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101.
102.
Louise Deldicque Patrice D. Cani Nathalie M. Delzenne Keith Baar Marc Francaux 《Journal of physiology and biochemistry》2013,69(2):215-225
Certain conditions, such as several weeks of high-fat diet, disrupt endoplasmic reticulum (ER) homeostasis and activate an adaptive pathway referred as the unfolded protein response. When the unfolded protein response fails, the result is the development of inflammation and insulin resistance. These two pathological states are known to be improved by regular exercise training but the mechanisms remain largely undetermined. As it has recently been shown that the unfolded protein response is regulated by exercise, we hypothesised that concomitant treadmill exercise training (HFD+ex) prevents ER homeostasis disruption and its downstream consequences induced by a 6-week high-fat diet (HFD) in mice by activating the protective unfolded protein response. Several well-documented markers of the unfolded protein response were measured in the soleus and tibialis anterior muscles as well as in the liver and pancreas. In HFD mice, an increase in these markers was observed (from 2- to 15-fold, P?<?0.05) in all tissues studied. The combination of HFD+ex increased the expression of several markers further, up to 100 % compared to HFD alone (P?<?0.05). HFD increased inflammatory markers both in the plasma (IL-6 protein, 2.5?±?0.52-fold; MIP-1α protein, 1.3?±?0.13-fold; P?<?0.05) and in the tissues studied, and treadmill exercise attenuated the inflammatory state induced by HFD (P?<?0.05). However, treadmill exercise could not reverse HFD-induced whole body glucose intolerance, assessed by OGTT (AUC, 1.8?±?0.29-fold, P?<?0.05). In conclusion, our results show that a HFD activated the unfolded protein response in mouse tissues in vivo, and that endurance training promoted this response. We speculate that the potentiation of the unfolded protein response by endurance training may represent a positive adaptation protecting against further cellular stress. 相似文献
103.
Chloe Louise Rackham Paramjeet Kaur Dhadda Pedro Cesar Chagastelles Sian Jazmine Shakara Simpson Anshi Anjili Dattani James Edward Bowe Peter Martin Jones Aileen Jean Fiona King 《Cytotherapy》2013,15(4):449-459
Background aimsWe recently showed that co-transplantation of mesenchymal stromal cells (MSCs) improves islet function and revascularization in vivo. Pre-transplant islet culture is associated with the loss of islet cells. MSCs may enhance islet cell survival or function by direct cell contact mechanisms and soluble mediators. We investigated the capacity of MSCs to improve islet cell survival or β-cell function in vitro using direct and indirect contact islet-MSC configurations. We also investigated whether pre-culturing islets with MSCs improves islet transplantation outcome.MethodsThe effect of pre-culturing islets with MSCs on islet function in vitro was investigated by measuring glucose-stimulated insulin secretion. The endothelial cell density of fresh islets and islets cultured with or without MSCs was determined by immunohistochemistry. The efficacy of transplanted islets was tested in vivo using a syngeneic streptozotocin-diabetic minimal islet mass model. Graft function was investigated by monitoring blood glucose concentrations.ResultsIndirect islet-MSC co-culture configurations did not improve islet function in vitro. Pre-culturing islets using a direct contact MSC monolayer configuration improved glucose-stimulated insulin secretion in vitro, which correlated with superior islet graft function in vivo. MSC pre-culture had no effect on islet endothelial cell number in vitro or in vivo.ConclusionsPre-culturing islets with MSCs using a direct contact configuration maintains functional β-cell mass in vitro and the capacity of cultured islets to reverse hyperglycemia in diabetic mice. 相似文献
104.
