Caratterizzazione tecnica e fisiologica della Muay Thai

La Muay Thai, comunemente detta “Boxe Thailandese” è un'arte marziale che rientra nella classificazione delle attività intermittenti con entrambi i sistemi energetici reclutati, aerobico e anaerobico, è inoltre caratterizzata dal fatto che il combattimento alla distanza si alterna alla lotta, denominata “clinch”. Nonostante la popolarità della Muay Thai, in ambito mondiale, stia progressivamente aumentando così come è in aumento il numero di atleti che la praticano, le ricerche incentrate su questa arte marziale e gli studi relativi agli aggiustamenti cardiometabolici nonché alle modalità temporali con cui gli specifici gesti atletici si possono succedere nel tempo durante un match, sono ancora estremamente esigui. L’oggetto del nostro studio è stato l’analisi della struttura temporale del combattimento, tramite la Match Analysis off line (analisi visiva del combattimento), con comparazione dei dati ottenuti tra il vincitore (winner) e il perdente (loser) e la valutazione dell’andamento di alcuni importanti parametri metabolici attraverso la misurazione del lattato e della HR, durante un incontro reale di Boxe Thailandese. La sperimentazione è stata condotta su un gruppo di dieci soggetti di sesso maschile, praticanti la disciplina ad un alto livello nazionale, la cui media ± deviazione standard (DS), di età, peso e altezza è di 24,6 ±4,01 anni, 69,4 ±7 kg e 174,1 ±4,3 cm. Gli atleti sono stati sottoposti, in due diverse giornate separate da almeno tre giorni, a due test; durante una prima seduta sperimentale preliminare abbiamo determinato il massimo consumo di ossigeno (VO2max) nel corso di un test sul nastro trasportare, con concomitante stima della Soglia anaerobica (SA) e misura della massima frequenza cardiaca (HR max). In una seconda seduta sperimentale abbiamo effettuato i test di combattimento in palestra e infine abbiamo analizzato i video degli incontri attraverso la Match Analysis. Dai risultati della Match - Analysis è scaturito che i vincitori hanno eseguito un numero più elevato di azioni efficaci (p < 0,05) rispetto ai non-vincitori, grazie ad un numero maggiore di combinazioni (C ) e di attacchi singoli (A) e un numero minore di difese (D) e di tecniche inefficaci. È così emerso come il livello delle realizzazioni sia quasi esclusivamente dovuto all’efficacia della tecnica e alla tattica delle azioni. Abbiamo quindi focalizzato la nostra attenzione sul clinch e sulle azioni di attacco perché si ipotizzava che potessero essere attività dispendiose e probabilmente responsabili dell’incremento di lattato durante il combattimento, dall’ analisi dei dati però non è stata riscontrata nessuna significativa correlazione tra l’andamento dei dati metabolici e le fasi di attacco e di lotta. Dai nostri risultati emerge in maniera interessante come durante le fasi attive del combattimento si siano raggiunti alti valori di lattato ematico e di frequenza cardiaca, rispettivamente di 12,55 mmol/L e di 182,68 b/min, ben oltre la SA rilevata nel test incrementale dove la HR si posizionava a 168,2 b/min. In conclusione si evidenzia come la Boxe Thailandese sia una disciplina caratterizzata da un considerevole impegno energetico-metabolico, sia aerobico che anaerobico. La predominanza del metabolismo lattacido è dimostrata dagli elevati valori di lattato osservati nel presente studio e dalla frequenza degli attacchi (8,6 ± 3,5 sec.). Questo studio potrà essere utilizzato dagli allenatori per la predisposizione di allenamenti specifici che inducano gli adattamenti propri della Muay Thai.

Changes in tumor stiffness for early prediction of tumor response to sorafenib: a proof-of-concept study with elastosonography in an animal model of Hepatocellular Carcinoma (HCC)

