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41.
Oana I. Stanisor Sophie A. van Diest Zhumei Yu Olaf Welting Noor Bekkali Jing Shi Wouter J. de Jonge Guy E. Boeckxstaens Rene M. van den Wijngaard 《PloS one》2013,8(6)
Background
The histamine-1 receptor (H1R) antagonist ketotifen increased the threshold of discomfort in hypersensitive IBS patients. The use of peripherally restricted and more selective H1R antagonists may further improve treatment possibilities. We examined the use of fexofenadine and ebastine to reverse post-stress visceral hypersensitivity in maternally separated rats.Methods
The visceromotor response to colonic distension was assessed in adult maternally separated and nonhandled rats pre- and 24 hours post water avoidance. Subsequently rats were treated with vehicle alone or different dosages of fexofenadine (1.8 and 18 mg/kg) or ebastine (0.1 and 1.0 mg/kg) and re-evaluated. Colonic tissue was collected to assess relative RMCP-2 and occludin expression levels by Western blot and histamine-1 receptor by RT-qPCR. β-hexosaminidase release by RBL-2H3 cells was used to establish possible mast cell stabilizing properties of the antagonists.Key results
Water avoidance only induced enhanced response to distension in maternally separated rats. This response was reversed by 1.8 and 18 mg/kg fexofenadine. Reversal was also obtained by 1.0 but not 0.1 mg/kg ebastine. RMCP-2 expression levels were comparable in these two ebastine treatment groups but occludin was significantly higher in 1.0 mg/kg treated rats. There were no differences in histamine-1 receptor expression between nonhandled and maternally separated rats. Fexofenadine but not ebastine showed mast cell stabilizing quality.Conclusions
Our results indicate that the peripherally restricted 2nd generation H1-receptor antagonists fexofenadine and ebastine are capable of reversing post stress visceral hypersensitivity in rat. These data justify future IBS patient trials with these well tolerated compounds. 相似文献42.
Mihály K. de Bie Maurits S. Buiten André Gaasbeek Mark J. Boogers Cornelis J. Roos Joanne D. Schuijf M. Jacqueline Krol Ton J. Rabelink Jeroen J. Bax Martin J. Schalij J. Wouter Jukema 《PloS one》2013,8(7)
Purpose
Significant obstructive coronary artery disease (CAD) is common in asymptomatic dialysis patients. Identifying these high risk patients is warranted and may improve the prognosis of this vulnerable patient group. Routine catheterization of incident dialysis patients has been proposed, but is considered too invasive. CT-angiography may therefore be more appropriate. However, extensive coronary calcification, often present in this patient group, might hamper adequate lumen evaluation. The objective of this study was to assess the feasibility of CT-angiography in this patient group.Methods
For this analysis all patients currently participating in the ICD2 trial (ISRCTN20479861), with no history of PCI or CABG were included. The major epicardial vessels were evaluated on a segment basis (segment 1–3, 5–8, 11 and 13) by a team consisting of an interventional and an imaging specialist. Segments were scored as not significant, significant and not interpretable.Results
A total of 70 dialysis patients, with a mean age of 66±8 yrs and predominantly male (70%) were included. The median calcium score was 623 [79, 1619].Over 90% of the analyzed segments were considered interpretable. The incidence of significant CAD on CT was 43% and was associated with cardiovascular events during follow-up. The incidence of cardiovascular events after 2-years follow-up: 36% vs. 0% in patients with no significant CAD (p<0.01).Conclusion
Despite the high calcium scores CT-angiography is feasible for the evaluation of the extent of CAD in dialysis patients. Moreover the presence of significant CAD on CT was associated with events during follow-up. 相似文献43.
Liselotte W. Wijsman Anton J. M. de Craen Stella Trompet Jacobijn Gussekloo David J. Stott Nicolas Rodondi Paul Welsh J. Wouter Jukema Rudi G. J. Westendorp Simon P. Mooijaart 《PloS one》2013,8(3)
Background
Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).Methods
Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.Results
Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.Conclusion
We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence. 相似文献44.
Sarah Berry Wouter Coppieters Stephen Davis Alayna Burrett Natalie Thomas David Palmer Van Kelly Vladimir Obolonkin Kathryn Sanders Richard Spelman Michel Georges Klaus Lehnert Russell Snell 《PloS one》2013,8(3)
The aim of this study was to determine a genetic basis for IgA concentration in milk of Bos taurus. We used a Holstein-Friesian x Jersey F2 crossbred pedigree to undertake a genome-wide search for QTL influencing IgA concentration and yield in colostrum and milk. We identified a single genome-wide significant QTL on chromosome 16, maximising at 4.8 Mbp. The polymeric immunoglobulin receptor gene (PIGR) was within the confidence interval of the QTL. In addition, mRNA expression analysis revealed a liver PIGR expression QTL mapping to the same locus as the IgA quantitative trait locus. Sequencing and subsequent genotyping of the PIGR gene revealed three divergent haplotypes that explained the variance of both the IgA QTL and the PIGR expression QTL. Genetic selection based on these markers will facilitate the production of bovine herds producing milk with higher concentrations of IgA. 相似文献
45.
