bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redox signalling and cardioprotection: translatability and mechanism
Authors: Pagliaro P , Penna C 
Published: October 2014

The morbidity and mortality from coronary artery disease (CAD) remain significant worldwide. The treatment for acute myocardial infarction has improved over the past decades, including early reperfusion of culprit coronary arteries. Although it is mandatory to reperfuse the ischaemic territory as soon as possible, paradoxically this leads to additional myocardial injury, namely ischaemia/reperfusion (I/R) injury, in which redox stress plays a pivotal role and for which no effective therapy is currently available. In this review, we report evidence that the redox environment plays a pivotal role not only in I/R injury but also in cardioprotection. In fact, cardioprotective strategies, such as pre‐ and post‐conditioning, result in a robust reduction in infarct size in animals and the role of redox signalling is of paramount importance in these conditioning strategies. Nitrosative signalling and cysteine redox modifications, such as S‐nitrosation/S‐nitrosylation, are also emerging as very important mechanisms in conditioning cardioprotection. The reasons for the switch from protective oxidative/nitrosative signalling to deleterious oxidative/nitrosative/nitrative stress are not fully understood. The complex regulation of this switch is, at least in part, responsible for the diminished or lack of cardioprotection induced by conditioning protocols observed in ageing animals and with co‐morbidities as well as in humans. Therefore, it is important to understand at a mechanistic level the reasons for these differences before proposing a safe and useful transition of ischaemic or pharmacological conditioning. Indeed, more mechanistic novel therapeutic strategies are required to protect the heart from I/R injury and to improve clinical outcomes in patients with CAD.Linked ArticlesThis article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8
Unravelling the theories of pre‐eclampsia: are the protective pathways the new paradigm?
Authors: Ahmed Asif , Ramma Wenda 
Published: October 2014

Pre‐eclampsia is a vascular disorder of pregnancy where anti‐angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre‐eclampsia. This review provides an alternative to the ‘two‐stage model’ of pre‐eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms‐like tyrosine kinase‐1 (sFlt‐1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre‐eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the ‘accelerator’. The ‘braking system’ includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO‐1) and cystathionine‐γ‐lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre‐eclampsia is an accelerator–brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti‐angiogenic factors sFlt‐1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line.Linked ArticlesThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐6
Annexin A2 complexes with S100 proteins: structure, function and pharmacological manipulation
Authors: Liu Yidong , Myrvang Helene K , Dekker Lodewijk V 
Published: October 2014

Annexin A2 (AnxA2) was originally identified as a substrate of the pp60v‐src oncoprotein in transformed chicken embryonic fibroblasts. It is an abundant protein that associates with biological membranes as well as the actin cytoskeleton, and has been implicated in intracellular vesicle fusion, the organization of membrane domains, lipid rafts and membrane‐cytoskeleton contacts. In addition to an intracellular role, AnxA2 has been reported to participate in processes localized to the cell surface including extracellular protease regulation and cell‐cell interactions. There are many reports showing that AnxA2 is differentially expressed between normal and malignant tissue and potentially involved in tumour progression. An important aspect of AnxA2 function relates to its interaction with small Ca2+‐dependent adaptor proteins called S100 proteins, which is the topic of this review. The interaction between AnxA2 and S100A10 has been very well characterized historically; more recently, other S100 proteins have been shown to interact with AnxA2 as well. The biochemical evidence for the occurrence of these protein interactions will be discussed, as well as their function. Recent studies aiming to generate inhibitors of S100 protein interactions will be described and the potential of these inhibitors to further our understanding of AnxA2 S100 protein interactions will be discussed.Linked ArticlesThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐7
Generation of β cell-specific human cytotoxic T cells by lentiviral transduction and their survival in immunodeficient human leucocyte antigen-transgenic mice
Authors: Babad J , Mukherjee G , Follenzi A , Ali R , Roep B O , Shultz L D , Santamaria P , Yang O O , Goldstein H , Greiner D L , DiLorenzo T P 
Published: October 2014

