Cuprizone induced-demyelination in mice alters brain expression of genes involved in arachidonic acid metabolism .

Chronic feeding with the copper chelator cuprizone in mice causes oligodendrocyte death and subsequent reversible demyelination. Although the mechanism of demyelination is unknown, activation of glia is integral to the process. Since metabolism of arachidonic acid (AA) is involved in glial activation, we hypothesized that cuprizone exposure would alter expression of AA cascade genes. Mice were fed 0.2 % cuprizone in the diet for 6 weeks and then returned to a normal diet. Histochemistry with the myelin stains Black Gold and Fluoromyelin demonstrated that frank demyelination and influx of glial cells into the corpus collosum begins at week 3 and peaks at week 5. A decrease in myelin and oligodendrocyte markers, accompanied by increased expression of markers of microglia (CD11b) and astrocytes (glial acidic fibrillary protein), was evident at week one. Gene expression of cyclooxygenase-2 and 15-lipoxygenase (LOX) was also changed at week one, suggesting that these genes are either involved in or respond to early demyelination. Expression of 5-LOX was not changed during early demyelination but it peaked during week 5, when glial markers and frank demyelination also reached their peak, suggesting that 5-LOX expression is a consequence of the massive influx of inflammatory cells into the area of demyelination. Our study is the first to demonstrate that multiple enzymes involved in arachidonic acid metabolism are altered in the cuprizone model of demyelination and remyelination. These data may help to develop new therapeutic targets to treat human demyelinating diseases, such as multiple sclerosis. Supported by the Intramural Research Program of the NIH, NIA

Processed meat and the risk of selected digestive tract and laryngeal neoplasms in Switzerland

Background: Processed meat has been related to the risk of digestive tract neoplasms but the evidence remains inconclusive. We examined data from a network of case-control studies conducted between 1992 and 2002 in the Swiss Canton of Vaud. Patients and methods: We studied 316 patients with incident, histologically confirmed oral and pharyngeal cancer, 138 patients with oesophageal cancer, 91 patients with laryngeal cancer and 323 patients with colorectal cancer. Controls were 1271 subjects admitted to the same hospital for a wide spectrum of acute non-neoplastic conditions, unrelated to long-term modification of diet. Results: There were strong direct trends in risk between consumption of processed meat and the various neoplasms considered: the multivariate odds ratios for the highest quartile of intake compared to the lowest were 4.7 for oral and pharyngeal cancer, 4.5 for oesophageal cancer, 3.4 for laryngeal cancer and 2.5 for colorectal cancer. The association was stronger in younger subjects, in moderate drinkers and in non-smokers. Conclusion: Processed meat represents a strong indicator of unfavourable diet for digestive tract and laryngeal cancer risk in this populatio

Emissions Pricing to Stablize Global Climate

http://globalchange.mit.edu/research/publications/2241In the absence of significant greenhouse gas (GHG) mitigation, many analysts project that atmospheric concentrations of species identified for control in the Kyoto protocol could exceed 1000 ppm (carbon-dioxide-equivalent) by 2100 from the current levels of about 435 ppm. This could lead to global average temperature increases of between 2.5° and 6° C by the end of the century. There are risks of even greater warming given that underlying uncertainties in emissions projections and climate response are substantial. Stabilization of GHG concentrations that would have a reasonable chance of meeting temperature targets identified in international negotiations would require significant reductions in GHG emissions below “business-as-usual” levels, and indeed from present emissions levels. Nearly universal participation of countries is required, and the needed investments in efficiency and alternative energy sources would entail significant costs. Resolving how these additional costs might be shared among countries is critical to facilitating a wide participation of large-emitting countries in a climate stabilization policy. The 2°C target is very ambitious given current atmospheric concentrations and inertia in the energy and climate system. The Copenhagen pledges for 2020 still keep the 2°C target within a reach, but very aggressive actions would be needed immediately after that

Aspirin and the risk of colorectal and other digestive tract cancers: an updated meta-analysis through 2019

Aspirin has been associated with a reduced risk of colorectal cancer, and possibly of a few other digestive tract cancers. The quantification of risk reduction and the optimal dose and duration of aspirin use for the prevention of colorectal and other digestive tract cancers remains unclear

