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Sintesi, studi SAR e valutazione biologica di nuove molecole a piattaforma naftiridinica quali inibitori dell'enzima fosfodiesterasi 10A
No full textPhosphodiesterase 10A (PDE10A) is a basal ganglia specific hydrolase, which plays an essential role in regulating cAMP/PKA and cGMP/PKG signalling cascades.
PDE10A is a relatively newly identified phosphodiesterase. In the brain, the enzyme is predominantly expressed in medium spiny neurons of the striatum, making it an interesting target for the treatment of central nervous system disorders associated to dysfunction in the basal ganglia circuit.
Recently, a series of pyrazolo-quinazolines and pyrazolo-naphthyridines with good IC50 values and high selectivity against other PDE isoforms has been developed. In this context, we have realized a new series of 1,6-naphthyridines, 2,6-naphthyridines, 2,7-naphthyridines and 1,7-naphtyridines, with various substitutions, as new potential inhibitors of Phosphodiesterase 10A.
Among them, 18Ac showed the highest affinity for PDE10A (IC50: 24 nM)
Comparative studies of ecological niche variation among central and peripheral populations of Mediterranean endemic plants
No full textThe Mediterranean basin is a biodiversity hotspot, characterized by its high plant richness and endemism. It is a place of prime interest to test biogeographical hypotheses, such as the centre-periphery hypothesis. Empirical evidences have brought little support to it as a rule, suggesting complex eco-evolutionary mechanisms shape genetic and demographic characteristics. This thesis proposes a new framework that supports a precise evaluation of species history, geography and ecology to investigate genetic and demographic variation. In this perspective, we set up a study of 11 Mediterranean vascular plants to investigate changes in the micro-ecological niche between central and peripheral populations. Several shifts appeared which emphasized the ecological originality of peripheral population. Peripheral populations subsist in cooler and wetter climate compared to their mean central relatives, but are not marginal regarding their climatic niche. Several species presented similar distribution patterns on restricted areas in France, which may result from their persistence in micro-refugia during Pleistocene glaciations. This historical perspective was fundamental to explain patterns of floral polymorphism in Narcissus dubius. Spatial isolation and ecological originality confer to peripheral isolates a high evolutionary potential, and understanding fine scale ecological characteristics and distribution history is essential to shed light on processes driving plant diversity
Variazione della prevalenza dell'infezione da H. pylori e ulcera peptica in pazienti dispeptici sardi
No full textBackground: Over the past 50 years the prevalence Helicobacter pylori infection has fallen as standards of living improved. The changes in the prevalence of infection and it manifestations (peptic ulcer disease and intestinal metaplasia) in a large cohort of Sardinians undergoing upper endoscopy for dyspepsia were investigated.
Aim: To analyze the prevalence trend of H. pylori infection and peptic ulcer disease in patients that underwent upper endoscopy for dyspeptic symptoms during the period when the prevalence of H. pylori was rapidly falling.
Methods: : A retrospective observational study was conducted involving patients undergoing endoscopy for dyspepsia from 1995 up to 2013. H. pylori status was assessed by histology, rapid urease test, and/or 13C-UBT. Gastric atrophy was assessed histologically.
Data including non steroidal anti-inflammatory drugs (NSAIDs) use and the presence of peptic ulcers were collected. The prevalence of H. pylori was calculated for each quartile and for each birth cohort from 1910 to 2000.
Results: 11,202 records were retrieved for the analysis (62.8% women). The overall prevalence of H. pylori infection was 43.8% (M: 46.6% vs. F: 42.0%; P = .0001). A dramatic decrease in prevalence infection occurred over the 19 year observation period. The birth cohort effect was evident in each category (quartile) reflecting the continuous decline in H. pylori acquisition. Over time the prevalence of ulcers also declined resulting in an increase in the proportion of H. pylori negative/NSAID positive and H. pylori negative/NSAID negative ulcers. The prevalence of atrophic changes also declined despite aging.
Conclusions: The decline in H. pylori prevalence over time likely reflects the improvement in socioeconomic conditions in Sardinia such that H. pylori infection and its clinical outcomes including peptic ulcer is becoming less frequent even among dyspeptic patients
Stress ossidativo e patologie neurodegenerative: ruolo protettivo di antiossidanti naturali e di sintesi su modelli cellulari
No full textAim: Oxidative stress plays pivotal role in neurodegeneration. An imbalance between antioxidants levels and reactive oxygen species (ROS) production leads to cell damage, particularly in the brain where cells are especially susceptible to oxidative stress. Nowadays, lots of natural and synthetic antioxidant products have been tested for their neuroprotective activities. In this work we tested antioxidant properties of natural and synthetic compounds on two different models of induced-oxidative stress.
Methods: Oxidative stress were induced on PC12 cell line by L-DOPA/MnCl2 or H2O2 treatment. Cell viability (MTT-assay; TrypanBlue assay) was evaluated to compare the antioxidant activity of the natural 4-4’dihydroxybiphenyl with its more hydrophilic synthetic analogue AD838. Cell viability (MTT-assay; TrypanBlue; LDH-assays), ROS levels (dichlorfluorescein; GSH-assay) and apoptosis (flow-cytometry analysis) were assessed to study the neuroprotective properties of the synthetic AD838 and the nanostructured cerium oxide (nanoceria).
