5,028 research outputs found
Impact of angiotensin-converting enzyme inhibition on platelet Tissue Factor expression in stroke-prone rats
No full textABSTRACT
Objective: Hypertension is a well-known risk factor for thrombotic events such as myocardial infarction and stroke. Platelets express tissue factor (TF), the key activator of blood coagulation and thrombus formation. The number of TF-positive platelets increases in pathological conditions characterized by thrombotic complications but whether this occurs in hypertension is unknown.
Here we investigated whether: 1) platelet TF expression is increased in a hypertensive status through a mechanism acting on megakaryocytes; 2) the phenomenon could be modulated by anti-hypertensive drug as captopril; 3) angiotensin influences platelet TF expression.
Methods: SHRSP rats received standard diet (StD) or a high-salt permissive diet (JpD). After 3 weeks, JpD animals were randomized to receive captopril or vehicle. Normotensive Wistar Kyoto (WKY) rats were used as controls. Cell-associated TF expression and activity were analyzed by flow cytometry and Calibrated Automated Thrombogram, respectively.
Results: Hypertensive StD-SHRSP showed an increased number of TF-positive platelet compared to normotensive WKY. After JpD administration, SHRSP developed severe hypertension and renal damage; the number of TF-positive megakaryocytes significantly increased compared to StD-SHRSP resulting in a higher number of TF-positive platelets with a faster kinetic of thrombin generation. These effects were reverted by captopril. Ex vivo stimulation of platelets, isolated from normotensive WKY and from healthy subjects, with angiotensin induced a concentration-dependent increase of surface-associated TF expression.
Conclusion: This study shows for the first time that in hypertension the number of TF-positive megakaryocytes increases thus releasing in the circulation more platelets carrying a functionally active TF. Angiotensin stimulates platelets to express TF
Do methodological differences account for the current controversy on tissue factor expression in platelets?
No full textAbstract
Tissue Factor (TF), the key activator of the blood coagulation cascade and of thrombus formation, is also expressed by circulating human platelets. Despite the documented in-depth characterization of platelet TF carried out in the past fifteen years, some authors still fail to identify TF in platelets, especially when assessment in platelet rich plasma (PRP) or washed platelets is carried out. This study aims to extend the characterization of the subset of TF-positive platelets in PRP from healthy subjects and to verify how different centrifugation forces, used to prepare the PRP, could affect the analysis of TF-positive platelets. Data indicate that large size platelets express significantly higher amount of TF compared to small size cells, both in terms of TF protein as well as of TF mRNA. Upon stimulation, large platelets readly expose on the cell membrane TF, which is functionally active, i.e. able to generate FXa as well as thrombin. By contrast, TF activity in small platelets is almost completely quenched by TFPI, becoming indeed detectable only after treatment with an anti-TFPI antibody.
Our data highlight that particular attention must be paid to the preparation and collection of the PRP since such pre-analytical variables may influence the platelet recovery and in turn affect subsequent analysis, whether it is flow cytometry, functional activity tests, proteome or transcriptome analysis. Indeed, the positive TF subset of large platelets can easily be lost if centrifugation protocols are not optimized, thus erroneously leading to a false negative result
Nuove acquisizioni sull'aterosclerosi: placca vulnerabile
No full textNuove acquisizioni sull’aterosclerosi: la placca vulnerabile
Marina Camera
Dip. Scienze Farmacologiche, Università degli Studi di Milano e Centro Cardiologico Monzino IRCCS Milano.
L'aterosclerosi è una patologia infiammatoria, degenerativa, a lenta progressione, caratterizzata dalla presenza di placche aterosclerotiche che possono andare incontro a rottura. L’evento trombotico conseguente alla rottura della placca è responsabile degli eventi cardiovascolari, quali angina instabile, infarto del miocardio e ictus cerebrale.
