Sclerostin does not play a major role in the pathogenesis of skeletal complications in type 2 diabetes mellitus

In contrast to previously reported elevations in serum sclerostin levels in diabetic patients, the present study shows that the impaired bone microarchitecture and cellular turnover associated with type 2 diabetes mellitus (T2DM)-like conditions in ZDF rats are not correlated with changes in serum and bone sclerostin expression. INTRODUCTION: T2DM is associated with impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin, a negative regulator of bone formation, is elevated in serum of diabetic patients. We aimed to relate changes in bone architecture and cellular activities to sclerostin production in the Zucker diabetic fatty (ZDF) rat. METHODS: Bone density and architecture were measured by micro-CT and bone remodelling by histomorphometry in tibiae and femurs of 14-week-old male ZDF rats and lean Zucker controls (n = 6/group). RESULTS: ZDF rats showed lower trabecular bone mineral density and bone mass compared to controls, due to decreases in bone volume and thickness, along with impaired bone connectivity and cortical bone geometry. Bone remodelling was impaired in diabetic rats, demonstrated by decreased bone formation rate and increased percentage of tartrate-resistant acid phosphatase-positive osteoclastic surfaces. Serum sclerostin levels (ELISA) were higher in ZDF compared to lean rats at 9 weeks (+40 %, p < 0.01), but this difference disappeared as their glucose control deteriorated and by week 14, ZDF rats had lower sclerostin levels than control rats (-44 %, p < 0.0001). Bone sclerostin mRNA (qPCR) and protein (immunohistochemistry) were similar in ZDF, and lean rats at 14 weeks and genotype did not affect the number of empty osteocytic lacunae in cortical and trabecular bone. CONCLUSION: T2DM results in impaired skeletal architecture through altered remodelling pathways, but despite altered serum levels, it does not appear that sclerostin contributes to the deleterious effect of T2DM in rat bone

Produktorienteret miljøindsats i landbrugssektoren - forudsætninger

For at styrke den produktorienterede miljøindsats i landbruget nedsatte Miljøstyrelsen primo 2003 et produktkædepanel for landbrugsområdet. Panelets primære mål er at fremme udvikling og afsætning af landbrugsprodukter, der set i et livscyklusperspektiv ("fra jord til jord") er mindre miljøbelastende end tilsvarende traditionelle produkter. Som fundament for panelets arbejde er udarbejdet denne rapport, som beskriver de eksisterende forudsætninger for en produktorienteret indsats i sektoren - i form af en kortlægning af relevante projekter/tiltag. Denne rapport har dannet udgangspunkt for udarbejdelsen af et såkaldt fremsyn på området, som er publiceret særskilt. Fremsynet og information om panelets arbejde i øvrigt kan fås på www.produktpanel-landbrug.dk. En produktorienteret indsats vil altid være et supplement til de eksisterende overordnede reguleringer af samfundets adfærd, forbrug og udledninger. Vi vil stadig i fremtiden opleve berettiget miljøarbejde, der tager udgangspunkt i en konkret produktion eller proces eller i ønsket om at reducere en arealbelastning. Med produktorientering følger en anderledes og mere nuanceret opfattelse af, hvad der er "godt og dårligt" for miljøet, hvilke områder, der skal prioriteres i fødevaresektorens miljøindsats, og hvad miljøarbejdet kan omfatte i alle led i fødevarernes produktkæde. Et produktorienteret miljøarbejde stiller krav til og udfordrer alle aktører i produktkæderne. Der skal ikke alene udveksles og håndteres oplysninger om produktets miljøpåvirkning bagud og fremad i produktkæden, men der skal også ageres på baggrund af de erkendelser, denne udveksling af oplysninger giver anledning til. Helhedsorienteringen skaber også muligheder for at synliggøre og dokumentere valg undervejs i produktkæden. Produktorientering giver dermed en enestående mulighed for aktører/virksomheder for at dokumentere adfærd og valg overfor aftagere (herunder forbrugeren). Også for landbrugs- og gartnerierhvervet er produktorienteringen en udfordring. En kvalificeret diskussion af muligheder og perspektiver i produktorienteringen i landbrugserhvervet er derfor langt fra kun et spørgsmål om værktøjer, opgørelsesmetoder og mulighederne for afsætning af miljødokumenterede varer. Produktorienteringen er i langt højere grad den ramme, hvori f.eks. nedenstående spørgsmål kan diskuteres: Hvilke langsigtede scenarier for landbrugserhvervet er tænkelige? Hvilke strategier kan anlægges for erhvervsudvikling, forskning, kompetenceudvikling etc. for bedst muligt at sigte på de mest attraktive scenarier? Hvordan bringes aktørerne i spil, og hvordan skal ansvar fordeles? De hidtidige erfaringer med produktorientering viser, at en væsentlig forudsætning for succes er åbenhed og kommunikation i produktkæderne

