Thyroid Cancer Resistance to Chemotherapeutic Drugs via Autocrine Production of Interleukin-4 and Interleukin-10

We investigated the mechanisms responsible for the widespread refractoriness to chemotherapeutic drugs observed in thyroid cancers. We show that malignant epithelial cells from papillary, follicular, and anaplastic thyroid carcinomas express high levels of Bcl-2 and Bcl-xL. Exogenous expression of either Bcl-2 or Bcl-xL in normal thyrocytes was sufficient to prevent chemotherapeutic drug-induced cytotoxicity. All of the histological thyroid cancer variants examined produced interleukin-4 (IL-4) and interleukin-10 (IL-10), which increased Bcl-2 and Bcl-xL levels and protected thyroid cells from chemotherapeutic agents. Exposure to neutralizing antibodies against IL-4 and IL-10 resulted in do…

Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study

It is estimated that one-third of the world’s population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcomeviadietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with c…

Is BRCA1-5083del19, identified in breast cancer patients of Sicilian origin, a Calabrian founder mutation?

Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these fa…

Automated untargeted stable isotope assisted lipidomics of liver cells on high glucose shows alteration of sphingolipid kinetics

Abstract Untargeted lipidomics is a powerful tool to discover new biomarkers and to understand the physiology and pathology of lipids. The use of stable isotopes as tracers to investigate the kinetics of lipids is another tool able to supply dynamic information on lipid synthesis and catabolism. Coupling the two methodology is then very appealing in the study of lipid metabolism. The main issue to face is to perform thousands of calculations in order to obtain kinetic parameters starting from the MS raw data. An automated computerized routine able to do accomplish such task is presented in this paper. We analyzed the lipid kinetics of palmitic acid (PA) in hepatoma liver cells cultured in v…

Characterization of Gut Microbiota Composition in Type 2 Diabetes Patients: A Population-Based Study.

(1) Background: A clinical laboratory index to assess gut dysbiosis is the F/B ratio < 0.8. In fact, an elevated proportion of Firmicutes and a reduced population of Bacteroides in diabetes type 2 (T2D) subjects has been observed. This study aimed to detail the dysbiosis status in the Italian population, focusing on some pathogenic spectra (T2D) or metabolic disorders. (2) Material and methods: A quantity of 334 fecal samples was analyzed in order to perform genetic testing and sequencing. (3) Results: A trend in over imbalance was observed in the percentage of Proteobacteria (median value: 6.75%; interquartile range (IQR): 3.57–17.29%). A statistically significant association (&ch…

Antioxidant activities of sicilian prickly pear (Opuntia ficus indica) fruit extracts and reducing properties of its betalains: betanin and indicaxanthin.

Sicilian cultivars of prickly pear (Opuntia ficus indica) produce yellow, red, and white fruits, due to the combination of two betalain pigments, the purple-red betanin and the yellow-orange indicaxanthin. The betalain distribution in the three cultivars and the antioxidant activities of methanolic extracts from edible pulp were investigated. In addition, the reducing capacity of purified betanin and indicaxanthin was measured. According to a spectrophotometric analysis, the yellow cultivar exhibited the highest amount of betalains, followed by the red and white ones. Indicaxanthin accounted for about 99% of betalains in the white fruit, while the ratio of betanin to indicaxanthin varied fr…

Occurrence of illicit drugs in two wastewater treatment plants in the South of Italy

In this study the occurrence and the behavior of illicit drugs and their metabolites have been investigated for two wastewater treatment plants (WWTPs) (namely, WWTP-1 and WWTP-2) located in Sicily (island of Italy). Samples were analyzed for methamphetamine, cocaine (COC), 3,4-methylenedioxymethamphetamine (MDMA), methadone (METH), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), 3,4-methylenedioxy amphetamine (MDA); 3,4-methylenedioxy ethylamphetamine (MDEA), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) and Benzoylecgonine (BEG). The BEG, COC, MOR and THC-COOH were found at the highest concentration in both WWTPs. The Wastewater-based epidemiology calculation for BEG, COC…

BRCA1/2 variants of uncertain clinical significance in patients with famlial and hereditary breast/ovarian cancer

OMEGA 3 FATTY ACIDS LEVEL: REDUCTION RISK OF SUDDEN DEATH FROM MYOCARDIAL INFARCTION

Determinazione degli elementi in tracce negli alimenti per celiaci tramite ICP-MS

Epstein-Barr virus infection as a trigger of autoimmune hepatitis: Case report

Abstract: The study underlines the importance of the differential diagnosis between primary Epstein- Barr virus EBV associated hepatitis with features of autoimmunity, in which there is a direct pathogenetic role of the virus, and EBV related autoimmune hepatitis, in which EBV could act as the trigger of the immune-mediated damage with probable differences between the two conditions with regard to the prognosis and the responsiveness to immunosuppressive treatment. Moreover we hypothesise that the favourable outcome in our patient, better than the most of autoimmune hepatitis cases, may be related either to the moderate necroinflammatory activity and to the low level of fibrosis at the begi…

