Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions.

AIMS: Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca2+ transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. MAIN METHODS: PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca2+-ATPase pump inhibitors. The role of Na+/Ca2+ exchanger was examined in experiments performed in zero Na+ medium. NO release and intracellular Ca2+ were measured through specific probes. KEY FINDINGS: In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca2+]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca2+ mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na+/Ca2+ exchanger and Ca2+-ATPase pump in restoring Ca2+ was found. SIGNIFICANCE: Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca2+ transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved

Quality of life in patients treated by adjuvant radiotherapy for endometrial and cervical cancers: correlation with dose\u2013volume parameters

INTRODUCTION: Modern multidisciplinary cancer treatments aim at obtaining minimal influence on patients' quality of life (QoL). The purpose of this study was to assess QoL and correlate it with dose-volume parameters of organ at risks (OARs) in patients who received adjuvant radiotherapy for endometrial and cervical cancers. MATERIALS AND METHODS: We administered the EORTC QLQ-C30 and EN24 or CX24 questionnaires to 124 patients, 100 with endometrial cancer and 24 with cervical cancer treated with postoperative radiotherapy \ub1 chemotherapy in regular follow-up. Bladder function, fecal incontinence or urgency and sexual functioning were investigated and correlated with dose-volume parameters of OAR by multiple linear regression analysis. This correlation was assessed by R (2) value. RESULTS: QoL was very high in the majority of patients (82.3 % of patients). Few patients referred urinary incontinence (3.2 %) or abdominal discomfort of high grade (4.0 %). We found a significant correlation between bladder V40, i.e., absolute percentage of bladder volume that received a dose of 40 Gy, and global health status (p < 0.05, R (2) = 0.17), urinary urgency (p < 0.05, R (2) = 0.24), urinary incontinence (p < 0.05, R (2) = 0.23) and dyspareunia (p < 0.05, R (2) = 0.04). We found also a correlation between global health status and mean dose to vagina (p < 0.05, R (2) = 0.17) and between maximum dose to lumbo-sacral plexus and abdominal pain (p < 0.05, R (2) = 0.07). CONCLUSIONS: Women treated with surgery and adjuvant radiotherapy for endometrial and cervical cancers have good QoL with minimal limitations of daily activities. QoL was correlated with dose-volume parameters such as bladder V40, mean dose to vagina, maximum dose to trigone and LSP

Some observations on the relationship of manifest and hidden esca to rainfall

This paper reports observations on the relationship between the yearly incidence of manifest esca (i.e. diseased plants which show foliar symptoms), hidden esca (that which remains asymptomatic throughout a growing season) and rainfall. Data from three vineyards (two in Tuscany and one in Emilia-Romagna, Italy) showed that rainfall in May-July or only in July was inversely related with hidden esca. For two vineyards, TB in Emilia-Romagna and CAR-3 in Tuscany, the spatial pattern of diseased vines in the first year of appearance of the foliar esca symp-toms was also determined. The maps of the vines in these vineyards indicated that diseased plants mostly occurred alone. This suggests that the disease had its origin in infected rooted cuttings or was triggered by inoculum aerially dispersed from distant sources and/or occurring, at least in hypothesis, in the soil

Molecular and phenotypic characterisation of novel Phaeoacremonium species isolated from esca diseased grapevines

Petri disease and esca are very destructive grapevine decline diseases that occur in most countries where grapevine (Vitis vinifera) is cultivated. Phaeoacremonium species are among the principal hyphomycetes associated with symptoms of the two diseases, producing a range of enzymes and phytotoxic metabolites. The present study compared the phylogeny of a global collection of 118 Phaeoacremonium isolates from grapevines, in order to gain a better understanding of their involvement in Petri disease and esca. Phylogenetic analyses of combined DNA sequence datasets of actin and β-tubulin genes revealed the presence of 13 species of Phaeoacremonium isolated from esca diseased grapevines. Phaeoacremonium aleophilum was the most frequently isolated species with an incidence up to 80 % of all isolates investigated. Species previously described mainly as human pathogenic species, namely Pm. alvesii, Pm. griseorubrum and Pm. rubrigenum are newly reported on grapevine from Turkey, Italy and Croatia, respectively. Phaeoacremonium viticola and Pm. scotyli represent new records for Italy, as well as Pm. mortoniae for Hungary and Croatia. In addition, four new species of Phaeoacremonium, namely Pm. croatiense, Pm. hungaricum, Pm. sicilianum and Pm. tuscanum are newly described from grapevine based on morphology, cultural characteristics, as well as molecular phylogeny

Older and More Recent Observations on Esca : A Critical Overview

The main research findings of studies in esca carried out over the last few years in a number of laboratories are discussed. The topics include: the disease model; the relationship between black dead arm and esca; the role of toxins and xylem cavitation in the development of leaf symptoms; the artificial reproduction of leaf symptoms and wood rot; the inoculum sources of the fungi Phaeomoniella chlamydospora, Phaeoacremonium aleophilum and Fomitiporia mediterranea, and the influence of climate on the incidence of esca. The purpose was to sum up the current state of esca research and where possible to present new suggestions and sometimes alternatives to the suggestions of other researchers. The ultimate aim was to draw attention to those questions in esca research that are open to differing and even opposing explanations because the hard data are still lacking

Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program

Background: The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods: Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results: A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions: The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab