Free radical reactions in atherosclerosis; An EPR spectrometry study

The copper catalysed oxidation of homocysteine has been studied by electron paramagnetic resonance (EPR) spectroscopy and spin trapping techniques to determine the nature of free radical species formed under varying experimental conditions. Three radicals; thiyl, alkyl and hydroxyl were detected with hydroxyl being predominant. A reaction mechanism is proposed involving Fenton chemistry. Inclusion of catalase to test for intermediate generation of hydrogen peroxide showed a marked reduction in amount of hydroxyl radical generated. In contrast, the addition of superoxide dismutase showed no significant effect on the level of hydroxyl radical formed. Enhanced radical formation was observed at higher levels of oxygen, an effect which has consequences for differential oxygen levels in arterial and venous systems. Implications are drawn for a higher incidence of atherosclerotic plaque formation in arteries versus veins. © 2006 - IOS Press and the authors. All rights reserved

Datasets of whole cell and mitochondrial oxysterols derived from THP-1, SH-SY5Y and human peripheral blood mononuclear cells using targeted metabolomics

The raw datasets of oxysterol quantifications from whole cell and mitochondrial fractions of THP-1 monocytes and macrophages, neuronal-like SH-SH5Y cells and human peripheral blood mononuclear cells are presented. Oxysterols were quantified using a new liquid chromatography-mass spectrometry (LC-MS) and multiple reaction monitoring analysis published in the article “A quantitative LC-MS/MS method for analysis of mitochondrial-specific oxysterol metabolism” in Redox Biology [1]. This method showed improved extraction efficiency and recovery of mono and dihydroxycholesterols from cellular matrix. The datasets derived from the three cell lines are included in the appendix. These datasets provide new information about the oxysterol distribution in THP-1 monocytes and macrophages, SH-SY5Y cells and peripheral blood mononuclear cells. These datasets can be used as a guide for oxysterol distribution in the three cell lines for future studies, and can used for future method optimization, and for comparison of oxysterol recovery with other analytical techniques

Thematic Research network for emergency and UnScheduled Treatment (TRUST): scoping the potential

<p>Abstract</p> <p>Background</p> <p>To identify the benefits of a network in emergency and unscheduled care research, a six week scoping study was undertaken. Objectives were to: draw together stakeholders; identify and prioritise research topics; identify sites for recruitment to studies; and agree a research strategy for a network.</p> <p>Methods</p> <p>A workshop was held to discuss and agree a research strategy based on results from four activities: visits to established research centres in emergency and unscheduled care; a literature overview; interviews with stakeholders in a GP out-of-hours service; and an exploration of the potential for routine data to support research in emergency care.</p> <p>Results</p> <p>Participants attended the workshop from user groups, primary care, the ambulance service, social care, the national telephone based health helpline, the Welsh Assembly Government and the academic sector. Site visits identified opportunities for collaboration. Gaps in knowledge were identified concerning the effectiveness of alternative models of emergency care delivery. Interview data highlighted a lack of evidence related to the quality of out-of-hours provision of primary care. The All Wales Injury Surveillance System (AWISS) was found to offer the potential to use routine data to support quantitative studies in emergency care. Three key issues emerged across all activities: working across boundaries; patient involvement; and triage.</p> <p>Conclusion</p> <p>The study included views from patient, provider, policy and academic perspectives and built the case for a research network in emergency care. Now funded, TRUST (Thematic Research network for emergency and UnScheduled Treatment) will allow the development of research proposals, building of research teams and recruitment of sites and patients both in Wales and across the UK. It aims to address the imbalance between investment and research in this area and help support provision of 'the right care to the right people at the right time'.</p

Spleen as a Site for Hematopoiesis of a Distinct Antigen Presenting Cell Type

While spleen and other secondary tissue sites contribute to hematopoiesis, the nature of cells produced and the environment under which this happens are not fully defined. Evidence is reviewed here for hematopoiesis occurring in the spleen microenvironment leading to the production of tissue-specific antigen presenting cells. The novel dendritic-like cell identified in spleen is phenotypically and functionally distinct from other described antigen presenting cells. In order to identify these cells as distinct, it has been necessary to show that their lineage origin and progenitors differ from that of other known dendritic and myeloid cell types. The spleen therefore represents a distinct microenvironment for hematopoiesis of a novel myeloid cell arising from self-renewing hematopoietic stem cells (HSC) or progenitors endogenous to spleen

Mental health literacy as a function of remoteness of residence: an Australian national study

