factor (SCF), which mediates its actions by interacting with the SCF receptor or c-kit on the cell surface. Mast cells continue their maturation and differentiation in peripheral tissue, developing into two well described subsets of cells, MCT and MCTC cells, varying in content of tryptase and chymase as well as in immunobiology. Mast cells are activated by numerous stimuli, including antigen (acting via the high affinity IgE receptor, Fc?RI), superoxides, complement proteins, neuropeptides and lipoproteins resulting in activation and degranulation. Following activation, these cells express mediators such as histamine, leukotrienes and prostanoids, as well as proteases, and many cytokines and chemokines, pivotal to the genesis of an inflammatory response. Recent data suggests that mast cells may play an active role in such diverse diseases as atherosclerosis, malignancy, asthma, pulmonary fibrosis and arthritis. Mast cells directly interact with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been demonstrated to have inhibitory effects on mast cell degranulation or mediator release.

Nd blood oxidative stress to acute exercise. Methods Nine males (18–30 yr) completed one maximal (Max) and three submaximal exercise sessions: 1) 45 min at 10% above (LT+) lactate threshold (LT), 2) 45 min at 10% below (LT−) LT, and 3) 10% below LT until caloric expenditure equaled the 10%+ trial (LT-kcal). Blood was sampled before (PRE), immediately (POST), 1 h, and 2 h after exercise to measure neutrophils, myeloperoxidase, superoxide (O2−), neutrophil activation (O2−/neutrophils), ascorbic acid, uric acid, malondialdehyde, and lipid hydroperoxides. Results Intensity-dependent neutrophilia occurred POST exercise with significant increases (P ≤ 0.05) after Max and LT+. A second neutrophilia wave occurred 2 h postexercise. Superoxide was elevated POST (Max) and 2 h post (Max and LT+). In contrast, O2−/neutrophils was increased at 2 h only (Max and LT+). These data indicate that immediately postexercise, total neutrophil number rather than activation best represents neutrophil-generated reactive species within blood. POST Max, ascorbic acid and uric acid were decreased indicating a blood oxidative stress occurred. Alternately, total energy expenditure was not related to any marker of neutrophilia or oxidative stress. Conclusion Exercise intensity plays a major role in postexercise blood oxidative stress, whereas total exercise energy expenditure does not. Further, neutrophils recruited into circulation during exercise may impose a threshold dependent oxidative stress in blood plasma after exercise....

Tocopherols are lipid soluble antioxidants that exist as eight structurally different isoforms. The intake of gamma-tocopherol is higher than alpha-tocopherol in the average US diet. The clinical results of the effects of vitamin E as a cancer preventive agent have been inconsistent. All published clinical trials with vitamin E have used alpha-tocopherol. Recent epidemiological, experimental and molecular studies suggest that gamma-tocopherol may be a more potent chemopreventive form of vitamin E compared to the more-studied alpha-tocopherol. Gamma-tocopherol exhibits differences in its ability to detoxify nitrogen dioxide, growth inhibitory effects on selected cancer cell lines, inhibition of neoplastic transformation in embryonic fibroblasts, and inhibition of cyclooxygenase-2 (COX-2) activity in macrophages and epithelial cells. Peroxisome proliferator activator receptor gamma (PPARgamma) is a promising molecular target for colon cancer prevention. Upregulation of PPARgamma activity is anticarcinogenic through its effects on downstream genes that affect cellular proliferation and apoptosis. The thiazolidine class of drugs are powerful PPARgamma ligands. Vitamin E has structural similarity to the thiazolidine, troglitazone. In this investigation, we tested the effects of both alpha and gamma tocopherol on the expression of PPARgamma mRNA and protein in SW 480 colon cancer cell lines. We also measured the intracellular concentrations of vitamin E in SW 480 colon cancer cell lines. We have discovered that the alpha and gamma isoforms of vitamin E upregulate PPARgamma mRNA and protein expression in the SW480 colon cancer cell lines. gamma-Tocopherol is a better modulator of PPARgamma expression than alpha-tocopherol at the concentrations tested. Intracellular concentrations increased as the vitamin E concentration added to the media was increased. Further, gamma-tocopherol-treated cells have higher intracellular tocopherol concentrations than those treated with the same concentrations of alpha-tocopherol. Our data suggest that both alpha and gamma tocopherol can upregulate the expression of PPARgamma which is considered an important molecular target for colon cancer chemoprevention. We show that the expression of PPARgamma mRNA and protein are increased and these effects are more pronounced with gamma-tocopherol. Gamma-tocopherol's ability to upregulate PPARgamma expression and achieve higher intracellular concentrations in the colonic tissue may be relevant to colon cancer prevention. We also show that the intracellular concentrations of gamma-tocopherol are several fold higher than alpha-tocopherol. Further work on other colon cancer cell lines are required to quantitate differences in the ability of these forms of vitamin E to induce apoptosis, suppress cell proliferation and act as PPAR ligands as well as determine their effects in conjunction with other chemopreventive agents. Upregulation of PPARgamma by the tocopherols and in particular by gamma-tocopherol may have relevance not only to cancer prevention but also to the management of inflammatory and cardiovascular disorders.

Colorectal cancer is the second most common cause of cancer deaths in the United States for both sexes. Considerable evidence suggests that the risk of this cancer is increased by the mutagenic actions of free radicals, which are produced during oxidation reactions. Dietary factors, the intestinal flora (bacteria), and endogenously produced metabolites contribute to the production of free radicals in the colon. Dietary antioxidants, such as vitamin E, should reduce the levels of these harmful oxidation products. In the absence of vitamin E, polyunsaturated fats can be oxidized in the colon to produce mutagens, such as lipid hydroperoxides and malondialdehyde. Furthermore, fecal bacteria can generate a high flux of reactive oxygen species (e.g., the superoxide radical [O ₂ * ^- ]) at the surface of the intestinal lumen, and inflammatory cells in close proximity to the colon can produce reactive nitrogen species (e.g., nitrogen dioxide [NO ₂ ]). Increasing evidence suggests that the different chemical (e.g., α- and γ-tocopherol) and stereochemical (e.g., RRR- and all-racemic-α-tocopherol) forms of vitamin E have distinct biologic potencies, pharmacokinetics, and different abilities to prevent neoplastic transformation. This review considers and evaluates recent studies relating vitamin E and oxidative stress to colon cancer, emphasizing the distinct roles of α-and γ-tocopherols. In addition, recent findings on the antioxidant/ pro-oxidant status of the digesta (ingested food) are discussed with respect to the use of antioxidants in chemoprevention trials for colon cancer.