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Sigad (iyo sheekooyin kale)
No full textUruris sheekooyin ku dheehan xigmad iyo suugaan maldahan, oo gabyaagu aragtadiisa ugu gudbinayaa dadweynaha, oo ku saabsan xaaladda cakkiran ee markaas ay soomaalidu ku sugnayd.Raccolta di alcuni racconti con il quale l'autore comunica al pubblico la situazione drammatica in cui la Somalia versava allora, attraverso uno stile letterario sofisticato ed ermetico.A collection of short stories through which the author talks about the Somali tragic situation at the time, using a sophisticated and allegoric literary style
La Rappresentanza Politica e il Diritto Elettorale nell'Ordinamento Giuridico della Somalia
No full textLa tesi di laurea affronta il tema della rappresentanza politica, le origini di tale istituto e l'evoluzione storica, la natura giuridica e approfondendo infine il caso della Somalia.Buuggan qalinjebin wuxuu ka hadlayaa mowduuca madaxda siyaasadeed, asalka xeerkooda iyo tadawirkooda taariikheed, dabeecadahooda sharciyeed iyo isagoo si gaar ah u falanqaynaayo xaaladda Soomaaliya.The dissertation is about political representation: the origin and historical evolution, the juridical nature, finally deepening the Somali case.Volume appartenente al fondo Renato Angeloni (messo a disposizione dalla Dott.ssa Marina Angeloni).Buug ka mid ah hantidii Renato Angeloni.Volume belonging to Renato Angeloni’s fund (made available by dr. Marina Angeloni)
L'amministrazione governativa centrale della Repubblica Somala
No full textTesi di diritto amministrativo sull'amministrazione pubblica e potere esecutivo in Somalia: il presidente della Repubblica, il governo e gli organi ausiliari.Buug qalinjebin oo ku saabsan xeerka maamulka ee maamulka taliska iyo awoodda fulinta ee Soomaaliya: madaxweynaha Jamhuuriyadda, xukuumadda iyo xubnaha kaaliyayaasha ah.Administrative law dissertation about public administration and executive power in Somalia: the president of the Republic, the government and auxiliary bodies.Volume appartenente al fondo Renato Angeloni (messo a disposizione dalla Dott.ssa Marina Angeloni).Buug ka mid ah hantidii Renato Angeloni.Volume belonging to Renato Angeloni’s fund (made available by dr. Marina Angeloni)
Keeping the Lifeline Open: UK remittances and markets in Somalia
No full textThis briefing shows how banks and regulators are in danger of inadvertently undermining this lifeline and driving it underground, as the interpretation of legislation on money laundering and counter terrorism becomes tighter in UK and USA, and banks become more risk-averse.Qoraalkani wuxuu muujinayaa sida bankiyada iyo mas'uuliyiinta wax kontroosha ay halista ugu gaysan karaan khatarta badbaadinta soomaalida, maadaama sharciga ladagaalanka argagixisada iyo lacagata sharcidarrada ah aad looga adkeeyey dalka UK iyo Maraykankaba.Questo briefing mostra come le banche e le autorità di regolamentazione rischiano di minare inavvertitamente questa ancora di salvezza per i somali, dal momento che la legislazione in materia di riciclaggio di denaro e contro il terrorismo diventa più restrittiva nel Regno Unito e negli USA
Automorphisms of Hyperkähler manifolds
No full textLa tesi consiste in una classificazione degli automorfismi di varietà Hyperkähler e contiene una generalizzazione di risultati noti sulle superfici K3. I risultati sono da dividere essenzialmente in due categorie: azione di gruppi finiti su varietà Hyperkähler e deformazioni di automorfismi in quelli che, in letteratura, sono definiti automorfismi naturali. Nel primo ambito è presente una classificazione dei possibili automorfismi simplettici su varietà equivalenti per deformazioni a schemi di Hilbert di n punti su una superficie K3, con alcuni esempi interessanti di automorfismi di ordine 11 e 15. Nel secondo ambito, sotto opportune condizioni topologiche, viene dimostrato che ogni automorfismo simplettico di ordine 2; 3 o 5 su una varietà di K3[2]-type può essere deformato fino ad ottenere un automorfismo naturale su uno schema di Hilbert di due punti su una superficie K3
Models and algorithms for the efficient operation and planning of energy production systems
No full textSince the last four decades the electrical industry has been characterized by important and
rapid changes around the world, regarding generation, transmission and distribution of electricity.
