PROGETTO DI UN PARCHEGGIO MULTIPIANO INTERRATO A CATANZARO

La presente Tesi di Laurea ha avuto come obiettivo il progetto di un parcheggio multipiano interrato da realizzare nella città di Catanzaro. L’area d’intervento particolarmente complessa dal punto di vista morfologico – la struttura dovrà sorgere su una pendice fortemente acclive - ha imposto al Comune lo studio sulla fattibilità dell’opera. Tale studio, dall’esito positivo, ha rappresentato il punto di partenza per le successive fasi di programmazione e progettazione dell’opera. In prima analisi è stato redatto il Documento preliminare all’avvio della progettazione (Dpp), introdotto dalla più recente normativa in materia di Lavori pubblici, con lo scopo di dare una corretta risposta alle esigenze del committente – utilizzatore. Il Dpp ha fornito le linee guida della successiva fase di progettazione. In questa fase sono stati sviluppati gli aspetti architettonici e strutturali dell’opera tenendo in debito conto la qualità dei materiali impiegati. Molta importanza è stata data all’aspetto della sicurezza antincendio e a quello dell’accessibilità. Lo studio svolto ha riguardato anche i collegamenti in superficie delle vie di entrata e di uscita con la viabilità esistente e la distribuzione sia degli stalli che dei servizi nei piani di parcamento. In ultima analisi sono state calcolate le strutture destinate ai piani di parcamento, strutturalmente indipendenti dal corpo centrale, destinato invece alle rampe e ai collegamenti verticali. Per tali strutture si è scelta una soluzione di tipo composto in acciaio-calcestruzzo che ha mostrato una buona risposta all’azione sismica. Il calcolo ha inoltre richiesto l’osservanza di norme specifiche per le strutture miste e la consultazione di pubblicazioni specialistiche

Genetic variants associated with gastrointestinal symptoms in Fabry disease.

Gastrointestinal symptoms (GIS) are often among the earliest presenting events in Fabry disease (FD), an X-linked lysosomal disorder caused by the deficiency of α-galactosidase A. Despite recent advances in clinical and molecular characterization of FD, the pathophysiology of the GIS is still poorly understood. To shed light either on differential clinical presentation or on intervariability of GIS in FD, we genotyped 1936 genetic markers across 231 genes that encode for drug-metabolizing enzymes and drug transport proteins in 49 FD patients, using the DMET Plus platform. All nine single nucleotide polymorphisms (SNPs) mapped within four genes showed statistically significant differences in genotype frequencies between FD patients who experienced GIS and patients without GIS: ABCB11 (odd ratio (OR) = 18.07, P = 0,0019; OR = 8.21, P = 0,0083; OR=8.21, P = 0,0083; OR = 8.21, P = 0,0083),SLCO1B1 (OR = 9.23, P = 0,0065; OR = 5.08, P = 0,0289; OR = 8.21, P = 0,0083), NR1I3 (OR = 5.40, P = 0,0191) and ABCC5 (OR = 14.44, P = 0,0060). This is the first study that investigates the relationships between genetic heterogeneity in drug absorption, distribution, metabolism and excretion (ADME) related genes and GIS in FD. Our findings provide a novel genetic variant framework which warrants further investigation for precision medicine in FD

Successful management of neonatal renal venous thrombosis

Renal vein thrombosis is the most common vascular condition involving the newborn kidney and it can result in severe renal damage. We report a newborn with renal vein thrombosis treated with continuous infusion of unfractionated heparin who had normal total renal function after 3 years of follow up, despite reduction of the functional contribution of the affected kidney

Unraveling the Mechanistic Complexity of the Glomerulocystic Phenotype in Dicer Conditional KO Mice by 2D Gel Electrophoresis Coupled Mass Spectrometry

Purpose: Dicer, an RNase III type endonuclease, is a key enzyme involved in miRNA biogenesis. It has been shown that this enzyme is essential for several aspects of postnatal kidney functions and homeostasis. In this study, we have examined conditional knockout (cKO) mice for Dicer in Pax8 (Paired-box gene 8) expressing cells to investigate the kidney protein profile. This specific model develops a glomerulocystic phenotype coupled with urinary concentration impairment, proteinuria, and severe renal failure. Experimental design: Proteomic analysis was performed on kidney tissue extracts from cKO and control (Ctr) mice by 2D Gel Electrophoresis coupled with mass spectrometry. Results: The analysis highlighted 120 protein spots differentially expressed in Dicer cKO tissue compared with control; some of these proteins were validated by Western blotting. Ingenuity Pathway Analysis led to the identification of some interesting networks; among them, the one having ERK as a central hub may explain, through the modulation of the expression of a number of identified protein targets, the metabolic and structural alterations occurring during kidney cyst development in Dicer cKO mouse model. Conclusions and clinical relevance: Our results contribute to gain new insights into molecular mechanisms through which Dicer endonuclease controls kidney development and physiological functions