SummarySeveral β cell antigens recognized by T cells in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D) are also T cell targets in the human disease. While numerous antigen-specific therapies prevent diabetes in NOD mice, successful translation of rodent findings to patients has been difficult. A human leucocyte antigen (HLA)-transgenic mouse model incorporating human β cell-specific T cells might provide a better platform for evaluating antigen-specific therapies. The ability to study such T cells is limited by their low frequency in peripheral blood and the difficulty in obtaining islet-infiltrating T cells from patients. We have worked to overcome this limitation by using lentiviral transduction to ‘reprogram’ primary human CD8 T cells to express three T cell receptors (TCRs) specific for a peptide derived from the β cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP265–273) and recognized in the context of the human class I major histocompatibility complex (MHC) molecule HLA-A2. The TCRs bound peptide/MHC multimers with a range of avidities, but all bound with at least 10-fold lower avidity than the anti-viral TCR used for comparison. One exhibited antigenic recognition promiscuity. The β cell-specific human CD8 T cells generated by lentiviral transduction with one of the TCRs released interferon (IFN)-γ in response to antigen and exhibited cytotoxic activity against peptide-pulsed target cells. The cells engrafted in HLA-A2-transgenic NOD-scid IL2rγnull mice and could be detected in the blood, spleen and pancreas up to 5 weeks post-transfer, suggesting the utility of this approach for the evaluation of T cell-modulatory therapies for T1D and other T cell-mediated autoimmune diseases.
Occupational irritant contact dermatitis diagnosed by analysis of contact irritants and allergens in the work environment
Authors: Friis Ulrik F. , Menné Torkil , Schwensen Jakob F. , Flyvholm Mari‐Ann , Bonde Jens P. E. , Johansen Jeanne D. 
Published: October 2014

SummaryBackgroundIrritant contact dermatitis (ICD) is a common diagnosis in patients with occupational contact dermatitis (OCD). Studies are lacking on the usefulness of material safety data sheets (MSDSs) in making the diagnosis of ICD.ObjectiveTo characterize irritant exposures leading to the diagnosis of occupational ICD (OICD), and to evaluate the occurrence of concomitant exposures to contact allergens.MethodsWe included 316 patients with suspected occupational hand dermatitis, referred to the Department of Dermato‐Allergology, Copenhagen University Hospital Gentofte, Denmark during January 2010–August 2011, in a programme consisting of a clinical examination, exposure assessment, and extensive patch/prick testing.ResultsOCD was diagnosed in 228 patients. Of these patients, 118 were diagnosed with OICD. The main irritant exposures identified were wet work (n = 64), gloves (n = 45), mechanical traumas (n = 19), and oils (n = 15). Exposure to specific irritant chemicals was found in 9 patients, and was identified from MSDSs/ingredients labelling in 8 of these patients. Review of MSDSs and ingredients labelling showed that 41 patients were exposed to 41 moderate to potent contact allergens, and 18 patients were exposed to 25 weak workplace contact allergens.ConclusionIn the present study, the systematic exposure assessment did not reveal any new irritants. MSDSs have a limited role in the investigation of ICD.
Type of opioids injected: Does it matter? A multicentric cross‐sectional study of people who inject drugs
Authors: Ambekar Atul , Rao Ravindra , Mishra Ashwani Kumar , Agrawal Alok 
Published: October 2014

