Long-term and long range migration of radioisotopes in terrestrial systems : mechanisms of radioisotopes (Cs, Sr, Pu, Am) mobilization in soils

Summary Artificial radionuclides were released in the environment during the atmospheric nuclear weapon tests and after accidental events involving nuclear industries. As a primary receptor of the deposition, the soil is a very sensitive compartment and understanding the interaction and migration of radionuclides within soils allows the development of scenario for the contamination risk of the population and of the environment. Most available field studies on radionuclides in soils only concern one or two isotopes, mostly 137Cs, and few physico-chemical soil parameters. The purpose of this study was a broader understanding of the radioecology of an Alpine valley. In a first part, we aimed to describe the depth distribution of 137Cs, 90Sr, 239+240Pu, and 241Am within different alpine soils and to identify some stable elements as indicators for accumulating layers. In the central part of the study, the goal was to investigate the repartition of ^Sr and 239Pu between the truly dissolved fraction and the colloidal fraction of the soil solutions and to identify the nature of colloids involved in the adsorption of ^Sr and 239Pu. These results were integrated in an "advection- sorption" transport model seeking to explain the migration of 239Pu and 90Sr within the soils and to assess the importance of colloidal transport for these two isotopes. A further aspect studied was the role of the competition between the radioisotopes (137Cs and 90Sr) and their stable chemical analogues (K and Ca) with respect to plant uptake by different plant species. The results on the depth distribution within the soils showed that 137Cs was mostly retained in the topsoil, to the exception of an organic-rich soil (Histosol 2) receiving important surface runoff, where migration down to a depth of 30 cm was observed. 137Cs depth distribution within the soils was similar to unsupported 210Pb depth distribution. The plant uptake of 137Cs clearly depended on the concentration of exchangeable potassium in the soils. Moreover, we showed that the 137Cs uptake by certain species of the taxonomic orders Poales and Rosales was more sensitive to the increase in exchangeable Κ compared to other orders. Strontium-90 was much more mobile in the soils than 137Cs and depth migration and accumulation in specific AI- and Fe-rich layers were found down to 30 cm. Copper and Ni showed accumulations in these same layers, indicating their potential to be used as indicators for the migration of ^Sr within the soils. In addition, we observed a 90Sr activity peak in the topsoil that can be attributable to recycling of 90Sr by plant uptake. We demonstrated for the first time that a part of 90Sr (at least 40%) was associated with the colloids in organic-rich soil solutions. Therefore, we predict a significant effect of the colloidal migration of ^Sr in organic-rich soil solutions. The plant uptake results for 90Sr indicated a phylogenetic effect between Non-Eudicot and Eudicots: the order Poales concentrating much less 90Sr than Eudicots do. Moreover, we were able to demonstrate that the sensitivity of the 90Sr uptake by 5 different Alpine plant species to the amount of exchangeable Ca was species-independent. Plutonium and 241Am accumulated in the second layer of all soils and only a slight migration deeper than 20 cm was observed. Plutonium and 241Am showed a similar depth distribution in the soils. The model results suggested that the present day migration of 239Pu was very slow and that the uptake by plants was negligible. 239Pu activities between 0.01 to 0.08 mBq/L were measured in the bulk soil solutions. Migration of 239Pu with the soil solution is dominated by colloidal transport. We reported strong evidences that humic substances were responsible of the sorption of 239Pu to the colloidal fraction of the soil solutions. This was reflected by the strong correlation between 239Pu concentrations and the content of (colloidal) organic matter in the soil solution. Résumé Certains radioéléments artificiels ont été disséminés dans l'environnement suite aux essais atmosphériques de bombes nucléaires et suite à des accidents impliquant les industries nucléaires. En tant que récepteur primaire de la déposition, le sol est un compartiment sensible et des connaissances sur les interactions et la migration des radioéléments dans le sol permettent de développer des modèles pour estimer la contamination de la population et de l'environnement. Actuellement, la plupart des études de terrain sur ce sujet concernent uniquement un ou deux radioéléments, surtout le 137Cs et peu d'études intègrent les paramètres du sol pour expliquer la migration des radioéléments. Le but général de cette étude était une compréhension étendue de la radio-écologie d'une vallée alpine. Notre premier objectif était de décrire la distribution en profondeur de 137Cs, ^Sr, 239+240pu et 241Am dans différents sols alpins en relation avec des éléments stables du sol, dans le but d'identifier des éléments stables qui pourraient servir d'indicateurs pour des horizons accumulateurs. L'objectif de la deuxième partie, qui était la partie centrale de l'étude, était d'estimer le pourcentage d'activité sous forme colloïdale du 239Pu et du 90Sr dans les solutions des sols. De plus nous avons déterminé la nature des colloïdes impliqués dans la fixation du ^Sr et 239Pu. Nous avons ensuite intégré ces résultats dans un modèle de transport développé dans le but de décrire la migration du 239Pu et 90Sr dans le sol. Finalement, nous avons étudié l'absorption de 137Cs et 90Sr par les plantes en fonction de l'espèce et de la compétition avec leur élément analogue stable (K et Ca). Les résultats sur la migration en profondeur du 137Cs ont montré que ce radioélément était généralement retenu en surface, à l'exception d'un sol