Background and aims: Sorafenib is the reference therapy for advanced Hepatocellular Carcinoma (HCC). No method exists to predict in the very early period subsequent individual response. Starting from the clinical experience in humans that subcutaneous metastases may rapidly change consistency under sorafenib and that elastosonography a new ultrasound based technique allows assessment of tissue stiffness, we investigated the role of elastonography in the very early prediction of tumor response to sorafenib in a HCC animal model. Methods: HCC (Huh7 cells) subcutaneous xenografting in mice was utilized. Mice were randomized to vehicle or treatment with sorafenib when tumor size was 5-10 mm. Elastosonography (Mylab 70XVG, Esaote, Genova, Italy) of the whole tumor mass on a sagittal plane with a 10 MHz linear transducer was performed at different time points from treatment start (day 0, +2, +4, +7 and +14) until mice were sacrified (day +14), with the operator blind to treatment. In order to overcome variability in absolute elasticity measurement when assessing changes over time, values were expressed in arbitrary units as relative stiffness of the tumor tissue in comparison to the stiffness of a standard reference stand-off pad lying on the skin over the tumor. Results: Sor-treated mice showed a smaller tumor size increase at day +14 in comparison to vehicle-treated (tumor volume increase +192.76% vs +747.56%, p=0.06). Among Sor-treated tumors, 6 mice showed a better response to treatment than the other 4 (increase in volume +177% vs +553%, p=0.011). At day +2, median tumor elasticity increased in Sor-treated group (+6.69%, range –30.17-+58.51%), while decreased in the vehicle group (-3.19%, range –53.32-+37.94%) leading to a significant difference in absolute values (p=0.034). From this time point onward, elasticity decreased in both groups, with similar speed over time, not being statistically different anymore. In Sor-treated mice all 6 best responders at day 14 showed an increase in elasticity at day +2 (ranging from +3.30% to +58.51%) in comparison to baseline, whereas 3 of the 4 poorer responders showed a decrease. Interestingly, these 3 tumours showed elasticity values higher than responder tumours at day 0. Conclusions: Elastosonography appears a promising non-invasive new technique for the early prediction of HCC tumor response to sorafenib. Indeed, we proved that responder tumours are characterized by an early increase in elasticity. The possibility to distinguish a priori between responders and non responders based on the higher elasticity of the latter needs to be validated in ad-hoc experiments as well as a confirmation of our results in humans is warranted.

Sleep-related changes in blood pressure in hypocretin-deficient narcoleptic mice

Objectives. Blood pressure (BP) physiologically has higher and lower values during the active and rest period, respectively. Subjects failing to show the appropriate BP decrease (10-20%) on passing form diurnal activity to nocturnal rest and sleep have increased risk of target organ damage at the cardiac, vascular and cerebrovascular levels. Hypocretin (HCRT) releasing neurons, mainly located in the lateral hypothalamus, project widely to the central nervous system. Thus HCRT neurons are involved in several autonomic functions, including BP regulation. HCRT neurons also play a key role in wake-sleep cycle regulation, the lack of which becomes evident in HCRT-deficient narcoleptic patients. I investigated whether chronic lack of HCRT signaling alters BP during sleep in mouse models of narcolepsy. Methods. The main study was performed on HCRT-ataxin3 transgenic mice (TG) with selective post-natal ablation of HCRT neurons, HCRT gene knockout mice (KO) with preserved HCRT neurons, and Wild-Type control mice (WT) with identical genetic background. Experiments where replicated on TG and WT mice with hybrid genetic background (hTG and hWT, respectively). Mice were implanted with a telemetric pressure transducer (TA11PA-C10, DSI) and electrodes for discriminating wakefulness (W), rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Signals were recorded for 3 days. Mean BP values were computed in each wake-sleep state and analyzed by ANOVA and t-test with significance at p<0.05. Results. The decrease in BP between either NREMS or REMS and W was significantly blunted in TG and KO with respect to WT as well as in hTG with respect to hWT. Conclusions. Independently from the genetic background, chronic HCRT deficiency leads to a decreased BP difference between W and sleep potentially adverse in narcoleptic subjects. These data suggest that HCRT play an important role in the sleep-dependent cardiovascular control.

Complex higher spins, Weyl invariance and tractors

In this thesis work I analyze higher spin field theories from a first quantized perspective, finding in particular new equations describing complex higher spin fields on Kaehler manifolds. They are studied by means of worldline path integrals and canonical quantization, in the framework of supersymmetric spinning particle theories, in order to investigate their quantum properties both in flat and curved backgrounds. For instance, by quantizing a spinning particle with one complex extended supersymmetry, I describe quantum massless (p,0)-forms and find a worldline representation for their effective action on a Kaehler background, as well as exact duality relations. Interesting results are found also in the definition of the functional integral for the so called O(N) spinning particles, that will allow to study real higher spins on curved spaces. In the second part, I study Weyl invariant field theories by using a particular mathematical framework known as tractor calculus, that enable to maintain at each step manifest Weyl covariance.