AbstractIntroduction and AimsInjecting pharmaceutical opioids for non‐medical purposes is a major concern globally. Though pharmaceutical opioids injection is reported in India, the exact proportion of people who inject drugs (PWID) using pharmaceutical opioids is unknown. The objectives of this study were to describe the various types of drugs that are injected by people in India and to analyse the differences between the commonly injected drugs.Design and MethodsA cross‐sectional, multicentric study covering 22 harm‐reduction sites from different regions of the country was conducted. First 50 subjects, chosen randomly from a list of PWIDs accessing services from each site and fulfilling study criteria, were interviewed using a structured questionnaire. Data from 902 male subjects are presented here.ResultsPharmaceutical opioid injectors (POI) accounted for 65% of PWIDs (buprenorphine: 30.8%, pentazocine: 21.8% and dextropropoxyphene: 11.9%). Heroin, injected by 34.3%, was prevalent in most states surveyed. Buprenorphine and pentazocine were not injected in the north‐east region, whereas dextropropoxyphene was injected in the north‐east alone. Univariate and multivariate logistic regression showed that, compared with heroin injectors, the POI group was more likely to consume alcohol and pharmaceutical opioids orally, inject frequently, share needle/syringes and develop injection‐site complications. Among individual POIs, buprenorphine injectors had significantly higher proportion of subjects injecting frequently, sharing needle/syringes and developing local complications. Irrespective of the opioid type, majority of subjects were opioid dependent.Discussion and ConclusionsPharmaceutical opioids are the most common drugs injected in India currently and have greater injection‐related risks and complications. Significant differences exist between different pharmaceutical opioids, which would be important considerations for interventions. [Ambekar A, Rao R, Mishra AK, Agrawal A. Type of opioids injected: Does it matter? A multicentric cross‐sectional study of people who inject drugs. Drug Alcohol Rev 2015;34:97–104]
Implications of enrolment eligibility criteria in alcohol treatment outcome research: Generalisability and potential bias in 1‐ and 6‐year outcomes
Authors: Storbjörk Jessica 
Published: October 2014

AbstractIntroduction and AimsIt has been acknowledged that participants in clinical trials differ from real‐world service users, primarily due to the extensive use of research eligibility criteria (EC). Generalisability and outcome bias become pressing issues when evidence‐based treatment guidelines, crystallised from outcome research, influence treatment provision. This study reports on the effects of EC on generalisability and short‐ and long‐term outcomes among real‐world treatment‐seekers.Design and MethodsTen of the most commonly used EC were operationalised and applied to a large representative service user sample (n = 1125) from Stockholm County, Sweden, to determine the percentage of real‐world problem alcohol users that would have been excluded by each EC and the extent to which EC bias the 1 and 6‐year alcohol outcomes.ResultsIndividual EC excluded between 5% and 80% of real‐world service users and 96% would have been excluded by at least one EC. Most of the EC introduced a positive/upwards bias in 1‐ and 6‐year outcomes. Most notably, the removal of the unmotivated/non‐compliant service users caused an upwards bias that would considerably boost estimates of treatment effectiveness. Other bias effects were smaller. Six‐year effects were generally higher than for 1 year.Discussion and ConclusionsOutcome studies that exclude complex and non‐compliant cases are not representative of real‐world service users, and thus effectiveness estimates from clinical trials are biased by several commonly used EC. EC should be used judiciously and be taken into account in practice guidelines. This burgeoning research area should be further developed. [Storbjörk J. Implications of enrolment eligibility criteria in alcohol treatment outcome research: Generalisability and potential bias in 1‐ and 6‐year outcomes. Drug Alcohol Rev 2014;33:604–11]
The effect of weightbearing and limb load cycling on equine lamellar perfusion and energy metabolism measured using tissue microdialysis
Authors: Medina‐Torres C. E. , Underwood C. , Pollitt C. C. , Castro‐Olivera E. M. , Hodson M. P. , Richardson D. W. , van Eps A. W. 
Published: October 2014

