Air Pollution Exposure Induces Vascular Injury and Hampers Endothelial Repair by Altering Progenitor and Stem Cells Functionality

Extensive evidence indicates an association of air pollution exposure with an increased risk of cardiovascular disease (CVD) development. Fine particulate matter (PM) represents one of the main components of urban pollution, but the mechanisms by which it exerts adverse effects on cardiovascular system remain partially unknown and under investigation. The alteration of endothelial functions and inflammation are among the earliest pathophysiological impacts of environmental exposure on the cardiovascular system and represent critical mediators of PM-induced injury. In this context, endothelial stem/progenitor cells (EPCs) play an important role in vascular homeostasis, endothelial reparative capacity, and vasomotor functionality modulation. Several studies indicate the impairment of EPCs’ vascular reparative capacity due to PM exposure. Since a central source of EPCs is bone marrow (BM), their number and function could be related to the population and functional status of stem cells (SCs) of this district. In this review, we provide an overview of the potential mechanisms by which PM exposure hinders vascular repair by the alteration of progenitor and stem cells’ functionality

Scanning Electron Microscopy Application in Clinical Research

Our personal experience on the application of scanning electron microscopy in cardiology, gastroenterology and ophthalmology is reviewed. SEM has not yet significantly contributed to myocardium pathology. However, in the near future, SEM could be a reliable technique to complete the information available from other sources. As to atherosclerosis, SEM allowed us to improve our knowledge of the early stages of the disease; some pathological features, not always detected by conventional morphological examinations, can be documented. An important contribution to gastrointestinal pathology was made by SEM investigations both in the staging of some important diseases (i.e., coeliac disease, peptic ulcer, Crohn\u27s disease, ulcerative colitis) and in the follow-up of mucosal changes during therapy. In the ophthalmological field,SEM provided three-dimensional new information to clinicians, who are familiar with the biomicroscopic images. Our experience in hematology is still limited. However, in the lost few years SEM joined to immunocytochemistry allowed us to characterize cell populations in several blood diseases. Some procedures of particular interest in the management of human bioptic specimens are stressed in order to get to a complete correlative microscopy. We conclude that continuous and simultaneous correlations have to be carried out between SEM and other methods and instruments available for morphological investigation

Beam Voltage Effects in the Study of Embedded Biological Materials by Secondary Electron Detectors

Thin and semithin sections were extensively examined by the secondary electron (SE) detector in a conventional scanning electron microscope (SEM), and in a transmission electron microscope with a scanning attachment (STEM). Various para-meters, in particular the beam voltage, were shown to affect the final SE image (SEI). As for SEM observation, a surface contrast was imaged at low primary electron (PE) voltages (0.6-2 kV), whereas a subsurface contrast predominated at higher energies (15-30 kV). In STEM, significant differences were not detected by varying the PE in the 20-100 kV range. Surface and subsurface in-formation was simultaneously imaged even though the SEI were better resolved at the highest energy

A New Approach for Studying Semithin Sections of Human Pathological Material: Intermicroscopic Correlation Between Light Microscopy and Scanning Electron Microscopy

In order to obtain useful and complete information on the study of pathological material, we observed by scanning electron microscopy (SEM) the same semithin sections observed by light microscopy (LM). For this purpose, the specimen must have, at the same time, chromatic and electron dense characteristics. We thus developed different specimen preparation methods, subjecting the semithin sections to specific polychromatic staining with high atomic number (Z) elements, to monochromatic staining followed by routine contrasting with uranyl acetate and lead citrate, and to specific cytochemical and immunocytochemical procedures. The specimens were examined in sequence by LM, by SEM equipped with secondary electron, backscattered electron, transmitted electron detectors and by scanning transmission electron microscopy (S(T)EM)

