1359 research outputs found
Sort by
New lipid nanovesicles as topical delivery sistems for ant-inflammatory drugs
Get PDFThe purpose of the present study was to formulate new vesicular carriers to optimize the topical delivery of anti-inflammatory drugs: diclofenac, quercetin and curcumin.
In the first work concentrated and interconnected penetration enhancer containing vesicles (PEVs) are proposed as carriers for dermal delivery of diclofenac. PEVs were prepared by using a commercial phosphatidylcholine mixture (180 mg/m) and transcutol in different amounts. Conventional liposomes were also prepared and tested as control. All vesicles showed a mean size ranging from 75 to 253 nm with fairly narrow size distribution, negative zeta potential value, and drug loading capacity between 48 and 70%. SWAXS studies showed that composition affected vesicle structure and morphology: 10 and 30% transcutol PEVs were unilamellar while liposomes and 20% transcutol PEVs were multilamellar. Rheological studies demonstrated that control liposomes and 10 and 30% transcutol containing PEVs behaved as Newtonian fluids while 20% transcutol containing PEVs showed a plastic behavior. Ex vivo (trans)dermal delivery experiments showed an improved skin deposition of diclofenac when PEVs were used. Vesicle toxicity and
uptake of fibroblasts, target of inflammation treatment, were evaluated by MTT test and fluorescence
microscopy. Control liposomes and PEVs were both able to interact and being internalized by the 3T3
fibroblasts at all time exposure tested. Furthermore, PEVs showed to be able to reduce the in vitro drug
toxicity.
The aim of the second study was to improve the knowledge of drug–glycol–phospholipid-interactions and their effects in lamellar vesicle suitability as drug delivery systems. Liposomes were prepared using hydrogenated soy phosphatidylcholine (P90H, 60 mg/ml) and diclofenac sodium salt at two con-centrations (5–10 mg/ml). To obtain innovative vesicles two permeation enhancers with glycol group, diethyleneglycol monoethyl ether and propylene glycol, were added to the water phase at different ratios (5%, 10%, and 20%). Vesicle organization was deeply investigated by physico-chemical characterization, including differen-tial scanning calorimetry and small-angle diffraction signal analysis while macroscopic structure behavior was evaluated by rheological studies. Results evidenced that the presence of the penetration enhancer and diclofenac sodium salt led to structural rearrangements within and among vesicles forming a tridi-mensional and complex architecture in which vesicles were closely packed and interconnected. This new design allowed a change in the physical state of dispersions that became highly viscous liquid or soft-solid-like, thus forming an ideal system for topical application able of both adhering to the skin and delivering the drug. © 2013 Elsevier B.V. All rights reserved.
In the last work biocompatible quercetin and curcumin nanovesicles were developed as a novel approach to prevent and restore skin tissue defects on chronic cutaneous pathologies. Stable and suitable quercetin- and curcumin-loaded phospholipid vesicles, namely liposomes and penetration enhancercontaining vesicles (PEVs), were prepared. Vesicles were made from a highly biocompatible mixture of phospholipids and alternatively a natural polyphenol, quercetin or curcumin. Liposomes were obtained by adding water, while PEVs by adding polyethylene glycol 400 and Oramix_CG110 to the water phase. Transmission electron microscopy, cryogenic-transmission electron microscopy and small- and wideangle X-ray scattering showed that vesicles were spherical, oligo- or multilamellar and small in size (112–220 nm). In vitro and in vivo tests underlined a good effectiveness of quercetin and curcumin nanovesicles in counteracting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced lesions and inflammation. Myeloperoxydase activity, used to gauge inflammation, was markedly inhibited by quercetin liposomes (59%) and curcumin liposomes and polyethylene glycol (PEG)-PEVs (_68%). Histology showed that PEG-PEVs provided an extensive re-epithelization of the TPA-damaged skin, with multiple layers of thick epidermis. In conclusion, nanoentrapped polyphenols prevented the formation of skin lesions abrogating the various biochemical processes that cause epithelial loss and skin damage
Low mass dimuon production with the ALICE muon spectrometer
Get PDFLow mass vector meson (ρ, ω,Φ ) production provides key information on the hot and dense state of strongly interacting matter produced in high-energy heavy ion collisions (called Quark Gluon Plasma). Strangeness enhancement is one of the possible signatures of the Quark Gluon Plasma formation and can be accessed through the measurement of Φ meson production with respect to ρ and
