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

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

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

The recent decline in mortality from Hodgkin lymphomas in central and eastern Europe

Background: Hodgkin lymphoma (HL) is a largely curable disease and its mortality had steadily declined in western Europe since the late 1960s. Only modest declines were, however, observed in central/eastern Europe. Materials and methods: We updated trends in mortality from HL in various European areas up to 2004 and analyzed patterns in incidence for selected European countries providing national data. Results: In most western European countries, HL mortality continued to steadily decline up to the mid 2000s. More recent reductions were also observed in eastern European countries. Overall, mortality from HL declined from 1.17/100 000 (age-standardized, world population) in 1980-1989 to 1.42/100 000 in 2000-2004 in men from the 15 member states of the European Union (EU) from western and northern Europe. In the EU 10 accession countries of central and eastern Europe, male mortality from HL was 1.42/100 000 in 1980-1984, 1.32 in 1990-1994, and declined to 0.76 in 2000-2004. Similar trends were observed in women. No consistent patterns were found for HL incidence. Conclusions: The present work confirms the persistent declines in HL mortality in western European countries, and shows favorable patterns over more recent calendar years in central/eastern ones, where rates, however, are still at levels observed in western Europe in the early 1990

Diet and cancer risk in Mediterranean countries: Open issues

Objective: To analyse various aspects of the Mediterranean diet in relation to the risk of several common cancers in Italy. Design: Data from a series of case-control studies conducted in northern Italy between 1983 and 2004 on over 20 000 cases of several major cancers and 18 000 controls. Results: For most digestive tract cancers, the risk decreased with increasing vegetable and fruit consumption, with relative risks between 0.3 and 0.7 for the highest level of intake, and the population-attributable risks for low intake of vegetables and fruit ranged between 15 and 40%. Less strong inverse relations were observed for other (epithelial) cancers, too. A number of micronutrients contained in vegetables and fruit showed an inverse relation with cancer risk. In particular, flavones, flavonols and resveratrol were inversely related to breast cancer risk. Olive oil, which is a typical aspect of the Mediterranean diet, has also been inversely related to cancers of the colorectum and breast, and mainly of the upper digestive and respiratory tract. Consumption of pizza, one of the most typical Italian foods, was related to a reduced risk of digestive tract cancers, although pizza may simply be an aspecific indicator of the Italian diet. Conclusions: Adherence to the Mediterranean diet is a favourable indicator of the risk of several common epithelial cancers in Italy. A score summarising the major characteristics of the Mediterranean diet was related to a priori defined reduced risks of several digestive tract neoplasms by over 50%