Results: When PC12 cells were pretreated with nanoceria, their viability after L-DOPA/MnCl2 injury raised of 15%. Flow-cytometry indicated that nanoceria reduced the apoptosis ratio of cells insulted by MnCl2. The viability of PC12 cells pretreated with AD838 before exposure to H2O2 was increased of 20%.The preliminary results suggest that its antioxidant activity seemed to be higher than its natural precursor. Moreover, AD838 pretreatment significantly attenuated H2O2-induced apoptotic cell accumulation of 15% and decreased GSH overproduction of 26%.
Conclusion: Each compound showed a different antioxidant activity in response to the several used oxidative models. In particular, cerium oxide proved effective on MnCl2/L-DOPA model in PC12 cells. The AD838 compound showed its antioxidant and protective role on H2O2 –induced oxidative stress even more than its structural precursor 4-4’-dihydroxybiphenyl
Studio di metalli pesanti in pazienti affetti da sclerosi laterale amiotrofica ed analisi delle correlazioni cliniche
No full textIn this work, a population-based case-control study on possible associations between human exposure to toxic metals and sporadic amyotrophic lateral sclerosis (ALS) was conducted. Following informed consensus, ALS patients were enrolled from different Care Centers of Sardinia, an Italian region characterized by elevated rates of ALS cases and significant history of mining activities. Aluminium, Cd, Hg, Mn and Pb concentrations were determined in blood, hair and urine by ICP-MS in 34 ALS patients (mean age, 62 ± 10 years, male/female ratio 1.6) and 30 controls (mean age, 65 ± 11 years; male/female ratio 1.5). Taking into account blood samples, concentrations of Al (p=0.045) and Pb (p=0.026) were higher in ALS patients than in control. In hair of ALS patients, a significant depletion of Al (p=0.006) and Mn (p=0.032) respect to controls was found. In contrast, there were not significant differences between cases and controls in urine samples. As well, cases and controls showed no differences in Hg patterns; however, ALS patients showed strong correlations among Hg levels in blood, urine and hair, while controls did not. In addition, metal-metal correlations were investigated, showing that Cd, Hg and Pb display synergic pattern, differently from Al and Mn (antagonistic pattern). In conclusion, even if a direct ALS-metals causative relationship cannot be established, this study suggests that some metals could be involved in the ALS pathology depending on environmental exposures to toxicants, as well as on internal degenerative process and metal-gene interactions
A Lattice dynamics study of ZK-4 microporous material under different temperature and pressure conditions
No full textThe stability of zeolites is essential for their wide range of applications. Many experimental and theoretical studies have been focused on the stability of zeolites upon both high temperature and pressure conditions. The main objective of the present research was to compare the behavior of zeolite ZK-4 (with a LTA framework type) under a wide range of temperature and pressure conditions. Lattice Dynamics calculations were performed using the software package GULP. We have obtained the unit cell parameters, angles, bond distances and characteristic vibrational properties of zeolite ZK-4 in the range of 0 ≤ P ≤ 6 GPa and 0 ≤ T ≤ 1200 K. The unit cell volume decreased with a temperature increased as an evidence of a Negative Thermal Expansion process. The computational results suggested the strong structural disorder due to the application of the external pressure. Major distortions were present in T–O–T angles, followed by O–T–O angles and T–O distances. In general, comparative analysis based on our results shows that the effect of external pressure is more striking than that of temperature. Elastic constants and bulk moduli for heated and pressurized structures were obtained
Perspective and potential of CO<sub>2</sub>: a focus on potentials for renewable energy conversion in the Mediterranean basin
No full textFigures commonly quoted on the soon shortage of generating energy from fossil sources which may give the impression that it will be possible to switch to renewable energies conversion as foundations for the future of industrial instances in the Mediterranean basin. In this study, CO2 energy potential and perspectives in the Mediterranean basin have been investigated in terms of efficiency, feasibility, geographical patterns and savings. Two conjoint mathematical protocols have been carried out in order to yield a simplified extracted scheme for prototype CO2 trapping/storage plants
Nuove prospettive di previsione e di controllo delle infestazioni e del danno di <i>Lymantria dispar</i> (L.) in Sardegna
No full textIn Sardinia (Italy) gypsy moth population density has been regularly evaluated through a monitoring network over thirty years based on egg masses counting at permanent sites. This activity allows to identify annually areas with the highest infestation density in order to define sites to be subjected to phytosanitary treatments.
To give an indication on the potential use of different microbiological products two years of efficacy trials with different Bacillus thuringiensis serovar kurstaki formulations were carried out in period 2012-2013. Tested formulations proved to be as effective as the reference products Foray 48B and Delfin in controlling L. dispar populations.
Historical series data on gypsy moth over-year-density were analyzed following two different study approaches. The first was based on a generalized linear model adopted to evaluate the statistical significance of the relationship between percentage of occupied sites and presence of damage. The results confirmed the validity of this method for an easier identification of forest areas exposed to damage in progradiation phase. In the second case, the use of incidence function model and other statistical approaches were investigated. Although the complexity in modelling L. dispar dynamics, results were promising for their use in defining the specific metapopulation dynamics pattern at forest district level
When the past makes news: cultivating media relations through brand heritage
No full textThe paper deals with heritage branding, investigating communication and PR models promoted by historical companies representing Made in Italy in the global market, in order to focus on their distinctive approach to media relations strategies and related practices. The study has adopted a multi-method approach, involving a panel of companies in the food & beverage sector. In-depth interviews from PR professionals highlight the potential of heritage branding to develop an authentic form of storytelling, based on quality branded contents and the strategic management of corporate history, thus cultivating long-standing relationships with the media
Serum BAFF levels, methypredsinolone therapy, Epstein-Barr virus and <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> infection in Multiple Sclerosis patients
No full textElevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies
paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease