Dissincronia meccanica del ventricolo destro nell'ipertensione ateriosa polmonare idiopatica

L’ipertensione arteriosa polmonare è una malattia grave caratterizzata da un progressivo aumento delle resistenze vascolari polmonari (PVR), che evolve nel tempo verso l’insufficienza cardiaca destra e la morte. Lo sviluppo di disfunzione ventricolare destra è un segno di prognosi sfavorevole nei pazienti con ipertensione polmonare ed è la loro più frequente causa di morbilità e mortalità. L’insufficienza del ventricolo destro (VD) è una sindrome clinica complessa che può derivare da qualsiasi alterazione cardiovascolare di natura strutturale o funzionale che riduce la capacità del ventricolo destro di riempirsi ed espellere sangue. Gli studi precedenti che hanno valutato lo status emodinamico e la prognosi nei pazienti con ipertensione polmonare, hanno dimostrato che le elevate pressioni atriali destre e la bassa gittata cardiaca sono, in maniera significativa, associate ad una ridotta sopravvivenza. Al contrario, il livello di pressione in arteria polmonare ha solo un modesto significato prognostico, dal momento che essa può in parte ridursi per l’instaurarsi di insufficienza ventricolare destra. A causa della sua forma complessa e dalla sua geometria scarsamente definita, è spesso difficile valutare la morfologia e la funzione del ventricolo destro. Tuttavia, l’individuazione di una disfunzione ventricolare in fase sub-clinica, può essere utile per l’ottimizzazione della terapia e per fornire informazioni prognostiche. Nel seguente studio è stato teorizzato che le anomalie nella performance regionale del ventricolo destro siano una misura sensibile del suo status funzionale rispetto ai parametri ottenuti mediante ecocardiografia bidimensionale standard. Il sovraccarico pressorio cronico influisce specificatamente sulla motilità regionale delle fibre longitudinali che forniscono il maggior contributo alla contrazione sistolica del ventricolo destro e, conseguentemente, producono effetti sul suo pattern di contrazione. Questa condizione potrebbe contribuire all’instaurarsi di una dissincronia meccanica nella camera ventricolare destra, con impatto significativo sul ventricolo già sovraccarico. Così si è ipotizzato che il picco dello strain longitudinale miocardico e la quantificazione dei tempi di attivazione della deformazione longitudinale tra le pareti, calcolati mediante ecocardiografia Speckle Tracking bidimensionale, potrebbero identificare precocemente, nei pazienti con ipertensione polmonare, una disfunzione ventricolare destra e quindi predirne il peggioramento clinico

Impact of heart rate on myocardial salvage in timely reperfused patients with STSegment elevation myocardial infarction. new insights from cardiovascular magnetic resonance

BACKGROUND: Previous studies evaluating the progression of the necrotic wave in relation to heart rate were carried out only in animal models of ST-elevated myocardial infarction (STEMI). Aim of the study was to investigate changes of myocardial salvage in relation to different heart rates at hospital admission in timely reperfused patients with STEMI by using cardiovascular magnetic resonance (CMR). METHODS: One hundred-eighty-seven patients with STEMI successfully and timely treated with primary coronary angioplasty underwent CMR five days after hospital admission. According to the heart rate at presentation, patients were subcategorized into 5 quintiles: <55 bpm (group I, n = 44), 55-64 bpm (group II, n = 35), 65-74 bpm (group III, n = 35), 75-84 bpm (group IV, n = 37), ≥85 bpm (group V, n = 36). Area at risk, infarct size, microvascular obstruction (MVO) and myocardium salvaged index (MSI) were assessed by CMR using standard sequences. RESULTS: Lower heart rates at presentation were associated with a bigger amount of myocardial salvage after reperfusion. MSI progressively decreased as the heart rates increased (0.54 group I, 0.46 group II, 0.38 group III, 0.34 group IV, 0.32 group V, p<0.001). Stepwise multivariable analysis showed heart rate, peak troponin and the presence of MVO were independent predictor of myocardial salvage. No changes related to heart rate were observed in relation to area at risk and infarct size. CONCLUSIONS: High heart rates registered before performing coronary angioplasty in timely reperfused patients with STEMI are associated with a reduction in salvaged myocardium. In particular, salvaged myocardium significantly reduced when heart rate at presentation is ≥85 bpm

ERK-1 MAP kinase prevents TNF-induced apoptosis through bad phosphorylation and inhibition of bax translocation in HeLa cells