Φ mesons, while the measurement of the Φ nuclear modification factor provides a powerful tool to probe the production dynamics and hadronization process in
relativistic heavy ion collisions. Vector mesons can be detected through their decays into muon pairs with the
ALICE muon spectrometer. This thesis presents the results on the measurement of the Φ differential cross section, as a function of the transverse momentum, in
pp collisions at √s = 2.76 TeV; the measurement of the Φ
fyield and of the nuclear modification factor RpA at forward and backward rapidity, as a function of the
transverse momentum, in p-Pb collisions at √s = 5.02 TeV; the measurement of the Φ/ (ρ+ω) ratio, as well as of the Φ nuclear modification factors RAA and RCP , as a function of the number of participating nucleons, in Pb-Pb collisions
at √sNN = 2.76 TeV
Analisi di un isolato sardo tramite il cromosoma Y: il caso Desulo
Get PDFThe Sardinian population is often analyzed in human genetic investigation because it shows a genetic peculiarity when compared with other European populations (Calò et al. 2013, 2012; Calò e Vona 2005; Capocasa et al. 2014; Cappello et al. 1996; Francalacci et al. 2003, 2013; Robledo et al.
2009; Vona 1995).
Moreover, it was observed a high internal heterogeneity probably due to founders effects, isolation
and bottleneck that occurred several times during Sardinia history.
In this work I have analyzed the population of Desulo: a small village, located in the archaic zone of
Sardinia (Vona 1995), that showed high level of endogamy (91.36%) and consanguinity (26.27%) between 1800 and 1974 (Sanna et al., 2004). The village of Desulo was composed until the 1920 by three separated neighborhoods: Issiria, Asuai and Ovolaccio, that subsisted as three independent
units.
Moreover, Desulo’s shepherds practiced transhumance towards the Sulcis Sardinian area. Hence, I wanted to test the level of population differentiation from different point of view: performing a comparison with other Sardinian populations, researching the presence of Desulo internal micro differentiation due to his subdivision in neighborhoods, and comparing it with other Mediterranean population.
To perform this study 17 Y-STRs were analyzed: DYS19, DYS385 a/b, DYS389І/ІІ, DYS390, DYS391, DYS392, DYS393, DYS438, DYS439, DYS437, DYS448, DYS456, DYS458, DYS635,
and YGATAH4. It was noteworthy the detection of the non consensus allele 18.2 in the locus DYS458. This frequencies is extremely low in the Caucasian and Italian populations (0.00317 and 0.014 respectively) but in Sardinian population it reaches the 0.1 % , furthermore all individuals carrying this allele belong to the haplogroup J1, confirming that the non consensus allele 18.2 can
be used to discriminate the J1 haplogroup as suggested in previous studies (Alves et al. 2007b; Ghiani et al. 2009). Sardinia population, when compared with Mediterranean through Principal Component Analysis (PCA), resulted located in a separated cluster, also far from the Italian
populations.
However, this work shows an elevated internal heterogeneity of Sardinians: in fact performing a PCA with only Sardinian population, the formation of two clusters can been seen: one including North Sardinia and Benetutti, and the other one Sulcis and Central Sardinia. Instead, Carloforte and
Desulo appear isolated. The latter is located very distant from Sulcis population, suggesting that despite the practice of transhumance, the two populations do not genetically interbred. The most frequent observed haplogroup is I2a1a determined by the M26 mutation, which reached the frequencies of 48% in the population of Desulo while in European population in extremely rare (<5%) (Ghiani et al. 2009). This high frequency can be due to founder effect occurred during the Paleolithic colonization of the Sardinia island (Contu et al. 2008; Francalacci et al. 2013; Varesi et al. 2000). For this reason it was chosen to study in deep the I2a1a subclades. All individuals
carrying the mutation M26 always have the L160 mutation (haplogroup I2a1a1). The frequency of analyzed mutations (PF4124, 18866539, PF4258, PF4461, 21841733 e M161), determining the different subclades, varies significantly in the Sardinian population. This suggest that the
sublclades variability of I2a1a haplogrup can be also due to genetics drift phenomena as founders
effect and bottleneck and have remained in these areas through isolation. The isolation effect is also
found at the micro geographic level in the village of Desulo. In fact, through the comparison with
haplotipic data, the Issiria and Asuai districts appear differentiated, while Ovolaccio, the central
district, seems to homogenate with the neighboring districts.
