87 research outputs found

    Lens epithelial cell apoptosis and intracellular Ca(2+) increase in the presence of xanthurenic acid

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    BACKGROUND: Xanthurenic acid is an endogenous product of tryptophan degradation by indoleamine 2,3-dioxygenase (IDO). We have previously reported that IDO is present in mammalian lenses, and xanthurenic acid is accumulated in the lenses with aging. Here, we studied the involvement of xanthurenic acid in the human lens epithelial cell physiology. METHODS: Human lens epithelial cells primary cultures were used. Control cells, and cells in the presence of xanthurenic acid grow in the dark. Western blot analysis and immunofluorescence studies were performed. RESULTS: In the presence of xanthurenic acid human lens epithelial cells undergo apoptosis-like cell death. In the control cells gelsolin stained the perinuclear region, whereas in the presence of 10 μM xanthurenic acid gelsolin is translocated to the cytoskeleton, but does not lead to cytoskeleton breakdown. In the same condition caspase-3 activation, and DNA fragmentation was observed. At low (5 to 10 μM) of xanthurenic acid concentration, the elongation of the cytoskeleton was associated with migration of mitochondria and cytochrome c release. At higher concentrations xanthurenic acid (20 μM and 40 μM) damaged mitochondria were observed in the perinuclear region, and nuclear DNA cleavage was observed. We observed an induction of calpain Lp 82 and an increase of free Ca(2+) in the cells in a xanthurenic acid concentration-dependent manner. CONCLUSIONS: The results show that xanthurenic acid accumulation in human lens epithelial cells disturbs the normal cell physiology and leads to a cascade of pathological events. Xanthurenic acid induces calpain Lp82 and caspases in the cells growing in the dark and can be involved in senile cataract development

    Red Blood Cell Fatty Acid Patterns and Acute Coronary Syndrome

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    BACKGROUND:Assessment of coronary heart disease (CHD) risk is typically based on a weighted combination of standard risk factors. We sought to determine the extent to which a lipidomic approach based on red blood cell fatty acid (RBC-FA) profiles could discriminate acute coronary syndrome (ACS) cases from controls, and to compare RBC-FA discrimination with that based on standard risk factors. METHODOLOGY/PRINCIPAL FINDINGS:RBC-FA profiles were measured in 668 ACS cases and 680 age-, race- and gender-matched controls. Multivariable logistic regression models based on FA profiles (FA) and standard risk factors (SRF) were developed on a random 2/3(rds) derivation set and validated on the remaining 1/3(rd). The area under receiver operating characteristic (ROC) curves (c-statistics), misclassification rates, and model calibrations were used to evaluate the individual and combined models. The FA discriminated cases from controls better than the SRF (c = 0.85 vs. 0.77, p = 0.003) and the FA profile added significantly to the standard model (c = 0.88 vs. 0.77, p<0.0001). Hosmer-Lemeshow calibration was poor for the FA model alone (p = 0.01), but acceptable for both the SRF (p = 0.30) and combined models (p = 0.22). Misclassification rates were 23%, 29% and 20% for FA, the SRF, and the combined models, respectively. CONCLUSIONS/SIGNIFICANCE:RBC-FA profiles contribute significantly to the discrimination of ACS cases, especially when combined with standard risk factors. The utility of FA patterns in risk prediction warrants further investigation

    Revisión de la literatura integradora acerca de intervenciones de la enfermería volcadas hacia el incremento del autocuidado entre pacientes con insuficiencia cardiaca

