The meaning of different forms of structural myocardial injury, immune response and timing of infarct necrosis and cardiac repair

Although a decline in the all-cause and cardiac mortality rates following myocardial infarction (MI) during the past 3 decades has been reported, MI is a major cause of death and disability worldwide. From a pathological point of view MI consists in a particular myocardial cell death due to prolonged ischemia. After the onset of myocardial ischemia, cell death is not immediate, but takes a finite period of time to develop. Once complete myocytes’ necrosis has occurred, a process leading to a healed infarction takes place. In fact, MI is a dynamic process that begins with the transition from reversible to irreversible ischemic injury and culminates in the replacement of dead myocardium by a fibrous scar. The pathobiological mechanisms underlying this process are very complex, involving an inflammatory response by several pathways, and pose a major challenge to ability to improve our knowledge. An improved understanding of the pathobiology of cardiac repair after MI and further studies of its underlying mechanisms provide avenues for the development of future strategies directed toward the identification of novel therapies. The chronologic dating of MI is of great importance both to clinical and forensic investigation, that is, the ability to create a theoretical timeline upon which either clinicians or forensic pathologists may increase their ability to estimate the time of MI. Aging of MI has very important practical implications in clinical practice since, based on the chronological dating of MI, attractive alternatives to solve therapeutic strategies in the various phases of MI are developing

Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction

Oxidative stress in heart failure or during ischemia/reperfusion occurs as a result of the excessive generation or accumulation of free radicals or their oxidation products. Free radicals formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks. Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. In the early phase of acute heart ischemia cytokines have the feature to be functional pleiotropy and redundancy, moreover, several cytokines exert similar and overlapping actions on the same cell type and one cytokine shows a wide range of biological effects on various cell types. Activation of cytokine cascades in the infarcted myocardium was established in numerous studies. In experimental models of myocardial infarction, induction and release of the pro-inflammatory cytokines like TNF-&alpha (Tumor Necrosis Factor &alpha), IL-1&beta (Interleukin- 1&beta) and IL-6 (Interleukin-6) and chemokines are steadily described. The current review examines the role of oxidative stress and pro-inflammatory cytokines response following acute myocardial infarction and explores the inflammatory mechanisms of cardiac injur

Confocal laser scanning microscope, raman microscopy and western blotting to evaluate inflammatory response after myocardial infarction

Cardiac muscle necrosis is associated with inflammatory cascade that clears the infarct from dead cells and matrix debris, and then replaces the damaged tissue with scar, through three overlapping phases: the inflammatory phase, the proliferative phase and the maturation phase. Western blotting, laser confocal microscopy, Raman microscopy are valuable tools for studying the inflammatory response following myocardial infarction both humoral and cellular phase, allowing the identification and semiquantitative analysis of proteins produced during the inflammatory cascade activation and the topographical distribution and expression of proteins and cells involved in myocardial inflammation. Confocal laser scanning microscopy (CLSM) is a relatively new technique for microscopic imaging, that allows greater resolution, optical sectioning of the sample and three-dimensional reconstruction of the same sample. Western blotting used to detect the presence of a specific protein with antibody-antigen interaction in the midst of a complex protein mixture extracted from cells, produced semi-quantitative data quite easy to interpret. Confocal Raman microscopy combines the three-dimensional optical resolution of confocal microscopy and the sensitivity to molecular vibrations, which characterizes Raman spectroscopy. The combined use of western blotting and confocal microscope allows detecting the presence of proteins in the sample and trying to observe the exact location within the tissue, or the topographical distribution of the same. Once demonstrated the presence of proteins (cytokines, chemokines, etc.) is important to know the topographical distribution, obtaining in this way additional information regarding the extension of the inflammatory process in function of the time stayed from the time of myocardial infarction. These methods may be useful to study and define the expression of a wide range of inflammatory mediators at several different timepoints providing a more detailed analysis of the time course of the infarct

Cardiovascular Involvement in Sepsis.

