537 research outputs found

    Front Lines of Thoracic Surgery

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    Front Lines of Thoracic Surgery collects up-to-date contributions on some of the most debated topics in today's clinical practice of cardiac, aortic, and general thoracic surgery,and anesthesia as viewed by authors personally involved in their evolution. The strong and genuine enthusiasm of the authors was clearly perceptible in all their contributions and I'm sure that will further stimulate the reader to understand their messages. Moreover, the strict adhesion of the authors' original observations and findings to the evidence base proves that facts are the best guarantee of scientific value. This is not a standard textbook where the whole discipline is organically presented, but authors' contributions are simply listed in their pertaining subclasses of Thoracic Surgery. I'm sure that this original and very promising editorial format which has and free availability at its core further increases this book's value and it will be of interest to healthcare professionals and scientists dedicated to this field

    Etiology and Pathogenesis of Aortic Aneurysm

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    Trauma Induced Secondary Cardiac Injury Clinical manifestations and underlying mechanisms

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    PhDSince 1933, studies have explored the concept of trauma induced secondary cardiac injury (TISCI), yet till 2012, it had not been defined as the incidence of cardiac events and rise in cardiac biomarkers following traumatic injury. Despite, improvements in early outcomes, trauma patients have reduced long-term mortality with cardiac disease being the major contributor. Although many putative mechanisms have been suggested for TISCI, the underpinning pathophysiology still remains unclear. In this thesis, a prospective study of 290 critically injured patients identifies a 13% incidence of adverse cardiac events (ACE) with consistently raised serum h-FABP levels in these patients. H-FABP was found to be a good predictor of ACE through ROC analysis and a h-FABP of 16.8 ng/ml used to define trauma induced secondary cardiac injury (TISCI). TISCI was associated with longer hospital stay and higher mortality. Patients who developed ACE had higher plasma levels of adrenaline and noradrenaline with a correlating increase in plasma h-FABP. On multivariate analysis, hypertension was the only independent risk factors for ACE. The increase in serum cardiac biomarkers was reflected by an increase in serum h- FABP in our group’s trauma hemorrhage murine models. The hearts of these models were used in the experiments that form the last experimental chapter of this thesis. Protein expression studies confirm this increase in serum h-FABP by evidence of concurrent leaching in the cardiac tissue, along with Troponin I. Myocardial injury was evident on electron microscopy with evidence of interstitial and organelle oedema, myofibrillar degeneration, nuclear condensation and changes in mitochondrial morphology. Immunohistochemistry and western blotting protein studies demonstrate the translocation of the mitochondrial death-related protein AIF to the cytosol and nucleus, where it becomes its active pro-apoptotic form. This thesis propositions the utility of the cardiac biomarker h-FABP in predicting ACE and outcomes in critically injured patients. Although increasing serum noradrenaline and adrenaline levels are associated with higher incidence of ACE and biochemical evidence of cardiac injury with rising h-FABP levels, multivariate analysis negates their value as independent predictors of ACE. Leaching out of the proteins h-FABP and Troponin I in the murine cardiac tissue confirmed the value of serum measurements of these proteins as markers of cardiac injury. This was associated with widespread ultrastructural myocardial damage in the TH mice with changes in mitochondrial morphology. The mitochondrial damage seen is associated with the translocation of the mitochondrial death-related protein AIF to the cytosol and the nucleus where I propose its canonical signaling leading to nuclear degradation and cell death is the driver of cardiac dysfunction

    Current Basic and Pathological Approaches to the Function of Muscle Cells and Tissues

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    This volume contains 17 short review articles classified into 3 parts. Part I consists of 7 articles dealing with basic aspects of contractile mechanism in skeletal and smooth muscle cells and also function of melanocytes having many properties common to those of smooth muscles. Part II and Part III contain articles dealing with pathological aspects of cardiac and smooth muscle cell functions, and dealing with factors influencing structure and function of cardiac and smooth muscle cells and tissues. The Editor believes that these articles are stimulating and informative for readers interested in basic, pathological and clinical aspects of muscle cells and tissues