Induction of Interferon-Stimulated Genes by Chlamydia pneumoniae in Fibroblasts Is Mediated by Intracellular Nucleotide-Sensing Receptors

BACKGROUND: Recognition of microorganisms by the innate immune system is mediated by pattern recognition receptors, including Toll-like receptors and cytoplasmic RIG-I-like receptors. Chlamydia, which include several human pathogenic species, are obligate intracellular gram-negative bacteria that replicate in cytoplasmic vacuoles. The infection triggers a host response contributing to both bacterial clearance and tissue damage. For instance, type I interferons (IFN)s have been demonstrated to exacerbate the course of Chlamydial lung infections in mice. METHODS/PRINCIPAL FINDINGS: Here we show that Chlamydia pneumoniae induces expression of IFN-stimulated genes (ISG)s dependent on recognition by nucleotide-sensing Toll-like receptors and RIG-I-like receptors, localized in endosomes and the cytoplasm, respectively. The ISG response was induced with a delayed kinetics, compared to virus infections, and was dependent on bacterial replication and the bacterial type III secretion system (T3SS). CONCLUSIONS/SIGNIFICANCE: Activation of the IFN response during C. pneumoniae infection is mediated by intracellular nucleotide-sensing PRRs, which operate through a mechanism dependent on the bacterial T3SS. Strategies to inhibit the chlamydial T3SS may be used to limit the detrimental effects of the type I IFN system in the host response to Chlamydia infection

The risk of oesophago-gastric cancer in symptomatic patients in primary care: A large case-control study using electronic records

BACKGROUND: Over 15 000 new oesophago-gastric cancers are diagnosed annually in the United Kingdom, with most being advanced disease. We identified and quantified features of this cancer in primary care. METHODS: Case-control study using electronic primary-care records of the UK patients aged ≥40 years was performed. Cases with primary oesophago-gastric cancer were matched to controls on age, sex and practice. Putative features of cancer were identified in the year before diagnosis. Odds ratios (ORs) were calculated for these features using conditional logistic regression, and positive predictive values (PPVs) were calculated. RESULTS: A total of 7471 cases and 32 877 controls were studied. Sixteen features were independently associated with oesophago-gastric cancer (all P5% in patients ≥55 years was for dysphagia. In patients <55 years, all PPVs were <1%. CONCLUSION: Symptoms of oesophago-gastric cancer reported in secondary care were also important in primary care. The results should inform guidance and commissioning policy for upper GI endoscopy

Winter mixed layer development in the central Irminger Sea : the effect of strong, intermittent wind events

Author Posting. © American Meteorological Society, 2008. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 38 (2008): 541-565, doi:10.1175/2007JPO3678.1.The impact of the Greenland tip jet on the wintertime mixed layer of the southwest Irminger Sea is investigated using in situ moored profiler data and a variety of atmospheric datasets. The mixed layer was observed to reach 400 m in the spring of 2003 and 300 m in the spring of 2004. Both of these winters were mild and characterized by a low North Atlantic Oscillation (NAO) index. A typical tip jet event is associated with a low pressure system that is advected by upper-level steering currents into the region east of Cape Farewell and interacts with the high topography of southern Greenland. Heat flux time series for the mooring site were constructed that include the enhancing influence of the tip jet events. This was used to force a one-dimensional mixed layer model, which was able to reproduce the observed envelope of mixed layer deepening in both winters. The deeper mixed layer of the first winter was largely due to a higher number of robust tip jet events, which in turn was caused by the steering currents focusing more storms adjacent to southern Greenland. Application of the mixed layer model to the winter of 1994–95, a period characterized by a high-NAO index, resulted in convection exceeding 1700 m. This prediction is consistent with hydrographic data collected in summer 1995, supporting the notion that deep convection can occur in the Irminger Sea during strong winters.KV and RP were supported by National Science Foundation Grant OCE-0450658. GWKM was supported by the Canadian Foundation for Climate and Atmospheric Sciences. MHR was supported by the Nordic Council of Ministers (West-Nordic Ocean Climate)