riche en matière organique dans lequel nous avons observé une nette migration en profondeur. Dans tous les sols, la distribution en profondeur du 137Cs était corrélée avec la distribution du 210Pb. L'absorption du 137Cs par les plantes, était dépendante de la concentration en Κ échangeable dans le sol, le potassium étant un compétiteur. De plus, nous avons observé que les espèces ne réagissaient pas de la même manière aux variations de la concentration de Κ échangeable. En effet, les espèces appartenant aux ordres des Poales et des Rosales étaient plus sensibles aux variations de potassium échangeable dans le sol. Dans tous les sols Le 90Sr était beaucoup plus mobile que le 137Cs. En effet, nous avons observé des accumulations de 90Sr dans des horizons riches en Fe et Al jusqu'à 30 cm de profondeur. De plus, le Cu et le Ni montraient des accumulations dans les mêmes horizons que le 90Sr, indiquant qu'il pourrait être possible d'utiliser ces deux éléments comme analogues pour la migration du 90Sr. D'après le modèle développé, le pic de 90Sr dans les premiers centimètres du sol peut être attribué à du recyclage par les plantes. Le 90Sr en solution était principalement sous forme dissoute dans des solutions de sols peu organique (entre 60 et 100% de 90Sr dissous). Par contre, dans des solutions organiques, un important pourcentage de 90Sr (plus de 40%) était associé aux colloïdes. La migration colloïdale du 90Sr peut donc être significative dans des solutions organiques. Comme pour le 137Cs, l'absorption du 90Sr par les plantes dépendait de la concentration de son analogue chimique dans la fraction échangeable du sol. Par contre, les espèces de plantes étudiées avaient la même sensibilité aux variations de la concentration du calcium échangeable. Le plutonium et l'américium étaient accumulés dans le deuxième horizon du sol et nous avons observé seulement une faible migration plus profondément que 20 cm. Selon le modèle, la migration actuelle du plutonium est très lente et l'absorption par les plantes semble négligeable. Nous avons mesuré entre 0.01 et 0.08 mBq/L de 239Pu dans les solutions de sol brutes. La migration du plutonium par la solution du sol est due principalement aux colloïdes, probablement de nature humique. Résumé grand public Dans les années 1950 à 1960, l'environnement a été contaminé par des éléments radioactifs (radioéléments) artificiels provenant des essais des armes atomiques et de l'industrie nucléaire. En effet, durant ces années, les premiers essais de bombes atomiques se faisaient dans l'atmosphère, libérant de grandes quantités d'éléments radioactifs. De plus certains accidents impliquant l'industrie nucléaire civile ont contribué à la dissémination d'éléments radioactifs dans l'environnement. Ce fut par exemple le cas de l'accident de la centrale atomique de Tchernobyl en 1986 qui a causé une importante contamination d'une grande partie de l'Europe par le 137Cs. Lorsqu'ils sont libérés dans l'atmosphère, les radioéléments sont dispersés et transportés par les courants atmosphériques, puis peuvent être déposés dans l'environnement, principalement par les précipitations. Une fois déposés sur le sol, les radioéléments vont interagir avec les composants du sol et migrer plus ou moins vite. La connaissance des interactions des éléments radioactifs avec le sol est donc importante pour prédire les risques de contamination de l'environnement et de l'homme. Le but général de ce travail était d'évaluer la migration de différents éléments radioactifs (césium-137, strontium-90, plutonium et américium-241) à travers le sol. Nous avons choisi un site d'étude en milieu alpin (Val Piora, Tessin, Suisse), contaminé en radioéléments principalement par les retombées de l'accident de Tchernobyl et des essais atmosphériques de bombes atomiques. Dans un premier temps, nous avons caractérisé la distribution en profondeur des éléments radioactifs dans le sol et l'avons comparée à divers éléments stables. Cette comparaison nous a permit de remarquer que le cuivre et le nickel s'accumulaient dans les mêmes horizons du sol que le strontium-90 et pourraient donc être utilisés comme analogue pour la migration du strontium-90 dans les sols. Dans la plupart des sols étudiés, la migration du césium-137, du plutonium et de l'américium-241 était lente et ces radioéléments étaient donc accumulés dans les premiers centimètres du sol. Par contre, le strontium-90 a migré beaucoup plus rapidement que les autres radioéléments si bien qu'on observe des accumulations de strontium-90 à plus de 30 cm de profondeur. Les radioéléments migrent dans la solution du sol soit sous forme dissoute, soit sous forme colloïdale, c'est-à-dire associés à des particules de diamètre < Ιμηι. Cette association avec des colloïdes permet à des radioéléments peu solubles, comme le plutonium, de migrer plus rapidement qu'attendu. Nous avons voulu savoir quelle était la part de strontium-90 et plutonium associés à des colloïdes dans la solution du sol. Les résultats ont montré que le plutonium en solution était principalement associé à des colloïdes de type organique. Quant au strontium-90, ce dernier était en partie associé à des colloïdes dans des solutions de sol riches en matière organique, par contre, il était principalement sous forme dissoute dans les solutions de sol peu organiques. L'absorption de radioéléments par les plantes représente une voie importante pour le transfert vers la chaîne alimentaire, par conséquent pour la contamination de l'homme. Nous avons donc étudié le transfert du césium-137 et du strontium-90 de plusieurs sols vers différentes espèces de plantes. Les résultats ont montré que l'absorption des radioéléments par les plantes était liée à la concentration de leur analogue chimique (calcium pour le strontium-90 et potassium pour le césium- 137) dans la fraction échangeable du sol. De plus certaines espèces de plantes accumulent significativement moins de strontium-90.