Extracellular signal-regulated kinase (ERK) 1/2 signaling is involved in tumor cell survival through the regulation of Bcl-2 family members. To explore this further and to demonstrate the central role of the mitochondria in the ERK1/2 pathway we used the HeLa cellular model where apoptosis was induced by tumor necrosis factor (TNF) and cycloheximide (CHX). We show that HeLa cells overexpressing ERK-1 displayed resistance to TNF and CHX. HeLa cells overexpressing a kinase-deficient form of ERK-1 (K71R) were more sensitive to TNF and CHX. In the ERK-1 cells, Bad was phosphorylated during TNF + CHX treatment. In the HeLa wt cells and in the K71R clones TNF and CHX decreased Bad phosphorylation. ERK-1 cells treated with TNF and CHX did not release cytochrome c from the mitochondria. By contrast, HeLa wt and K71R clones released cytochrome c. Bax did not translocate to the mitochondria in ERK-1 cells treated with TNF + CHX. Conversely, HeLa wt and K71R clones accumulated Bax in the mitochondria. In the HeLa wt cells and in both ERK-1 transfectants Bid was cleaved and accumulated in the mitochondria. The caspase-8 inhibitor IETD-FMK and the mitochondrial membrane permeabilization inhibitor bongkrekic acid (BK), partially prevented cell death by TNF + CHX. Anisomycin, a c-Jun N-terminal kinases activator, increased TNF-killing. The ERK-1 cells were resistant to TNF and anisomycin, whereas K71R clones resulted more sensitive. Our study demonstrates that in HeLa cells the ERK-1 kinase prevents TNF + CHX apoptosis by regulating the intrinsic mitochondrial pathway through different mechanisms. Inhibition of the intrinsic pathway is sufficient to almost completely prevent cell death. © 2009 Wiley-Liss, Inc

Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments

BACKGROUND: It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential. RESULTS: In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC). Cells were treated with: (1) TPA, forskolin, IBMX, FGF-1 or (2) retinoic acid and 2-mercaptoethanol (BME). Treatment (1) induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1) compared with treatment (2). In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments. CONCLUSION: Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage

Socio-demographic determinants of coinfections by HIV, hepatitis B and hepatitis C viruses in central Italian prisoners

BACKGROUND: The coinfections HIV/HCV/HBV are an important health issue in penitentiary communities. The aim of the study was to examine HIV, HBV and HCV coinfections determinants amongst prisoners in the jails of Southern Lazio (Central Italy), in the period 1995-2000. METHODS: Diagnosis of seropositivities for HIV, HBV and HCV was made using ELISA method. A multiple logistic regression analysis was conducted to verify the influence of socio-demographic factors on the HIV/HBV/HCV coinfections. RESULTS: HIV/HCV, HBV/HCV and HIV/HBV coinfections were detected in 42 (4%), 203 (17.9%) and 31 (2.9%) inmates, respectively. These coinfections are significantly associated with the status of drug addiction (OR = 16.02; p = 0.012; OR = 4.15; p < 0.001; OR = 23.57; p = 0.002), smoking habits (OR = 3.73; p = 0.033; OR = 1.42; p = 0.088; OR = 4.25; p = 0.053) and Italian nationality (OR = 7.05; p = 0.009; OR = 2.31; p < 0.001; OR = 4.61; p = 0.04). CONCLUSION: The prevalence of HIV, HBV and HCV seropositivity in jails suggests that information and education programs for inmates could be useful to reduce the spread of such infections

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Bicoherence Interpretation in EEG Requires Signal to Noise Ratio Quantification: An Application to Sensorimotor Rhythms

In the electroencephalogram (EEG) the quadratic phase coupling (QPC) phenomenon indicates the presence of non-linear interactions among brain rhythms that could affect the interpretation of their physiological meaning. We propose the use of the bicoherence as a QPC quantification method to understand the nature of brain rhythm interplay

Significant increase of flow kinetic energy in “nonresponders” patients to cardiac resynchronization therapy