    The role of telomeres an telomerase during zebrafish heart regeneration

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    Tesis doctoral in√©dita le√≠da en la Universidad Aut√≥noma de Madrid, Facultad de Medicina, Departamento de Bioqu√≠mica. Fecha de lectura: 23-11-2015Telomeres are specialized nucleoprotein structures that protect the ends of chromosomes from DNA repair and degradation activities. The maintenance of telomeres is essential for chromosome stability. Without new synthesis, telomeres (TTAGGG repeats) undergo progressive shortening with each cell division. Telomere shortening can lead to the appearance of critically short telomeres triggering the activation of a persistent DNA damage response and the subsequent induction of cellular senescence or apoptosis. Telomerase is a reverse transcriptase that elongates telomeres, efficiently compensating telomere attrition during cell division. A common feature of the telomerase-positive cells is their highly regenerative capability. Zebrafish (Danio rerio) has emerged as an excellent model to study tissue regeneration due to its remarkable capacity to fully repair several organs, including the heart. In contrast to mammals, this lower vertebrate is able to replace damaged cardiac muscle after an insult with newly formed fully functional myocardium. During the regeneration process of the zebrafish heart, differentiated cardiac myocytes dedifferentiate and robustly proliferate. Telomerase activity can be detected in the zebrafish model not only in young animals, but also in old ones. Here we demonstrate that after cardiac injury in zebrafish, telomerase become hyperactivated and telomeres transiently elongate, preceding a peak of cardiomyocyte proliferation and full organ recovery. We have used tert-/- animals to analyze the role of telomerase in zebrafish heart regeneration. We show that under the high demands imposed by heart injury telomere reserves cannot be maintained without telomerase. Absence of telomerase decouples dedifferentiation from proliferation, drastically impairing proliferation and leading to accumulation of DNA damage. Instead of regenerating myocardial tissue and regressing cardiac fibrosis tert-/- hearts increment the percentage of cells that present DNA damage and senescence characteristics, leading to blockade in the regeneration process. Our results provide direct evidence for the essential role of telomerase during the zebrafish heart regeneration and reveal a role of this enzyme in cardiac cell protection from the injury-induced elevated levels of DNA damage.Los tel√≥meros son estructuras nucleoprote√≠cas que protegen los extremos de los cromosomas de mecanismos de reparaci√≥n y de degradaci√≥n del ADN. Pese a que el mantenimiento de los tel√≥meros (repeticiones TTAGGG) es esencial para la estabilidad de los cromosomas, √©stos se acortan progresivamente con cada divisi√≥n celular. Los tel√≥meros cr√≠ticamente cortos desencadenan un da√Īo persistente al ADN conduciendo a la senescencia o la apoptosis de la c√©lula. La telomerasa es una reverso transcriptasa que alarga los tel√≥meros, compensando eficientemente su desgaste. Una caracter√≠stica com√ļn de las c√©lulas en las que la telomerasa est√° activa es su gran capacidad regenerativa. El pez cebra (Danio rerio) es un excelente modelo para el estudio de la regeneraci√≥n tisular debido a su notable capacidad para regenerar √≥rganos, incluyendo el coraz√≥n. A diferencia de los mam√≠feros, el pez cebra es capaz de reemplazar el m√ļsculo cardiaco da√Īado por nuevo miocardio completamente funcional. Durante el proceso de regeneraci√≥n del coraz√≥n los cardiomiocitos diferenciados sufren un proceso de desdiferenciaci√≥n y proliferan. En el pez cebra la actividad telomerasa es detectable durante toda la vida del animal. Los resultados de esta tesis demuestran que tras la lesi√≥n cardiaca en el pez cebra se produce un aumento de la telomerasa, un alargamiento telom√©rico y un incremento en la proliferaci√≥n de los cardiomiocitos, conduciendo a la recuperaci√≥n del √≥rgano. Mediante el uso de animales carentes de telomerasa (tert-/-) se observ√≥ que esta enzima es esencial para el mantenimiento de las reservas telom√©ricas tras la lesi√≥n. La ausencia de telomerasa afecta dr√°sticamente a la proliferaci√≥n de los cardiomiocitos y conduce a la acumulaci√≥n de da√Īo en el ADN. En lugar de regenerarse, los corazones tert-/- presentan un incremento en el n√ļmero de c√©lulas con da√Īo al ADN y caracter√≠sticas senescentes, bloqueando el proceso de regeneraci√≥n. Nuestros resultados demuestran que la telomerasa es esencial para la regeneraci√≥n del coraz√≥n del pez cebra y revelan una nueva funci√≥n de esta enzima protegiendo a las c√©lulas card√≠acas de los elevados niveles de da√Īo en el ADN tras la lesi√≥n.During this period Dorota Bednarek was supported by a PhD Fellowship from the Ministerio de Econom√≠a y Competitividad BES-2010-033554/ SAF2009-10480)

