1,721,033 research outputs found
Neo-linfogenesi nelle lesioni aterosclerotiche della biforcazione carotidea
Full text linkINTRODUCTION:
The indications for surgical or pharmacologic treatment of the patients with carotid stenosis are based
on the macroscopic characteristics of the atherosclerotic carotid plaque (obtained by diagnostic
investigations: ECD/CT).
The stability of the plaque depends on inflammatory cells, inflammatory cytokines and on the
neoangiogenesis. In the literature there are many studies about atherosclerotic plaques but the
mechanism of development, progression and instability of the plaque are not known.
A lot of studies show how the progression and instability of the plaques would depend on the
formation of new blood vessels that are responsible for the migration of inflammatory plaques and
intraplaque haemorrhage.
The new “actors” in the atherosclerotic plaques are lymphatic vessels but their role is unknown.
AIM:
The aim of this project is to evaluate the inflammatory cells in atherosclerotic carotid plaque, the
lymphatic and blood vessels, their location and their relationship with inflammatory cells in the
plaque.
MATERIAL AND METHOD:
In this project, 31 patients with atherosclerotic carotid plaques were enrolled (10 plaques of patients
were used to develop the method) and undergone to carotid endarterectomy (CEA) following ESVS
guidelines at the Vascular Surgery Unit of the Ospedale di Circolo in Varese. For each clinical and
biological data were collected.
The carotid plaques were classified independently of clinical symptoms by their morphology (stenosis
and plaque composition) by computed-tomography angiography into fatty/soft (< 60 Hounsfield units
(HU), mixed 60>HU<129) and calcified (> 130 HU). The calcified plaques were excluded from this
study.
Carotid endarterectomy tissue samples, during CEA, were removed with minimal trauma and
immediately placed in paraformaldehyde for histological evaluations researching inflammatory cells,
lymphatic and blood vessels in the plaques.
The Immunohistochemestry slides were processed with MIAquant that is a novel system for
automatic segmentation, measurement and localization comparison of different biomarkers from
serialized histological slices. This software would allow to analyze, with objective criteria, a large
number of images but, especially, the entire surface of the section.
RESULTS:
In soft plaques there are a lot of inflammatory cells and vessels (lymphatic and blood) compared to
mix plaques.
Working on serial plaque sections, I focused on the localization of neovascularization, using Ulex to
detect blood vessels and Podoplanin (D2-40) as marker of lymphatic vessels.
In the soft plaques, the expression of D2-40 (lymphatic vessels) is near the lipidic core, unlike the
blood vessels are localized in soft and mixed plaques, predominantly near the cap of the plaques
and there isn’t any relationship with the lipid core.
For a better understanding of the origin and function of lymphatic and blood vessels inside
atherosclerotic carotid plaques, some components of the inflammatory infiltrate were examined,
particularly, I have analysed T lymphocytes (CD-3) and two different macrophage populations
(CD-68, CD-163). In addition to this, their position was also evaluated against lymphatic and blood
vessels.
In atherosclerotic carotid plaques Lymphocytes (CD-3) are near blood vessels and are spread
homogenously in the plaques.
T lymphocytes and hematic vessels are not localized in the same territory of lymphatic vessels marked
with D2-40.
The macrophages cells (CD-68, CD-163) are located near the lipid core, in the same layer of
lymphatic vessels.
The colocation of lymphocytes with blood vessels and macrophages with lymphatic vessels were
confirmed by double coloration with confocal microscopy.
To achieve comparable and reproducible data, all soft plaque sections have been examined
automatically, by MIAquant software, to obtain a localization image for each segmented marker
(map), which shows the locations of all markers inside the atherosclerotic carotid plaques.
Furthermore, the software allows to create an histogram with united density value of markers of all
plaques. This software allow to confirm that macrophages cells and lymphatic vessels in all plaques
are located near the lipid core, in particular at a distance of 0-400 pixels. Instead blood vessels and
lymphocytes are spread homogenously.
The co-location analysis of lymphatic vessels and macrophage cells was further scrutinized by way
of immunofluorescence in confocal microscopy. Taking advantage of the resolution power of
confocal microscopy, it observed that only rarely we can find tubular structures attributable to one or
collapsed lymphatic vessels, this is frequently seen in structures that could also be isolated cells near
macrophage cells CD68. In some cases, cells seem that they express both markers.