Geographic patterns in the distribution of social systems in terrestrial arthropods.

The role of ecology in the evolution and maintenance of arthropod sociality has received increasing research attention in recent years. In some organisms, such as halictine bees, polistine wasps, and social spiders, researchers are investigating the environmental factors that may contribute to high levels of variation in the degree of sociality exhibited both among and within species. Within lineages that include only eusocial members, such as ants and termites, studies focus more on identifying extrinsic factors that may contribute to the dramatic variation in colony size, number of queens, and division of labour that is evident across these species. In this review, I propose a comparative approach that seeks to identify environmental factors that may have a common influence across such divergent social arthropod groups. I suggest that seeking common biogeographic patterns in the distribution of social systems or key social traits may help us to identify ecological factors that play a common role in shaping the evolution of sociality across different organisms. I first review previous studies of social gradients that form along latitudinal and altitudinal axes. Within families and within species, many organisms show an increasing degree of sociality at lower latitudes and altitudes. In a smaller number of cases, organisms form larger groups or found nests cooperatively at higher latitudes and altitudes. I then describe several environmental factors that vary consistently along such gradients, including climate variables and abundance of predators, and outline their proposed role in the social systems of terrestrial arthropods. Finally, I map distributions of a social trait against several climatic factors in five case studies to demonstrate how future comparative studies could inform empirical research.

Shallow-platform palaeoenvironmental conditions recorded in deep-shelf sediments: C and stable isotopes in Upper Jurassic sections of southern Germany (Oxfordian-Kimmeridgian)

A high-resolution carbon and oxygen isotope analysis of Late Oxfordian-Early Kimmeridgian deep-shelf sediments of southern Germany is combined with investigation of nannofossil assemblage composition and sedimentological interpretations in order to evaluate the impact of regional palaeoenvironmental conditions on isotopic composition of carbonates. This study suggests that carbonate mud was essentially derived from the Jura shallow platform environments and also that the isotopic signature of carbonates deposited in the Swabian Alb deep shelf indirectly expresses the palaeoenvironmental evolution of the platform. Short-term fluctuations in delta(13) C and delta(18)O are probably controlled by changes in salinity (fresh-water input versus evaporation) in platform environments. Long-term fluctuations in carbon and oxygen isotope record throughout the Late Oxfordian-Early Kimmeridgian result from the interplay of increasing temperature and decreasing humidity, which both control the trophic level. Changes from mesotrophic to oligotrophic conditions in platform environments and in the deep-shelf surface waters are inferred. During the Late Oxfordian (Bimammatum Subzone to Planula Zone), the delta(13)C curve displays a positive shift of about 1 parts per thousand, which is comparable in intensity to global perturbations of the carbon cycle. This evident isotopic shift has not been documented yet in other basinal settings. It can be reasonably explained by local palaeoenvironmental changes on the Jura platform (salinity, temperature, and nutrient availability) that controlled platform carbonate production, and the geochemistry of overlying waters. However, increasing carbonate production on the Jura platform and related positive delta(13)C shifts recorded in the Swabian Alb deep shelf are the regional signatures of climatic changes affecting other palaeogeographical domains of Europe in which the carbonate production increased throughout the Late Oxfordian. (C) 2002 Elsevier Science B.V. All rights reserved.