Mucoadhesive Solid Lipid Microparticles (SLM) for sustained release of corticosteroids to the lungs

Pulmonary delivery is the preferred route of drug administration in the treatment of many respiratory disease, such as asthma and chronic obstructive pulmonary disease (COPD). Over the years, several kinds of carriers have been studied for sustained release of corticosteroids and bronchodilators to the lungs. Solid Lipid Microparticles (SLM) due to their biocompatibility and size (3-5 µm) can reach the bronchial epithelium directly, circumvent first pass metabolism and avoid systemic toxicity [1,2]. In this work we describe the preparation and the characterization of two different systems subjected to chitosan and alginate coating for sustained release of fluticasone propionate (FP) into th…

High Levels of Exogenous C2-Ceramide Promote Morphological and Biochemical Evidences of Necrotic Features in Thyroid Follicular Cells

CD95 and ceramide are known to be involved in the apoptotic mechanism. The triggering of CD95 induces a cascade of metabolic events that progressively and dramatically modifies the cell shape by intense membrane blebbing, leading to apoptotic bodies production. Although the CD95 pathway has been abundantly described in normal thyrocytes, the effects of cell permeable synthetic ceramide at morphological and biochemical levels are not fully known. In the present study, we show that thyroid follicular cells (TFC) exposed to 20 μM of C2-ceramide for 4 h are characterized by morphological features of necrosis, such as electron-lucent cytoplasm, mitochondrial swelling, and loss of plasma membrane…

Analysis of TP53, Ki-Ras and P16INK4A promoter methylation as potential prognostic factors in patients with colorectal cancer

Consumo abituale di pesce, funzione endoteliale e concentrazioni ematiche di metalli pesanti

Islet Beta-Cell Apoptosis Triggered in Vivo by Interleukin-1 Is Not Related to the Inducible Nitric Oxide Synthase Pathway: Evidence for Mitochondrial Function Impairment and Lipoperoxidation

Mass spectrometry of surfactant aggregates.

In contrast with the enormous amount of literature produced during many decades in the field of surfactant aggregation in liquid, liquid crystalline and solid phases, only a few investigations concerning surfactant self-assembling in the gas phase as charged aggregates have been carried out until now. This lack of interest is disappointing in view of the remarkable theoretical and practical importance of the inherent knowledge. The absence of surfactant–solvent interactions makes it easier to study the role of surfactant–surfactant forces in determining their peculiar self-assembling features as well as the ability of these assemblies to incorporate selected solubilizate molecules. Thus, t…

Changes in brain natriuretic peptide levels and bioelectrical impedance measurements after treatment with high-dose furosemide and hypertonic saline solution versus high-dose furosemide alone in refractory congestive heart failure: a double-blind study.

OBJECTIVES: The aim of this study was to evaluate the effect of a new treatment for refractory congestive heart failure (CHF) on brain natriuretic peptide (BNP) plasma levels and hydration station. BACKGROUND: The study was aimed at evaluating the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) in refractory CHF patients. METHODS: A total of 94 patients (34 women/60 men) with refractory CHF (age 55 to 80 years) were enrolled. They had to have an ejection fraction <35%, serum creatinine <2 mg/dl, blood urea nitrogen <60 mg/dl, a reduced urinary volume, and a low natriuresis (<500 ml/24 h and <60 mEq/24 h, respectively). Pati…

Transplacental permeability of heavy metals in relation to newborn sex - evidence from the neurodevelopment project

Introduction: Gender medicine is an innovative medical approach that studies how some biological variables are influenced by the male or female sex and gender. This issue is under debate because it characterizes the impact of tailored or individual medicine. In this scenario, the aim of this study is to study the correlation between heavy metal exposure and pathologies of neurodevelopment, according to the sex of newborns. In particular, this is an observational study under the name of the Neurosviluppo Project, involving 217 mother-child couples. Material and methods: The correlation with phenotype small for gestational age and congenital malformations were studied, but above all we focuse…

Micromaterials lipid-based for topic release of fluticasone propionate for the COPD treatment

Blood metal levels after minimally invasive repair of pectus excavatum

Abstract   OBJECTIVES Minimally invasive repair of pectus excavatum (MIRPE) is the most popular surgical approach for paediatric patients with pectus excavatum. A substernal stainless still bar is inserted and left in place for 3 years and then removed. Our goal was to investigate blood metal levels after MIRPE and to correlate them with surgical details, such as the numbers of bars and stabilizers and the length of time the bar was in place. METHODS Blood levels of iron, chromium, manganese, molybdenum and nickel were analysed in 130 teenagers (108 boys and 22 girls) who had MIRPE using inductively coupled plasma mass spectrometry. A total of 62 patients were operated on using MIRPE (study…

Implementation of quality system in the biomedical laboratories

SCOPE To study and to diffuse the better strategies for the planning and the validation of inner methods that assure the significance of the analytical data INTRODUCTION Today the ISO/IEC 17025 and the ISO 15189 are sure the better methodologies and internationally recognized in order to assure in the biomedical laboratories the appropriatness of the methods and the quality of the analytical data The ISO/IEC 17025 standard specifies the general requirements a laboratory has to met if it is to be recognized as competent to carry out tests and/or calibrations, including sampling. METHODOLOGY AND RESULTS The planning of an inner method can be constituted from following is made: Recognition of …

