Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Expanded endothelial progenitor cells (eEPC) improve global left ventricular function in experimental myocardial infarction (MI). Erythropoietin beta (EPO) applied together with eEPC may improve regional myocardial function even further by anti-apoptotic and cardioprotective effects. Aim of this study was to evaluate intramyocardial application of eEPCs and EPO as compared to eEPCs or EPO alone in experimental MI.</p> <p>Methods and Results</p> <p>In vitro experiments revealed that EPO dosed-dependently decreased eEPC and leukocyte apoptosis. Moreover, in the presence of EPO mRNA expression in eEPC of proangiogenic and proinflammatory mediators measured by TaqMan PCR was enhanced. Experimental MI was induced by ligation and reperfusion of the left anterior descending coronary artery of nude rats (n = 8-9). After myocardial transplantation of eEPC and EPO CD68+ leukocyte count and vessel density were enhanced in the border zone of the infarct area. Moreover, apoptosis of transplanted CD31 + TUNEL + eEPC was decreased as compared to transplantation of eEPCs alone. Regional wall motion of the left ventricle was measured using Magnetic Resonance Imaging. After injection of eEPC in the presence of EPO regional wall motion significantly improved as compared to injection of eEPCs or EPO alone.</p> <p>Conclusion</p> <p>Intramyocardial transplantation of eEPC in the presence of EPO during experimental MI improves regional wall motion. This was associated with an increased local inflammation, vasculogenesis and survival of the transplanted cells. Local application of EPO in addition to cell therapy may prove beneficial in myocardial remodeling.</p

Why so serious? Theorising playful model-driven group decision support with situated affectivity

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.An integrative approach to theorising behavioural, affective and cognitive processes in modeldriven group decision support (GDS) interventions is needed to gain insight into the (micro-)processes by which outcomes are accomplished. This paper proposes that the theoretical lens of situated affectivity, grounded in recent extensions of scaffolded mind models, is suitable to understand the performativity of affective micro-processes in model-driven GDS interventions. An illustrative vignette of a humorous micro-moment in a group decision workshop is presented to reveal the performativity of extended affective scaffolding processes for group decision development. The lens of situated affectivity constitutes a novel approach for the study of interventionist practice in the context of group decision making (and negotiation). An outlook with opportunities for future research is offered to facilitate an integrated approach to the study of cognitive-affective and behavioural micro-processes in model-driven GDS interventions.This work was supported in part by the EU FP7-ENERGY- SMARTCITIES-2012 (314277) project STEEP (Systems Thinking for Comprehensive City Efficient Energy Planning

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

O uso de procedimentos de estruturação de rotina em indivíduos com anóxia cerebral: relato de caso Procedures to improve daily activities performance in individuals with cerebral anoxia: case report

OBJETIVO: Apresentar um estudo de caso de reabilitação com procedimentos de estruturação de rotina para realização das atividades de vida diária (AVDs). PACIENTE: Quadro de anóxia cerebral, com déficit de memória verbal e visual, desorientação temporal, abulia e bradipsiquismo. MÉTODO: Estruturação de horários fixos na rotina diária; exposição a um calendário 3 vezes ao dia; caminhadas diárias; monitorização do familiar na execução de tarefas de auto cuidado, fornecendo auxílio mediante comandos verbais curtos e pistas específicas. RESULTADOS: Foram observados aumento da iniciativa, maior autonomia nas AVDs, diminuição do período de latência para qualquer resposta, melhora da atenção, orientação temporal e bradipsiquismo. CONCLUSÕES: Estratégias de controle do comportamento trazem ganhos e limitações para pacientes e familiares. Embora obriguem a adaptação a uma rotina pouco flexível, promovem o aprendizado através da automatização de procedimentos que se valem de mecanismos de memória implícita preservados. Estes recursos podem elevar o grau de autonomia do paciente em casa.<br>OBJECTIVE: To present a rehabilitation case study; procedures to improve the performance on daily activities were used by the caregiver. PATIENT: Cerebral anoxia due to cardiac arrest. He presented memory deficits for both visual and verbal material, temporal disorientation, abulia, psychomotor slowing and bradypsychism. METHODS: daily activities were developed in fixed hours; calendar was presented 3 times a day ; daily walks were performed; self-care activities were performed by the patient with short verbal commands and cues from the caregiver. RESULTS: We observed improvement on initiative and autonomy for daily activities, attention, temporal orientation and bradypsychism. There was also reduction on response time. CONCLUSIONS: Behavioral control strategies result on improvement for patients and their family although limit their routine. Behavioral control strategy promotes learning through the preserved implicit memory mechanism and results on enhancement at patient's autonomy at home