OSSERVAZIONI SULL’ATTIVAZIONE DEL RECETTORE ARILICO (AHR) IN CORRELAZIONE ALLA CONTAMINAZIONE AMBIENTALE DA METALLI PESANTI IN TUMORI SPONTANEI DI CANI DELLA REGIONE CAMPANIA. Correlation between Aryl hydrocarbon Receptor (AhR ) expression and environmental heavy metals contamination in canine tumors.

Osservazioni sull’attivazione del recettore arilico (Ahr) in correlazione alla contaminazione ambientale da metalli pesanti in tumori spontanei di cani della regione Campania. La storia e l’evoluzione delle malattie riflette spesso la storia delle modificazioni che sono occorse nell’ambiente. In seguito al moderno sviluppo tecnologico l’inquinamento ambientale ha subìto un forte incremento e, come conseguenza, anche l’incidenza di malattie legate alla contaminazione ambientale ha sofferto di un aumento. Tuttavia, risulta non agevole dimostrare una relazione di tipo causa-effetto tra i due fenomeni. Generalmente la presenza di una correlazione spaziale tra altre concentrazioni di alcuni elementi tossici (ad esempio: Hg, Pb, Cd) nei suoli e nei sedimenti e la particolare incidenza di alcune malattie non implica apriori che gli elementi chimici in eccesso abbiano avuto un ruolo nel processo di sviluppo di un’infermità o che vi sia un’aumentata probabilità che uno specifico metallo tossico sia causa dell’insorgenza di un tumore. Gli elementi in traccia presenti in natura, metalli e non metalli, sono fondamentali nei processi di nutrizione degli esseri umani ma gli stessi elementi possono avere effetti negativi sulla salute umana ed animale se presenti in quantità anomale. L’obiettivo di questo lavoro è di valutare le possibili interazioni esistenti tra l’attivazione di fattori oncogeni , in particolare del recettore arilico per gli idrocarburi (AhR ) e la concentrazione anomala di metalli pesanti tossici in tumori spontanei di cani vissuti nel territorio della Regione Campania. L’AhR è un recettore citoplasmatico espresso nei mammiferi in numerosi tessuti, si tratta di un fattore di trascrizione ligando-dipendente con struttura elica-loop-elica che regola l’espressione di diversi geni. L’attivazione del recettore acrilico provoca l’induzione genica degli enzimi della famiglia citocromo P450 ( CYPs), ciò può essere considerato come una risposta adattativa, che permette alla cellula, ai tessuti, all’organismo di liberarsi dei composti nocivi. La stimolazione di questa risposta adattativa può , però, generare tossicità, per esempio, attraverso la formazione di composti reattivi o l’interferenza con i pathways di segnalazione cellulari endogeni. La sostanza tossica induttrice entra all’interno della cellula attraverso la membrana plasmatica e si lega quindi con il recettore citosolico AhR. In seguito al legame si presume che AhR vada incontro ad un cambiamento di conformazione che permette di esporre una sequenza di localizzazione nucleare, con conseguente traslocazione del complesso nel nucleo. Diversi studi in vitro dimostrano chiaramente che metalli pesanti come mercurio, piombo e rame possono attivare direttamente il recettore arilico e modulare l’espressione genica CYP1A1 sia a livello trascrizionale che posttrascrizionale. Allo scopo di indagare la relazione esistente tra l’attivazione del recettore arilico e la presenza ambientale di metalli pesanti sono stati selezionarti 32 soggetti inseriti nel Registro dei tumori canini dell’Istituto di Anatomia Patologica della Facoltà di Medicina Veterinaria dell’ Università degli Studi di Napoli. Il campionamento è stato effettuato in base all’area geografica di provenienza dei soggetti ( 22 campioni provenienti dalla Provincia di Napoli e 10 campioni dalla provincia di Salerno) e dell’istotipo tumorale precedentemente diagnosticato, utilizzando solo animali padronali. I tessuti prelevati sono stati processati con metodica HRP per immunoistochimica con anticorpi diretti contro AhR e contro CYP1A1 e sottoposti ad indagine con ICP-MS per valutare la concentrazione dei metalli pesanti. I risultati dell’indagine immunoistochimica mostrano l’attivazione dell’AhR e del CYP1A1 ed in particolare, è stato evidenziato che :nei tessuti controllo e nei tumori di grado basso la positività era debole a livello citoplasmatico ed assente a livello nucleare , mentre all’aumentare del grado e dello stadio tumorale si denotava una crescente positività sia a livello citoplasmatico che nucleare. In particolare nei casi con maggiore atipia cellulare la positività era fortemente nucleare. Tali dati sono stati correlati con i risultati ottenuti dalla misurazione della concentrazione dei metalli pesanti. In tutti i casi , ma con valori diversificati, è possibile evidenziare la presenza di metalli pesanti in concentrazione maggiore rispetto ai controlli. Tali risultati, in relazione all’area geografiche di provenienza dei campioni, ci fanno supporre la possibilità reale di un’attivazione dei meccanismi oncogeni da parte di alcuni metalli pesanti. Tale studio pone le basi per la realizzazione di un progetto più ampio che comprenda l’adozione di linee guida per la valutazione del rischio ambientale attraverso la monitoraggio di animali considerati “sentinella” e la realizzazione di mappe di rischio di cui potranno beneficiare non solo gli animali ma soprattutto le popolazioni di un territorio