    Essentials of pathology

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    This manual was written in conformance with training program in Pathomorphology for higher educational establishments and based on European credit-transfer system principles. Its first part covers one module - general pathologic processes and tumors growth, second part covers systematic and infectious pathology. Notional modules include theoretical knowledge of pathologic processes macroscopic and microscopic manifestations. The aim of the book is clearly and easily assist student to acquire habits of synthetic generalization of pathologic processes demonstration and their interpretation in cause-effect correlations

    Glutamine : A novel and potent therapeutic for acute spinal cord injury

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    Spinal cord injury occurs at a rate of 11.5 - 53.4 per million in developed countries with great emotional and financial consequences. The damage caused by the initial injury is followed by secondary damage, a complex cascade of mechanisms including ischemia, oxidative stress, inflammation and apoptosis. Although nothing can be done to reverse the initial damage to the spinal cord once it occurs, the secondary damage can be targeted by therapeutics to improve recovery. Following injury, concentrations of the potent antioxidant glutathione (GSH) are decreased in the spinal cord which potentiates mechanisms of secondary damage. In an attempt to maintain the GSH concentrations, the non-essential amino acid glutamine was tested as it was shown to increase GSH concentrations both in vivo and in vitro. Glutamine is being used extensively in clinical research in an expansive number of physiological and pathological conditions including brain trauma. To examine the therapeutic potential of glutamine after spinal cord trauma, two compression injury models, the modified aneurysm clip and the modified forceps, were used to induce an injury in male Wistar rats. We have demonstrated the ability of glutamine treatment (1 mmol/kg), given 1 hour after a 30 g aneurysm clip injury to increase GSH not only in whole blood samples but within the spinal tissue at the site of injury. Increasing GSH in this way also resulted in improved locomotor scores and maintenance of white matter tissue at the injury epicenter. Experiments using the forceps model were then performed to determine if the potency of glutamine treatment would be carried over to a different model and at a variety of severities. Glutamine, again, demonstrated the ability to improve maintenance of whole blood GSH, locomotor scores and tissue histology. In our experiments, glutamine has proven to be a potent therapeutic for spinal cord injury with an effect that is matched by few compounds currently being studied and well exceeding the standard therapeutic, methylprednisolone. Given the breadth of knowledge regarding the effects of glutamine clinically in numerous paradigms and the potency of the therapeutic effect seen in these studies, we believe that glutamine is fit for clinical trial and has a high potential for success

    Developmental pathways and gene function in canine myxomatous mitral valve disease