Stable isotopes in lake Geneva carbonate sediments and molluscs: Review and new data

New isotopic results on bulk carbonate and mollusc (gastropods and bivalves) samples from Lake Geneva (Switzerland), spanning the period from the Oldest Dryas to the present day, are compared with pre-existing stable isotope data. According to preliminary calibration of modern samples, Lake Geneva endogenic calcite precipitates at or near oxygen isotopic equilibrium with ambient water, confirming the potential of this large lake to record paleoenvironmental and paleoclimatic changes. The onset of endogenic calcite precipitation at the beginning of the Allerod biozone is clearly indicated by the oxygen isotopic signature of bulk carbonate. A large change in delta(13)C values occurs during the Preboreal. This carbon shift is likely to be due to a change in bioproductivity and/or to a `'catchment effect'', the contribution of biogenic CO2 from the catchment area to the dissolved inorganic carbon reservoir of the lake water becoming significant only during the Preboreal. Gastropods are confirmed as valuable for studies of changes in paleotemperature and in paleowater isotopic composition, despite the presence of a vital effect. Mineralogical evidence indicates an increased detrital influence upon sedimentation since the Subboreal time period. On the other hand, stable isotope measurements of Subatlantic carbonate sediments show values comparable to those of pure endogenic calcite and of gastropods (taking into account the vital effect). This apparent disagreement still remains difficult to explain.

Study of isotopic variations in black powder: reflections on the use of stable isotopes in forensic science for source inference.

Isotope ratio mass spectrometry (IRMS) has recently made its appearance in the forensic community. This high-precision technology has already been applied to a broad range of forensic fields such as illicit drugs, explosives and flammable liquids, where current, routinely used techniques have limited powers of discrimination. The conclusions drawn from the majority of these IRMS studies appear to be very promising. Used in a comparative process, as in food or drug authentication, the measurement of stable isotope ratios is a new and remarkable analytical tool for the discrimination or the identification of a substance with a definite source or origin. However, the research consists mostly of preliminary studies. The significance of this 'new' piece of information needs to be evaluated in light of a forensic framework to assess the actual potential and validity of IRMS, considering the characteristics of each field. Through the isotopic study of black powder, this paper aims at illustrating the potential of the method and the limitations of current knowledge in stable isotopes when facing forensic problems.

Plutonium and americium isotopes as alternative chronostratigraphic markers in tropical regions: An application in the Havana Bay (Cuba)

The low 137Cs activity observed in marine sediments of tropical regions often precludes its use as chronostratigraphic marker. Here we present a study on the use of Pu and Am radioisotopes as alternative markers to constrain the 210Pb ages in a sediment core of the Havana Bay (Cuba). Mean activity ratios of 238Pu/239,240Pu, 241Am/239,240Pu and 241Pu/239,240Pu indicated that the nuclear weapon tests fallout is the main source of the anthropogenic radionuclides. While the inventory of 137Cs in the sediments is lower than the expected fallout inventory, 239,240Pu accumulates in the sediments with inventories higher than the expected fallout inventory. The high fluxes of 239,240Pu are nevertheless corroborated here through use of 210Pb, and confirm that focusing of solid particles is of great importance in the investigated site. 239,240Pu showed to be a useful time tracer in marine sites where the 137Cs signal is very low.

Surveillance for European bat lyssavirus in Swiss bats.