Studi anatomo-patologici e clinici hanno ormai chiarito che il rischio di rottura è legato più alle caratteristiche istomorfologiche della placca che alle sue dimensioni e al grado di stenosi luminale che essa provoca. Placche instabili sono caratterizzate da un grosso core lipidico, un cappuccio fibroso sottile, un ricco infiltrato di cellule infiammatorie macrofagiche e scarse cellule muscolari lisce. Negli ultimi due decenni, particolare attenzione è stata rivolta al concetto di "placca vulnerabile" come strumento per migliorare la stratificazione del rischio cardiovascolare e per portare, potenzialmente, a nuove opzioni terapeutiche invasive e non per prevenire e curare la malattia cardiovascolare aterotrombotica. È inoltre ipotizzabile che nei prossimi anni le nuove tecniche di imaging ad alta risoluzione saranno in grado di individuare le caratteristiche fondamentali che definiscono una placca vulnerabile che rischia di rompersi. Per ogni placca aterosclerotica potrebbe quindi essere generato un sistema di valutazione finalizzato a valutare il rischio specifico di instabilità con lo scopo di identificare prospetticamente gli eventi coronarici acuti. Inoltre, l'associazione di specifiche informazioni morfologiche con marcatori sistemici di vulnerabilità potrebbe consentire, in un prossimo futuro, di prevedere il rischio reale di infarto miocardico acuto per ogni singolo paziente
Discovery of cyanophage genomes which contain mitochondrial DNA polymerase
No full textDNA polymerase γ is a family A DNA polymerase responsible for the replication of mitochondrial DNA in eukaryotes. The origins of DNA polymerase γ have remained elusive because it is not present in any known bacterium, though it has been hypothesized that mitochondria may have inherited the enzyme by phage-mediated nonorthologous displacement. Here, we present an analysis of two full-length homologues of this gene which were found in the genomes of two bacteriophages which infect the chlorophyll-d containing cyanobacterium Acaryochloris marina. Phylogenetic analyses of these phage DNA polymerase γ proteins show they branch deeply within the DNA polymerase γ clade and therefore share a common origin with their eukaryotic homologues. We also found homologues of these phage polymerases in the environmental Community Cyberinfrastructure for Advanced Microbial Ecology Research and Analysis (CAMERA) database, which fell in the same clade. An analysis of the CAMERA assemblies containing the environmental homologues together with the filter fraction metadata indicated some of these assemblies may be of bacterial origin. We also show that the phage encoded DNA polymerase γ is highly transcribed as the
phage genomes are replicated. These findings provide data which may assist in reconstructing the evolution of mitochondria
The Dikkowita Marina Project
No full textThe large fishery harbour of Dikkowita faces some problems with respect to revenues and conflicts between the users. To create a higher revenue and to avoid these conflicts, a marina will be implemented. This report discusses the different aspects implementing a marina in the harbour of Dikkowita.Civil Engineering and Geoscience
Marina Martín Garcia
No full textIsla Martín Garcia is founded on a rock outcrop in the Río de la Plata which is a natural protected area between Argentina and Uruguay. Due to the extension of the runway at the local airport, wetlands between Isla Timoteo Domínguez and Isla Martín Garcia developed during the last decades. The bay, where the old port was located, was loaded with sediment. After the waters between the two islands sedimented, Isla Hércules is formed and a channel is created. For the location of the marina, three possible options are selected: at the pier, south of Isla Hércules and in the sedimented bay north of Isla Martín Garcia. By using a multi criteria analysis, a marina at the pier is chosen as the best option because of its small dredging area and minor environmental impact. In consultation with the consultative authorities, a marina at the bay is chosen as the elaborated alternative. The recovery of the old situation in which the marina is located in the bay is the main reason for this choice.Implementation of the marina at Isla Martín Garcia involves cooperation between two parties: the government and a second investor. The government is responsible for the island, and a certain amount of liquidity is required to boost tourism on the island. A second party, like a private investor, is introduced for the maintenance and exploration of the project. This cooperation needs to invest 22.9 million dollars; this includes the 16.4 million dollars for the government and 6.5 million dollars for the second party. Without involving an external investor the internal rate of return (IRR) is 1.77% which is very low. When involving a private investor the IRR increases, the external investor receives an IRR of 7.71 % over the entire lifetime of the marina.Hydraulic EngineeringCivil Engineering and Geoscience
Nuove acquisizioni sull'aterosclerosi: placca vulnerabile : relazione su invito
No full textNuove acquisizioni sull’aterosclerosi: la placca vulnerabile
Marina Camera
Dip. Scienze Farmacologiche, Università degli Studi di Milano e Centro Cardiologico Monzino IRCCS Milano.
L'aterosclerosi è una patologia infiammatoria, degenerativa, a lenta progressione, caratterizzata dalla presenza di placche aterosclerotiche che possono andare incontro a rottura. L’evento trombotico conseguente alla rottura della placca è responsabile degli eventi cardiovascolari, quali angina instabile, infarto del miocardio e ictus cerebrale.