Progress with PXIE MEBT Chopper

A capability to provide a large variety of bunch patterns is crucial for the concept of the Project X serving MW-range beam to several experiments simultaneously. This capability will be realized by the Medium Energy Beam Transport's (MEBT) chopping system that will divert 80% of all bunches of the initially 5mA, 2.1 MeV CW 162.5 MHz beam to an absorber according to a pre-programmed bunch-by-bunch selection. Being considered one of the most challenging components, the chopping system will be tested at the Project X Injector Experiment (PXIE) facility that will be built at Fermilab as a prototype of the Project X front end. The bunch deflection will be made by two identical sets of travelling-wave kickers working in sync. Currently, two versions of the kickers are being investigated: a helical 200 Ohm structure with a switching-type 500 V driver and a planar 50 Ohm structure with a linear 250 V amplifier. This paper will describe the chopping system scheme and functional specifications for the kickers, present results of electromagnetic measurements of the models, discuss possible driver schemes, and show a conceptual mechanical design.Comment: 3 pp. 3rd International Particle Accelerator Conference (IPAC 2012) 20-25 May 2012. New Orleans, Louisian

Phenotypically Heterogeneous Podoplanin-expressing Cell Populations Are Associated with the Lymphatic Vessel Growth and Fibrogenic Responses in the Acutely and Chronically Infarcted Myocardium

Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of LYVE-1-negative cells dispersed between myocytes, predominantly in the vicinity of the infarcted region. Podoplanin-carrying populations displayed a mesenchymal progenitor marker PDGFRalpha, and intermittently expressed Prox-1, a master regulator of the lymphatic endothelial fate. At the stages of scar formation and maturation, concomitantly with the enlargement of lymphatic network in the injured myocardium, the podoplanin-rich LYVE-1-negative multicellular assemblies were apparent in the fibrotic area, aligned with extracellular matrix deposits, or located in immediate proximity to activated blood vessels with high VEGFR-2 content. Of note, these podoplanin-containing cells acquired the expression of PDGFRbeta or a hematoendothelial epitope CD34. Although Prox-1 labeling was abundant in the area affected by MI, the podoplanin-presenting cells were not consistently Prox-1-positive. The concordance of podoplanin with VEGFR-3 similarly varied. Thus, our data reveal previously unknown phenotypic and structural heterogeneity within the podoplanin-positive cell compartment in the infarcted heart, and suggest an alternate ability of podoplanin-presenting cardiac cells to generate lymphatic endothelium and pro-fibrotic cells, contributing to scar development

Phenotypically Heterogeneous Podoplanin-expressing Cell Populations Are Associated with the Lymphatic Vessel Growth and Fibrogenic Responses in the Acutely and Chronically Infarcted Myocardium

Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of LYVE-1-negative cells dispersed between myocytes, predominantly in the vicinity of the infarcted region. Podoplanin-carrying populations displayed a mesenchymal progenitor marker PDGFRalpha, and intermittently expressed Prox-1, a master regulator of the lymphatic endothelial fate. At the stages of scar formation and maturation, concomitantly with the enlargement of lymphatic network in the injured myocardium, the podoplanin-rich LYVE-1-negative multicellular assemblies were apparent in the fibrotic area, aligned with extracellular matrix deposits, or located in immediate proximity to activated blood vessels with high VEGFR-2 content. Of note, these podoplanin-containing cells acquired the expression of PDGFRbeta or a hematoendothelial epitope CD34. Although Prox-1 labeling was abundant in the area affected by MI, the podoplanin-presenting cells were not consistently Prox-1-positive. The concordance of podoplanin with VEGFR-3 similarly varied. Thus, our data reveal previously unknown phenotypic and structural heterogeneity within the podoplanin-positive cell compartment in the infarcted heart, and suggest an alternate ability of podoplanin-presenting cardiac cells to generate lymphatic endothelium and pro-fibrotic cells, contributing to scar development

Endothelialization of a New Dacron Graft in an Experimental Model: Light Microscopy, Electron Microscopy and Immunocytochemistry

Two types of synthetic vascular grafts, Dacron Triaxial and Dacron Gelseal Triaxial, were implanted into both the common carotids of sheep. The animals were sacrificed 1, 2, 8, and 16 weeks after surgery. Multiple specimens, obtained from grafts and anastomoses, were studied by light microscopy, transmission and scanning electron microscopy. A parallel immunocytochemical analysis was performed on some specimens. Dacron Triaxial grafts failed to develop a complete neointimal coverage. Myofibroblasts and fibroblasts were the dominant cells in such synthetic graft. Moreover, focal areas of stripping, platelet deposition, and thrombosis were observed at 8 and 16 weeks. In contrast, a stable endothelial coverage developed on the Gelseal Triaxial grafts after 16 weeks