In conclusion, when Sardinia is compared with Mediterranean populations it appears homogeneous, but if we are going to observe in detail only Sardinian population notice a large internal
heterogeneity, detectable even at micro geographic level as in the case of the village of Desulo.
For this reason it would be important to create, both for forensic and population genetics purposes,
a database in which are recorded the different haplotypes detected in the Sardinian population.
Moreover, with this study it was possible to clarify some doubt on the genetic Sardinian heterogeneity, but unfortunately exclusively inherent in the male line; therefore, it would be desirable to continue this study analyzing the mitochondrial DNA to see if the results obtained on the male line are also overlapping on the female line
Robust Observation and Control of Complex Networks
Get PDFThe problem of understanding when individual actions of interacting agents display to a coordinated collective behavior has receiving a considerable attention in many research fields. Especially in control engineering, distributed applications in cooperative environments
are achieving resounding success, due to the large number of relevant applications, such as formation control, attitude synchronization tasks and cooperative applications in large-scale systems.
Although those problems have been extensively studied in Literature, themost of classic approaches use to consider the unrealistic scenario in which networks always consist of
identical, linear, time-invariant entities. It’s clear that this assumption strongly approximates the effective behavior of a network. In fact agents can be subjected to parameter uncertainties,
unmodeled dynamics or simply characterized by proper nonlinear dynamics.
Therefore, motivated by those practical problems, the present Thesis proposes various approaches for dealing with the problem of observation and control in both the framework
of multi-agents and complex interconnected systems. The main contributions of this Thesis consist on the development of several algorithms based on concepts of discontinuous slidingmode control. This techniques can be employed for solving in finite-time problems of robust
state estimation and consensus-based synchronization in network of heterogenous nonlinear systems subjected to unknown but bounded disturbances and sudden topological changes.
Both directed and undirected topologies have been taken into account. It is worth to mention also the extension of the consensus problem to networks of agents governed by a class parabolic partial differential equation, for which, for the first time, a boundary-based robust local interaction protocol has been presented
Power and Dams in Central Asia
Get PDFThe purpose of this research is to analyse and understand the role of state power in transboundary water relations, providing an in–depth analysis of the evolution of interstate relations in Central Asia in the field of water in the period 1991-2011. Taking as a case study the planned construction of the Rogun and Kambarata dams in Tajikistan and Kyrgyzstan, the research looks at the various forms of overt and covert power shaping interstate relations and at the way hegemonic and counter-hegemonic measures are put in place in an international river basin. The overarching hypothesis driving this study is that the intimate correlation between the concepts of power and hegemony can offer key insights to the analysis and understanding of transboundary water relations. While, on the one hand, the analytical focus is placed on state power, on the other hand, hegemonic and counter-hegemonic tactics represent the ways in which power is wielded and observed.
This research makes an original contribution to the literature on hydropolitics in Central Asia, offering fresh theoretical interpretations to the subjects of power and counter-hegemony in the Aral Sea basin and presenting the original “circle of hydro-hegemony”, an analytical framework in which the various forms of power are “connective” in the function of hegemony. A further value is added by three timelines expressly created for the research and that represent, at the time of writing, the most detailed reference-supported collection of events of this kind for the Central Asian region in the period 1991-2011
Enviromental influences on the spatio-temporal distribution of Aristeus Antennatus (Risso, 1816) and Aristaeomorpha Foliacea (Risso, 1827) in the Central-Western Mediterranean
Get PDFAccording to the Food and Agriculture of United Nations, almost 80% of the world fish populations are overexploited, depleted or in a state of collapse. In general the Mediterranean Sea is characterized by the 33% of assessed stocks fully exploited, 50% overexploited and the remaining 17% non-fully exploited. Bottom trawling fleets predominate in many Mediterranean fisheries, being responsible for a high share of total catches and, in many cases, yielding the highest earnings among all the fishing sub-sectors.
The deep-sea fishing began only in the first decades of the last century, as a result of the development of new technologies that made fisheries in deeper waters possible. The main target species of the Mediterranean deep-sea bottom fishery are the red shrimps Aristeus antennatus (Risso, 1816) and Aristaeomorpha foliacea (Risso, 1827), that represent one of the most important commercial species. In general both species coexist in large part of their distribution range, but in the Mediterranean Sea, where the large part of studies have been undertaken, their distribution is patchy and seems to shows an antagonistic longitudinal gradient.
In this context different hypotheses have been formulated by several authors to explain the different distribution observed. Some of them correlated various environmental variables with the presence/absence of these species to explain the spatial distribution and the temporal fluctuations in landings of these two species. All the identified factors seems not to act in synergy in determining the spatio-temporal variation of the species and which is the parameter that has a significant predictive effect is still unclear. Considering the high degree of interaction between marine organisms and the environment, a more holistic approach incorporating interspecific interactions and physical environmental influences would contribute to greater sustainability by reducing the uncertainty in predictions and promoting an ecosystem based management.
In the light of the above, this thesis applies a multi-disciplinary approach to study the dynamic of the Mediterranean deep-water red shrimps. The main purpose of this thesis is to better understand how the abiotic factors could impact on the spatio-temporal distributions of the decapod crustaceans A. antennatus and A. foliacea.
The first part provides information on the abundance and geographical distribution of deep-water red shrimps using 19 years of trawl survey data. Both red shrimps species occur almost exclusively on the “meso-bathyal” stratum (500-800 m). The distribution pattern appears quite different for the two species, and the abundance indexes as well the spatial maps, evidenced local higher abundances (hotspots) where the blue and red shrimp and the giant red shrimp are mainly concentrated. In
general, a very high interannual variability was detected in all areas probably linked with some environmental factors that occurs in Sardinian waters.
In particular the investigation of the hydrographic conditions of the shelf-slope areas, developed in the second part of the thesis, highlight presences of the typical water masses already detected in literature. In our study area the water masses occurring on the continental shelf-slope zones, where the deep water red shrimps are catched, are mainly These water masses overlap and even partially mix each other during their displacement across the Sardinian shelf-slope area according to the general topography of the lands and the bottoms. Results showed that the distribution of the main water masses is comparable to the literature, moreover, the results confirmed that the great variability between basins and year of sampling is clearly associated with waters of very different origin that follow converging routes and mix together in the study area.
The analysis carried out in third part underlined the influence of peculiar areas, such as seamounts, on the structure of the middle-slope assemblages as well as the behavioural rhythms of the deep water red shrimps. Their daily and nocturnal movements from the base of the seamount to the edge of the continental shelf increase the range of their distribution. This results highlights the fact that shrimps and other species in the Baronie seamount, move during a day-night cycle, probably influenced by some parameter indirectly related to their activity. These nektobenthic displacements are known to occur also in the continental shelf and slope, but in the canyon and seamounts they are broadened and can be studied more easily. These displacements could produce a bias in trawl survey data according to the time of day with effects on population assessment and demographic evaluation.
The fourth part of the thesis provided also the identification of the spawning and nursery grounds, and their relationship to major, oceanographic processes The location of the area appears to be correlated with the spatial pattern of the main persistent oceanographic processes, identified in the Sardinia Sea, such as enrichment due the upwelling present in the south west shelf-slope area. Other important areas of aggregation for both juveniles and mature females were found over the bathyal zones in canyon and seamounts environments, where productivity is reported higher than elsewhere. These privileged areas for recruitment, rich in nutrients thanks to the effect of different currents, would seem to guarantee the regeneration of the resource. Finally, the analysis also suggested the existence of a seasonal bathymetric distribution of the nursery areas. The juveniles of A. foliacea are located in the upper part of the continental slope in spring-summer and reach greater depths in autumn. For A. antennatus, for which nursery areas appear only in autumn, an opposite ontogenic migration from deep sea to upper slope, has been noted during the summer.