These changes create the need for more e cient operation and planning of energy generation
systems. Global energy demand is increasing, but most of the energy sources which are used
to produce electricity nowadays are characterized by a limited scope, and electric energy is not
suitable to be stored. Performing proper operation and planning of energy generation systems
leads to a more e cient utilization of the available resources and to a limitation in the global
environmental impact.
The recent changes of electrical market structures, like privatization, restructuring and dereg-
ulation lead to maximize the expected value of the electricity market pro ts. Moreover, the inte-
gration of di erent types of energy sources in conventional electrical systems is assuming growing
importance, like renewable sources such as wind and solar energy. These aspects have to be consid-
ered to perform a proper energy production scheduling, taking into account both the uncertainty
related to energy demand load forecast and the uncertainty related to not conventional energy.
For these issues researchers from mathematics, operations research and engineering have fo-
cused for many years on applying mathematical modeling and optimization techniques, in order
to solve the optimization problems related to energy generation systems.
Di erent types of optimization problems are considered and solved, according to the energy
industry process that is involved; typically, generation, transmission and distribution of electricity,
or a combination of them. These optimization problems are characterized by an objective function,
variables and constraints. Generally, the economic e ciency or the utilities pro ts are represented
by the objective function, system operating and technical requirements are represented by the
constraints, while the variables are used to model decisions, which can be taken in long-term,
medium-term, short-term or on-line periods.
In a long-term period (months and years), the Power Expansion Problem is solved, in order
to determine the type, the capacity and the number of generating units that the energy system
should have.
In a medium-term period (days and weeks), the objective is to determine the best combina-
tion of generating units in terms of their status (committed or uncommitted) and their output
(power). This schedule has to satisfy the forecast demand at minimum total production cost,
under the operating, technical and environmental system constraints. This problem is known as
Unit Commitment Problem (UC).
In a short-term and on-line period (hours and minutes), the Economic Dispatch Problem (ED)
is solved, in order to determine the power that each unit, scheduled in the previous phase (solving
the UC problem) must produce in order to meet the system demand at real time.
Part of our research activities focused on analyzing the modeling aspects related with the
production and the scheduling of electrical systems. In particular, we have studied the limits and
the simpli cations mainly used in the classical UC models presented in the literature, in order to
develop more realistic formulations for this problem.
UC models are usually characterized by a combination of several di culties like the presence
of continuous and binary decision variables at the same time, a very large-scale dimension, several non-linearities (for instance, in fuel costs modeling) and uncertainty of the problem data (for
example, in load demand forecasts, fuel pricing models, stream
ows to reservoirs and generating
units failures). For these reasons, numerous simpli ed variants of models and algorithms for UC
have been proposed in the literature.
Traditional UC models are based on two main hypotheses. First, the power can be instanta-
neously adjusted. Second, the power output is constant in an assigned time interval (i.e. 1 hour),
so that the energy produced in each hour is equal to the power level multiplied by 1 hour. These
assumptions greatly simplify the model, because energy and power can be represented by the same
entity even if they are di erent from a physical point of view; nevertheless the model does not
properly re
ect the realistic operating behavior of the generating units.