Most countries in Western Europe are currently free of rabies in terrestrial mammals. Nevertheless, rabies remains a residual risk to public health due to the natural circulation of bat-specific viruses, such as European bat lyssaviruses (EBLVs). European bat lyssavirus types 1 and 2 (EBLV-1 and EBLV-2) are widely distributed throughout Europe, but little is known of their true prevalence and epidemiology. We report that only three out of 837 brains taken from bats submitted to the Swiss Rabies Centre between 1976 and 2009 were found by immunofluorescence (FAT) to be positive for EBLVs. All three positive cases were in Myotis daubentoni, from 1992, 1993 and 2002. In addition to this passive surveillance, we undertook a targeted survey in 2009, aimed at detecting lyssaviruses in live bats in Switzerland. A total of 237 bats of the species M. daubentoni, Myotis myotis, Eptesicus serotinus and Nyctalus noctula were captured at different sites in western Switzerland. Oropharyngeal swabs and blood from each individual were analysed by RT-PCR and rapid fluorescent focus inhibition test (RFFIT), respectively. RNA corresponding to EBLV-2 was detected from oropharyngeal swabs of a single M. daubentoni bat, but no infectious virus was found. Molecular phylogenetic analysis revealed that the corresponding sequence was closely related to the other EBLV-2 sequences identified in previous rabies isolates from Swiss bats (particularly to that found at Geneva in 2002). Three M. daubentoni bats were found to be seropositive by RFFIT. In conclusion, even though the prevalence is low in Switzerland, continuous management and surveillance are required to assess the potential risk to public health.

Rosickyite (monoclinic gamma-sulphur) from La Presta Asphalt Mine, Neuchatel, Switzerland: new X-ray powder diffraction data

Rosickyite, the natural monoclinic gamma -form of sulphur, exists in only a few localities around the globe. In the old asphalt mine at La Presta, Neuchatel. Switzerland, rosickyite occurs locally as small, but very well formed crystals suitable for crystallographic studies. It grows as an alteration product of pyrite-rich asphalt. Rosickyite from La Presta mine is pure molecular sulphur, as revealed by gas chromatography-mass spectrometry. The X-ray powder diffraction data of La Presta rosickyite does not match the one previously published for this species. Therefore, a single crystal study was undertaken and a new indexed X-ray powder diffraction diagram for natural rosickyite is proposed.

Climatic niche shifts are rare among terrestrial plant invaders.

The assumption that climatic niche requirements of invasive species are conserved between their native and invaded ranges is key to predicting the risk of invasion. However, this assumption has been challenged recently by evidence of niche shifts in some species. Here, we report the first large-scale test of niche conservatism for 50 terrestrial plant invaders between Eurasia, North America, and Australia. We show that when analog climates are compared between regions, fewer than 15% of species have more than 10% of their invaded distribution outside their native climatic niche. These findings reveal that substantial niche shifts are rare in terrestrial plant invaders, providing support for an appropriate use of ecological niche models for the prediction of both biological invasions and responses to climate change.

Liver kidney microsomes type 1 antibodies are associated with 80% reduction of the CYP2D6 activity in patients with chronic hepatitis C

Introduction Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease CYP2D6 activity in vitro. We investigated whether LKM-1 antibodies might reduce CYP2D6 activity also in vivo.Materials and Methods All patients with chronic hepatitis C and LKM-1 antibodies enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were assessed: ten were eligible and fi tted to patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specifi c substrate using the dextromethorphan/dextrorphan (DEM/DOR) metabolic ratio to classify patients into four activity phenotypes (i.e. ultrarapid, extensive, intermediate and poor metabolizers). The concordance between phenotype based on DEM/DOR ratio and phenotype expected from genotype was examined in LKM-1 positive and negative patients. Groups were compared with respect to the DEM/DOR metabolic ratio.Results All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with CYP2D6 genotype in most LKM-negative patients, whereas only three (30%) LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was six-fold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, p = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies.Conclusion In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies in the setting of new protease inhibitor therapies

Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel

Aim: The diagnosis of inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), continues to present difficulties due to unspecific symptoms and limited test accuracies. We aimed to determine the diagnostic delay (time from first symptoms to IBD diagnosis) and to identify associated risk factors in a national cohort in Switzerland.¦Materials and Methods: A total of 1,591 IBD patients (932 CD, 625 UC, 34 indeterminate colitis) from the Swiss IBD cohort study (SIBDCS) were evaluated. The SIBDCS collects data on a large sample of IBD patients from hospitals and private practice across Switzerland through physician and patient questionnaires. The primary outcome measure was the diagnostic delay.¦Results: Diagnostic delay in CD patients was significantly longer compared to UC patients (median 9 vs. 4 months, P < 0.001). Seventy-five percent of CD patients were diagnosed within 24 months compared to 12 months for UC and 6 months for IC patients. Multivariate logistic regression identified age <40 years at diagnosis (OR 2.15, P = 0.010) and ileal disease (OR 1.69, P = 0.025) as independent risk factors for long diagnostic delay in CD (>24 months). A trend for long diagnostic delay (>12 months) was associated with NSAID intake (OR 1.75, P = 0.093) and male gender (OR 0.59, P = 0.079) in UC patients.¦Conclusions: Whereas the median delay for diagnosing CD, UC, and IC seems to be acceptable, there exists a long delay in a considerable proportion of CD patients. More public awareness work needs to be done in order to reduce patient's and doctor's delay in this target population.

