MESSA PUNTO E VALIDAZIONE DI UN METODO PER LA DETERMNAZIONE DELL\ubfACIDO SALICILICO E ACIDO FERULICO NELL\ubfUOMO, E STUDIO DELL'INFLUENZA DEL PATTERN DI MEDITERRANEIT\uc0 DELLA DIETA SULLE CONCENTRAZIONI EMATICHE DI DUESTE DUE MOLECOLE.

A chronic systemic inflammation is reported to be involved in atherosclerosis, coronary heart disease, diabetes and the metabolic syndrome. Evidences suggest that elevated levels of circulating pro-inflammatory markers (interleukin 6, C-reactive protein and tumor necrosis factor alpha) are risk factors for many chronic diseases (Battezzati A, 2005). Food choices play an important role because of macro and micronutrients may interact with human body producing specific metabolic and inflammatory responses relevant to the prevention of chronic-degenerative diseases (Dauchet L, 2009, Pelucchi C, 2009). Particularly, fruit and vegetable provide measurable amounts of bioactive compounds, such as Salicylic acid (SA) that is an ubiquitous hormone in plants. Circulating SA in human is related to fruit and vegetable consumption [Spadafranca et al 2006]. However, only few studies report the effect of acute meal administration on the blood concentrations of salicylic acid. The aim of this study therefore was to investigate the short-term effect of a single meal of fruit on blood concentrations of salicylic acid and the effects of fruit intake on metabolic and inflammatory parameters are unknown. Based on these considerations, a simple, highly selective, and sensitive method using stable isotope dilution and gas chromatography\u2013mass spectrometry has been developed to quantify Salicylic acid and Ferulic acid at concentrations naturally occurring in human serum. This method involves: \u2022 deproteinization with ACN; \u2022 enzymatic hydrolysis with beta-glucuronidase. \u2022 Liquid-liquid extraction with ethylacetate and diethyl ether \u2022 derivatization with BSFTA+TMS1% \u2022 GC-MS- electron impact-selective ion monitoring analysis. We therefore administrated to 26 healthy subjects a peach shake (PSM), of known SA content and centesimal composition, and an isoglucidic solution (MSM). The evening before the tests Group1 (n=16) abstained from FV consumption; Group2 (n=10) kept a free diet. During the tests circulating SA, glucose, insulin, FFA, IL-6 and CRP were measured. Basal SA was lower (p<0,001) in Group1 (0.09\ub10.02 \u3bcmol/l) than in Group2 (0,30\ub10,03 \u3bcmol/l). After PSM, SA peaked at 90 min in Group1 (0,18\ub10,01 \u3bcmol/l, p<0.01) and Group2 (0,38\ub10,02 \u3bcmol/l, p<0.05) and remained above baseline (p<0.05) up to 3 hours. Glycemia increased more slowly with PSM than MSM (+9,69\ub10,70 vs +28,21\ub13,15 mg/dl at 15 min, p<0.01) with a lower average glucose excursion (p<0.05). Insulin peaked at 45 min with PSM and MSM (41,49\ub15,94 vs 38,40\ub15,56 \ub5IU/ml) and decrease less rapidly with PSM. FFA were percentually more suppressed (p<0,01) after PSM. IL-6 increased less (p<0.05) with PSM than MSM. CRP was similar between the meals. In conclusion, peach consumption increases circulating SA for more than three hours. Compared to a watery carbohydrates mix, fruit results in a slower plasma glucose increment, and a lower glucose excursion a smaller increment of inflammatory cytokines. Our results confirm that SA is normally present in the blood of people that does not take salicylates drugs. Fruit and vegetables are the main dietary sources of SA and subjects on a free diet, showed concentrations of SA three times higher than individuals who abstained from fruit and vegetables consumption. However, we noticed that SA is still present in blood in individuals who abstained from eating fruits and vegetables in the previous twelve hours. This phenomenon could be due to the long half-life of SA (Hare LG, 2003) either to endogenous metabolic pathways as recently suggested by Paterson (Paterson JR, 2008). Moreover it is interesting to notice that the concentrations of SA achieved in our study are similar to those found by Xu et al (Xu, 1999) to be effective in inhibiting COX-2 gene transcription in HUVE cells. Even though ASA is clinically used at doses that are two orders of magnitude greater than the doses naturally delivered in our study, we demonstrated that after a fruit meal, basal circulating SA may be reach concentrations comparable with those found by Blacklock et al, 2001 in vegetarians and may overlap those of subjects chronically taking aspirin 75 mg/die