For this reason, in our research activities we have de ned more realistic mathematical formu-
lations for the UC than the ones proposed in the literature, in order to overcome most of their
main drawbacks. In particular, we propose new Mixed-Integer Quadratic Programming (MIQP)
models for UC, based on power instead of energy. We have also de ned and proposed new UC
models integrated with the ED problem, where the variables are associated with the power levels,
that are assumed to change linearly in each time period, while the energy levels are then computed
accordingly. We have thus derived more realistic models that e ectively represent the constraints
imposed on the units in order to avoid mechanical stresses to the rotors for conventional units, or
to avoid the use of more units in peak hours.
Conventional electrical systems are highly fossil fuel dependent, being the major contributors
to the greenhouse gas emissions and to the depletion of global fossil fuel resources which are
characterized by more volatile prices. For this reason, the use of clean renewable energy sources
for electricity generation is acquiring global relevance. Several world countries actively support the
growing use of renewable energy sources, such as wind, in order to meet Kyoto Protocol targets
for reducing greenhouse gas emissions. Wind energy contributes to this target with a signi cant
percentage. In some world and European countries, such as Italy, Spain, Germany, and Denmark,
wind is an important part of the electricity supply.
Nevertheless, the integration of wind energy into the electrical systems is complex and sig-
ni cantly challenging, especially when large amounts of variable wind generation are introduced.
Even if there exist positive aspects related with the utilization of wind energy, it is necessary
to take into account some practical considerations. For instance, when wind power plants are
connected to the electrical network, it is necessary to improve transmission lines, in order to avoid
grid stability problems, needing additional operational costs. Furthermore, when the uncertainty
associated with the electricity produced by wind energy sources becomes greater than the uncer-
tainty of the demand, it is no longer possible to maintain the same power system reliability with
the conventional power plant scheduling techniques.
For these reasons, even if the integration of wind energy sources into conventional electrical
system is growing in importance - due to its economical and environmental development bene ts
- particular attention must be devoted to the related practical operational aspects. This leads
to the necessity to modify the current industry procedures, such as the UC and the ED, to take
into account large amounts of wind power production. Even if an exhaustive literature exists on
the general UC problem, focused on how improve its mathematical formulation and its solution
algorithm, the research that considers the UC problem in presence of wind energy resources is
limited.
Part of our research activities has then focused on the development of new UC models in
presence of wind energy sources. The objective of the new proposed UC models is to integrate
renewable energy sources in a conventional electrical system. These models formulate and solve
the problem of determining the best con guration (optimal mix) of available thermal, hydro and
wind power plants.
The ongoing integration and deregulation of electricity markets in Europe and in the world
requires that part of the electricity production is traded daily on power pools where producers
state how much electricity they will provide up to 36 hours in advance. This market structure induces additional costs for wind power producers due to the greater unpredictability of wind
power at these time horizons. These issues motivate the importance of wind power forecasting
techniques that are fundamental to provide accurate forecasts on wind production. In particular,
wind generation requires complex forecasting techniques which take into account wind speed,
wind direction, hub height, geographical conditions, wind farm size, wind turbine technical and
operational characteristics and so on.
Since the use of wind energy sources and its integration into power generation systems is as-
suming increasing importance, new generation models for synthetic wind data are needed, in order
to properly generate forecasts of wind speed and power. This data is fundamental in simulations
carried out to analyze and improve the performances of wind generating units, individuating the
technical parameters of wind turbines that directly a ect power production.
Part of our research activities focused also on developing a new model in order to generate real-
istic synthetic wind data. In this model, wind speed is assumed to behave as aWeibull distribution,
while wind speed forecast error is simulated using First-Order Auto-Regressive Moving Average
- ARMA time-series models. Mathematical Operations Research formulations of the Assignment
Problem are used to model wind speed persistence features, which, as shown by simulation results,
are essential to properly obtain wind speed and power output forecasts.
Furthermore, wind synthetic data, generated with the new generation model proposed, has
been used to carry out simulations studies to individuate wind turbines operational parameters
that mainly a ect wind generators performances. In particular, an experimental function which
expresses the average energy produced by a wind turbine in a 24 hours time horizon in a typical day
has been determined, considering the main simulation parameters related withWeibull distribution
and wind turbines.