In the last part of the thesis, the influences of in situ hydrographic variables on the distribution of the Aristeid stocks on the fishing grounds of Sardinia were analysed. The comparison between hydrographic and biological data evidenced that both species seem to be connected to the peculiar features and fate of the LIW (Levantine Intermediate Water) between 400 and 600 m. In fact, in the south-eastern part, the LIW properties predominate and A. foliacea is the main species, while in the western and northern areas of Sardinia the LIW loses intensity in favor of A. antennatus, which prefers colder temperatures. Besides the oceanographic features influencing the distribution pattern of these species, the variation left unexplained by the model may be attributed to different sources of variation such as the presence of geomorphological structures or reproduction and recruitment phenomena.
In conclusion, following a multidisciplinary approach, this thesis tries to give a substantial contribution to the knowledge of the spatio-temporal dynamics of the two Mediterranean deep-water red shrimps. The results highlight how these patterns of distribution strongly correlated not only with the main oceanographic process (LIW properties) but also with local hydrographic conditions. Among these conditions, upwelling events and the particular geomorphology that characterized the Sardinian shelf-slope region seem to be the most important factors. In addition life history traits of these two species linked to a heavy prolonged fisheries exploitation, could determine a masking effect that makes difficult to interpret the whole picture of the distribution of the two species. For this reason, these results should take in to account for the assessment and management of these important resources
Diagnosi molecolare della Distrofia Muscolare di Duchenne e della Neurofibromatosi tipo 1 con la tecnologia di sequenziamento Next Generation
Get PDFDuchenne/Becker muscular dystrophies (DMD/BMD) are the most frequent inherited neuromuscular diseases caused by mutations in the dystrophin gene (DMD). Neurofibromatosis type 1 (NF1), caused by mutations in the neurofibromin gene (NF1), is a multisystem genetic disorder that commonly is associated with cutaneous, neurologic, and orthopedic manifestations. Full characterisation of the mutational spectrum is necessary for genetic counselling, prenatal diagnosis and selecting the patients eligible for future mutation-‐specific treatments. Identification of the DMD and NF1 point mutations, that account for approximately 30% of DMD and 90% of NF1, cannot be achieved easily because these genes are very large and complex, lacking mutational "hot spots". Next Generation Sequencing (NGS) technology is useful for molecular diagnosis of diseases where laborious sequencing efforts are required. The aim of this study was to work out a method to use the high-‐throughput NGS technology in a diagnostic settings for Duchenne/Becker muscular dystrophies and Neurofibromatosis type 1. We studied 17 patients (10 DMD and 7 NF1) using the Ion Torrent PGM NGS platform. The results proved that Ion Torrent NGS is suitable for routine clinical practice, with shorter turnaround time, higher accuracy, and better insight into comprehensive genetic information
Studio del Promoter ATP7B. Ruolo potenziale nella variabilità fenotipica presente nella malattia di Wilson
Get PDFWilson disease (WD) is an autosomal recessive disorder of copper transport, characterized by
decreased copper biliary exrection and reduced copper incorporation into ceruloplasmin. This
results in copper overload and tissue damage. In the last years we have carried out mutation analysis
in approximately 644 unrelated familes of mediterranean origin and identified 175 Wilson disease
causing mutations. One of identified mutations –441_427del, a 15 nt mutation is the only diseasecausing
defect detected in the promoter region of the ATP7B gene. Functional characterization
assays revealed a 75% impairment in the promoter activity as compared to the normal control.
Recently we have identified 8 new rare mutations in the promoter region of the gene detected in cis
with two known promoter polymorphisms. Functional studies were performed with transient
transfection of two cell lines HepG2 and SH-SY5Y and showed that promoter activity was different
in the different analyzed constructs according to haplotype. These data suggest a potential role for
promoter ATP7B gene polymorphisms to copper resistance and phenotypic variability in WD
patients. In this study we propose to clarify the role of ATP7B gene promoter polymorphisms in Cu
resistance using functional characterization assays of promoters carrying different combinations of
detected polymorphisms
Infortuni e malattie nel sottosuolo: prevenzione e assistenza sanitaria nella miniera di Montevecchio (1863 – 1996)
Get PDFStarting from the investigations conducted in the last few years in the field of medicine and welfare, this research has its main aim in identifying and understanding the functions, the role and the internal structure of healthcare camps within Sardinian mining sector., and particularly in the mining site of Montevecchio, through the census of archival sources retrieved in the island’s mining archives.