Risk factors for postoperative delirium in the elderly

Background: Delirium is defined as an acute disorder of attention and cognition. Delirium is common in hospitalized elderly patient and is associated with increased morbidity, length of stay and patient care costs. Although Delirium can develop at any time during hospitalization, it typically presents early in the post-operative period (Post-Operative Delirium, POD) in the surgery context. The molecular mechanism and possible genetics basis of POD onset are not known, as well as all the risk factors are not completely defined. Our hypothesis is that genetic risk factor involving the inflammatory response could have possible effects on the immunoneuroendocrine system. Moreover, our previous data (inflamm-aging) suggest that aging is associated with an increase of inflammatory status, favouring age-related diseases such as neurodegenerative diseases, frailty, depression among other. Some pro-inflammatory or anti-inflammatory cytokines, seem to play a crucial role in increasing the inflammatory status and in the communication and regulation of immunoneuroendocrine system. Objective: this study evaluated the incidence of POD in elderly patients undergoing general surgery, clinical/physical and psychological risk factors of POD insurgency and investigated inflammatory and genetic risk factors. Moreover, this study evaluated the consequence of POD in terms of institutionalization, development of permanent cognitive dysfunction or dementia and mortality Methods: patients aged over 65 admitted for surgery at the Urgency Unit of S.Orsola-Malpighi Hospital were eligible for this case–control study. Risk factors significantly associated with POD in univariate analysis were entered into multivariate analysis to establish those independently associated with POD. Preoperative plasma level of 9 inflammatory markers were measured in 42 control subjects and 43 subjects who developed POD. Functional polymorphisms of IL-1 α , IL-2, IL-6, IL-8, IL-10 and TNF-alpha cytokine genes were determined in 176 control subjects and 27 POD subjects. Results: A total of 351 patients were enrolled in the study. The incidence of POD was 13•2 %. Independent variables associated with POD were: age, co-morbidity, preoperative cognitive impairment, glucose abnormalities. Median length of hospital stay was 21 days for patients with POD versus 8 days for control patients (P < 0•001). The hospital mortality rate was 19 and 8•4 % respectively (P = 0•021) and mortality rate after 1 year was also higher in POD (P= 0.0001). The baseline of IL-6 concentration was higher in POD patients than patients without POD, whereas IL-2 was lower in POD patients compared to patients without POD. In a multivariate analysis only IL-6 remained associated with POD. Moreover IL-6, IL-8 and IL-2 are associated with co-morbidity, intra-hospital mortality, compromised functional status and emergency admission. No significant differences in genotype distribution were found between POD subjects and controls for any SNP analyzed in this study. Conclusion: In this study we found older age, comorbidity, cognitive impairment, glucose abnormalities and baseline of IL-6 as independent risk factors for the development of POD. IL-6 could be proposed as marker of a trait that is associated with an increased risk of delirium; i.e. raised premorbid IL-6 level predict for the development of delirium.

Depicting the role of CDKN2A/ARF alterations in adult BCR-ABL1-positive acute lymphoblastic leukemia patients: from genomic deletions to prognostic impact

This 9p21 locus, encode for important proteins involved in cell cycle regulation and apoptosis containing the p16/CDKN2A (cyclin-dependent kinase inhibitor 2a) tumor suppressor gene and two other related genes, p14/ARF and p15/CDKN2B. This locus, is a major target of inactivation in the pathogenesis of a number of human tumors, both solid and haematologic, and is a frequent site of loss or deletion also in acute lymphoblastic leukemia (ALL) ranging from 18% to 45% 1. In order to explore, at high resolution, the frequency and size of alterations affecting this locus in adult BCR-ABL1-positive ALL and to investigate their prognostic value, 112 patients (101 de novo and 11 relapse cases) were analyzed by genome-wide single nucleotide polymorphisms arrays and gene candidate deep exon sequencing. Paired diagnosis-relapse samples were further available and analyzed for 19 (19%) cases. CDKN2A/ARF and CDKN2B genomic alterations were identified in 29% and 25% of newly diagnosed patients, respectively. Deletions were monoallelic in 72% of cases and in 43% the minimal overlapping region of the lost area spanned only the CDKN2A/2B gene locus. The analysis at the time of relapse showed an almost significant increase in the detection rate of CDKN2A/ARF loss (47%) compared to diagnosis (p = 0.06). Point mutations within the 9p21 locus were found at very low level with only a non-synonymous substition in the exon 2 of CDKN2A. Finally, correlation with clinical outcome showed that deletions of CDKN2A/B are significantly associated with poor outcome in terms of overall survival (p = 0.0206), disease free-survival (p = 0.0010) and cumulative incidence of relapse (p = 0.0014). The inactivation of 9p21 locus by genomic deletions is a frequent event in BCR-ABL1-positive ALL. Deletions are frequently acquired at the leukemia progression and work as a poor prognostic marker.

La Restless Legs Syndrome aumenta il rischio cardiovascolare e la mortalità a breve termine nei pazienti emodializzati

Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality. Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

Influence of genetic variants and post transcriptional factors on imatinib transporters as determinants of the pharmacological response

Introduction – Although imatinib (IM) is a recognized gold standard in chronic myeloid leukemia (CML) therapy, resistance has emerged in a significant proportion of patients. Aim – The aim of this study was: (1) to investigate the role of genetic variants in genes encoding for IM transporters, as candidate of IM responsiveness and (2) to test the influence of miRNAs on IM response, focusing on efflux transporters. Methods – As a first step, a panel of polymorphisms (SNPs) was genotyped in a subgroup population of 189 patients enrolled in the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial. The association with cytogenetic response and molecular response (MR) was assessed for each SNP. As a second step, an in vitro IM-resistant model (K-562 CML cell line) was established. miRNAs profiles were analyzed using Taqman arrays and in silico search was performed for miRNAs deregulated after IM treatment. mRNA and protein expression were quantified using TaqMan realtime PCR and Western blotting, respectively. Results – (1) Among Caucasian patients, ABCB1 rs60023214 significantly correlated with complete MR (P = 0.005). Concerning SNPs combination in IM uptake transporters, the associations with treatment outcomes were statistically significant for both major and complete MR (P = 0.005 and P = 0.01, respectively). (2) ABCB1 protein was not expressed under any conditions of treatment, differently from ABCG2. Two deregulated miRNAs, namely miR-212 and miR-328, were identified to be inversely correlated with ABCG2 (r2= 0.57; p=0.03 and r2=0.47; p=0.06, respectively). Experiments of loss and gain of function confirmed the functional influence of these miRNAs on ABCG2. Conclusion – The multiple candidate gene approach identified single and combination of SNPs that can be proposed as predictor of IM response. The in vitro study suggested that IM resistance could be mediated by miRNA-dependent mechanism. Further studies are needed to validate these preliminary findings.

International cooperation in endourology: percutaneous and flexible ureteroscopic treatment of lower pole kidney stones