Below we describe the structure of this dissertation.
In Part I we describe how conventional electrical systems work, focusing our attention on the
UC problem which is solved for their e cient operation and planning. In particular, in Chapter 1
we present the main characteristics of a conventional electrical system and we illustrate how the
energy is traded in the electrical market and how the electricity production is properly scheduled.
Chapter 2 and Chapter 3 illustrate the basic features of the UC, presenting the state of the art of
the models and for methods use to solve this problem, respectively.
Part II deals with the new proposed models for the UC, which represent an improvement
of the conventional electrical systems, since - as previously anticipated - they are based on novel
assumptions which have been neglected in the literature so far. In particular, Chapter 4 illustrates
the novel formulations for the UC with power variables, while in Chapter 5 the new model for the
UC integrated with the ED is presented.
In Part III, the integration of wind energy sources into conventional electrical systems is
treated. In particular, the problems and the challenges that this integration imposes to the
already existing systems are presented in Chapter 6, where the new model for the UC in presence
of wind energy sources is proposed. The importance of wind speed and power output forecasts
for a proper energy production scheduling is described in Chapter 7, where the new model to
generate synthetic wind data is presented. Chapter 8 describes how this new generation model
can be applied to properly compute the average energy of a typical wind turbine, illustrating the
main parameters of the wind generator that a ect the calculation of the energy.
Finally, in the last part of this dissertation, conclusions are drawn and interesting directions
for future research are discussed
Identification and functional analysis of virulence determinants of Verocytotoxin-producing Escherichia coli (VTEC)
No full textVerocytotoxin(VT)-producing Escherichia coli (VTEC) are important zoonotic pathogens whose natural reservoir is the gastrointestinal tract of ruminants. The transmission of the infections mainly occurs via the ingestion of contaminated food of animal origin. VTEC pathogenicity relies on the production of the VTs and on the action of accessory virulence factors constituting the virulome, which has not been completely identified yet. The main objective of this piece of research was the identification of the genomic structures forming the VTEC virulome. An additional goal was the analysis of their distribution in different VTEC sub-populations. Finally, a function for some of the factors identified and involved in the pathogenetic mechanism has been proposed. The work presented here has been largely based on the genomic comparison of VTEC strains isolated from human and animal sources and held in the collections of the EU RL VTEC and of the collaborating institutions Statens Serum Institut (Copenhagen, DK) and University of Extremadura (Caceres, ES). This approach led to the identification and characterisation of two pathogenicity islands (PAIs) proposed to be part of the virulome of VTEC strains commonly isolated from cases of human disease. The two PAIs harbour genes encoding factors involved in the colonization (adfO, OI-57, Chapter 4 and tia, SE-PAI, Chapter 3) or specifying an allelic variant of the Subtilase cytotoxin (subAB2, SE-PAI, Chapter 3).
The identification and characterization of the open reading frames carried by the two PAIs allowed making inference on the function of the encoded proteins and on their role in the pathogenetic process.
As a matter of fact, the tia and shiA genes (SE-PAI, Chapter 3) have been proposed to be part of the colonization machinery of VTEC strains lacking the ability to cause attaching-and-effacing (A/E) lesions on the intestinal mucosa, a typical feature of the VTEC associated with the most severe forms of the infection. The products of genes homologues to tia and shiA have been in fact described respectively to have a role in the process of cell invasion used by some enterotoxigenic E. coli strains or in the attenuation of host inflammatory response upon infection of another invasive enteric pathogen: Shigella flexneri.