Proteomics Analysis to Assess the Role of Mitochondria in BRCA1-Mediated Breast Tumorigenesis

Mitochondria are the organelles deputed to energy production, but they are also involved in carcinogenesis, cancer progression, and metastasis, playing a role in altered energy metabolism in cancer cells. Mitochondrial metabolism is connected with several mitochondrial pathways such as ROS signaling, Ca2+ homeostasis, mitophagy, and mitochondrial biogenesis. These pathways are merged in an interactive super-network that seems to play a crucial role in cancer. Germline mutations of the BRCA1 gene account for 5–10% of breast cancers and confer a risk of developing the disease 10- to 20-fold much higher than in non-carriers. By considering metabolic networks that could reconcile both genetic and non-genetic causal mechanisms in BRCA1 driven tumorigenesis, we herein based our study on the hypothesis that BRCA1 haploinsufficiency might drive metabolic rewiring in breast epithelial cells, acting as a push toward malignant transformation. Using 2D-DIGE we analyzed and compared the mitochondrial proteomic profile of sporadic breast cancer cell line (MCF7) and BRCA1 mutated breast cancer cell line (HCC1937). Image analysis was carried out with Decider Software, and proteins differentially expressed were identified by LC-MS/MS on a quadrupole-orbitrap mass spectrometer Q-Exactive. Ingenuity pathways analysis software was used to analyze the fifty-three mitochondrial proteins whose expression resulted significantly altered in response to BRCA1 mutation status. Mitochondrial Dysfunction and oxidative phosphorylation, and energy production and nucleic acid metabolism were, respectively, the canonical pathway and the molecular function mainly affected. Western blotting analysis was done to validate the expression and the peculiar mitochondrial compartmentalization of specific proteins such us HSP60 and HIF-1α. Particularly intriguing is the correlation between BRCA1 mutation status and HIF-1α localization into the mitochondria in a BRCA1 dependent manner. Data obtained led us to hypothesize an interesting connection between BRCA1 and mitochondria pathways, capable to trigger metabolic changes, which, in turn, sustain the high energetic and anabolic requirements of the malignant phenotype

Proteomics-Driven Analysis of Ovine Whey Colostrum

The aim of this study was to shed light in to the complexity of the ovine colostrum proteome, with a specific focus on the low abundance proteins. The ovine colostrum is characterized by a few dominating proteins, as the immunoglobulins, but it also contains less represented protein species, equally important for the correct development of neonates. Ovine colostrum, collected immediately after lambing, was separated by 1D SDS-PAGE. Proteins bands were digested with trypsin and the resulting peptides were analyzed by LC-MS/MS. On the basis of the Swiss-Prot database, a total of 343 unique proteins were identified. To our knowledge, this study represents the most comprehensive analysis of ovine colostrum proteome

Urine Bikunin as a Marker of Renal Impairment in Fabry's Disease

Fabry’s disease is a rare lysosomal storage disorder caused by the deficiency of α-galactosidase A that leads to the accumulation of neutral glycosphingolipids in many organs including kidney, heart, and brain. Since end-stage renal disease represents a major complication of this pathology, the aim of the present work was to evaluate if urinary proteoglycan/glycosaminoglycan excretion could represent a useful marker for monitoring kidney function in these patients at high risk. Quali-quantitative and structural analyses were conducted on plasma and urine from 24 Fabry’s patients and 43 control subjects. Patients were sorted for presence and degree of renal impairment (proteinuria/renal damage). Results showed that levels of urine bikunin, also known as urinary trypsin inhibitor (UTI), are significantly higher in patients with renal impairment than in controls. In this respect, no differences were evidenced in plasma chondroitin sulfate isomers level/structure indicating a likely direct kidney involvement. Noteworthy, urine bikunin levels are higher in patients since early symptoms of renal impairment occur (proteinuria). Overall, our findings suggest that urine bikunin level, as well as proteinuria, could represent a useful parameter for monitoring renal function in those patients that do not present any symptoms of renal insufficiency

Co-inheritance of G6PD and PK deficiencies in a neonate carrying a Novel UGT1A1 genotype associated to Crigler-Najjar type II syndrome

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