The intravenous administration of superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) to animals with induced inflammation suppresses the inflammatory response and inhibits leukocyte infiltration into the challenged site, suggesting that neutrophil-generated superoxide reacts with an extracellular precursor to generate a substance chemotactic for neutrophils. Plasma exposed to superoxide in vitro becomes potently chemotactic. The appearance of chemotactic activity is inhibited by superoxide dismutase but not by catalase. The chemotactic factor does not stimulate superoxide production or degranulation in neutrophils. Intradermal injection of superoxide-treated plasma or of a superoxide-generating system causes heavy infiltration of neutrophils to the injection site but does not cause overt signs of inflammation. The chemotactic factor consists of a chloroform-extractable component bound to serum albumin. The superoxide-dependent chemotactic factor appears to play a major role in communication in neutrophil-mediated inflammatory events. Prevention of production of this factor appears to be the major anti-inflammatory action of superoxide dismutase.

ObjectivesTo determine and compare the incidence of cancer among the 8 Arctic States and their northern regions, with special focus on 3 cross-national indigenous groups – Inuit, Athabaskan Indians and Sami.MethodsData were extracted from national and regional statistical agencies and cancer registries, with direct age-standardization of rates to the world standard population. For comparison, the “world average” rates as reported in the GLOBOCAN database were used.FindingsAge-standardized incidence rates by cancer sites were computed for the 8 Arctic States and 20 of their northern regions, averaged over the decade 2000–2009. Cancer of the lung and colon/rectum in both sexes are the commonest in most populations. We combined the Inuit from Alaska, Northwest Territories, Nunavut and Greenland into a “Circumpolar Inuit” group and tracked cancer trends over four 5-year periods from 1989 to 2008. There has been marked increase in lung, colorectal and female breast cancers, while cervical cancer has declined. Compared to the GLOBOCAN world average, Inuit are at extreme high risk for lung and colorectal cancer, and also certain rare cancers such as nasopharyngeal cancer. Athabaskans (from Alaska and Northwest Territories) share some similarities with the Inuit but they are at higher risk for prostate and breast cancer relative to the world average. Among the Sami, published data from 3 cohorts in Norway, Sweden and Finland show generally lower risk of cancer than non-Sami.ConclusionsCancer among certain indigenous people in the Arctic is an increasing public health concern, especially lung and colorectal cancer.

Background. Asthma and depression are important public-health concerns worldwide. While some epidemiologic studies have shown asthma and wheezing to be associated with depression and anxiety, the patterns are unclear at the multinational level due to the lack of cross-study comparability. Our study examined the associations of self-reported asthma diagnosis and current wheezing with self-reported depression diagnosis and 30-day anxiety using an international survey. Methods. Using the 2002 World Health Survey, a standardized international survey conducted by the WHO, we estimated the associations between diagnosed asthma and current wheezing with diagnosed depression and 30-day anxiety via multiple logistic regressions for 54 countries worldwide. Results. Diagnosed depression and 30-day anxiety were associated with diagnosed asthma in 65% and 40% of the countries, respectively. Diagnosed depression and 30-day anxiety were associated with current wheezing in 83% and 82% of the countries, respectively. Conclusions. The association between asthma and depression was generally seen at the global level. These results indicated the importance of addressing the asthma-depression comorbidity as public-health and clinical management priorities, in order to improve the overall health of the countries.

Ceramide, a product arising from sphingomyelinase activity, has been shown to act as an intracellular second messenger in effecting growth inhibition, cellular differentiation, and apoptosis. In the present study, the relative effects of cell-permeable ceramides, N-acetylsphingosine (C2-ceramide) and N-hexanoylsphingosine (C6-ceramide), on neutrophil responses were measured. When cells were activated with fMet-Leu-Phe, C2-ceramide both potentiated (< 1 microM) and inhibited (> 1 microM) superoxide generation. C2- and C6-ceramide inhibited phorbol ester-induced superoxide release from neutrophils at IC50 values of 5 and 120 microM, respectively. C2-ceramide had no effect on semipurified protein kinase C activity. Neither ceramide affected significantly the general level of phosphorylated proteins in phorbol ester-treated cells. C2-ceramide (1-20 microM) alone did not change cytosolic free Ca2+ levels but inhibited Ca2+ and Mn2+ influx in fMet-Leu-Phe-activated neutrophils. In contrast, sphingosine enhanced Ca2+ entry; thus, ceramide conversion to sphingosine was not significant. Unlike C2-ceramide, C2-dihydroceramide failed to block superoxide generation or Ca2+ influx. Preincubation of cells with 10 nM okadaic acid reversed slightly the effects of C2-ceramide. Calyculin A, tautomycin, and much higher concentrations of okadaic acid inhibited agonist-induced Ca2+ influx. We postulate that C2-ceramide may inhibit neutrophil superoxide release by activation of type 2A protein phosphatases. Results suggest that protein phosphatase type 1 up-regulates Ca2+ entry, whereas type 2A (or a ceramide-activated subtype) forestalls Ca2+ entry by inactivating a calcium influx factor.