The genomic approach has also been used to investigate on the VT-producing Enteroaggregative E. coli O104:H4 that caused an outbreak in Germany in 2011. This peculiar VTEC is characterised by a rare combination of virulence traits from Enteroaggregative E. coli (EAEC) and VTEC, two different E. coli pathotypes responsible for enteric infections in low-income areas and common in industrialized countries respectively. Before the German outbreak, VTEC O104:H4 had been isolated in a few sporadic cases of infection, sometimes with an epidemiological connection with travel in North Africa. Similarly, the strain that caused the German outbreak was introduced into the EU with fenugreek seeds produced in Egypt. These observations, together with the genomic stability observed for some of the VTEC O104 strain (Chapter 5), led to the hypothesis that such chimeric strains may have emerged in developing countries. The high loads of enteric pathogens causing diarrhoea and lack of wastewater treatment in these geographic regions, cause the diffuse faecal contamination of the environment, particularly of the aquatic ecosystem often shared with ruminants, facilitating the exchange of mobile genetic elements between human and animal E. coli pathotypes and leading to the formation of new combinations of virulence features such as those characterising the VT-producing EAEC O104:H4
Telomeri e stabilità genomica in cellule di mammifero irradiate : effetto del tipo di radiazione, range di dose e della condizione funzionale dei mitocondri
No full textThe most important ionizing radiation (IR) target in eukaryotic cells is the chromosomal asset. The radio-sensitivity of cycling cells, is generally dependent on their damage repair ability and a set of factors which promotes the maintenance of genome integrity.
The aim of this work, dealing with several types of IRs and their effects on cycling cell cultures, is manifold: it is a study on the cytogenetic damage of low doses on normal human fibroblasts (i), it is a study addressed to investigate any hypothetic radiation sensitizer role of the dysfunctions of the telomere homeostasis on lymphoblastoid human cells (ii), and finally (iii) it is addressed to highlight the role of the cytosolic reactive oxygen species (ROS) activity and its contribution to the cytogenetic radio-induced damage on normal human fibroblasts pharmacologically treated to this purpose.
(i) For a long time the response of a biological system to IR exposure has been supposed proportional to the dose delivery, even the low-dose range, according to the so-called Linear No Threshold Model. Indeed it is a practical and conservative approach due to the general lack of data in that dose range. Based on deterministic data obtained at higher doses, it is suitable as guideline for the risk assessment in a variety of different situations.
Things have changed since a set of non-linear trends (§ 1.16) emerged, such as the low-dose hyper-radio-sensitivity/induced-radio-resistance, the bystander effect, and the adaptive response. So far, the cell survival is the most used endpoint to test the occurrence of such non-linear phenomena, in this work instead, cytogenetic skills have used in order to verify hypothetic non-linear behaviors of endpoints such as the chromosomal damage, the telomere length modulation, and the induced genome instability, in dependence on the dose and the type of IR (low- and high- LET).
According to the LNTM the fitted functions of the dose-response charts should be strictly monotonic even in the low-dose range, whilst in event of non-linear behaviors, abnormal peaks or flat trends should be reported.
We measured the radio-induced damage in two ways: as induction of chromosome exchanges and breakages, through a whole karyotype painting technique (§ 3.1), and as induction of chromatine bridges in anaphase (§ 3.3), through traditional staining. About the induction of such aberrations, the outcome is that no substantial deviation from linearity has been demonstrated. The underlying model is mere probabilistic: the yield and complexity of damage depends only on the dose delivery, the Relative Biological Effectiveness (RBE) of the radiation (fig 14, 15, 18) and the DNA content of the target (fig 16) without hypersensitivity or threshold effects (§ 4.1, 4.2.1).
(ii) Coming to the effect of IR exposure on the telomere, to be reminded that it is an important genome stabilizing factor: it avoids the chromosomal termini to be processed as Double Strand Breaks (DSBs), and the chromosome end-end fusion. An effect of IRs on the modulation of telomere length, in terms both of elongation and shortening depending on the radiation type used, has been reported for high doses. Instead, on the basis of our data, such a modulation is missing in the low-dose range (§ 3.2) for all the radiation types tested. Moreover, the telomere does not significantly participate in the genomic instability triggered on by IRs as revealed by the anaphase bridges analysis (§3.3 fig 18). On the basis of this outcome relative to the low-dose range, speculations on a linearity failure are allowed (§ 4.2.1).