This special issue wants to contribute to a better understanding of cardiac involvement in sepsis. Sepsis is a complex syndrome that has recently been defined as “life-threatening organ dysfunction due to a dysregulated host response to infection”. It should be considered a major public health problem since it affects millions of people worldwide each year, and it accounts for most deaths in critically ill patients. The presence of myocardial dysfunction in sepsis is associated with higher mortality. A great attention has been dedicated to improving our knowledge and understanding of the intricate mechanisms underlying sepsis. However, data from the literature suggest the need to implement strategies to reliably measure sepsis morbidity and mortality. In fact, methods based on analyses of insurance claim data using sepsis-specific codes or separate codes for infection and organ dysfunction are unreliable in informing or measuring the effects of policy changes, and the postmortem diagnosis of sepsis is often elusive since postmortem investigations lack certain pathognomonic macroscopic and histopathological findings. From a morphological and diagnostic point of view, the term “septic disease” has been created to describe the cardiac involvement in the syndrome. However, this definition, rather than describing a morphological finding, was instead referred to the clinical setting. Although in recent years the concept of septic cardiomyopathy has evolved and it involves pathological alterations of myocardial cells in response to the multiplicity of acting mechanism of damage, the importance of structural changes during sepsis is often overlooked. In patients with sepsis, death is usually the result of a progressive multiorgan dysfunction, overlooking the primary infection through the hyperinflammation. The cardiac involvement as fundamental part of septic multiorgan dysfunction syndrome has been discussed for a long time

A theoretical timeline for myocardial infarction: immunohistochemical evaluation and western blot quantification for Interleukin-15 and Monocyte chemotactic protein-1 as very early markers

Background: Experimental and human studies have demonstrated that innate immune mechanisms and consequent inflammatory reaction play a critical role in cardiac response to ischemic injury. Thus, the detection of immuno-inflammatory and cellular phenomena accompanying cardiac alterations during the early inflammatory phase of myocardial infarction (MI) may be an excellent diagnostic tool. Current knowledge of the chronology of the responses of myocardial tissue following the occurrence of ischemic insult, as well as the existence of numerous studies aiming to identify reliable markers in dating MI, induced us to investigate the myocardial specimens of MI fatal cases in order to better define the age of MI. Methods: We performed an immunohistochemical study and a Western blot analysis to evaluate detectable morphological changes in myocardial specimens of fatal MI cases and to quantify the effects of cardiac expression of inflammatory mediators (CD15, IL-1 β, IL-6, TNF-α, IL-15, IL-8, MCP-1, ICAM-1, CD18, tryptase) and structural and functional cardiac proteins. Results: We observed a biphasic course of MCP-1: it was strongly expressed in the very early phase (0-4 hrs), to diminish in the early period (after 6-8 hrs). Again, our choice of IL-15 is explained by the synergism with neutrophilic granulocytes (CD15) and our study shows the potential for striking cytokine synergy in promoting fast, local neutrophil response in damaged tissues. A progressively stronger immunoreaction for the CD15 antibody was visible in the areas where the margination of circulating inflammatory cells was detectable, up to very strong expression in the oldest ones (>12 hours). Further, the induction of CD15, IL-15, MCP-1 expression levels was quantified by Western blot analysis. The resultswereasfollows:IL-15/β-actin 0.80, CD15/ β-actin 0.30, and MCP-1/β-actin 0.60, matching perfectly with the results of immunohistochemistry. Control hearts from traumatic death cases did not show any immunoreactivity to the pro-inflammatory markers, neither were there any reactions in Western blot analysis. Conclusions: Essential markers (i.e. IL-15, MCP-1) are suitable indicators of myocardial response to ischemic insult involving very early phase reaction (inflammatory response and cytokine release). In the very near future, proteomics may help clinicians and pathologists to better understand mechanisms relating to cardiac repair and remodeling and provide targets for future therapies

Bridging the gap between 3D navigation and semantic search. The INCEPTION platform

The paper presents the main outcomes and future development of the INCEPTION project, “Inclusive Cultural Heritage in Europe through 3D semantic modelling”, funded by the European Commission under the Horizon 2020 Work Programme Europe in a changing world – inclusive, innovative and reflective Societies (Call Reflective-7-2014, Advanced 3D modelling for accessing and understanding European cultural assets) and completed in May 2019. In particular, the key-targeted project achievement will be presented: a specific cloud-based platform conceived to accomplish the main objectives of accessing, understanding and strengthening European Cultural Heritage by means of enriched 3D models. The need for digital data interpretation, in addition to documentation, guided the overall process of the cross-disciplinary work methodology, based on new methods and tools for 3D surveying and H-BIM modelling, new approaches and methodologies for Cultural Heritage 3D data inclusive access and exploitation by means of the Platform

Bridging the gap between 3D navigation and semantic search. The INCEPTION platform