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    Objective: to analyze and summarize knowledge concerning critical components of interventions that have been proposed and implemented by nurses with the aim of optimizing self-care by heart failure patients.Methods: PubMed and CINAHL were the electronic databases used to search full peer-reviewed papers, presenting descriptions of nursing interventions directed to patients or to patients and their families and designed to optimize self-care. Forty-two studies were included in the final sample (n=4,799 patients).Results: this review pointed to a variety and complexity of nursing interventions. As self-care encompasses several behaviors, interventions targeted an average of 3.6 behaviors. Educational/counselling activities were combined or not with cognitive behavioral strategies, but only about half of the studies used a theoretical background to guide interventions. Clinical assessment and management were frequently associated with self-care interventions, which varied in number of sessions (1 to 30); length of follow-up (2 weeks to 12 months) and endpoints.Conclusions: these findings may be useful to inform nurses about further research in self-care interventions in order to propose the comparison of different modalities of intervention, the use of theoretical background and the establishment of endpoints to evaluate their effectiveness.Objetivo:analisar e sintetizar o conchecimento relacionado aos componentes críticos das intervençoes que têm, sido propostas e implementadas por enfermeiros(as) com objetivo de optimizar o auto-cuidado de pacientes portadores de insuficiência cardíaca.Método:PubMed e CINAHL foram as bases de dados electrônicas utilizadas para investigar artigos revisados por pares (peer review), apresentando as descrições das intervenções dirigidas ao paciente ou ao paciente e sua familia, visando melhorar o auto-cuidado. Foram incluídos 42 estudos na amostra final (n=4799 pacientes).Resultados:esta revisão apontou variedade e complexidade das intervenções de enfermagem. Como o auto-cuidado envolve diferentes comportamentos, as intervenções visaram em média 3,6 comportamentos. As Atividades de educação e aconselhamento foram combinadas ou não com estratégias cognitivo-comportamentais, mas somente a metade dos estudos utilizaram suporte teórico para guiar as intervenções. A avaliação e o manejo clínico foram frequentemente associados às intervenções de auto-cuidado, as quais variam em número de sessões (1 a 30), duração do seguimento (2 semanas a 12 meses) e desfechos.Conclusão:estes resultados podem ser úteis para guiar os enfermeiros no que se refere à futuros estudos sobre intervenções de auto-cuidado, de maneira a propor a comparação de diferentes modalidades de intervenção, uso de suporte teórico e estabelecimento de desfechos para melhor avaliar sua eficácia.Objetivo:analizar y sintetizar el conocimiento relacionado a componentes críticos de intervenciones que han sido propuestas e implementadas por enfermeros(as) con el objetivo de optimizar el autocuidado entre pacientes con insuficiencia cardiaca.Método:PUBMED y CINAHL han sido las bases de datos electrónicas usadas para investigar artículos revisados por pares (peer review), presentando descripciones de intervenciones destinadas a perfeccionar el autocuidado dirigido al paciente o al paciente y a su familia. Se incluyeron 42 estudios en la muestra final (n=4799 pacientes).Resultados:esta revisión apuntó a una variedad y complejidad de intervenciones de enfermería. Como el autocuidado abarca varios comportamientos, las intervenciones tuvieron como blanco, en media, 3,6 comportamientos. Actividades de educación/consejería fueron combinadas o no con estrategias cognitivo-comportamentales, pero tan solo cerca de la mitad de los estudios tenían aporte teórico para guiar intervenciones. La gestión y la evaluación clínica fueron frecuentemente asociadas a intervenciones de autocuidado, las cuales oscilaron en número de sesiones (1 a 30), duración del seguimiento (2 semanas a 12 meses) y objetivos.Conclusiones:estos resultados pueden ser útiles para informar a las enfermeras acerca de nuevas investigaciones en intervenciones de autocuidado, de modo a proponer la comparación de distintas modalidades de intervención, el uso de un aporte teórico y el establecimiento de objetivos para evaluar su eficacia

    Protection of Visual Functions by Human Neural Progenitors in a Rat Model of Retinal Disease

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    BACKGROUND: A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. METHODOLOGY/PRINCIPAL FINDINGS: Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90–100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. CONCLUSIONS/SIGNIFICANCE: Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in vivo

    Protocol for an economic evaluation alongside the University Health Network Whiplash Intervention Trial: cost-effectiveness of education and activation, a rehabilitation program, and the legislated standard of care for acute whiplash injury in Ontario

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    Background: Whiplash injury affects 83% of persons in a traffic collision and leads to whiplash-associated disorders (WAD). A major challenge facing health care decision makers is identifying cost-effective interventions due to lack of economic evidence. Our objective is to compare the cost-effectiveness of: 1) physician-based education and activation, 2) a rehabilitation program developed by Aviva Canada (a group of property and casualty insurance providers), and 3) the legislated standard of care in the Canadian province of Ontario: the Pre-approved Framework Guideline for Whiplash developed by the Financial Services Commission of Ontario. Methods/Design. The economic evaluation will use participant-level data from the University Health Network Whiplash Intervention Trial and will be conducted from the societal perspective over the trial's one-year follow-up. Resource use (costs) will include all health care goods and services, and benefits provided during the trial's 1-year follow-up. The primary health effect will be the quality-adjusted life year. We will identify the most cost-effective intervention using the incremental cost-effectiveness ratio and incremental net-benefit. Confidence ellipses and cost-effectiveness acceptability curves will represent uncertainty around these statistics, respectively. A budget impact analysis will assess the total annual impact of replacing the current legislated standard of care with each of the other interventions. An expected value of perfect information will determine the maximum research expenditure Canadian society should be willing to pay for, and inform priority setting in, research of WAD management. Discussion. Results will provide health care decision makers with much needed economic evidence on common interventions for acute whiplash management. © 2011 van der Velde et al; licensee BioMed Central Ltd