Anti-inflammatory and antioxidant activity of polyphenolic extracts from Lactuca sativa (var. Maravilla de Verano ) under different farming methods

BACKGROUND Besides their nutritional value, vegetables are a source of health-promoting compounds, such as polyphenols, and their content can be influenced by the particular farming method. In this study polyphenolic extracts from Lactuca sativa (var. Maravilla de verano) plants cultivated with different farming methods were chemically characterised and tested in vitro and ex vivo inflammation models. RESULTS The tested extacts (250–2.5 µg mL−1) were able to reduce both the inflammatory and oxidative stress in LPS-stimulated J774A.1 murine monocyte macrophage cells, by lowering the release of nitric oxide (NO) and reactive oxygen species (ROS) and promoting nuclear translocation of nuclear …

LIPIDOMICS OF HUMAN SKIN FIBROBLASTS IN NEIMANN-PICK DISEASE TYPE C

Neimann-Pick Disease type C is a hereditary lysosomal storage disease due to mutations of the NPC1 or NPC2 genes. The products of these genes encodes for components of a lysosomal machinery that transport different kinds of lipids across the lysosomal membrane. The main abnormalities of NPC1 de ciency phenotype is the accumulation of free cholesterol (FC) and sphingolipids (GL) in brain, liver and other organs cells. Neurodegeneration and hepato-splenomegaly are common ndings. The NPC disease, in his severe onset, leads to a precocious exitus, though the inhibition of glyco-SL synthesis by miglustat has shown some clinical bene t. Recently the physiopathological mechanism has been partly el…

LA GESTIONE DELLE VERIFICHE ANALITICHE PER IL CONTROLLO DEGLI ALIMENTI ASPETTI NORMATIVI, CRITERI DI QUALITA', CONTROLLO DI PROCESSO, ANALISI ALIMENTARE

Ricerche finalizzate al recupero e alla conservazione del germoplasma della vite sulle Madonie (Sicilia settentrionale)

Biocompatible Lipid Nanoparticles as Carriers to Improve Curcumin Efficacy in Ovarian Cancer Treatment

Curcumin is a natural molecule with proved anticancer efficacy on several human cancer cell lines. However, its clinical application has been limited due to its poor bioavailability. Nanocarrier-based drug delivery approaches could make curcumin dispersible in aqueous media, thus overtaking the limits of its low solubility. The aim of this study was to increase the bioavailability and the antitumoral activity of curcumin, by entrapping it into nanostructured lipid carriers (NLCs). For this purpose here we describe the preparation and characterization of three kinds of curcumin-loaded NLCs. The nanosystems allowed the achievement of a controlled release of curcumin, the amounts of curcumin r…

GENOTYPE ANALYSIS OF COLORECTAL CARCINOMAS THROUGH LASER PRESSURE CATAPULTING (LPC)

ABITUDINI AL FUMO E ALL’ ALCOOL E DISTURBI ALIMENTARI DEGLI STUDENTI DI UNA SCUOLA MEDIA E DI UNA SCUOLA SUPERIORE SICILIANA CAMPIONE DI BAGHERIA

La metodica wastewater based epidemiology come proxy di quantificazione del consumo di sostanze stupefacenti nella popolazione: l’esperienza della città di Palermo.

INTRODUZIONE Le istituzioni europee e la comunità scientifica hanno, recentemente, definito un nuovo modello di sorveglianza attiva della potenziale diffusione delle droghe nella collettività, la Wastewater Based Epidemiology (WBE), attraverso la ricerca analitica delle molecole e dei loro metaboliti nelle acque reflue cittadine. Lo scopo di questo lavoro è stato la valutazione di una preliminare applicazione di METODIca WBE nella città di Palermo, poco studiata in precedenti analisi a livello nazionale e internazionale. METODI Sono stati prelevati 28 campioni (2 litri cad) di refluo medio delle 24 ore in ingresso ai due depuratori di Palermo (WP1=45.000 ab. eq.; WP2=330.000 ab. eq.) in un …

BISPHOSPHONATES SENSITIZE OSTEOSARCOMA CELLS TO CHEMOTHERAPEUTIC DRUGS

BRCA 1/2 GENES MUTATIONAL SCREENING IN SICILIAN BREAST AND/OR OVARIAN CANCER FAMILIES

III-Po/35) The role of the left choleic artery in the rectum anterious resection with colo-anal anastomosis: technique and considerations of anastomosis oxigenation through nitric oxide valutation.

Vitamin D Deficiency in Cushing’s Disease: Before and After Its Supplementation

Background: The primary objective of the study was to assess serum 25-hydroxyvitamin D [25(OH)D] values in patients with Cushing’s disease (CD), compared to controls. The secondary objective was to assess the response to a load of 150,000 U of cholecalciferol. Methods: In 50 patients with active CD and 48 controls, we evaluated the anthropometric and biochemical parameters, including insulin sensitivity estimation by the homeostatic model of insulin resistance, Matsuda Index and oral disposition index at baseline and in patients with CD also after 6 weeks of cholecalciferol supplementation. Results: At baseline, patients with CD showed a higher frequency of hypovitaminosis deficiency (p = 0…

The Clinical Significance of Unknown Sequence Variants in BRCA Genes.