MEDITS-based information on the deep water red shrimps Aristaeomorpha foliacea and Aristeus antennatus (Crustacea: Decapoda: Aristeidae)

Special Volume: Mediterranean marine demersal resources: the Medits international trawl survey (1994-1999)The application of statistical models on a time series of data arising from the MEDITS International Trawl Survey, an experimental demersal resources survey carried out during six years (1994-1999) in the same season of the year (late spring - early summer) using the same fishing gear in a large part of the Mediterranean, has allowed for a study to compare, for the first time, the space-time distribution, abundance, and size structure of the two Aristeids Aristaeomorpha foliacea and Aristeus antennatus throughout most of the Mediterranean Sea. This research has shown a large variability among the six reference areas, that were arbitrarily defined within the basin. In particular the two shrimps do not seem to present any correlation or yield continuity in the years. The same lack of homogeneity was also observed in the time trend of the abundances and frequencies of each of the two species. These data seem to confirm the intrinsic variability of the species, the cause of which is still unknown and undocumented. Nevertheless, a longitudinal gradient of catches has been observed where A. antennatus is more abundant in the west and A. foliacea in the east of the basinVersión del editor1,006

Low-grade gliomas in patients with Noonan syndrome: case-based review of the literature

Noonan syndrome (NS) is a congenital autosomic dominant condition characterized by a variable spectrum from a clinical and genetical point of view. Germline mutations in more than ten genes involved in RAS–MAPK signal pathway have been demonstrated to cause the disease. An higher risk for leukemia and solid malignancies, including brain tumors, is related to NS. A review of the published literature concerning low grade gliomas (LGGs) in NS is presented. We described also a 13-year-old girl with NS associated with a recurrent mutation in PTPN11, who developed three different types of brain tumors, i.e., an optic pathway glioma, a glioneuronal neoplasm of the left temporal lobe and a cerebellar pilocytic astrocytoma. Molecular characterization of the glioneuronal tumor allowed to detect high levels of phosphorylated MTOR (pMTOR); therefore, a therapeutic approach based on an mTOR inhibitor (everolimus) was elected. The treatment was well tolerated and proved to be effective, leading to a stabilization of the tumor, which was surgical removed. The positive outcome of the present case suggests considering this approach for patients with RASopathies and brain tumors with hyperactivated MTOR signaling

CUX1-related neurodevelopmental disorder: deep insights into phenotype-genotype spectrum and underlying pathology

Heterozygous, pathogenic CUX1 variants are associated with global developmental delay or intellectual disability. This study delineates the clinical presentation in an extended cohort and investigates the molecular mechanism underlying the disorder in a Cux1+/− mouse model. Through international collaboration, we assembled the phenotypic and molecular information for 34 individuals (23 unpublished individuals). We analyze brain CUX1 expression and susceptibility to epilepsy in Cux1+/− mice. We describe 34 individuals, from which 30 were unrelated, with 26 different null and four missense variants. The leading symptoms were mild to moderate delayed speech and motor development and borderline to moderate intellectual disability. Additional symptoms were muscular hypotonia, seizures, joint laxity, and abnormalities of the forehead. In Cux1+/− mice, we found delayed growth, histologically normal brains, and increased susceptibility to seizures. In Cux1+/− brains, the expression of Cux1 transcripts was half of WT animals. Expression of CUX1 proteins was reduced, although in early postnatal animals significantly more than in adults. In summary, disease-causing CUX1 variants result in a non-syndromic phenotype of developmental delay and intellectual disability. In some individuals, this phenotype ameliorates with age, resulting in a clinical catch-up and normal IQ in adulthood. The post-transcriptional balance of CUX1 expression in the heterozygous brain at late developmental stages appears important for this favorable clinical course.CAG was supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number P50 HD103525. This work was funded by PID2020-112831GB-I00 AEI /10.13039/501100011033 (MN). SS was supported by a grant from the NIH/NINDS (K23NS119666). SWS is supported by the Hospital for Sick Children Foundation, Autism Speaks, and the University of Toronto McLaughlin Center. EM-G was supported by a grant from MICIU FPU18/06240. EVS. was supported by a grant from the NIH (EY025718). CRF was supported by the fund to support clinical research careers in the Region of Southern Denmark (Region Syddanmarks pulje for kliniske forskerkarriereforløb).Peer reviewe