Introduction Lower pole kidney stones represent at time a challenge for the urologist. The gold standard treatment for intrarenal stones <2 cm is Extracorporeal Shock Wave Lithotripsy (ESWL) while for those >2 cm is Percutaneous Nephrolithotomy (PCNL). The success rate of ESWL, however, decreases when it is employed for lower pole stones, and this is particularly true in the presence of narrow calices or acute infundibular angles. Studies have proved that ureteroscopy (URS) is an efficacious alternative to ESWL for lower pole stones <2 cm, but this is not reflected by either the European or the American guidelines. The aim of this study is to present the results of a large series of flexible ureteroscopies and PCNLs for lower pole kidney stones from high-volume centers, in order to provide more evidences on the potential indications of the flexible ureteroscopy for the treatment of kidney stones. Materials and Methods A database was created and the participating centres retrospectively entered their data relating to the percutaneous and flexible ureteroscopic management of lower pole kidney stones. Patients included were treated between January 2005 and January 2010. Variables analyzed included case load number, preoperative and postoperative imaging, stone burden, anaesthesia (general vs. spinal), type of lithotripter, access location and size, access dilation type, ureteral access sheath use, visual clarity, operative time, stone-free rate, complication rate, hospital stay, analgesic requirement and follow-up time. Stone-free rate was defined as absence of residual fragments or presence of a single fragment <2 mm in size at follow-up imaging. Primary end-point was to test the efficacy and safety of flexible URS for the treatment of lower pole stones; the same descriptive analysis was conducted for the PCNL approach, as considered the gold standard for the treatment of lower pole kidney stones. In this setting, no statistical analysis was conducted owing to the different selection criteria of the patients. Secondary end-point consisted in matching the results of stone-free rates, operative time and complications rate of flexible URS and PCNL in the subgroup of patients harbouring lower pole kidney stones between 1 and 2 cm in the higher diameter. Results A total 246 patients met the criteria for inclusion. There were 117 PCNLs (group 1) and 129 flexible URS (group 2). Ninety-six percent of cases were diagnosed by CT KUB scan. Mean stone burden was 175±160 and 50±62 mm2 for groups 1 and 2, respectively. General anaesthesia was induced in 100 % and 80% of groups 1 and 2, respectively. Pneumo-ultrasonic energy was used in 84% of cases in the PCNL group, and holmium laser in 95% of the cases in the flexible URS group. The mean operative time was 76.9±44 and 63±37 minutes for groups 1 and 2 respectively. There were 12 major complications (11%) in group 1 (mainly Grade II complications according to Clavidien classification) and no major complications in group 2. Mean hospital stay was 5.7 and 2.6 days for groups 1 and 2, respectively. Ninety-five percent of group 1 and 52% of group 2 required analgesia for a period longer than 24 hours. Intraoperative stone-free rate after a single treatment was 88.9% for group 1 and 79.1% for group 2. Overall, 6% of group 1 and 14.7% of group 2 required a second look procedure. At 3 months, stone-free rates were 90.6% and 92.2% for groups 1 and 2, respectively, as documented by follow-up CT KUB (22%) or combination of intra-venous pyelogram, regular KUB and/or kidney ultrasound (78%). In the subanalysis conducted comparing 82 vs 65 patients who underwent PCNL and flexible URS for lower pole stones between 1 and 2 cm, intreoperative stone-free rates were 88% vs 68% (p= 0.03), respectively; anyway, after an auxiliary procedure which was necessary in 6% of the cases in group 1 and 23% in group 2 (p=0.03), stone-free rates at 3 months were not statistically significant (91.5% vs 89.2%; p=0.6). Conversely, the patients undergoing PCNL maintained a higher risk of complications during the procedure, with 9 cases observed in this group versus 0 in the group of patients treated with URS (p=0.01) Conclusions These data highlight the value of flexible URS as a very effective and safe option for the treatment of kidney stones; thanks to the latest generation of flexible devices, this new technical approach seems to be a valid alternative in particular for the treatment of lower pole kidney stones less than 2 cm. In high-volume centres and in the hands of skilled surgeons, this technique can approach the stone-free rates achievable through PCNL in lower pole stones between 1 and 2 cm, with a very low risk of complications. Furthermore, the results confirm the high success rate and relatively low morbidity of modern PCNL for lower pole stones, with no difference detectable between the prone and supine position.

Ruolo ecologico di Ficopomatus enigmaticus (Polychaetae: Serpulidae) nelle lagune dell’Oristanese.