Studi anatomo-patologici e clinici hanno ormai chiarito che il rischio di rottura è legato più alle caratteristiche istomorfologiche della placca che alle sue dimensioni e al grado di stenosi luminale che essa provoca. Placche instabili sono caratterizzate da un grosso core lipidico, un cappuccio fibroso sottile, un ricco infiltrato di cellule infiammatorie macrofagiche e scarse cellule muscolari lisce. Negli ultimi due decenni, particolare attenzione è stata rivolta al concetto di "placca vulnerabile" come strumento per migliorare la stratificazione del rischio cardiovascolare e per portare, potenzialmente, a nuove opzioni terapeutiche invasive e non per prevenire e curare la malattia cardiovascolare aterotrombotica. È inoltre ipotizzabile che nei prossimi anni le nuove tecniche di imaging ad alta risoluzione saranno in grado di individuare le caratteristiche fondamentali che definiscono una placca vulnerabile che rischia di rompersi. Per ogni placca aterosclerotica potrebbe quindi essere generato un sistema di valutazione finalizzato a valutare il rischio specifico di instabilità con lo scopo di identificare prospetticamente gli eventi coronarici acuti. Inoltre, l'associazione di specifiche informazioni morfologiche con marcatori sistemici di vulnerabilità potrebbe consentire, in un prossimo futuro, di prevedere il rischio reale di infarto miocardico acuto per ogni singolo paziente
Characterisation of bacteriophages that infect Acaryochloris
No full textThe cyanobacterium Acaryochloris marina was isolated in 1996 and solved a 50 year old mystery as to the origin of the pigment chlorophyll d, which was thought to be a pigment of red algae or a breakdown product of the universal chlorophyll, chlorophyll a. Over the next decade, new Acaryochloris spp. were isolated from all over the world as the genus received international interest from the scientific community, with the majority of research directed towards understanding the mechanisms of photosynthesis of this uniquely pigmented cyanobacterium, using A. marina as the model organism of the genus. During this project, characterisation of different aspects of photosynthesis in Acaryochloris spp. was performed including an investigation of pigment adaptation and composition and the growth and characterisation of A. marina biofilms. However, the main focus of the thesis concerns the isolation and characterisation of cyanophages A-HIS1 and AHIS2, which infect A. marina as a basis to investigate and understand the impact of phage on host physiology in this new model system. A-HIS1 and A-HIS2 were characterised by their morphology, growth behaviour and genomes. Experiments were designed and implemented to investigate interactions between the phages and host. Interestingly, an analysis of novel genes in these phages revealed a surprising evolutionary history of phages A-HIS1 and A-HIS2 providing new insights into the origin of DNA polymerase, which is found only in the mitochondria of eukaryotes
Developing a framework for an ecosystem-based approach to sustainable marina development: Including a framework application case study for a marina on the island of Mauritius, Indian Ocean
No full textThis thesis report considers the topic of sustainable marina development. This term can be understood to be a combination of two terms; “sustainable development” and “marina”. Sustainable development in this research study has been considered in relation to the coastal zone and basically entails an approach to ensure a balance between the environment and economic development. A marina, being a coastal (economic) development, interacts with the environmental conditions of the coastal zone and as such, affects the balance for sustainable development. Sustainable marina development is subsequently defined as the development of a marina in such a way and capacity, that the marina integrates its natural, social and economic environment. Additionally, a marina cannot be deemed sustainable by itself, as important principles for sustainable development like the cumulative impacts, multiple (long-term) objectives and sustainability need to be considered on the level of the larger coastal zone, or ecosystem. Currently, marina design is considered to lack an integrated development approach, and is inadequately represented in current marina development guidelines. Especially the initial stages of marina development, involving important development considerations like location selection and alternatives evaluation, lack the assessment of a marina’s integration in its natural, social and economic environment; a key element of sustainable development.Civil Engineering and GeosciencesHydraulic Engineerin
La Corte europea dei diritti dell’uomo: il divieto di eterologa non viola la Convenzione europea sui diritti umani. Nota in margine alla sentenza della Grande Camera del 3 novembre 2011
No full textLa Corte europea dei diritti dell’uomo: il divieto di eterologa non viola la Convenzione europea sui diritti umani. Nota in margine alla sentenza della Grande Camera del 3 novembre 201
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