Objectives
The current study investigates the acceptability, effectiveness and uptake of internet-delivered cognitive behavioural therapy (iCBT) amongst older individuals (>60 years) seeking psychiatric treatment in general practice.Methods
The sample consisted of 2413 (mean age 39.5; range 18–83 years) patients prescribed iCBT through This Way Up clinic by their primary care clinician. The intervention consisted of six fully automated, unassisted online lessons specific to four disorders major depression, generalised anxiety disorder, panic disorder or social phobia. Patients were categorised into five age groups (18–29 years, 30–39 years, 40–49 years, 50–59 years, 60 years and above). 225 (9.3%) patients were aged over 60 years. Analyses were conducted across the four disorders to ensure sufficient sample sizes in the 60 years and older age group. Age differences in adherence to the six lesson courses were assessed to demonstrate acceptability. Age-based reductions in psychological distress (Kessler Psychological Distress Scale; K10) and disability (the World Health Organisation Disability Assessment Schedule; WHODAS-II) were compared to demonstrate effectiveness. To evaluate the uptake of iCBT, the age distribution of those commencing iCBT was compared with the prevalence of these disorders in the 2007 Australian National Survey of Mental Health and Well-Being.Results
Older adults were more likely to complete all six lessons when compared with their younger counterparts. Marginal model analyses indicated that there were significant reductions in the K10 and WHODAS-II from baseline to post-intervention, regardless of age (p<0.001). The measurement occasion by age interactions were not significant, indicating that individuals showed similar reductions in the K10 and WHODAS-II regardless of age. In general, the age distribution of individuals commencing the iCBT courses matched the age distribution of the four diagnoses in the Australian general population, indicating that iCBT successfully captures older individuals who need treatment.Conclusion
iCBT is effective and acceptable for use in older populations. 相似文献105.
Emma Louise Clifford Margaret M. Collins Claire M. Buckley Anthony P. Fitzgerald Ivan J. Perry 《PloS one》2013,8(12)
Objectives
To study the determinants of health-related quality of life (HRQoL) in Irish patients with diabetes using the Centres for Disease Controls'' (CDC''s) ‘Unhealthy Days’ summary measure and to assesses the agreement between this generic HRQoL measure and the disease-specific Audit of Diabetes Dependant Quality of Life (ADDQoL) measure.Research Design and Methods
Data were analysed from the Diabetes Quality of Life Study, a cross-sectional study of 1,456 people with diabetes in Ireland (71% response rate). Unhealthy days were assessed using the CDC''s ‘Unhealthy days’ summary measure. Quality of life (QoL) was also assessed using the ADDQoL measure. Analyses were conducted primarily using logistic regression. The agreement between the two QoL instruments was measured using the kappa co-efficient.Results
Participants reported a median of 2 unhealthy days per month. In multivariate analyses, female gender (P = 0.001), insulin use (P = 0.030), diabetes complications (P = <0.001) were significantly associated with more unhealthy days. Older patients had fewer unhealthy days per month (P = 0.003). Agreement between the two measures of QoL (unhealthy days measure and ADDQoL) was poor, Kappa = 0.234Conclusions
The findings highlight the determinants of HRQoL in patients with diabetes using a generic HRQoL summary measure. The ‘Unhealthy Days’ and the ADDQoL have poor agreement, therefore the ‘Unhealthy Days’ summary measure may be assessing a different construct. Nonetheless, this study demonstrates that the generic ‘Unhealthy Days’ summary measure can be used to detect determinants of HRQoL in patients with diabetes. 相似文献106.
Louise S. Dalb?ge Dorthe L. C. Almholt Trine S. R. Neerup Efstathios Vassiliadis Niels Vrang Lars Pedersen Keld Fosgerau Jacob Jelsing 《PloS one》2013,8(12)
Aim
To characterise changes in pancreatic beta cell mass during the development of diabetes in untreated male C57BLKS/J db/db mice.Methods
Blood samples were collected from a total of 72 untreated male db/db mice aged 5, 6, 8, 10, 12, 14, 18, 24 and 34 weeks, for measurement of terminal blood glucose, HbA1c, plasma insulin, and C-peptide. Pancreata were removed for quantification of beta cell mass, islet numbers as well as proliferation and apoptosis by immunohistochemistry and stereology.Results
Total pancreatic beta cell mass increased significantly from 2.1 ± 0.3 mg in mice aged 5 weeks to a peak value of 4.84 ± 0.26 mg (P < 0.05) in 12-week-old mice, then gradually decreased to 3.27 ± 0.44 mg in mice aged 34 weeks. Analysis of islets in the 5-, 10-, and 24-week age groups showed increased beta cell proliferation in the 10-week-old animals whereas a low proliferation is seen in older animals. The expansion in beta cell mass was driven by an increase in mean islet mass as the total number of islets was unchanged in the three groups.Conclusions/Interpretation
The age-dependent beta cell dynamics in male db/db mice has been described from 5-34 weeks of age and at the same time alterations in insulin/glucose homeostasis were assessed. High beta cell proliferation and increased beta cell mass occur in young animals followed by a gradual decline characterised by a low beta cell proliferation in older animals. The expansion of beta cell mass was caused by an increase in mean islet mass and not islet number. 相似文献107.