Ultimately, low doses of IRs induce chromosome instability, but not via the telomere homeostasis perturbation, despite its well-known role played in the chromosome asset destabilization/stabilization. Therefore, we have been persuaded to weight the telomere role in the radio-resistance at doses of X-rays of therapeutic order of magnitude.
As the functional telomere is one genome stabilizing factor, IRs are by definition destabilizing agents, able to induce cell inactivation through the genome injury. Moreover, a cell is characterized by a mean telomere length, and a mean spontaneous lack of some telomeres (basal telomere loss frequency). On the aforementioned assumptions, an enhanced radio-sensitivity rationally is expected in case of telomere homeostasis dysfunction.
As amid the same cell line the telomere length is spread around a mean value different from cell to cell, then the telomere-related genome stability is supposed to differ from cell to cell (§ 3.4.1), and by hypothesis it may result in a different inherent radio-resistance.
We tested this speculation on several monoclonal lymphoblastoid lines: several clones have been isolated, independently cultured and characterized for the telomere functionality and for the radio-resistance. The outcome is that the short telomeres do not confer radio-sensitivity to the line, while a frequency of telomere loss beyond a threshold does (§ 3.4.6 fig 25), thus the telomere dysfunction may be involved in the differential radio-sensitivity of clones obtained from the same population (§ 4.2.2), and shows potential as radio-sensitivity marker.
(iii) The mitochondrion is a physiological source of ROS and the main player of their homeostasis, therefore it is supposed to have some indirect involvement in the radio-damage mechanisms. To be reminded in fact that DNA is injured both by direct radiolysis and by means of reactive species released by the water radiolysis.
Far to be clear, this role is object of several speculations: for example, irradiated mitochondria are supposed to establish a long-term ROS release, moreover, the mitochondrial metabolism is supposed to amplify the activity of ROS generated by IRs (§ 1.15).
The increased ROS activity, generated by mitochondrial impairment, has been related to chromosomal abnormalities, genomic instability, and telomere damage. On the other hand, ROS overproduction, due to the same impairment, paradoxically may be seen as cytoprotective, through engaging countermeasures, as in the so-called adaptive response (§ 1.18).
To address the role of mitochondria-related ROS activity in the response to IRs, we pharmacologically set a fibroblast line upset in the mitochondrial functionality, that showed an increase of the basal ROS activity due to ROS homeostasis imbalance (§ 3.5.1). This model, in which mitochondria are turned into ROS diffusers (fig 29), is aimed to report, through the analysis of cytogenetic endpoints, any differential response to the IRs in comparison to a control line, to ultimately verify whether the increased endogenous ROS activity acts additively or synergistically with the exogenous radio-damage.
The pharmacological treatment resulted in a basal increased frequency of DSB (§ 3.5.5) and spontaneous chromosomal fragmentation (§ 3.5.7), conversely no damage on the telomere was detected (§ 3.5.6 fig 30, 31). After irradiation, we observed that the cytogenetic damage yield was the sum of the radio-induced and the basal ROS-induced damage via mitochondrial impairment, without synergistic effect.
In conclusion, relatively to our data the mitochondrion is not an important player in the damage induction via IRs (§ 4.3)
Effetto dello stress ossidativo caratterizzante il Diabete Mellito sulla struttura e funzione del VWF : rilevanza nell’insorgenza di complicanze trombotiche in questo contesto clinico
No full textThe Von Willebrand Factor (VWF) is a plasmatic glycoprotein with a large multimeric structure, produced in endothelial cells and megakaryocytes and involved in primary haemostasis. VWF induces adhesion and aggregation of platelets at sites of vascular injury, playing an important role in both haemorrhagic and thrombotic processes.
The turnover of VWF depends on the cleavage specifically operated by ADAMTS13 in the A2 domain of VWF and in particular, at the Tyr1605–Met1606 peptide bond. Methionine and tyrosine represent substrates particularly sensible to oxidative modifications, that may easily be transformed in methionine-sulfoxide and 3-nitrotyrosine, respectively.