SummaryReasons for performing studyLamellar perfusion is thought to be affected by weightbearing and limb load cycling; this may be critical in the development of supporting limb laminitis.ObjectivesTo document the effects of unilateral weightbearing and altered limb load cycling on lamellar energy metabolism and perfusion.Study designRandomised, controlled (within subject), experimental trial.MethodsNine Standardbred horses were instrumented with microdialysis probes in the foot lamellar tissue and skin (over the tail base). Urea (20 mmol/l) was added to the perfusate. Samples were collected every 15 min for a 1 h control period, then during periods of unilateral weightbearing (opposite limb held off the ground for 1 h); enhanced static limb load cycling (instrumented limb lifted every 10 s for 30 min); reduced limb load cycling activity (i.v. detomidine sedation) and continuous walking (30 min). Dialysate concentrations of glucose, lactate, pyruvate and urea were measured and lactate:glucose (L:G) and lactate:pyruvate (L:P) ratios were calculated. For each intervention, values were compared with baseline using nonparametric statistical testing.ResultsLamellar dialysate glucose increased andL:Gdecreased significantly during enhanced static limb load cycling. Glucose and pyruvate increased, andL:G,L:Pand urea decreased significantly during walking. Simultaneous skin dialysate values did not change significantly. There were no significant dialysate changes during unilateral weightbearing or after detomidine administration, but only the latter resulted in a significant decrease in limb load cycling frequency.ConclusionsIncreases in limb load cycling frequency (particularly walking) caused dialysate changes consistent with increased lamellar perfusion. Unilateral weightbearing (1 h) and a sedation‐induced reduction in limb load cycling frequency did not have a detectable effect on lamellar perfusion. More research is needed to confirm the role of hypoperfusion in supporting limb laminitis, but strategies to increase limb load cycling may be important for prevention.
Electric current‐induced lymphatic activation
Authors: Kajiya Kentaro , Matsumoto‐Okazaki Yuko , Sawane Mika , Fukada Kaedeko , Takasugi Yuya , Akai Tomonori , Saito Naoki , Mori Yuichiro 
Published: October 2014

AbstractThe lymphatic system in skin plays important roles in drainage of wastes and in the afferent phase of immune response. We previously showed that activation of vascular endothelial growth factor receptor (VEGFR), specifically the VEGFC/VEGFR‐3 pathway, attenuates oedema and inflammation by promoting lymphangiogenesis, suggesting a protective role of lymphatic vessels against skin inflammation. However, it remains unknown how physical stimuli promote lymphatic function. Here, we show that lymphatic endothelial cells (LECs) are activated by direct‐current (DC) electrical stimulation, which induced extension of actin filaments of LECs, increased calcium influx into LECs, and increased phosphorylation of p38 mitogen‐activated protein kinase (MAPK). An inhibitor of focal adhesion kinase, which plays a role in cellular adhesion and motility, diminished the DC‐induced extension of F‐actin and abrogated p38 phosphorylation. Time‐lapse imaging revealed that pulsed‐DC stimulation promoted proliferation and migration of LECs. Overall, these results indicate that electro‐stimulation activates lymphatic function by activating p38 MAPK.
DAMP molecules S100A9 and S100A8 activated by IL‐17A and house‐dust mites are increased in atopic dermatitis
Authors: Jin Shan , Park Chang Ook , Shin Jung U , Noh Ji Yeon , Lee Yun Sun , Lee Na Ra , Kim Hye Ran , Noh Seongmin , Lee Young , Lee Jeung‑Hoon , Lee Kwang Hoon 
Published: October 2014

