Activation of Stress Kinases in the Brain of Mucopolysaccharidosis IIIB mice

The accumulation of heparan sulfate (HS) in lysosomes is the primary consequence of the enzyme defect (α-N-acetylglucosaminidase) in mucopolysaccharidosis type IIIB. This accumulation triggers a cascade of pathological events that progressively leads to CNS pathology. Here we examined the activation of the three major stress kinases in the neuronal tissue of a murine model of the disease. ERK1/2 was significantly higher in the cortex of 1–2-month-old affected animals compared with wild-type (Wt) littermates. Similarly, ERK1/2 was stimulated in neurons cultured from MPS IIIB mice. SAPK/JNK was also found to be activated in the cortex of 1–2-month-old affected animals compared with Wt subjects, and the same was found for cultured neurons. In contrast, the active form of p38MAPK was lower in the cortex of 1-month-old MPS IIIB mice compared with Wt animals, but no significant difference was found between the two p38MAPK analyzed in normal and affected neurons cultured in vitro. These data indicate the possible involvement of MAPK dysregulation in the early stage of MPS IIIB brain disease. © 2011 Wiley-Liss, Inc

Long-term treatment with high-dose of sildenafil in a thalassemic patient with pulmonary hypertension

We report a case of a 37-years-old man, affected by thalassemia major, hypogonadotropic hypogonadism, chronic HCV-hepatitis, diabetes mellitus, severe osteoporosis, prior septic pulmonary embolism and pulmonary artery hypertension was performed a long-term treatment with highdose of sildenafil (120 mg/die) with reduction of pulmonary arterial systolic pressure and of the dyspnea

Intermittent vertebral flow in asymptomatic progression of aortic dissection

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Intermittent vertebral flow in asymptomatic progression of aortic dissection.

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Neutrophil/lymphocyte ratio predicts in‐hospital complications in Takotsubo syndrome. Results from a prospective multi‐center registry

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Sildenafil improves clinical and functional status of an elderly postmenopausal female with 'out of proportion' PH associated with left heart disease

We report a case of an elderly woman with heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH), refractory to conventional therapy for left heart failure and successfully treated by sildenafil

Investigating the Role of Guanosine on Human Neuroblastoma Cell Differentiation and the Underlying Molecular Mechanisms

Neuroblastoma arises from neural crest cell precursors failing to complete the process of differentiation. Thus, agents helping tumor cells to differentiate into normal cells can represent a valid therapeutic strategy. Here, we evaluated whether guanosine (GUO), a natural purine nucleoside, which is able to induce differentiation of many cell types, may cause the differentiation of human neuroblastoma SH-SY5Y cells and the molecular mechanisms involved. We found that GUO, added to the cell culture medium, promoted neuron-like cell differentiation in a time- and concentration-dependent manner. This effect was mainly due to an extracellular GUO action since nucleoside transporter inhibitors reduced but not abolished it. Importantly, GUO-mediated neuron-like cell differentiation was independent of adenosine receptor activation as it was not altered by the blockade of these receptors. Noteworthy, the neuritogenic activity of GUO was not affected by blocking the phosphoinositide 3-kinase pathway, while it was reduced by inhibitors of protein kinase C or soluble guanylate cyclase. Furthermore, the inhibitor of the enzyme heme oxygenase-1 but not that of nitric oxide synthase reduced GUO-induced neurite outgrowth. Interestingly, we found that GUO was largely metabolized into guanine by the purine nucleoside phosphorylase (PNP) enzyme released from cells. Taken together, our results suggest that GUO, promoting neuroblastoma cell differentiation, may represent a potential therapeutic agent; however, due to its spontaneous extracellular metabolism, the role played by the GUO-PNP-guanine system needs to be further investigated

Sildenafil improves clinical and functional status of an elderly postmenopausal female with ‘out of proportion’ PH associated with left heart disease

We report a case of an elderly woman with heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH), refractory to conventional therapy for left heart failure and successfully treated by sildenafil

Statin therapy blunts inflammatory activation and improves prognosis and left ventricular performance assessed by Tissue Doppler Imaging in subjects with chronic ischemic heart failure: results from the Daunia Heart Failure Registry

BACKGROUND: A limited number of studies have used Tissue Doppler Imaging (TDI) to evaluate the effect of statin therapy on left ventricular dysfunction in patients with chronic heart failure. In this work, we aimed to determine whether statin administration influenced prognosis, inflammatory activation and myocardial performance evaluated by Tissue Doppler Imaging in subjects enrolled in the Daunia Heart Failure Registry, a local registry of patients with chronic heart failure. METHODS: This study retrospectively analyzed 353 consecutive outpatients with chronic heart failure (mean follow-up 384 days), based on whether statin therapy was used. In all patients, several Tissue Doppler Imaging parameters were measured; circulating levels of interleukin (IL)-6, IL-10 and C-reactive protein were also assayed. RESULTS: Statin administration in 128 subjects with ischemic heart disease was associated with a lower incidence of adverse events (rehospitalization for HF 15% vs. 46%, p<0.001; ventricular arrhythmias 5% vs. 21%, p<0.01; cardiac death 1% vs. 8%, p<0.05), lower circulating levels of IL-6 (p<0.05) and IL-10 (p<0.01), lower rates of chronic heart failure (p<0.001) and better Tissue Doppler Imaging performance (E/E' ratio 12.82 + 5.42 vs. 19.85 + 9.14, p<0.001; ET: 260.62+ 44.16 vs. 227.11 +37.58 ms, p<0.05; TP: 176.79 + 49.93 vs. 136.7 + 37.78 ms, p<0.05 and St: 352.35 + 43.17 vs. 310.67 + 66.46 + 37.78 ms, p<0.05). CONCLUSIONS: Chronic ischemic heart failure outpatients undergoing statin treatment had fewer readmissions for adverse events, blunted inflammatory activation and improved left ventricular performance assessed by Tissue Doppler Imaging