Gli agglomerati calcarei costruiti dalla specie invasiva Ficopomatus enigmaticus, polichete serpulide, possono influenzare i sistemi lagunari e produrre effetti negativi per la pesca e alterazioni nell’ambiente. Le lagune di Corru S’Ittiri (CI), San Giovanni-Marceddì (GM) e Santa Giusta (SG) sono state studiate al fine di definire le condizioni ecologiche che favoriscono le formazione delle costruzioni biogeniche di F. enigmaticus. In questo lavoro sono riportati i risultati preliminari, osservati in ogni laguna, sulle caratteristiche del sedimento (granulometria, sostanza organica e carbonati) e della comunità macrozoobentonica (abbondanza, biomassa e diversità), in due condizioni contrastanti: presenza e assenza dei reef, in due tempi di campionamento (maggio e ottobre 2012). I campioni di sedimento sono stati prelevati esclusivamente nel primo tempo di campionamento. La granulometria dei sedimenti era differente nelle tre lagune: CI e SG si sono rivelate più sabbiose, mentre GM era più fangosa. Sono stati osservati diversi valori nei contenuti di sostanza organica e carbonati senza rivelarsi significativamente diversi. Nel primo tempo di campionamento l’abbondanza di zoobentos varia tra le zone di presenza (P) e le zone di assenza (A) dei reef; in CI l’abbondanza è maggiore in P rispetto ad A, mentre in GM e SG invece è maggiore in A rispetto a P. La stessa situazione si verifica nel secondo tempo di campionamento. La biomassa, al tempo uno, è risultata maggiore nelle zone P rispetto alle zone A in CI e SG; in GM le zone A la biomassa è risultata maggiore rispetto a P. Nel secondo tempo di campionamento i valori risultano maggiori in P rispetto ad A in CI e GM; valori maggiori in A rispetto a P si sono riscontrati in SG. Importante da evidenziare la presenza di un altro costruttore di barriere, Hudroides dianthus, con abbondanze superiori rispetto a quelle di F. enigmaticus in particolare in CI e SG. Sono stati anche trovati diversi individui di Musculista sonhousia in CI e GM. M. senhousia è noto come specie invasiva in molte lagune del Mediterraneo ed è stato recentemente individuato nella zone di Oristano. Questo lavoro ha dimostrato come le caratteristiche dei sedimenti lagunari, la struttura della comunità macrozoobentonica, così come la natura e l’abbondanza delle specie costruttrici di reef può variare tra le lagune e le diverse zone delle lagune. È importante indagare sulle condizioni chimico-fisiche e idrodinamiche delle singole lagune per capire cosa influenza il reale sviluppo dei reef dei biocostruttori.

Cellular and Molecular Biomarkers for Risk Assessment of Colorectal cancer

The detection of Colorectal Cancer (CRC), at early stages, is one of the proven strategies resulting in a higher cure rate. In recent years, several studies have appeared identifying potential cancer markers in serum, plasma and stool in an attempt to improve actual screening procedures. Thus, the aim of the study was (1) Evaluate MN frequency, (2) Evaluate plasma ultrafiltrate capacity to induce MN formation, (3) Evaluate SEPT9 and NOTCH3 promoter methylation profile in peripheral blood lymphocytes from subjects resulted positive to fecal occult blood test and examined by colonoscopy. MN frequency was significantly higher in subjects with histological diagnosis of CRC and adenoma than control (p ≤ 0.001 and p ≤ 0.01, respectively). About, CF-MN analysis, a statistically significant difference was observed between CRC and control (p ≤ 0.05). On the other hand, SEPT9 and NOTCH3 promoter methylation status was significantly lower in CRC subjects than controls; additionally, NOTCH3 promoter methylation status was significantly lower in CRC subjects than adenoma subjects (p ≤ 0.01). The results obtained allow conclude that MN frequency varies according CRC pathologic status and, together with other variables, is a valid biomarker for adenoma and CRC risk. Additionally, the plasma of patients affected with CRC not only serve as a biomarker for oxidative stress but also as biomarker of genetic damage correlated with the carcinogenic process that verifies in colon-rectum. SEPT9 and NOTCH3 promoter methylation status, at peripheral blood level, varies according hystopathological changes observed in colon-rectum, suggesting that promoter methylation profile of these genes could be a reliable biomarker for CRC risk.

Predictive Ability of NGAL as a Marker of Renal Damage: evaluation of Multiple Clinical Settings

Introduction. Neutrophil Gelatinase-Associated Lipocalin (NGAL) belongs to the family of lipocalins and it is produced by several cell types, including renal tubular epithelium. In the kidney its production increases during acute damage and this is reflected by the increase in serum and urine levels. In animal studies and clinical trials, NGAL was found to be a sensitive and specific indicator of acute kidney injury (AKI). Purpose. The aim of this work was to investigate, in a prospective manner, whether urine NGAL can be used as a marker in preeclampsia, kidney transplantation, VLBI and diabetic nephropathy. Materials and methods. The study involved 44 consecutive patients who received renal transplantation; 18 women affected by preeclampsia (PE); a total of 55 infants weighing ≤1500 g and 80 patients with Type 1 diabetes. Results. A positive correlation was found between urinary NGAL and 24 hours proteinuria within the PE group. The detection of higher uNGAL values in case of severe PE, even in absence of statistical significance, confirms that these women suffer from an initial renal damage. In our population of VLBW infants, we found a positive correlation of uNGAL values at birth with differences in sCreat and eGFR values from birth to day 21, but no correlation was found between uNGAL values at birth and sCreat and eGFR at day 7. systolic an diastolic blood pressure decreased with increasing levels of uNGAL. The patients with uNGAL <25 ng/ml had significantly higher levels of systolic blood pressure compared with the patients with uNGAL >50 ng/ml ( p<0.005). Our results indicate the ability of NGAL to predict the delay in functional recovery of the graft. Conclusions. In acute renal pathology, urinary NGAL confirms to be a valuable predictive marker of the progress and status of acute injury.