Expression pattern of sirtuins in innate immune cells and influence of Sirtuin 1/2 inhibition on innate immune responses to Toll-like receptor ligands and to infection

Purpose/Objective: The family of histone deacetylases comprises 18 members in mammals, among which seven sirtuins (SIRT1-7). Sirtuins are NADP-dependent enzymes that have been involved in the control of cell metabolism, proliferation and survival. The expression pattern of sirtuins and their influence on host response to microbial infection remain largely unknown. The aim of the study was to analyze the expression of SIRT1-7 and to address the effects of SIRT1/2 inhibition on innate immune responses in vitro and in vivo.. Materials and methods: in vitro: Bone marrow (BM), BM-derived macrophages (BMDMs) and dendritic cells (BMDCs) and RAW 264.7 and J774.1 macrophage cell lines were stimulated for 0, 2, 6 and 18 h with LPS, Pam3CSK4 and CpG ODN. SIRT1-7 mRNA was quantified by real time-PCR. TNF was measured by ELISA. In vivo: BALB/c mice were challenged with LPS (350 lg i.p.) with or without a SIRT1/2 inhibitor. Blood and organs were collected after 0, 1, 4, 8 and 24 h to quantify SIRT1-7 and TNF. Mortality was assessed daily. Results: Bone marrow, macrophages and DCs express, in order of abundance, SIRT2 > > SIRT1, SIRT3 and SIRT6 > SIRT4, SIRT5 and SIRT7. Microbial products decrease the expression of all sirtuins except SIRT6 in a time dependent manner in BMDMs (0_24 h). SIRT2 is the most expressed sirtuin also in the liver, kidney (together with SIRT3) and spleen. Upon LPS challenge, SIRT1, SIRT3, SIRT4 and SIRT7 mRNA levels decrease in the liver (from 4 h to 24 h), whereas SIRT1-7 mRNA levels decrease within 1 h in both kidney and spleen. Pharmacological inhibition of SIRT1/2 decreases TNF production by macrophages stimulated with LPS, Pam3CSK4 and CpG ODN (n = 6; P < 0.001). In agreement, prophylactic treatment with a SIRT1/2 inhibitor decreases TNF production (n = 8; P = 0.04) and increases survival (n = 13, P = 0.03) of mice challenged with LPS. Conclusions: Sirtuins are expressed in innate immune cells. Inhibition of SIRT1/2 activity decreases cytokine production by macrophages and protects from endotoxemia, suggesting that sirtuin inhibitors may represent novel adjunctive therapy for treating inflammatory disorders such as sepsis.

Cancer mortality in Europe, 2000-2004, and an overview of trends since 1975.

BACKGROUND: To update the pattern of cancer mortality in Europe. Materials and methods: We analysed cancer mortality in 34 European countries during 2000-2004, with an overview of trends in 1975-2004 using data from the World Health Organization. RESULTS: From 1990-1994 to 2000-2004, overall cancer mortality in the European Union declined from 185.2 to 168.0/100 000 (world standard, -9%) in men and from 104.8 to 96.9 (-8%) in women, with larger falls in middle age. Total cancer mortality trends were favourable, though to a variable degree, in all major European countries, including Russia, but not in Romania. The major determinants of these favourable trends were the decline of lung (-16%) and other tobacco-related cancers in men, together with the persistent falls in gastric cancer, and the recent appreciable falls in colorectal cancer. In women, relevant contributions came from the persistent decline in cervical cancer and the recent falls in breast cancer mortality, particularly in northern and western Europe. Favourable trends were also observed for testicular cancer, Hodgkin lymphomas, leukaemias, and other neoplasms amenable to treatment, though the reductions were still appreciably smaller in eastern Europe. CONCLUSION: This updated analysis of cancer mortality in Europe showed a persistent favourable trend over the last years.