The tormented sequel of events characterising this mining site have resulted in a conspicuous documentary production later stored in a number of archive groups partitioned amongst various archival institution: the Archivio Storico del Comune di Iglesias (Historical Archive of the Council of Iglesias), the Archivio Documentale della Miniera di Montevecchio (Documentary Archive of Montevecchio Mine) and the Archivio del Distretto Minerario della Sardegna (Archive of the Mining District of Sardinia). The in-depth archival research resulted in the retrieval of 476 units, including fascicules and registries covering the time frame from 1990 to 1991: The first seeach step was that of outlining an analytic data sheet, which would allow the researcher to identify the relevant data for a census of the documents, while a second step consisted in a more detailed analysis of the documentary sources, divided according into two main strands: documents on work-related injuries and documents on industrial disease (“scadenziari” of injuries, court records, patients’ lists, etc.)
For each document another data sheet has been produce in order to describe any data useful for the research. The results have been ‘normalised’ and transcribed in the documentary appendix, resulting into two fairly complete instruments to conduct further research: the first one contains the archival units on work-related injuries and supplies the consultation indexes catalogued and divided within each single mining site; the second one focuses on ‘techno-pathologies’ (pathologies whose origin comes from the typology of job) and, as in the first case, enriched by consultation indexes divided according to the categories of mining sites, industrial diseases, job tasks and names of the workers.
At the same time that the archival research was conducted, a study on the norms regulating the mining sector from 1865 to 1959 has been conducted with the aim of verifying whether any specific norm concerning the prevention of injuries and industrial diseases existed at the time.
Finally, the last phase of the research included the analysis of the documents in light of the main literature on the subject. The situation of the injury paths in Sardinian mining contexts has been traced back with a focus on the years 1880-1970, and particularly on the situation of Montevecchio mine. Regarding the latter, all fatal injuries occurred between 1863 and 1996 have been identified listed.
For what concerns industrial diseases, though a study on the medical literature dealing with heath issues for workers employed in mining sites, a list of pathologies afflicting Montevecchio’s workers form the 1930s to the 1980s has been drafted.
Given the results produced, this research can be considered a paradigm to be used in the future to conduct further studies on base metals mines within broader Italian and international scenarios and, at the same time I t can be intended as a first step towards a clearer definition of the characteristic of mining compartment within Sardinia
Isolamento sociale nel ratto adolescente:differenze di genere nella sensibilità allo stress ed influenza sulla generazione successiva
Get PDFSocial isolation in male rats at weaning results in reduced basal levels of the neuroactive steroid allopregnanolone (AP) in the brain and plasma as well as in increased anxiety-like behavior. Moreover, social isolation induced an enhanced neurosterogenesis in response to acute stressful
stimuli and impairs negative feedback regulation of HPA axis.
Socially isolated female rats also manifest a reduced basal cerebrocortical concentration of AP as well as an anxiety-like profile in the elevated plus-maze and Vogel’s conflict tests compared with group-housed controls. At variance, socially isolated female showed less sensitivity the acute stress induced by foot-shock: there was no significant change in the plasma and brain concentration of AP, and an attenuation of corticosterone release. The basal level of corticotrophin releasing factor (CRF) was not changed by social isolation, however, we found that the CRF receptor type 1 in the pituitary was significantly decreased compared to group-housed. Immunoblot analysis revealed that
hippocampal abundance of glucocorticoid receptors was significantly higher in the socially isolated female rats; on the contrary, social isolation significantly decreased mineralocorticoid receptors in the same brain area. The effect of social isolation was also evaluated in the neuroendocrine profile during pregnancy and in the quality of maternal care. The pattern of plasmatic variations of
17b-estradiol, oxytocin and vasopressin was not different in the two groups of rats. The analysis of maternal behavior revealed that socially isolated dams displayed less arched-back nursing than control across all day of the observation period.
Despite the fact that they were raised under normal conditions, adult male offspring of male and female rats subjected to social isolation before mating exhibited an increased basal cerebrocortical level of AP. These animals also showed a blunted corticosterone release induced by foot-shock stress compared to group-housed offspring. Moreover, the exposure to a chronic stress (social
isolation) failed to decrease plasma AP levels in socially isolated offspring.
The results indicate that there are same sex differences in the effect of social isolation and that
offspring of socially isolated parents can be classified as a resilient.