Upregulation of inducible NO synthase by exogenous adenosine in vascular smooth muscle cells activated by inflammatory stimuli in experimental diabetes

BACKGROUND: Adenosine has been shown to induce nitric oxide (NO) production via inducible NO synthase (iNOS) activation in vascular smooth muscle cells (VSMCs). Although this is interpreted as a beneficial vasodilating pathway in vaso-occlusive disorders, iNOS is also involved in diabetic vascular dysfunction. Because the turnover of and the potential to modulate iNOS by adenosine in experimental diabetes have not been explored, we hypothesized that both the adenosine system and control of iNOS function are impaired in VSMCs from streptozotocin-diabetic rats. METHODS: Male Sprague-Dawley rats were injected with streptozotocin once to induce diabetes. Aortic VSMCs from diabetic and nondiabetic rats were isolated, cultured and exposed to lipopolysaccharide (LPS) plus a cytokine mix for 24 h in the presence or absence of (1) exogenous adenosine and related compounds, and/or (2) pharmacological agents affecting adenosine turnover. iNOS functional expression was determined by immunoblotting and NO metabolite assays. Concentrations of adenosine, related compounds and metabolites thereof were assayed by HPLC. Vasomotor responses to adenosine were determined in endothelium-deprived aortic rings. RESULTS: Treatment with adenosine-degrading enzymes or receptor antagonists increased iNOS formation in activated VSMCs from nondiabetic and diabetic rats. Following treatment with the adenosine transport inhibitor NBTI, iNOS levels increased in nondiabetic but decreased in diabetic VSMCs. The amount of secreted NO metabolites was uncoupled from iNOS levels in diabetic VSMCs. Addition of high concentrations of adenosine and its precursors or analogues enhanced iNOS formation solely in diabetic VSMCs. Exogenous adenosine and AMP were completely removed from the culture medium and converted into metabolites. A tendency towards elevated inosine generation was observed in diabetic VSMCs, which were also less sensitive to CD73 inhibition, but inosine supplementation did not affect iNOS levels. Pharmacological inhibition of NOS abolished adenosine-induced vasorelaxation in aortic tissues from diabetic but not nondiabetic animals. CONCLUSIONS: Endogenous adenosine prevented cytokine- and LPS-induced iNOS activation in VSMCs. By contrast, supplementation with adenosine and its precursors or analogues enhanced iNOS levels in diabetic VSMCs. This effect was associated with alterations in exogenous adenosine turnover. Thus, overactivation of the adenosine system may foster iNOS-mediated diabetic vascular dysfunction

Efficacy of acoustic waves in preventing Streptococcus mutans adhesion on dental unit water line

Background: nei riuniti odontoiatrici, la qualità dell'acqua utilizzata per la refrigerazione e il risciacquo di manipoli, siringhe e altri componenti è un aspetto di notevole importanza sanitaria. L'acqua attraversa questi dispositivi mediante un circuito interconnesso di tubi di piccole dimensioni (circa 2 mm di diametro), denominato “dental unit water line” (DUWL). I DUWL possono essere fortemente colonizzati da varie specie batteriche sia in fase planctonica, che adesi o organizzati in biofilm, rappresentando una potenziale causa di infezione, non solo per i professionisti che usano abitualmente questi dispositivi, ma anche per pazienti occasionali, in particolare per i pazienti immunocompromessi. La contaminazione dei DUWL può essere prevenuta o ridotta con l'uso dei disinfettanti, ma l'eradicazione dei microrganismi adesi alle superfici interne dei DUWL o organizzati in forma di biofilm, è una sfida assai più complessa e spesso i normali metodi di disinfezione non sono pienamente efficaci. Inoltre, in ambito odontoiatrico, i disinfettanti utilizzati abitualmente per disinfettare i DUWL possono alterare la capacità adesiva del materiale utilizzato nella pratica restaurativa. Obiettivi: individuare una strategia innovativa, in grado di contrastare l'adesione batterica alle superfici dei DUWL mediante un approccio di tipo fisico, che sia più efficace nel superare il problema della contaminazione dei DUWL e ridurre il rischio di infezione rispetto ai normali metodi già in uso. A tal fine, fra le molte specie batteriche potenzialmente riscontrabili nei circuiti idrici odontoiatrici, si è deciso di avviare questo studio pilota utilizzando la specie batterica patogena S. mutans, per il suo indubbio interesse in ambito odontoiatrico e per la sua spiccata capacità di aderire e persistere su superfici inerti. Metodi: utilizzo di onde acustiche elastiche ad alta energia nel contrastare l'adesione di Streptococcus mutans alle pareti interne di un circuito idrico sperimentale riproducente un DUWL. Per evidenziare l’efficacia delle onde acustiche anche in condizioni estreme, è stata utilizzata un’elevata carica contaminante di S. mutans. Risultati: Si osserva una significativa riduzione dei batteri adesi soggetti a trattamento con onde acustiche rispetto al controllo (P = 0,003)

Evaluation of a new e-learning resource for calibrating OSCE examiners on the use of rating scales

ACKNOWLEDGEMENTS We would like to thank the medical team at the University of Aberdeen to help with the recordings of the videos and developing the website for examiners training.Peer reviewedPostprin

Media Representation of Male Violence towards Women: Analysis of Trump's and Weinstein's Sexual Misconduct Cases in the British Press.

