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

SiO collimated outflows driven by high-mass YSOs in G24.78+0.08

We imaged the molecular outflows towards the cluster of high-mass young stellar objects G24.78+0.08 at high-angular resolution using SiO emission, which is considered the classical tracer of protostellar jets. We performed SiO observations with the VLA interferometer in the J = 1-0 v=0 transition and with the SMA array in the 5-4 transition. A complementary IRAM 30-m single-dish survey in the (2-1), (3-2), (5-4), and (6-5) SiO lines was also carried out. Two collimated SiO high-velocity outflows driven by the A2 and C millimeter continuum massive cores have been imaged. On the other hand, we detected no SiO outflow driven by the young stellar objects in more evolved evolutionary phases that are associated with ultracompact (B) or hypercompact (A1) HII regions. The LVG analysis reveals high-density gas (10^3-10^4 cm-3), with well constrained SiO column densities (0.5-1 10^15 cm-2). The driving source of the A2 outflow is associated with typical hot core tracers such as methyl formate, vinyl cyanide, cyanoacetilene, and acetone. The driving source of the main SiO outflow in G24 has an estimated luminosity of a few 10^4 Lsun (typical of a late O-type star) and is embedded in the 1.3 mm continuum core A2, which in turn is located at the centre of a hot core that rotates on a plane perpendicular to the outflow main axis. The present SiO images support a scenario similar to the low-mass case for massive star formation, where jets that are clearly traced by SiO emission, create outflows of swept-up ambient gas usually traced by CO.Comment: Astronomy & Astrophysics, in pres

Discovery of Water Vapor in the High-redshift Quasar APM 08279+5255 at z = 3.91

We report a detection of the excited 2_(20)-2_(11) rotational transition of para-H_2O in APM 08279+5255 using the IRAM Plateau de Bure Interferometer. At z = 3.91, this is the highest-redshift detection of interstellar water to date. From large velocity gradient modeling, we conclude that this transition is predominantly radiatively pumped and on its own does not provide a good estimate of the water abundance. However, additional water transitions are predicted to be detectable in this source, which would lead to an improved excitation model. We also present a sensitive upper limit for the hydrogen fluoride (HF) J = 1-0 absorption toward APM 08279+5255. While the face-on geometry of this source is not favorable for absorption studies, the lack of HF absorption is still puzzling and may be indicative of a lower fluorine abundance at z = 3.91 compared with the Galactic interstellar medium

The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options.

Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the balance between innate and adaptive phases is dysregulated and chronic ocular surface inflammation can result, leading to chronic dry eye disease (DED). According to the Tear Film and Ocular Surface Society Dry Eye Workshop II definition, DED is a multifactorial disorder of the ocular surface characterized by impairment and loss of tear homeostasis (hyperosmolarity), ocular discomfort or pain, and neurosensory abnormalities. Dysregulated ocular immune responses result in ocular surface damage, which is a further contributing factor to DED pathology. Several therapeutics are available to break the vicious circle of DED and prevent chronic disease and progression, including immunosuppressive agents (steroids) and immunomodulators (cyclosporine and lifitegrast). Given the chronic inflammatory nature of DED, each of these agents is commonly used in clinical practice. In this study, we review the immunopathology of DED and the molecular and cellular actions of current topical DED therapeutics to inform clinical decision making

Radiative corrections to the three-body region of the Dalitz plot of baryon semileptonic decays with angular correlation between polarized emitted baryons and charged leptons: The initial-baryon rest frame case

We complement the results for the radiative corrections to the s2.l angular correlation of baryon semileptonic decays of Ref. [1] with the final results in the rest frame of the decaying baryon.Comment: 7 pages, Revtex4, no figure

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