Non invasive assessment of right ventricle in patients with operated tetralogy of Fallot

The objective of this study was to evaluate right ventricular function in patients with right ventricular volume overload in patients with (tetralogy of Fallot, and pulmonary atresia + VSD ) underwent corrective surgery; with echocardiography measure that can be easily applied; and to study the relationship between ProBNP and the contractile function of the right ventricle, dilated right atrium, and the consequences of pulmonary insufficiency . Methods: The study included 50 patients (50% males, mean age 30.64 ± 13.30 years) with prior cardiac surgical intervention of TDF (90%) or pulmonary atresia + VSD (10%). (49 pz) have performed a cardiac MRI and clinical evaluation, (47 pz) echocardiogram, (48 pz) ECG, (34 pz) a cardiopulmonary exercise testing, (29 pz) a dosage of ProBNP. Results: The S-wave velocity (p <0.0001), the TAPSE (p <0.0001) correlated significantly with RVEF estimated by cardiac MRI. The VO2 max was 27.93 ± 12.91 ml / kg / min, 15% of patients had VE/VCO2 The peak> 35. ProBNP correlated positively and significantly with the area of the right atrium (p = 0.0001), and negative and significant with VO2 max (p = 0.04). Those who have increased pulmonary insufficiency (PVR fraction> 30%) have a significantly increased RVED volume (p = 0.01), reduced VO2 max (p = 0.04), and lower ejection fraction of LV (p = 0.02) than the group of patients with PVR ≤ 30. Conclusion: The TAPSE and S-wave velocity are fundamental and may become the technique of choice for routine assessment of RV systolic function in adult patients with TOF. The monitoring of the Pro BNP is probably a choice, given the simplicity and their information that correlate with the test cardiopulmonary. In view of the ventricular-ventricular interaction, so measures to maintain or restore the functioning of the pulmonary valve could preserve biventricular function.

Autoantibodies in patients with psoriasis on anti-TNFalpha therapy

Introduction: Anti-TNF-alfa therapy has been effective in the treatment of patients with refractory psoriasis and psoriasic arthritis. However, the risk of developing autoantibodies in these patients undergoing this therapy is not clear. Objective: To evaluate the induction of specific autoantibodies after anti-TNFα therapy in patients with psoriasis and psoriasic arthritis and, to evaluate the influence of the use of methotrexate on the values of autoantibodies developed during this therapy. Patients and methods: Serum samples from 120 patients, obtained before(baseline) the introduction of anti-TNF-alpha therapy and approximately each 3-6 months during the therapy.O f these 120 patients, 113 were found negative for autoantibodies before starting anti -TNFalpha therapy, 7 were found positive for ANA. The analysis included detection of antinuclear antibodies (ANA) and anti-dsDNA antibodies (indirect immunofluorescence on Hep-2 cells and Crithidia luciliae, respectively); anti extractable nuclear antigens antibodies( ENA)(ELISA). RESULTS: Infliximab is associated with the highest occurrence rate of ANA, anti-dsDNA, ENA with approximately 69,2%, 11,5%, 7,6% of patients treated testing positive. In comparison, only 20%, 6,6%, 2,2% of patients treated with Adalimumab, and 19%, 2,3%, 2,3% of patients treated with Etanercept were positive for ANA, Anti-dsDNA, ENA respectively. As regard the seven patients who were positive at baseline, six of them (85.7%) in addition to being remained positive during the therapy they have also increased the autoantibodies ’s titers. Conclusion: our study have shown that Infliximab is associated with the highest rate of autoantibodies. The concomitant treatment with methotrexate did not modify the titers of autoantibodies developed during the therapy anti-TNFalph. The incidence of ANA, anti-dsDNA antibodies did not correlate with development of Lupus-like syndromes. The difference in the frequency of autoantibodies between psoriasis and psoriatic arthritis was not statistically significant (p = 0.867).