Saleela M. Ruwanpura Louise McLeod Andrew R. Lilja Gavin Brooks Lovisa F. Dousha Huei J. Seow Steven Bozinovski Ross Vlahos Paul J. Hertzog Gary P. Anderson Brendan J. Jenkins 《PloS one》2013,8(10)
Myeloid differentiation factor 88 (MyD88) and MyD88-adaptor like (Mal)/Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) play a critical role in transducing signals downstream of the Toll-like receptor (TLR) family. While genetic ablation of the TLR4/MyD88 signaling axis in mice leads to pulmonary cell death and oxidative stress culminating in emphysema, the involvement of Mal, as well as TLR2 which like TLR4 also signals via MyD88 and Mal, in the pathogenesis of emphysema has not been studied. By employing an in vivo genetic approach, we reveal here that unlike the spontaneous pulmonary emphysema which developed in Tlr4−/− mice by 6 months of age, the lungs of Tlr2−/− mice showed no physiological or morphological signs of emphysema. A more detailed comparative analysis of the lungs from these mice confirmed that elevated oxidative protein carbonylation levels and increased numbers of alveolar cell apoptosis were only detected in Tlr4−/− mice, along with up-regulation of NADPH oxidase 3 (Nox3) mRNA expression. With respect to Mal, the architecture of the lungs of Mal−/− mice was normal. However, despite normal oxidative protein carbonylation levels in the lungs of emphysema-free Mal−/− mice, these mice displayed increased levels of apoptosis comparable to those observed in emphysematous Tlr4−/− mice. In conclusion, our data provide in vivo evidence for the non-essential role for TLR2, unlike the related TLR4, in maintaining the normal architecture of the lung. In addition, we reveal that Mal differentially facilitates the anti-apoptotic, but not oxidant suppressive, activities of TLR4 in the lung, both of which appear to be essential for TLR4 to prevent the onset of emphysema. 相似文献
108.
109.
Katherine J. Nicholas Emily K. Zern Louise Barnett Rita M. Smith Shelly L. Lorey Courtney A. Copeland Shanmugalakshmi Sadagopal Spyros A. Kalams 《PloS one》2013,8(12)
Infection with Human Immunodeficiency Virus Type 1 (HIV-1) induces defects of both cellular and humoral immune responses. Impaired CD4+ T cell help and B cell dysfunction may partially explain the low frequency of broadly neutralizing antibodies in HIV-infected individuals. To understand the extent of B cell dysfunction during HIV infection, we assessed the level of B cell activation at baseline and after stimulation with a variety of antigens. Increased levels of viremia were associated with higher baseline expression of the activation marker CD86 on B cells and with decreased ability of B cells to increase expression of CD86 after in vitro stimulation with inactivated HIV-1. In a series of cell isolation experiments B cell responses to antigen were enhanced in the presence of autologous CD4+ T cells. HIV infected individuals had a higher frequency of PD-1 expression on B cells compared to HIV- subjects and PD-1 blockade improved B cell responsiveness to HIV antigen, suggesting that inhibitory molecule expression during HIV-1 infection may contribute to some of the observed B cell defects. Our findings demonstrate that during chronic HIV infection, B cells are activated and lose full capacity to respond to antigen, but suppression of inhibitory pressures as well as a robust CD4+ T cell response may help preserve B cell function. 相似文献
110.
Gözde Gürdeniz Louise Hansen Morten Arendt Rasmussen Evrim Acar Anja Olsen Jane Christensen Thaer Barri Anne Tjønneland Lars Ove Dragsted 《Metabolomics : Official journal of the Metabolomic Society》2013,9(5):1073-1081
In metabolomics studies, liquid chromatography mass spectrometry (LC–MS) provides comprehensive information on biological samples. However, extraction of few relevant metabolites from this large and complex data is cumbersome. To resolve this issue, we have employed sparse principal component analysis (SPCA) to capture the underlying patterns and select relevant metabolites from LC–MS plasma profiles. The study involves a small pilot cohort with 270 subjects where each subject’s time since last meal (TSLM) has been recorded prior to plasma sampling. Our results have demonstrated that both PCA and SPCA can capture the TSLM patterns. Nevertheless, SPCA provides more easily interpretable loadings in terms of selection of relevant metabolites, which are identified as amino acids and lyso-lipids. This study demonstrates the utility of SPCA as a pattern recognition and variable selection tool in metabolomics. Furthermore, amino acids and lyso-lipids are determined as dominating compounds in response to TSLM. 相似文献