Lung cancer mortality in European women: recent trends and perspectives

Background: Lung cancer mortality in men has been declining since the late 1980s in most European countries. In women, although rates are still appreciably lower than those for men, steady upward trends have been observed in most countries. To quantify the current and future lung cancer epidemic in European women, trends in lung cancer mortality in women over the last four decades were analyzed, with specific focus on the young. Patients and methods: Age-standardized (world standard) lung cancer mortality rates per 100 000 women—at all ages, and truncated 35-64 and 20-44 years—were derived from the WHO for the European Union (EU) as a whole and for 33 separate European countries. Joinpoint regression analysis was used to identify points where a significant change in trends occurred. Results: In the EU overall, female lung cancer mortality rates rose by 23.8% between 1980-1981 and 1990-1991 (from 7.8 to 9.6/100 000), and by 16.1% thereafter, to reach the value of 11.2/100 000 in 2000-2001. Increases were smaller in the last decade in several countries. Only in England and Wales, Latvia, Lithuania, Russia and Ukraine did female lung cancer mortality show a decrease over the last decade. In several European countries, a decline in lung cancer mortality in young women (20-44 years) was observed over the last decade. Conclusions: Although female lung cancer mortality is still increasing in most European countries, the more favorable trends in young women over recent calendar years suggest that if effective interventions to control tobacco smoking in women are implemented, the lung cancer epidemic in European women will not reach the levels observed in the US

Cancer mortality in the European Union, 1970-2003, with a joinpoint analysis

Background: Cancer mortality peaked in the European Union (EU) in the late 1980s and declined thereafter. Materials and methods: We analyzed EU cancer mortality data provided by the World Health Organization in 1970-2003, using joinpoint analysis. Results: Overall, cancer mortality levelled off in men since 1988 and declined in 1993-2003 (annual percent change, APC = −1.3%). In women, a steady decline has been observed since the early 1970s. The decline in male cancer mortality has been driven by lung cancer, which levelled off since the late 1980s and declined thereafter (APC = 2.7% in 1997-2003). Recent decreases were also observed for other tobacco-related cancers, as oral cavity/pharynx, esophagus, larynx and bladder, as well as for colorectal (APC = −0.9% in 1992-2003) and prostate cancers (APC = −1.0% in 1994-2003). In women, breast cancer mortality levelled off since the early 1990s and declined thereafter (APC = −1.0% in 1998-2003). Female mortality declined through the period 1970-2003 for colorectal and uterine cancer, while it increased over the last three decades for lung cancer (APC = 4.6% in 2001-2003). In both sexes, mortality declined in 1970-2003 for stomach cancer and for a few cancers amenable to treatment. Conclusion: This update analysis of the mortality from cancer in the EU shows favorable patterns over recent years in both sexe

A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe

Background To update and compare mortality from primary liver cancer (PLC) and intrahepatic cholangiocarcinoma (ICC) in Europe in 1990-2010. Materials and methods We used data from the World Health Organization (WHO) to compute age-standardized (world population) mortality rates, and used joinpoint analysis to identify substantial changes. Results Between 2002 and 2007, PLC rates in the European Union (EU) declined from 3.9 to 3.6/100 000 men. Around 2007, the highest male rates were in France (6.2/100 000), Spain (4.9), and Italy (4.0), while the lowest ones were in Sweden (1.1), the Netherlands (1.2), and the UK (1.8). In women, mortality was lower (0.8/100 000 in 2007 in the EU), and showed more favourable trends, with a decline of over 2% per year over the last two decades as compared with 0.4% in men, in the EU. In contrast, the EU mortality from ICC increased by around 9% in both sexes from 1990 to 2008, reaching rates of 1.1/100 000 men and 0.75/100 000 women. The highest rates were in UK, Germany, and France (1.2-1.5/100 000 men, 0.8-1.1/100 000 women). Conclusions PLC mortality has become more uniform across Europe over recent years, with an overall decline; in contrast, ICC mortality has substantially increased in most Europ