Previous studies demonstrated that notable levels of oxidative stress contribute to pro-thrombotic effects, by inhibiting VWF cleavage by ADAMTS13. This kind of resistance to the hydrolysis operated by the metalloprotease leads to accumulation of high molecular weight VWF multimers (Ultra Large-VWF, UL-VWF), that have the highest ability to bind and activate platelets.
Basing on these considerations, I focused the researches performed during the course of my PhD on discovering the differences in VWF hydrolysis when performed by leukocyte serine proteases (LSPs) or ADAMTS13, in different pathological settings characterized by conditions of high oxidative stress.
Recent studies showed in fact that not only ADAMTS-13, but even the three polymorphonuclear (PMN) proteases, human neutrophil elastase (HNE), proteinase 3 (PR3) and cathepsin G (CG), are able to cleave VWF.
Beginning from such evidence, with our experiments we discovered that PR3 and CG can cleave VWF (as a peptide mimicking its A2 domain or as full length protein) near or at the same cleavage site as ADAMTS13, either under conditions of normal or increased oxidation.
The same results were even obtained with stimulated PMN secreting both reactive oxygen species (ROS) and LSPs, in the presence or in absence of ROS scavengers or LSPs inhibitors, from where we observed that not only VWF hydrolysis by LSPs is not affected by PMN-generated ROS, but it is even accelerated.
In the light of the obtained data, we could hence consider the LSPs-dependent VWF hydrolysis as a limiting step for the adhesion of those bacteria (i.e., S.aureus) that use VWF for adhering to vessels and migrate into tissues, particularly in a high oxidant environment, where VWF hydrolysis by ADAMTS13 results inefficient.
On the other hand, the reduced hydrolysis of VWF by ADAMTS13 in the presence of high oxidative stress remains a point still requiring investigations, particularly in those pathological settings characterized by both high ROS levels and the onset of thrombotic events.
My researches have been therefore focused on Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD), two pathologies that, in addition to the above characteristics, even showed a strong accumulation of circulating UL-VWF.
In particular, concerning DM, it was highlighted the role of oxidative stress in acquired thrombotic micro- and macro-angiopathy related to the interaction between VWF and ADAMTS13.
When compared to a matched group of healthy subjects, T2DM patients showed increased plasma proteins and VWF carbonyl levels (used as a marker of oxidative stress), increased VWF antigen and activity levels and ADAMTS13 antigen and activity values within the normal range, meaning that the reduced cleavage of VWF in T2 diabetics did not depend on impaired ADAMTS13 quantity or functionality.
The level of VWF-bound carbonyls was even found correlated with the presence of either UL-VWF forms and several degrees of micro- or macro-angiopathic complications in T2DM. Moreover, samples characterized by the highest carbonyl content even resulted more resistant to the cleavage by ADAMTS13 when compared to a control group, after 60 minutes of incubation with the enzyme.
Altogether, the obtained evidences led us to conclude that in T2DM, the ROS-mediated induction of UL-VWF release
from endothelial cells causes the observed elevation of VWF levels, which is associated with the increase of major adverse cardiovascular diseases proper of this pathological setting.
As last, we investigated the role of VWF in CKD, another pathology characterized by conditions of high oxidative stress as well as a persistent inflammatory state. Patients suffering from CKD have increased risk of developing cardiovascular and septic complications.
In our research, we purified VWF from CKD patients and characterized its oxidative state, noting even in this case increased levels of both UL-VWF and carbonyl content and a relevant resistance to the cleavage by ADAMTS13.
These results led us to conclude that VWF oxidation, impairing ADAMTS13 cleavage, determines UL-VWF polymers accumulation, inducing in turn platelets’ recruitment and activation and enhancing, at the same time, UL-VWF binding to bacterial adhesins, resulting in the development of thrombotic and septic complications in CKD