To characterise macrophage cells and to better understand how they could influence new lymph
genesis, an analysis of macrophage cells CD-68 was done on the confocal microscope with doublemarkings and I observed the presence in the plaques of cells that show positive labelling for CD-68
and they don’t express HLA-DR. Such features are characteristic for myeloid-derived suppressor
cells (MDSC) of the monocyte-macrophage line.
DISCUSSION:
These data show that the lymphatic and blood vessels are located in different place in the carotid
atherosclerotic plaque. The blood vessels co-locate with lymphocyte CD-3 cells, these cells are
important to determinate the development of the lesions, in fact they can cause apoptosys and they
produce cytokines that promote the endothelial proliferation and develop of neo-vessels.
Furthermore they reduce macrophages proliferation and so they cause plaque instability.
The lymphatic vessels, near the lipid core in atherosclerotic plaque, could be the attempt to absorb
and metabolize lipids and cholesterol. In fact in physiological conditions they have a key role in the
reverse transport of lipid and cholesterol in peripheral blood. These data are further support by the
co-location of lymphatic vessels and macrophage cells, in fact it is known that the macrophage cells
in atherosclerosis are important in the process of phagocytosis of lipid and cholesterol performing the
role of “scavenger”.
Macrophages localize in the proximity of the lymphatic vessels and co-localize with themselves,
probably because they represent inflammatory cells mainly involved in the lymphogenesis process.
They determine lymphogenesis via two methods: the production of paracrine signals represents the
first one on behalf of macrophages; the second one is symbolized by the differentiation of
macrophages in lymphatic endothelial cells.
The first mechanism of macrophages that supports lymphogenesis, is determined by the up-regulation
of VEGF-C during the inflammatory process inside the atherosclerotic plaque. In fact, macrophages
produce TNF-α that activates the TNFR1 receptor facilitating the creating of the VEGF-C, which
activates VEGFR-3 promoting the development and the activation of lymphatic endothelial cells.
In addition to the paracrine mechanism, macrophages contribute to lymphogenesis using transdifferentiation in lymphatic endothelial cells.
Through this investigation, I have also recognized the presence of myeloid-derived suppressor cells
of the monocyte-macrophage line inside the atherosclerotic carotid plaques. These cells inside
neoplasms have a dual function: trying to inhibit T lymphocytes activity from avoiding self-inflicted
damage, although, at the same time, they facilitate neo-angiogenesis and neo-lymphogenesis, and
thus tumor’s growth and its dissemination.
In atherosclerotic carotid plaques, these cells will probably inhibit T cells’ activity, as they do not
localize near such cells, and they foster lymphogenesis more extensively that angiogenesis, given
their localization close to lymphatic vessels and not near blood vessels.
CONCLUSIONS:
Lymphatic vessels are new actors in atherosclerotic carotid plaques but it is unknown if they
determine the progression, stability or instability of the plaques.
This project might be an optimal start point to continue the study trying to identify the functions of
myeloid-derived suppressor cells in particular, by pinpointing the cytokines that they produce, to
understand that type of activity they possess inside the atherosclerotic plaque.
Therefore, this investigation, regardless of the riveting and not yet identified data in the literature, it
represents the preliminary phase of other possible examinations of atherosclerotic carotid plaques.
The inspection of new plaques and additional markers will allow us to acquire significant results for
an overall assessment of the plaque, and hopefully, to the identification of areas at a higher
atheroembolic risk inside the atherosclerotic carotid plaque
Complex abdominal aortic aneurysm open repair: giant aneurysm, venous anomalies and renal arteries variants
No full text
AL TEMPO DEL COVID-19: EMERGENZA E SOLITUDINE DEI NUMERI ULTIMI/THE AGE OF COVID-19: EMERGENCY AND LONELYNESS OF THE LAST NUMBERS
No full textThe author presents an analysis of the current Italian pandemic situationconcerning the increase in socio-economic and health inequality. In thefirst part of this paper, the author analyzes the precarious condition thatis aggravated by the pandemic situation and by the spending cuts comein the welfare state system for the last twenty years. In the second part,the author examines the meaning of “dangerousness to society” during theCOVID-19 epidemic. In the last part, the author points out some humancondition of great suffering and certain suicide cases caused by pandemicmanagement.Keywords:COVID-19, Pandemic, Socio-economic Distress, Mental and PsychicSuffering, Suicide
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