Los planteamientos lingüísticos feministas (Spender, 1980) destacan la importancia de la revisión del lenguaje como parte de la lucha por la igualdad de las mujeres. Adoptando las ideas del Relativismo Lingüístico y tomando el Análisis Crítico del Discurso (Fairclough, 1989, 1995) como marco teórico, este trabajo tratará de mostrar las maneras en las que dos periódicos británicos de ideologías opuestas, The Guardian y The Daily Mail, retratan la violencia sexual ejercida por hombres blancos de indiscutible poder como Donald Trump y Harvey Weinstein. Se llevará a cabo un análisis cualitativo centrado especialmente en los aspectos evaluativos (Hunston y Thompson, 2011), entre otros. Al comparar los distintos enfoques que se dan a los mismos hechos, se mostrará cómo el relato resultante retrata a los agresores, a las denunciantes y a los hechos en sí de diferente manera, contribuyendo así al refuerzo ideológico del lector meta. <br /

The biofilm matrix of Pseudomonas sp. OX1 grown on phenol is mainly constituted by alginate oligosaccharides

The structure of the major constituent of the biofilm matrix produced by Pseudomonas sp. OX1, when grown on phenol as the sole carbon source is described. This investigation, carried out by chemical analysis, NMR spectroscopy and MALDI-TOF MS spectrometry, showed the presence of an oligosaccharide blend with the typical alginate structure, namely (1-->4) substituted beta-D-mannuronic (ManA) and alpha-L-guluronic acid (GulA). GulA residues were non-acetylated whereas ManA was always O-acetylated at C-2 or C-3

Comunità per minori: realtà tra ascolto e rieducazione

openT.SEF.15/16.

Advances in the treatment of relapsing-remitting multiple sclerosis - Critical appraisal of fingolimod

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs for MS in Europe, and two second-line treatments. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side effects. Despite disease-modifying drugs being well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Therefore, the development of new therapeutic strategies is warranted. Several oral compounds are in late stages of development for treating MS. fingolimod is an oral sphingosine-1-phosphate receptor modulator that has demonstrated superior efficacy compared with placebo and interferon β-1a in phase III studies. It has already been approved in the treatment of MS. This review focuses on advances in current and novel oral treatment approaches in MS. We summarily review the oral compounds in this study, focusing on the recent development, approval, and the clinical experience with fingolimod

Perinatal mental health around the world: priorities for research and service development in Italy

In Italy, most studies on perinatal mental health and initiatives aimed at improving the early detection and management of perinatal mental disorders have been carried out at the local level. National population-based studies are lacking. A study of pregnant women, recruited and diagnosed by a university hospital, found a 12.4% prevalence of minor and major depression during pregnancy, and a prevalence of 9.6% in the postpartum period. In a population-based surveillance system, covering 77% of national births, suicide was identified to be one of the main causes of maternal death within the first year after birth, yet half of those who were known to have a high suicide risk during the postpartum period had not been referred to a mental health service. The value of recognising depressive or anxiety symptoms early, during pregnancy, has been emphasised by recent research and should be linked to multi-professional psychosocial interventions. Since 2017, the Italian public primary care services that are dedicated to pregnancy assistance (Family Care Centres) have been tasked to provide free psychological assessment to pregnant and postpartum women. Action is now needed in order to improve access to Italian Family Care Centres for pregnant women and to develop an integrated care model involving obstetric and mental health services

Intracranial tuberculous mass lesions treated with thalidomide in an immunocompetent child from a low tuberculosis endemic country: A case report

Rationale: Tuberculous meningitis is a highly morbid, often fatal disease. Patient concern: We describe a case of an Italian child. Diagnoses: we diagnosed early a Tuberculous meningitis complicated by the occurrence of hydrocephalus, stroke, and paradoxical reaction with brain pseudo-abscesses. Interventions: The child started readily a specific therapy associated with steroids and thalidomide was introduced few month later. Outcomes: the patient had a favorable outcome without neurologic sequelae. Lessons: Despite the prompt specific anti-tubercular and adjuvant corticosteroid therapies, only the addition of thalidomide to the treatment allow to a favorable clinical outcome