Abstract: Germline mutations in BRCA1/2 genes are responsible for a large proportion of hereditary breast and/or ovarian cancers. Many highly penetrant predisposition alleles have been identified and include frameshift or nonsense mutations that lead to the translation of a truncated protein. Other alleles contain missense mutations, which result in amino acid substitution and intronic variants with splicing effect. The discovery of variants of uncertain/unclassified significance (VUS) is a result that can complicate rather than improve the risk assessment process. VUSs are mainly missense mutations, but also include a number of intronic variants and in-frame deletions and insertions. Over …

Islet beta-cell apoptosis triggered in vivo by interleukin-1beta is not related to the inducible nitric oxide synthase pathway: evidence for mitochondrial function impairment and lipoperoxidation.

IL-1beta is recognized as an effector cytokine contributing to islet beta-cell destruction during diabetes. We have previously shown in vitro that IL-1beta induces nitric oxide (NO) and beta-cell damage. Here, we show that IL-1beta administration in vivo to Wistar rats transiently increases manganese superoxide dismutase activity, whereas inducible NO synthase is not detected, and the levels of nitrate+nitrate do not change. Moreover, a significant decrease of mitochondrial aconitase, leading to a rise of hydroperoxides, and islet beta-cell apoptosis, involving caspase-3 and -8, is observed. Analysis of adhesion molecules in beta-cells showed that intercellular adhesion molecule-1 is highly…

BRCA 1/2 VARIANTS OF UNCERTAIN CLINICAL SIGNIFICANCE IN PATIENTS WITH FAMILIAL AND HEREDITARY BREAST/OVARIAN CANCER

Diagnostic Accuracy of a New Antigen Test for SARS-CoV-2 Detection

Background and aims: Quick and reliable diagnostic tools play an important role in controlling the spread of the SARS-Cov-2 pandemic. The aim of this study was to evaluate the diagnostic accuracy of a new cyto-salivary antigen test aimed at detecting the presence of antigens for SARS-CoV-2, as compared by the gold standard RT-PCR and a lateral flow test. Methods: A total of 433 healthy volunteers were enrolled in the study and the sensitivity and specificity of the new cyto-salivary antigen test were calculated, as compared to the RT-PCR nasopharyngeal swab and to the lateral flow test. Results: A total of 433 samples were collected and tested at the Mediterranean Fair in Palermo from Febru…

Il contenuto di ABVT durante il processo di maturazione della bottarga di tonno

Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells

Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin‐releasing hormone, luteinizing hormone, and follicle‐stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real‐time PCR. The results obtained show that testosterone levels increase at a 3.9 μM concentration of nandrolone and return to the ba…

THE M3 MUSCARINIC RECEPTOR IS INVOLVED IN THE ACTIVATION OF AIRWAY EPITHELIUM IN VITRO

Setting up of a machine learning algorithm for the identification of severe liver fibrosis profile in the general US population cohort

Background: The progress of digital transformation in clinical practice opens the door to transforming the current clinical line for liver disease diagnosis from a late-stage diagnosis approach to an early-stage based one. Early diagnosis of liver fibrosis can prevent the progression of the disease and decrease liver-related morbidity and mortality. We developed here a machine learning (ML) algorithm containing standard parameters that can identify liver fibrosis in the general US population.Materials and methods: Starting from a public database (National Health and Nutrition Examination Survey, NHANES), representative of the American population with 7265 eligible subjects (control populati…

Impact on Glucose Homeostasis: Is Food Biofortified with Molybdenum a Workable Solution? A Two-Arm Study

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to c…

Review: Mass spectrometry of surfactant aggregates

In contrast with the enormous amount of literature produced during many decades in the field of surfactant aggregation in liquid, liquid crystalline and solid phases, only a few investigations concerning surfactant self-assembling in the gas phase as charged aggregates have been carried out until now. This lack of interest is disappointing in view of the remarkable theoretical and practical importance of the inherent knowledge. The absence of surfactant–solvent interactions makes it easier to study the role of surfactant–surfactant forces in determining their peculiar self-assembling features as well as the ability of these assemblies to incorporate selected solubilizate molecules. Thus, th…

Serum concentrations of persistent organic pollutants (POPs) in the inhabitants of a Sicilian city.