Association of bovine papillomavirus type 2 (BPV-2) and urinary bladder tumours in cattle from the Azores archipelago

Copyright (c) 2010 Elsevier Ltd. All rights reserved.Urinary bladder tumours in cattle are caused by chronic ingestion of bracken fern and BPV-1/2 infection. The objective of the present study was to assess if BPV-2 was present in urinary bladder lesions from cattle with chronic enzootic haematuria (CEH) from the Azores archipelago (Portugal), in order to gain further information regarding the epidemiologic distribution of this virus. Samples were analysed using PCR specific primers for BPV-2 DNA and an immunohistochemistry for BPV E5 oncoprotein detection. We found a 28% incidence rate of BPV-2 DNA in different types of tumours and cystitis cases (13 out of 46 samples). Tested positive samples for PCR were also positive for the viral E5 oncoprotein; protein immunolabeling was mainly detected within the cytoplasm of urothelial cells, displaying a juxtanuclear distribution. This is the first report of BPV-2 detection in urinary bladder tumours associated with CEH in cattle from the Azores archipelago.Direcção Regional da Ciência e Tecnologia, Governo dos Açores, Portugal; Università degli Studi di Napoli Federico-II (Italia); CIRN (Centro de Investigação em Recursos Naturais, Universidade dos Açores) (Portugal)

Conical emission, pulse splitting and X-wave parametric amplification in nonlinear dynamics of ultrashort light pulses

The precise observation of the angle-frequency spectrum of light filaments in water reveals a scenario incompatible with current models of conical emission (CE). Its description in terms of linear X-wave modes leads us to understand filamentation dynamics requiring a phase- and group-matched, Kerr-driven four-wave-mixing process that involves two highly localized pumps and two X-waves. CE and temporal splitting arise naturally as two manifestations of this process

Systematic review on spheroids from adipose‐derived stem cells: Spontaneous or artefact state?

Three‐dimensional (3D) cell cultures represent the spontaneous state of stem cells with specific gene and protein molecular expression that are more alike the in vivo condition. In vitro two‐dimensional (2D) cell adhesion cultures are still commonly employed for various cellular studies such as movement, proliferation and differentiation phenomena; this procedure is standardized and amply used in laboratories, however their representing the original tissue has recently been subject to questioning. Cell cultures in 2D require a support/substrate (flasks, multiwells, etc.) and use of fetal bovine serum as an adjuvant that stimulates adhesion that most likely leads to cellular aging. A 3D environment stimulates cells to grow in suspended aggregates that are defined as “spheroids.” In particular, adipose stem cells (ASCs) are traditionally observed in adhesion conditions, but a recent and vast literature offers many strategies that obtain 3D cell spheroids. These cells seem to possess a greater ability in maintaining their stemness and differentiate towards all mesenchymal lineages, as demonstrated in in vitro and in vivo studies compared to adhesion cultures. To date, standardized procedures that form ASC spheroids have not yet been established. This systematic review carries out an in‐depth analysis of the 76 articles produced over the past 10 years and discusses the similarities and differences in materials, techniques, and purposes to standardize the methods aimed at obtaining ASC spheroids as already described for 2D cultures

Effects of bariatric and metabolic surgical procedures on dyslipidemia: a retrospective, observational analysis.

Aim: Obesity and co-existing metabolic comorbidities are associated with increased cardiovascular (CV) morbidity and mortality risks, generally clustered to risk factors such as dyslipidemia. The aim of this study was to evaluate the lipid profile changes in subjects with severe obesity undergoing different procedures of bariatric and metabolic surgery (BMS), sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB) in a real-world, clinical setting. Methods: A single-center, retrospective, observational clinical study was performed enrolling patients undergoing BMS. The primary outcome was the change in total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol, and triglycerides. Results: In total, 123 patients were enrolled (males 25.2% and females 74.8%) with a mean age of 48.2 ± 7.9 years and a mean BMI of 47.0 ± 9.1 kg/m2. All patients were evaluated until 16.9 ± 8.1 months after surgery. Total and HDL cholesterol did not change after surgery, while a significant reduction in triglyceride levels was recorded. Moreover, a rapid decline of both LDL and non-HDL cholesterol among follow-up visits was observed. In particular, significant inverse correlations were found between total cholesterol, LDL cholesterol, non-HDL cholesterol, and triglycerides and the number of months elapsed after bariatric surgery. Similarly, a direct correlation was found considering HDL cholesterol. Moreover, total cholesterol, LDL cholesterol, non-HDL cholesterol, and triglycerides significantly changed among visits after RYGB, while no changes were observed in the SG group. Finally, considering lipid-lowering therapies, the improvement in lipid asset was detected only in non-treated patients. Conclusion: This study corroborates the knowledge of the improvement in lipid profile with BMS in clinical practice. Together with sustained weight loss, the BMS approach efficiently corrects dyslipidemia, contributing to decreasing the CV risk