The paper presents the main outcomes and future development of the INCEPTION project, “Inclusive Cultural Heritage in Europe through 3D semantic modelling”, funded by the European Commission under the Horizon 2020 Work Programme Europe in a changing world – inclusive, innovative and reflective Societies (Call Reflective-7-2014, Advanced 3D modelling for accessing and understanding European cultural assets) and completed in May 2019. In particular, the key-targeted project achievement will be presented: a specific cloud-based platform conceived to accomplish the main objectives of accessing, understanding and strengthening European Cultural Heritage by means of enriched 3D models. The need for digital data interpretation, in addition to documentation, guided the overall process of the cross-disciplinary work methodology, based on new methods and tools for 3D surveying and H-BIM modelling, new approaches and methodologies for Cultural Heritage 3D data inclusive access and exploitation by means of the Platform

Semantic Web Technologies Meet BIM for Accessing and Understanding Cultural Heritage

Within the EU funded project INCEPTION – Inclusive Cultural Heritage in Europe through 3D semantic modelling, the key-targeted achievement is the development of a specific cloud based platform, in order to accomplish the main objectives of accessing, understanding and strengthening European Cultural Heritage by means of enriched 3D models. The whole INCEPTION project is based on the close connection between state-of-the-art architectural modeling technologies (BIM, Building Information Modeling) and the latest cutting-edge web technologies. The platform is grounded on semantic web technologies and makes extensive use of WebGL and RESTful APIs, in order to enrich heritage 3D models by using Semantic Web standards. The INCEPTION platform will be a space for interchange of information and for the dialogue among professionals, students, scholars, curators, non-expert users, etc. Furthermore, the Semantic Web structure interlinks the platform with external Cultural Heritage available linked data and makes it gradually enhanced by specific flexible data structures provided as project specific ontologies. The paper will describe solutions based on the match between BIM, Cloud and Semantic Web

Role of post mortem CT (PMCT) in high energy traumatic deaths

Background. Post Mortem Computed Tomography (PMCT) is being increasingly implemented in forensic field and could be an adjuvant to classic autopsies. In this study we evaluated the feasibility of complementation of conventional autopsy in trauma victims with PMCT. Materials and methods. A total of 21 subjects, who had sustained various types of blunt high-energy trauma, were selected from the casuistry of the Section of Legal Medicine at University of Pisa: before autopsy, a PMCT examination (Toshiba Aquilion 16 CT scanner) was performed, and after the acquisition of the raw images, MPR and VR reconstructions were performed with dedicated software. Results. PMCT is more sensitive than conventional autopsy in detecting skeletal injuries, whilst autopsy constitutes the method of choice for the detection of thoracic and abdominal visceral injuries. Conclusion. PMCT should be considered a useful tool in addition to conventional autopsy in evaluating trauma victims: it detects further bone fractures in body parts difficult to investigate during autopsy (i.e. posterior regions), facilitating the pathologist in the reconstruction of events and in determining the cause of death

Kill rate as a tool in efficiency evaluation of Neoseiulus californicus (Acari: Phytoseiidae) mass reared on factitious food

The predatory mites of the Phytoseiidae family are crucial biological control agents widely utilized in biological pest management targeting phytophagous mites and insects. Key factors in these control strategies are that phytoseiids must be able to find their main target prey and to maintain high populations and efficacy. To reduce expenses and time-consuming production methods of mass rearing of phytoseiids, pollen and other factitious (i.e., non-natural/nontarget) hosts need to be present as an alternative food for predatory mite populations. The mass-rearing possibilities of these predators on alternative food sources, such as astigmatid mites (i.e., house and stored mites) and pollen, must be evaluated not only by the cost of rearing settings but on the basis of their efficiency maintenance in killing prey. The pest kill rate (km) is the average daily lifetime killing of the pest by the natural enemy under consideration and can represent a useful indicator for phytoseiids efficacy to rank them as BCAs on the basis of their effective killing/predation on target prey. In this study, we evidenced that 2 astigmatid mites, Glycyphagus domesticus (De Geer) and Lepidoglyphus destructor (Schrank), and Quercus ilex L. pollen can be successfully adopted as substitute food sources for mass rearing of the phytoseiid Neoseiulus californicus (MgGregor); then, we determined that these populations of BCAs maintained a consistent km at new/first impact on the main target pest, Tetranychus urticae Koch