Sara Vandenwijngaert Peter Pokreisz Hadewich Hermans Hilde Gillijns Marijke Pellens Noortje A. M. Bax Giulia Coppiello Wouter Oosterlinck Agnes Balogh Zoltan Papp Carlijn V. C. Bouten Jozef Bartunek Jan D'hooge Aernout Luttun Erik Verbeken Marie Christine Herregods Paul Herijgers Kenneth D. Bloch Stefan Janssens 《PloS one》2013,8(3)
Background
The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC).Methodology/Principal Findings
In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dtmax and dP/dtmin with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro.Conclusions/Significance
Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target. 相似文献46.
Impact of land‐use change to Jatropha bioenergy plantations on biomass and soil carbon stocks: a field study in Mali
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Jeroen Degerickx Joana Almeida Pieter C.J. Moonen Leen Vervoort Bart Muys Wouter M.J. Achten 《Global Change Biology Bioenergy》2016,8(2):443-455
Small‐scale Jatropha cultivation and biodiesel production have the potential of contributing to local development, energy security, and greenhouse gas (GHG) mitigation. In recent years however, the GHG mitigation potential of biofuel crops is heavily disputed due to the occurrence of a carbon debt, caused by CO2 emissions from biomass and soil after land‐use change (LUC). Most published carbon footprint studies of Jatropha report modeled results based on a very limited database. In particular, little empirical data exist on the effects of Jatropha on biomass and soil C stocks. In this study, we used field data to quantify these C pools in three land uses in Mali, that is, Jatropha plantations, annual cropland, and fallow land, to estimate both the Jatropha C debt and its C sequestration potential. Four‐year‐old Jatropha plantations hold on average 2.3 Mg C ha?1 in their above‐ and belowground woody biomass, which is considerably lower compared to results from other regions. This can be explained by the adverse growing conditions and poor local management. No significant soil organic carbon (SOC) sequestration could be demonstrated after 4 years of cultivation. While the conversion of cropland to Jatropha does not entail significant C losses, the replacement of fallow land results in an average C debt of 34.7 Mg C ha?1, mainly caused by biomass removal (73%). Retaining native savannah woodland trees on the field during LUC and improved crop management focusing on SOC conservation can play an important role in reducing Jatropha's C debt. Although planting Jatropha on degraded, carbon‐poor cropland results in a limited C debt, the low biomass production, and seed yield attained on these lands reduce Jatropha's potential to sequester C and replace fossil fuels. Therefore, future research should mainly focus on increasing Jatropha's crop productivity in these degraded lands. 相似文献
47.
Wouter A A de Steenhuijsen Piters Elisabeth G W Huijskens Anne L Wyllie Giske Biesbroek Menno R van den Bergh Reinier H Veenhoven Xinhui Wang Krzysztof Trzciński Marc J Bonten John W A Rossen Elisabeth A M Sanders Debby Bogaert 《The ISME journal》2016,10(1):97-108
Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research. 相似文献
48.
Wouter Suykerbuyk Tjeerd J. Bouma Laura L. Govers Kris Giesen Dick J. de Jong Peter Herman Jan Hendriks Marieke M. van Katwijk 《Ecosystems》2016,19(2):296-310
Changes in the seascape often result in altered hydrodynamics that lead to coinciding changes in sediment dynamics. Little is known on how altered sediment dynamics affect long-term seagrass persistence. We studied the thresholds of sediment dynamics in relation to seagrass presence by comparing sediment characteristics and seagrass presence data of seven separate seagrass meadows. All meadows had a long-term (>20 years) presence. Within these meadows, we distinguish so-called “hotspots” (areas within a meadow where seagrass was found during all mapping campaigns) and “coldspots” (with infrequent seagrass presence). We monitored static sediment characteristics (median grain size, bulk density, silt content) and sediment dynamics (that is, bed level change and maximum sediment disturbance depth), bioturbation (that is, lugworm densities and induced fecal pit and mound relief), and seagrass cover. We statistically analyzed which sediment characteristic best explains seagrass cover. Densely vegetated hotspots were shown to have lower sediment dynamics than sparsely vegetated hotspots and coldspots, whereas static sediment characteristics were similar (grain size, bulk density). The vegetation cover was either low (2–15%) or high (>30%) and sediment dynamics showed a threshold for vegetation cover. From this correlative finding, we postulate a self-sustaining feedback of relatively dense seagrass via sediment stabilization and accordingly a runaway feedback once the seagrass cover becomes too sparse. The sensitivity for sediment dynamics shown in our study implies that future existence of seagrass meadows may be at risk as ongoing climate change might directly (increased environmental extremes) or indirectly (changing seascapes) negatively affect seagrass beds. 相似文献
49.
50.
Five typhloplanoids from the Australian East Coast are reported, three of them new to science. Two taxa are members of Promesostomidae: Vauclusia conica n.g. n.sp., characterised by a cone-shaped stylet, the presence of a female bursa and a very long, partially-swollen female duct; Brinkmanniella australiensis n.sp. has a funnel-shaped stylet with a smooth distal tip. Pilamonila bimascula n.g. n.sp. is a representative of the Solenopharyngidae, characterised by a stylet within a cirrus. The known species found are Ceratopera axi and Ptychopera scutulifer. 相似文献