Exploring the Potential of Lactic Acid Fermentation for the Recovery of Exhausted Vanilla Beans

The market value of vanilla is constantly growing, as it is the aroma most appreciated by consumers worldwide. The key component of the aroma of vanilla beans is vanillin, which can be directly extracted from the plant, produced by chemical synthesis, or by bioconversion of natural precursors. Due to the increasing consumers' demand for products labeled as “natural,” extraction from vanilla pods results in a more valuable aroma source. Once the extraction is completed, what remains are the exhausted beans that still contain small seeds and other compounds, including varying amounts of vanillin trapped in the cellular structures of the plant. The application of fermentation of exhausted vanilla beans is proposed here as a strategy to recover “natural” vanillin and other valuable aroma compounds as a result of the metabolic conversion by lactic acid bacteria (LAB). The aim of this study was to verify the fermentability of exhausted vanilla beans by-products for their valorization, allowing the recovery of high-value molecules or new applications in food products. Design of Experiment (DoE) was used to screen a library of LAB strains to identify the best condition of fermentation in response to varying cultivation conditions. A comparison between mono and co-culture of LAB was assessed. Moreover, sensory panel tests and the evaluation of the aromatic components by Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry analysis were carried out to better understand the modification of the aroma profile after fermentation. Fermentation with LAB changed the volatile profile and sensory characteristics of the exhausted vanilla beans and represents a promising method for the valorization of these by-products

Moderate hypofractionated radiotherapy after prostatectomy for cancer patients: toxicity and clinical outcome

Background: After radical prostatectomy (RP) radiotherapy (RT) plays a role, both as adjuvant or salvage treatment. If negative features are present such as extracapsular extension, seminal vesicle invasion, lymph invasion, and positive surgical margins, RT after RP reduces the risk of recurrence, although it is associated with an increased risk of acute and late toxicities. An intensified RT delivered in a shortened time could improve clinical outcome and be safely combined with hormonal therapy (HT). The aim of this study was to determine the acute and late toxicities associated with hypofractionated RT and to assess the impact of the addition of HT to RT in high-risk prostate cancer (PC) patients on overall response and toxicity. Materials and methods: Sixty-four PC patients undergoing RP were included in this retrospective study. All patients were recommended to receive adjuvant or salvage RT. Prescription doses were 62.5 Gy in 25 fractions to prostate bed, 56.25 Gy in 25 fractions to seminal vesicles bed, and 50 Gy in 25 fractions to pelvis if indicated. HT was administered to patients with additional adverse pathologic features including Gleason score >7, prostate-specific antigen >20 ng/mL before surgery, or prostate-specific antigen with rapid doubling time after relapse or nodal involvement. After completion of RT, patients were observed after 4 weeks, and then followed-up every 3\u20136 months. Acute and late toxicities were assessed using Common Terminology Criteria for Adverse Events v4 and Radiation Therapy Oncology Group scale, respectively. Results: For acute toxicity, only grade 1 gastrointestinal and genitourinary toxicities were detected in 17% and 11% of patients, respectively. As regards late toxicity, only 5% of the patients developed grade 1 gastrointestinal adverse event; grade 1, grade 2, and grade 3 genitourinary toxicity was recorded in 5%, 3.3%, and 3.3% of patients, respectively. Two and 5 years overall survival were 98% and 96%, respectively. The curves stratified for treatment show a slight difference between patients receiving RT or RT+HT, but the differences did not reach statistical significance (p=0.133). Conclusion: In patients with PC undergoing RP, hypofractionated RT may contribute to achieve a high overall survival with an acceptable toxicity profile. Combination of RT and HT is also well tolerated and efficacious

Far-field spectral characterization of conical emission and filamentation in Kerr media

By use of an imaging spectrometer we map the far-field ($\theta-\lambda$) spectra of 200 fs optical pulses that have undergone beam collapse and filamentation in a Kerr medium. By studying the evolution of the spectra with increasing input power and using a model based on stationary linear asymptotic wave modes, we are able to trace a consistent model of optical beam collapse high-lighting the interplay between conical emission, multiple pulse splitting and other effects such as spatial chirp.Comment: 8 pages, 9 figure