Polychlorinated biphenyls (PCBs) and organochlorine pesticides are common environmental contaminants that have been associated with human health problems. OBJECTIVES: To assess serum concentrations of several organochlorine contaminants in general population living in a city with an ancient agricultural tradition and to identify possible exposure sources in Sicily. METHODS: A cross-sectional study was conducted on 101 individuals. Each participant answered a face-to-face questionnaire submitted by well-trained personnel and provided a serum sample which was analyzed for the concentrations of PCBs, HCB, HCHs and DDTs by using gas-chromatography coupled with mass spectrometry. RESULTS: HCB, p…

The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity: Focus on Sicilian Long-Living Individuals (LLIs)

Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the pathophysiology of ageing and to identify new markers of longevity, we analysed the activity levels of MMP-2 and MMP-9 in association with some relevant haematochemical parameters in a Sicilian population, including long-living individuals (LLIs, ≥95 years old). A cohort of 154 healthy subjects (72 men and 82 women) of different ages (age range 20-112) was recruited. The cohort was divided into five subgroups: the first group with subjects less than…

Aplotype analysis in four sicilian families with 5083del19bp-BRCA1.

DETERMINATION OF MACRO ELEMENTS IN GLUTEN-FREE FOOD FOR CELIAC PEOPLE BY ICP-OES

This paper is the first analytical approach to the study of seven nutrients in the gluten-free foods for celiac people. The ICP-OES technique was used. One of the advantages about the use of ICP-OES for this characterization is the high selectivity and low interferences for studied elements. The concentration values of K, Li, Sr, Na, Ca, Mg and Al in seventeen gluten-free food samples are reported. Considering the average concentrations of the elements analyzed, excluding lithium, in the present study it can be concluded that they are inadequate if compared with the recommended daily intake by international organisms, providing only from 1.5 to 20% of the RDI for the essential metals. In pa…

Evaluation of BNP levels and bioelectrical impedance measurements after a novel therapy of refractory congestive heart failure

Determination of trace elements in gluten-free food for celiac people by ICP-MS

Abstract This paper is the first analytical approach to the study of twenty heavy metals in the gluten-free foods for celiac people. Only the ICP-MS technique was used. One of the advantages about the use of ICP-MS for this characterization is the high sensitivity that improved the limits of quantification levels for some elements that are present at low quantities in some samples. The concentration values of As, Ba, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Sb, Se, Sn, V and Zn in seventeen gluten-free food samples are reported. The highest arsenic and molybdenum levels were measured in Rice noodle from China (0.088 and 0.47 mg kg − 1 , respectively). The highest concentrations of some metal…

Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components

Abstract The aim of this study was to investigate whether nandrolone decanoate (ND) use affects testosterone production and testicular morphology in a model of trained and sedentary mice. A group of mice underwent endurance training while another set led a sedentary lifestyle and were freely mobile within cages. All experimental groups were treated with either ND or peanut oil at different doses for 6 weeks. Testosterone serum levels were measured via liquid chromatography–mass spectrometry. Western blot analysis and quantitative real‐time PCR were utilized to determine gene and protein expression levels of the primary enzymes implicated in testosterone biosynthesis and gene expression leve…

SANIST: optimization of a technology for compound identification based on the European Union directive with applications in forensic, pharmaceutical and food analyses

Electrospray Ionization and collision induced dissociation tandem mass spectrometry are usually employed to obtain compound identification through a mass spectra match. Different algorithms have been developed for this purpose (for example the nist match algorithm). These approaches compare the tandem mass spectra of the unknown analyte with the tandem mass spectra spectra of known compounds inserted in a database. The compounds are usually identified on the basis of spectral match value associated with a probability of recognition. However, this approach is not usually applied to multiple reaction monitoring transition spectra achieved by means of triple quadrupole apparatus, mainly due to…

NF-κB protects Behçet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins

Objective To determine whether prolongation of the inflammatory reaction in patients with Behcet's disease (BD) is related to apoptosis resistance and is associated with the up-regulation of antiapoptotic factors. Methods The percentage of cell death was evaluated by flow cytometry in peripheral blood mononuclear cells from 35 patients with BD and 30 healthy volunteers. The expression levels of antiapoptotic factors and NF-κB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-κB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-κB small interfering RNA. Results Althou…

Technical and health governance aspects of the External Quality Assessment Scheme for the SARS-CoV-2 molecular tests: institutional experience performed in all clinical laboratories of a Regional Health Service

Abstract Objectives Since December 2019, the worldwide public health has been threatened by a severe acute respiratory syndrome caused by Coronavirus-2. From the beginning, a turning point has been the identification of new cases of infection, in order to minimize the virus spreading among the population. For this reason, it was necessary introducing a panel of tests able to identify positive cases, which became crucial for all countries. Methods As a Regional Reference Centre, the CRQ Laboratory (Regional Laboratory for the Quality Control) developed and conducted an External Quality Assessment (EQA) panel of assay, so as to evaluate the quality of real-time reverse transcription polymeras…

VUS variants in BRCA genes of hereditary breast/ovarian cancer

Illicit drugs consumption evaluation by wastewater-based epidemiology in the urban area of Palermo city (Italy)

Introduction. A wastewater-based epidemiology approach was performed to estimate the drug consumption in Palermo city, the fifth largest city of Italy with a population of 671 696 inhabitants, and to investigate the monthly variability of drug loads in wastewater from different areas of the city. A seven-months detection campaign was conducted at the two wastewater treatment plants of the city. Methods. Following a pre-treatment, 32 samples of wastewater were analyzed by liquid chromatography-tandem mass spectrometry. Results. We estimated a mean cocaine use in Palermo of 0.19 g/day/1000 people, corresponding to 1.90 doses/1000 people and cannabinoids use of 2.85 g/day/1000 people, correspo…