<p>Abstract</p> <p>Background</p> <p>Although there have been many population studies of mental health literacy, little is known about the mental health literacy of people who reside in rural areas. This study sought to determine the impact of remoteness on public knowledge of depression and schizophrenia.</p> <p>Methods</p> <p>The mental health literacy of residents of major cities, inner regional, and outer-remote (including outer regional, remote, and very remote) regions were compared using data from a 2003–04 Australian national survey of the mental health literacy of 3998 adults. Measures included the perceived helpfulness of a range of professionals, non-professionals and interventions, and the causes, prognosis, and outcomes after treatment for four case vignettes describing depression, depression with suicidal ideation, early schizophrenia and chronic schizophrenia. Participant awareness of Australia's national depression initiative and depression in the media, their symptoms of depression and exposure to the conditions depicted in the vignettes were also compared.</p> <p>Results</p> <p>Mental health literacy was similar across remoteness categories. However, inner regional residents showed superior identification of the disorders depicted in the suicidal ideation and chronic schizophrenia vignettes. They were also more likely to report having heard of Australia's national depression health promotion campaign. Conversely, they were less likely than major city residents to rate the evidence-based treatment of psychotherapy helpful for depression. Both inner regional and outer-remote residents were less likely to rate psychologists as helpful for depression alone. The rural groups were more likely to rate the non-evidence based interventions of drinking and painkillers as helpful for a depression vignette. In addition, outer-remote residents were more likely to identify the evidence based treatment of antipsychotics as harmful for early schizophrenia and less likely to endorse psychiatrists, psychologists, social workers and general practitioners as helpful for the condition.</p> <p>Conclusion</p> <p>Mental health awareness campaigns in rural and remote regions may be most appropriately focused on communicating which interventions are effective for depression and schizophrenia and which mental health and other professionals are trained in the best-practice delivery and management of these. There is also a need to communicate to rural residents that alcohol and pain relievers are not an effective solution for depression.</p

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

Models in the delivery of depression care: A systematic review of randomised and controlled intervention trials

<p>Abstract</p> <p>Background</p> <p>There is still debate as to which features, types or components of primary care interventions are associated with improved depression outcomes. Previous reviews have focused on components of collaborative care models in general practice settings. This paper aims to determine the effective components of depression care in primary care through a systematic examination of both general practice and community based intervention trials.</p> <p>Methods</p> <p>Fifty five randomised and controlled research trials which focused on adults and contained depression outcome measures were identified through PubMed, PsycInfo and the Cochrane Central Register of Controlled Trials databases. Trials were classified according to the components involved in the delivery of treatment, the type of treatment, the primary focus or setting of the study, detailed features of delivery, and the discipline of the professional providing the treatment. The primary outcome measure was significant improvement on the key depression measure.</p> <p>Results</p> <p>Components which were found to significantly predict improvement were the revision of professional roles, the provision of a case manager who provided direct feedback and delivered a psychological therapy, and an intervention that incorporated patient preferences into care. Nurse, psychologist and psychiatrist delivered care were effective, but pharmacist delivery was not. Training directed to general practitioners was significantly less successful than interventions that did not have training as the most important intervention. Community interventions were effective.</p> <p>Conclusion</p> <p>Case management is important in the provision of care in general practice. Certain community models of care (education programs) have potential while others are not successful in their current form (pharmacist monitoring).</p

TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide

Endothelial dysfunction is implicated in the development and aggravation of cardiovascular complications. Among the endothelium-released vasoactive factors, hydrogen sulfide (H2S) has been investigated for its beneficial effects on the vasculature through anti-inflammatory and redox-modulating regulatory mechanisms. Reduced H2S bioavailability is reported in chronic diseases such as cardiovascular disease, diabetes, atherosclerosis and preeclampsia, suggesting the value of investigating mechanisms, by which H2S acts as a vasoprotective gasotransmitter. We explored whether the protective effects of H2S were linked to the mitochondrial health of endothelial cells and the mechanisms by which H2S rescues apoptosis. Here, we demonstrate that endothelial dysfunction induced by TNF-α increased endothelial oxidative stress and induced apoptosis via mitochondrial cytochrome c release and caspase activation over 24 h. TNF-α also affected mitochondrial morphology and altered the mitochondrial network. Post-treatment with the slow-releasing H2S donor, GYY4137, alleviated oxidising redox state, decreased pro-caspase 3 activity, and prevented endothelial apoptosis caused by TNF-α alone. In addition, exogenous GYY4137 enhanced S-sulfhydration of pro-caspase 3 and improved mitochondrial health in TNF-α exposed cells. These data provide new insights into molecular mechanisms for cytoprotective effects of H2S via the mitochondrial-driven pathway

The Chiral Potts Models Revisited

In honor of Onsager's ninetieth birthday, we like to review some exact results obtained so far in the chiral Potts models and to translate these results into language more transparent to physicists, so that experts in Monte Carlo calculations, high and low temperature expansions, and various other methods, can use them. We shall pay special attention to the interfacial tension $\epsilon_r$ between the $k$ state and the $k-r$ state. By examining the ground states, it is seen that the integrable line ends at a superwetting point, on which the relation $\epsilon_r=r\epsilon_1$ is satisfied, so that it is energetically neutral to have one interface or more. We present also some partial results on the meaning of the integrable line for low temperatures where it lives in the non-wet regime. We make Baxter's exact results more explicit for the symmetric case. By performing a Bethe Ansatz calculation with open boundary conditions we confirm a dilogarithm identity for the low-temperature expansion which may be new. We propose a new model for numerical studies. This model has only two variables and exhibits commensurate and incommensurate phase transitions and wetting transitions near zero temperature. It appears to be not integrable, except at one point, and at each temperature there is a point, where it is almost identical with the integrable chiral Potts model.Comment: J. Stat. Phys., LaTeX using psbox.tex and AMS fonts, 69 pages, 30 figure