AbstractS100A9 and S100A8 are called damage‐associated molecular pattern (DAMP) molecules because of their pro‐inflammatory properties. Few studies have evaluated S100A9 and S100A8 function as DAMP molecules in atopic dermatitis (AD). We investigated how house‐dust mites affect S100A9 and S100A8 expression in Th2 cytokine‐ and Th17 cytokine‐treated keratinocytes, and how secretion of these molecules affects keratinocyte‐derived cytokines. Finally, we evaluated expression of these DAMP molecules in AD patients. S100A9 expression and S100A8 expression were strongly induced in IL‐17A‐ and Dermatophagoides (D.) farinae‐treated keratinocytes, respectively. Furthermore, co‐treatment with D. farinae and IL‐17A strongly increased expression of S100A9 and S100A8 compared with D. farinae‐Th2 cytokine co‐treatment. The IL‐33 mRNA level increased in a dose‐dependent manner in S100A9‐treated keratinocytes, but TSLP expression did not change. S100A8/A9 levels were also higher in the lesional skin and serum of AD patients, and correlated with disease severity. Taken together, S100A9 and S100A8 may be involved in inducing DAMP‐mediated inflammation in AD triggered by IL‐17A and house‐dust mites.
Mass balance and life cycle assessment of biodiesel from microalgae incorporated with nutrient recycling options and technology uncertainties
Authors: Yuan Juhong , Kendall Alissa , Zhang Yizhen 
Published: October 2014

AbstractThis article presents mass balances and a detailed life cycle assessment (LCA) for energy and greenhouse gases (GHGs) of a simulated microalgae biodiesel production system. Key parameters of the system include biomass productivity of 16 and 25 g m−2 day−1 and lipid content of algae of 40% and 25% for low and normal nitrogen conditions respectively. Based on an oil extraction efficiency from wet biomass of 73.6% and methane yields from anaerobically digested lipid‐extracted biomass of 0.31 to 0.34 l per gram of volatile solids, the mass balance shows that recycling growth media and recovering nutrients from residual biomass through anaerobic digestion can reduce the total demand for nitrogen by 66% and phosphorus by 90%. Freshwater requirements can be reduced by 89% by recirculating growth media, and carbon requirements reduced by 40% by recycling CO2 from biogas combustion, for normal nitrogen conditions. A variety of technology options for each step of the production process and allocation methods for coproducts used outside the production system are evaluated using LCA. Extensive sensitivity and scenario analysis is also performed to provide better understanding of uncertainty associated with results. The best performing scenario consists of normal nitrogen cultivation conditions, bioflocculation and dissolved air flotation for harvesting, centrifugation for dewatering, wet extraction with hexane, transesterification for biodiesel production, and anaerobic digestion of biomass residual, which generates biogas used in a combined heat and power unit for energy recovery. This combination of technologies and operating conditions results in life cycle energy requirements and GHG emissions of 1.02 MJ and 71 g CO2‐equivalent per MJ of biodiesel, with cultivation and oil extraction dominating energy use and emissions. Thus, even under optimistic conditions, the near‐term performance of this biofuel pathway does not achieve the significant reductions in life cycle GHG emissions hoped for from second‐generation biofuel feedstocks.
Stocking rate effects on liveweight gain of ewes and their twin lambs when grazing subterranean clover–perennial grass pastures
Authors: Ates S. , Lucas R. J. , Edwards G. R. 
Published: October 2014

AbstractTwo grazing experiments were conducted on non‐irrigated tall fescue–subterranean clover and cocksfoot–subterranean pastures subject to summer‐dry conditions in Canterbury, New Zealand, to measure the effect of low (8·3–10 ewes and their twin lambs ha−1) vs. high (13·9–20 ewes and their twin lambs ha−1) stocking rates (SR) on lamb and ewe liveweight gain in spring. In tall fescue–subterranean clover pasture, lambs grew faster at low (374 g per head d−1) than high (307 g per head d−1) SR, but total liveweight gain per ha was greater at high (12·3 kg ha−1 d−1) than low (7·5 kg ha−1 d−1) SR. In successive years in spring in cocksfoot–subterranean clover pastures, lambs grew faster at low (327, 385 g per head d−1) than high (253, 285 g per head d−1) SR but total liveweight gain per ha was greater at high (7·26, 7·91 kg ha−1) than low (5·43, 6·38 kg ha−1) SR. These studies indicate that in summer‐dry areas, subterranean clover‐based pastures will support high twin lamb growth rates in spring, with lower SR leading to higher lamb growth rates and more lambs reaching slaughter weights before the onset of dry conditions.