    Thoracic dysfunction in whiplash associated disorders: A systematic review

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    © 2018 Heneghan 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 credited. Background Research investigating Whiplash Associated Disorder (WAD) has largely focused on the cervical spine yet symptoms can be widespread. Thoracic spine pain prevalence is reported ~66%; perhaps unsurprising given the forceful stretch/eccentric loading of posterior structures of the spine, and the thoracic spine’s contribution to neck mobility/function. Approximately 50% WAD patients develop chronic pain and disability resulting in high levels of societal and healthcare costs. It is time to look beyond the cervical spine to fully understand anatomical dysfunction in WAD and provide new directions for clinical practice and research. Purpose To evaluate the scope and nature of dysfunction in the thoracic region in patients with WAD. Methods A systematic review and data synthesis was conducted according to a pre-defined, registered (PROSPERO, CRD42015026983) and published protocol. All forms of observational study were included. A sensitive topic-based search strategy was designed from inception to 1/06/16. Databases, grey literature and registers were searched using a study population terms and key words derived from scoping search. Two reviewers independently searched information sources, assessed studies for inclusion, extracted data and assessed risk of bias. A third reviewer checked for consistency and clarity. Extracted data included summary data: sample size and characteristics, outcomes, and timescales to reflect disorder state. Risk of bias was assessed using the Newcastle-Ottawa Scale. Data were tabulated to allow enabling a semi-qualitative comparison and grouped by outcome across studies. Strength of the overall body of evidence was assessed using a modified GRADE. Results Thirty eight studies (n>50,000) which were conducted across a range of countries were included. Few authors responded to requests for further data (5 of 9 contacted). Results were reported in the context of overall quality and were presented for measures of pain or dysfunction and presented, where possible, according to WAD severity and time point post injury. Key findings include: 1) high prevalence of thoracic pain (>60%); higher for those with more severe presentations and in the acute stage, 2) low prevalence of chest pain

    JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis

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    Acute pancreatitis is a common disease with an annual incidence of between 5 and 80 people per 100 000 of the population. The two major etiological factors responsible for acute pancreatitis are alcohol and cholelithiasis (gallstones). The proportion of patients with pancreatitis caused by alcohol or gallstones varies markedly in different countries and regions. The incidence of acute alcoholic pancreatitis is considered to be associated with high alcohol consumption. Although the incidence of alcoholic pancreatitis is much higher in men than in women, there is no difference in sexes in the risk involved after adjusting for alcohol intake. Other risk factors include endoscopic retrograde cholangiopancreatography, surgery, therapeutic drugs, HIV infection, hyperlipidemia, and biliary tract anomalies. Idiopathic acute pancreatitis is defined as acute pancreatitis in which the etiological factor cannot be specified. However, several studies have suggested that this entity includes cases caused by other specific disorders such as microlithiasis. Acute pancreatitis is a potentially fatal disease with an overall mortality of 2.1%–7.8%. The outcome of acute pancreatitis is determined by two factors that reflect the severity of the illness: organ failure and pancreatic necrosis. About half of the deaths in patients with acute pancreatitis occur within the first 1–2 weeks and are mainly attributable to multiple organ dysfunction syndrome (MODS). Depending on patient selection, necrotizing pancreatitis develops in approximately 10%–20% of patients and the mortality is high, ranging from 14% to 25% of these patients. Infected pancreatic necrosis develops in 30%–40% of patients with necrotizing pancreatitis and the incidence of MODS in such patients is high. The recurrence rate of acute pancreatitis is relatively high: almost half the patients with acute alcoholic pancreatitis experience a recurrence. When the gallstones are not treated, the risk of recurrence in gallstone pancreatitis ranges from 32% to 61%. After recovering from acute pancreatitis, about one-third to one-half of acute pancreatitis patients develop functional disorders, such as diabetes mellitus and fatty stool; the incidence of chronic pancreatitis after acute pancreatitis ranges from 3% to 13%. Nevertheless, many reports have shown that most patients who recover from acute pancreatitis regain good general health and return to their usual daily routine. Some authors have emphasized that endocrine function disorders are a common complication after severe acute pancreatitis has been treated by pancreatic resection
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