IMPLEMENTATION OF QUALITY SYSTEMS IN THE BIOMEDICAL LABORATORIES

Molecular analysis of TP53, Ki-Ras and P16 methylation status in tissue and plasma of subjects affected by gastrointestinal cancer

Diallyldimethylammonium Chloride (DADMAC) in Water Treated with Poly-Diallyldimethylammonium Chloride (PDADMAC) by Reversed-Phase Ion-Pair Chromatography—Electrospray Ionization Mass Spectrometry

Poly-diallyldimethylammonium (PDADMAC) chloride is a flocculant agent extensively used in water clarification treatments. Commercial polyelectrolyte formulations often contain residual monomer (DADMAC), reaction by-products and other reactants as contaminants that could potentially affect human health. In the present study, we optimized an analytical method based on reversed-phase ion-pair chromatography coupled with mass spectrometry for quantifying ultra-trace levels of DADMAC, without preliminary treatments, in drinking water distributed by the Palermo aqueduct. The method was validated in terms of accuracy (recovery between 80 to 120%), precision (RSD < 10%), linearity range (from 0.…

Bisphosphonates sensitize osteosarcoma cells to chemoterapeutic drugs

Improvement of a rapid direct blood culture microbial identification protocol using MALDI-TOF MS and performance comparison with SepsiTyper kit

Fast diagnosis of pathogens is critical to guarantee the most adequate therapy for infections; bacterial culture methods, which constitute the actual gold standard, are precise and sensitive but rather slow. Today, new methods have been made available to enable faster diagnosis, with the Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry (MALDI-TOF MS) technique being the most promising. Even if simpler and faster than traditional bacterial culture methods, analysis of positive blood cultures via MALDI-TOF MS requires a preliminary extraction process of samples. In this study, we compared two extraction protocols for bacterial identification directly from positive …

Current Perspectives on Adult Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Biological Features and Clinical Indications.

Extracellular vesicles (EVs) constitute one of the main mechanisms by which cells communicate with the surrounding tissue or at distance. Vesicle secretion is featured by most cell types, and adult mesenchymal stromal cells (MSCs) of different tissue origins have shown the ability to produce them. In recent years, several reports disclosed the molecular composition and suggested clinical indications for EVs derived from adult MSCs. The parental cells were already known for their roles in different disease settings in regulating inflammation, immune modulation, or transdifferentiation to promote cell repopulation. Interestingly, most reports also suggested that part of the properties of pare…

IL CONTENUTO IN ABVT DURANTE IL PROCESSO DI MATURAZIONE DELLA BOTTARGA DI TONNO

Abstract In the past few years the alimentary consumptions have not shown signs of resumption and the fish field has endured not only one concentration of the consumptions but also the competition of the Countries Emergents . In this phase of stall in the sales and a market of remarkable competitive pushes, the attention of the producers has been that one to increase sale politics above all heading at the quality and the voluntary certification of product. The botargo of tuna it is a product that is lend to this politics in how much high target of the consumers. Between several the parameters of appraisal of the quality of the products fish sure the content in basic nitrogen flown them tota…

Beta Agonists in Liver-Validation Method

BRCA1/BRCA2 genes mutational screening in Sicilian breast and/or ovarian cancer families.

Erratum: FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease (Analytical and Bioanalytical Chemistry DOI: 10.1007/s00216-015-9229-6)

Erratum to: FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer’s disease

NEW A PPROACHES TO THE EXPANDÉD NEW BORN SCREENING PROGRAMS BY TANDEM MASS SPECTROMETRY: REDUCTION OF FALSE-POSITlVES FOR C5, C50H, C6DC.

EGFR genomic alterations in cancer: prognostic and predictive values.

The role of EGFR in cancer development and progression has been recognized for long time in a variety of human malignancies including lung, head and neck, colon, breast, ovary and glioma. Recently its role as a target of antineoplastic agents has also been identified and a variety of EGFR-targeted drugs is already being used in a clinical setting and others are at present under investigation. Many data involving EGFR protein expression are now available for the choice of anti-EGFR monoclonal antibodies in colorectal cancer and with regard to EGFR gene mutations for the choice of tyrosine kinase inhibitors in lung cancer. Other EGFR-related molecular factors, including the EGFR gene copy num…

The role of the left choleic artery in the rectum anterious resection with colo-anal anastomosis: technique and considerations of anastomosis oxigenation through nitric oxide valutation.