Backgrounds: It’s still unclear if different patterns of intraventricular flow dynamics may be detected in patients nonresponders to cardiac resynchronization therapy (CRT) as compared to responders ones. Aim of this study was to evaluate the characteristics of left ventricular (LV) flow dynamics 6-months after CRT to identify Echo-particle imaging velocity (PIV) patterns were more frequently detected in nonresponders patients. Methods: Thirty-two patients with dilated cardiomyopathy, undergoing CRT, were enrolled in this study. All patients underwent 2D and 3D echo and fluid dynamics assessment 6 months after CRT, during active CRT (CRT-ON) and during a temporarily discontinued state (CRT-OFF). LV volumes systolic and diastolic volumes (LVESV and LVEDV), ejection fraction (LVEF), global longitudinal strain (GLS), systolic dyssynchrony index (SDI), and several geometrical and functional Echo-PIV- derived parameters were calculated. Patients were divided in two groups: “responders” to CRT (decrease in LVESV>15% 6 months after CRT) and “nonresponders.” Results: During CRT-OFF, LVEF, LS were lower, while SDI and LVESV were higher in nonresponders group (P=.030, P=.051, P=.035, and P=.025, respectively). Energy dissipation, vortex area, and vorticity fluctuation were higher in “nonresponders” patients during CRT-OFF (P=.038, P=.054, and P=.035, respectively). During CRT-ON, energy dissipation, vortex area, and vorticity fluctuation further increase in nonresponders patients (P=.020, P=.038, and P=.030, respectively) with concomitant worsening of SDI (P=.045). Conclusion: Our data show a significant worsening in flow-derived parameters in CRT “nonresponders” patients as compared with responders. Further larger longitudinal studies are necessary to assess whether these more chaotic intraventricular flow-patterns may contribute to a persistent adverse remodeling observed in this subset of patiientsBackgrounds: It’s still unclear if different patterns of intraventricular flow dynamics may be detected in patients nonresponders to cardiac resynchronization therapy (CRT) as compared to responders ones. Aim of this study was to evaluate the characteristics of left ventricular (LV) flow dynamics 6-months after CRT to identify Echo-particle imaging velocity (PIV) patterns were more frequently detected in nonresponders patients. Methods: Thirty-two patients with dilated cardiomyopathy, undergoing CRT, were enrolled in this study. All patients underwent 2D and 3D echo and fluid dynamics assessment 6 months after CRT, during active CRT (CRT-ON) and during a temporarily discontinued state (CRT-OFF). LV volumes systolic and diastolic volumes (LVESV and LVEDV), ejection fraction (LVEF), global longitudinal strain (GLS), systolic dyssynchrony index (SDI), and several geometrical and functional Echo-PIV- derived parameters were calculated. Patients were divided in two groups: “responders” to CRT (decrease in LVESV>15% 6 months after CRT) and “nonresponders.” Results: During CRT-OFF, LVEF, LS were lower, while SDI and LVESV were higher in nonresponders group (P=.030, P=.051, P=.035, and P=.025, respectively). Energy dissipation, vortex area, and vorticity fluctuation were higher in “nonresponders” patients during CRT-OFF (P=.038, P=.054, and P=.035, respectively). During CRT-ON, energy dissipation, vortex area, and vorticity fluctuation further increase in nonresponders patients (P=.020, P=.038, and P=.030, respectively) with concomitant worsening of SDI (P=.045). Conclusion: Our data show a significant worsening in flow-derived parameters in CRT “nonresponders” patients as compared with responders. Further larger longitudinal studies are necessary to assess whether these more chaotic intraventricular flow-pattern

Kaempferol Induces Apoptosis in Two Different Cell Lines Via Akt Inactivation, Bax and SIRT3 Activation, and Mitochondrial Dysfunction

Kaempferol (3,4',5,7-tetrahydroxyflavone) is a flavonoid with anti- and pro-oxidant activity present in various natural sources. Kaempferol has been shown to posses anticancer properties through the induction of the apoptotic program. Here we report that treatment of the chronic myelogenous leukemia cell line KG62 and promyelocitic human leukemia U937 with 50 mu M kaempferol resulted in an increase of the antioxidant enzymes Mn and Cu/Zn superoxide dismutase (SOD). Kaempferol treatment induced apoptosis by decreasing the expression of Bcl-2 and increasing the expressions of Bax. There were also induction of mitochondrial release of cytochrome c into cytosol and significant activation of caspase-3, and -9 with PARP cleavage. Kaempferol treatment increased the expression and the mitochondria localization of the NAD-dependent deacetylase SIRT3. K562 cells stably overexpressing SIRT3 were more sensitive to kaempferol, whereas SIRT3 silencing did not increase the resistance or K562 cells to kaempferol. Inhibition of PI3K and de-phosphorylation of Akt at Ser473 and Thr308 was also observed after treating both K562 and U937 cells with kaempferol. In conclusion our study shows that the oxidative stress induced by kaempferol in K562 and U937 cell lines causes the inactivation of Akt and the activation of the mitochondrial phase of the apoptotic program with an increase of Bax and SIRT3, decrease of Bcl-2, release of cytochrome c, caspase-3 activation, and cell death. J. Cell. Biochem. 106: 643-650, 2009. (C) 2009 Wiley-Liss, Inc