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    Canine myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs affecting all breeds, and it shares many similarities with the equivalent human disease. From the only transcriptomic report for canine MMVD published in 2006, serotonin signalling was identified as a contributing factor and has been widely studied since. Two transcriptomic profiling studies in human MMVD have also identified oxidative stress response and bone morphogenic protein signalling contributing to disease pathology. All studies at the transcriptional level have identified a variety of biological functions in MMVD suggesting dynamic extracellular matrix (ECM) remodelling processes are on-going. Moreover, cellular changes found in MMVD are somewhat reminiscent of the events seen in early heart valve, suggesting possible re-activation of signalling pathways of which those driving development and endothelial-to-mesenchymal transition (EndoMT) are particularly interesting. EndoMT, in which endothelial cells change their identity to mesenchymal phenotype and migrate into the cardiac jelly underneath the endothelium, is a crucial mechanism in valvulogenesis. Whether or not gene regulation of EndoMT and valve development also plays a role in MMVD is unknown. In this study, the MMVD cellular changes in the Cavalier King Charles Spaniel (CKCS), a breed with the highest prevalence, earliest onset, and rapid progression of the disease, was investigated. Secondly, transcriptional profiling was conducted using the latest canine microarray chips, a single affected breed (CKCSs), stringent sample quality control and statistical thresholds, with quantitative polymerase chain reaction (Q-PCR) for data validation. After transcriptional mapping, multi-platform in silico analysis was conducted to identify relationship between differentially expressed genes and their relevant biological functions. Next, a comparison study using immunohistochemistry was performed on different severities of myxomatous valves to localize the proteins of interest. Finally, to model the transcriptional factors and their downstream targets, mitral valve endothelial cell (MVEC) clones were derived from the canine normal mitral valves for future in vitro studies. Cellular changes of MMVD between CKCS and non-CKCS populations showed no difference in their distribution, number and phenotypic markers. Global genomic expression analysis identified similar (inflammation, up-regulation of serotonin receptor and bone morphogenic protein) and novel biological functions (epithelial-to-mesenchymal transition) compared to the previous study in 2006. Key transcriptional factors and genes associated with EndoMT including SNAI1, TAGLN, ACTA2, ACTG2, HAS2, and CTNNB1 were found up-regulated, and NID1, LAMA2, CDH5 were down-regulated in the MMVD group. In myxomatous mitral valves, increased expression of HAS2 in myofibroblasts, SNAI1 expression in endothelial cells, and co-expression of CDH5 and őĪ-smooth muscle actin (őĪ-SMA) also suggested the presence of EndoMT compared to normal valves. Nevertheless, there is also evidence of EndoMT in normal valves (őĪ-SMA positive endothelial cells) which might suggest contribution to life-long valve re-modelling. In addition, there was a decreased expression of microRNAs associated with modulation of extracellular matrix transcripts, including miR-23, miR-29, and miR-218, indicating epigenetic regulation in MMVD. Based on the cellular changes, MMVD in CKCS appears to be representative of MMVD in all breeds and the early-onset of MMVD in that breed does not lead to different end-stage pathology. Novel biological functions such as EndoMT, were identified by transcriptional profiling, and by using powerful bioinformatic tools providing insight into understanding gene regulation in MMVD. Furthermore, a relationship between developmental biology processes and MMVD pathogenesis was established, with a likely important role for epigenetics in disease pathogenesis

    Hypercholesterolemia

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    This book is aimed to accentuate the importance of hypercholesterolemia, since targeting and treating the hypercholesterolemia is increasingly well known as an essential strategy in the prevention of atherosclerosis-induced cardiovascular disease. It is important to look at hypercholesterolemia as it is proved to be crucial as well as the early stage of atherogenesis and can also be managed with appropriate treatment. This book describes the basics of hypercholesterolemia and its causes and various experimental animal models to understand and study the pathophysiology of hypercholesterolemia as well as to present practice-based clinical approaches to treat hypercholesterolemia. Further, the book describes various treatment strategies of hypercholesterolemia in detail, especially the appropriate use of statin. It is well known that the use of statin is an ideal as well as a potent therapy to lower cholesterol level and also has various beneficial pharmacological effects to prevent cardiovascular diseases. However, there exists less awareness about the use of statin. Hence, it is important to understand the appropriate use of statin in terms of doses for different stages of hypercholesterolemia, side effects, resistance of its use, and also interaction of statin with other drugs, which are well described in this book. In short, the major aim of this compendium is to present to the readers comprehensive, updated, and current research perspectives on hypercholesterolemia
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