Genotype analysis of colorectal carcinomas through laser pressare catapulting (LPC)

Recently, new chemotherapy agents which target the non-structural components of mitosis have been developed. An important protein involved in several mitotic phases is the Aurora-A protein. By means of the phosphorylation of different substrates, Aurora-A regulates the correct development of the various phases of mitosis. The kinase activity of this protein makes Aurora-A an excellent candidate as an oncogene. The first data of Aurora-A involvement in cancer regarded the identification of Aurora-A overexpression in primary breast and colon tumour samples. With regard to the predictive role of Aurora-A, it has been shown that its overexpression disrupts the spindle checkpoint activated by pa…

Bisphosphonates sensitise osteosarcoma cells to chemotherapeutic drugs

Analysis of Ki-Ras mutations in stage I rectal carcinomas and respective regional lymph nodes.

In this work we show that the percentage of Ki-RAS mutations in codons 12 and 13 in rectal cancer are sensibly lower than in colon cancer, providing further evidence that these two kinds of tumors should be considered two different entities. Moreover, we show that the detection in regional lymph nodes of the same mutation of primary tumor might represent an indicator of lymph nodes metastasis in rectal carcinoma not detected in routine histologic examination.

Quantification and metabolic aspects of trans fatty acids

SCOPE To inquire with certainty of the analytical data on the effects of fat acids. INTRODUCTION The consumption of trans isomers of unsaturated fatty acids has been associated with untoward metabolic effects. Several clinical investigations demonstrated that trans fatty acids increase plasma LDL-cholesterol and lipoprotein (a) and reduce HDL-cholesterol concentrations. These alterations of plasma lipid profiles indicate an atherogenic effect of trans fatty acids. Moreover, in infant and children, trans fatty acids in blood plasma may impair human growth. METHODOLOGY We have put to point one methodology analytics in order to dose trans fatty acids in the blood. Such methodology analytics pr…

Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure.

Introduction Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide. Methods Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0–24 h…

Cigarette Smoke Extract Induces p38 MAPK-Initiated, Fas-Mediated Eryptosis

Eryptosis is a physiological mechanism for the clearance of senescent or damaged erythrocytes by phagocytes. Excessive eryptosis is stimulated under several pathologies and associated with endothelial injury and thrombosis. Cigarette smoke (CS) is an established risk factor for vascular diseases and cigarette smokers have high-levels of eryptotic erythrocytes. This study, for the first time, investigates the mechanism by which CS damages red blood cells (RBCs). CS extract (CSE) from commercial cigarettes was prepared and standardized for nicotine content. Cytofluorimetric analysis demonstrated that treatment of human RBCs with CSE caused dose-dependent, phosphatidylserine externalization an…

Clinical and hormonal characteristics in heterozygote carriers of congenital adrenal hyperplasia

Abstract Non-classical congenital adrenal hyperplasia (NC-CAH) includes a group of genetic disorders due to a broad class of CYP21A2 variants identifying a disease-causing ‘C’ genotype. The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated. With the aim of obtaining a more accurate delineation of the phenotype of heterozygous carrier of CAH, we analyzed clinical, biochemical and molecular characteristics in a cohort of Sicilian subjects. Fifty-seven females with biallelic and monoallelic CYP21A2 variants classifying NC-CAH (24) and heterozygous carrier…

LYPOXYGENASE INDUCES CHEMORESISTANCE IN THYROID CANCER

Xanthine dehydrogenase processes retinol to retinoic acid in human mammary epithelial cells

Retinoic acid is considered to be the active metabolite of retinol, able to control differentiation and proliferation of epithelia. Retinoic acid biosynthesis has been widely described with the implication of multiple enzymatic activities. However, our understanding of the cell biological function and regulation of this process is limited. In a recent study we evidenced that milk xanthine oxidase (E.C. 1.17.3.2.) is capable to oxidize all-trans-retinol bound to CRBP (holo-CRBP) to all-trans-retinaldehyde and then to all-trans-retinoic acid. To get further knowledge regarding this process we have evaluated the biosynthetic pathway of retinoic acid in a human mammary epithelial cell line (HME…

FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease

Lipidomic analysis is able to measure simultaneously thousands of compounds belonging to a few lipid classes. In each lipid class, compounds differ only by the acyl radical, ranging between C10:0 (capric acid) and C24:0 (lignoceric acid). Although some metabolites have a peculiar pathological role, more often compounds belonging to a single lipid class exert the same biological effect. Here, we present a lipidomics workflow that extracts the tandem mass spectrometry data from individual files and uses them to group compounds into structurally homogeneous clusters by chemical structure hierarchical clustering analysis (CHCA). The case-to-control peak area ratios of the metabolites are then a…

Molecular analysis of TP53, Ki-Ras and P16 methylation status in tissue and plasma of subjects affected by gastrointestinal cancer (GIC)

BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same…

Dietary Supplements as Surrogate of Mediterranean Diet in Healthy Smoking Subjects

The interventions to slow aging, favoring active life expectancy, represent the new perspectives in ageing investigation. Some mechanisms that delay or prevent the onset of aging pathologies have been identified. Between them, a healthy lifestyle seems to reduce many risk factors. In particular, eating habits represent the most concrete, low-cost way to act on aging process. Mediterranean diet has received much attention since its antioxidant and anti-inflammatory effects have been consistently demonstrated. Unfortunately, many people follow a Western diet, poor in phytochemicals that represent the main source of beneficial effects of this dietary pattern. So, supplements administration sho…

What are the Cancer Risks in BRCA Carriers Apart from Those Regarding the Breast and the Ovary?

Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose to familial breast and/or ovarian cancer. The lifetime risk of members of families with genetic predisposition depends on the mutations of susceptibility genes. BRCA1 mutations seem to confer the highest risk of developing neoplastic diseases. Apart from breast and ovarian cancer mutations in BRCA, related pathways are supposed to confer a smaller risk for additional cancers (colon, melanoma, pancreas, lymphoma, prostate, liver). All these tumors have an inherited component not necessarily associated with genetic susceptibility to BRCA genes. To date he main focus of this review has been argued still with difficulty…

FORENSIC INVESTIGATION OF KERATIN MATRIX: DEVELOPMENT OF A METHOD BY TURBOFLOW™ HPLC-MS/MS FOR CANNABINOIDS QUANTITATIVE ANALYSIS

The products of cannabis are the most frequently used illicit drugs of abuse detected in workplace drug-testing programs or in cases of driving under the influence of drugs. For this reason, there is a great need for sensitive and specific methods which can confirm the chronic exposure and which take account of the cut-off values that have been proposed in Italy by the GTFI Guidelines (Group of Italian Forensic Toxicologists). The method currently more appropriate for quantification of Δ9-Tetrahydrocannabinol (THC) and its major metabolite 11-nor-9-Carboxy-Δ9-THC (THCA) appears to be one that involves HPLC-MS/MS and keratin matrix. The purpose of this work, performed at the Mass Spectrometr…

Heparin induces an accumulation of atherogenic lipoproteins during hemodialysis in normolipidemic end-stage renal disease patients

Dyslipidemias may account for the excess of cardiovascular mortality in end-stage renal disease (ESRD). Lipoprotein studies in ESRD patients are usually relative to prehemodialysis samples even if significative changes may occur after dialysis. In this study, we aimed to investigate the effects of ESRD on triglyceride-rich lipoproteins (TRL) subpopulations distribution and acute change following hemodialytic procedures, including the relative contribution of heparin administration. We selected a group of normolipidemic male middle-aged ESRD patients free of any concomitant disease affecting lipoprotein remnant metabolism compared with controls. We separated TRL subfractions according to den…

Exposure to cigarette smoke extract and lipopolysaccharide modifies cytoskeleton organization in bronchial epithelial cells

The integrity of the respiratory epithelium is crucial for airway homeostasis. Tobacco smoke exposure and recurrent infections of the airways play a crucial role in the progression and in the decline of the respiratory function in chronic obstructive pulmonary disease (COPD). The aim of this study was to detect differentially expressed proteins in a bronchial epithelial cell line (16-HBE) stimulated with cigarette smoke extract (CSE) and lipopolysaccharide (LPS), a constituent of gram-negative bacteria, alone and/or in combination, by using two-dimensional electrophoresis (2DE) analysis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Western blot a…

RAPID ANALYSIS OF NEFAs AS METHYL ESTERS FROM SMALL VOLUME OF PLASMA AND OTHERS DIFFERENT BIOLOGICAL SPECIMENS BY GC AND GCMS AFTER ONLY ONE STEP ESTERIFICATION

Anti-endothelin drugs in solid tumors

Importance of the field: The endothelin (ET) axis, which includes the biological functions of ETs and their receptors, has played a physiological role in normal tissue, acting as a modulator of vasomotor tone, tissue differentiation and development, cell proliferation and hormone production. Interestingly, it also functions in the growth and progression of various tumors. Several researchers have identified the blockade of the ET-1 receptor as a promising therapeutic approach. Areas covered in this review: The clinical investigation of an orally bioavailable ET antagonist, atrasentan, in prostate cancer, is encouraging. In this neoplasia, it has shown antitumor activity, bone metastasis con…

How Much of Familial Breast Cancer Risk is Currently Explained by the Known Genes?

The need to answer the question “how much of the familial risk is currently explained by the known genes?” has increased ,and although BRCA1 and BRCA2 are considered the two major breast cancer (BC) susceptibility genes, they do not justify the entire percentage of all hereditary BC cases. The current consensus is that other BC predisposing genes could explain at least a portion of the remaining non-mutated familial cases, including not only other high- penetrance BC genes, but also moderate and low-penetrance genes. Considering these three different categories of genes, a gap of risk estimation in breast cancer can be observed. Moreover, different researchers tried to give significance to …

Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells

Zoledronic acid (ZOL) is the most potent nitrogen-containing bisphosphonate (N-BPs) that strongly binds to bone mineral and acts as a powerful inhibitor of bone resorption, already clinically available for the treatment of patients with osteolytic metastases. Recent data also suggest that ZOL, used in breast cancer, may provide more than just supportive care modifying the course of the disease, though the possible molecular mechanism of action is still unclear. As breast cancer is one of the primary tumours with high propensity to metastasize to the bone, we investigated, for the first time, differential gene expression profile on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells tre…

TP53, Ki-Ras and P16INK4A gene molecular analysis in salivary gland tumors.