117,703 research outputs found

    Cambiano i luoghi, mutano le forme

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    affianca il Salone Internazionale dell’edilizia SAIE. In particolare dopo un commento al tema individuato per il dibattito: innovazione e nuove centralità urbane, l’articolo va ad approfondire, attraverso la presa in esame di alcuni progetti, la figura degli architetti Adolfo Natalizi, Peter Cook, Helmut Jahn, Coop Himmelb(l)au e Marco Casamenti, tutti ospiti del convegno

    MAINTENANCE of HEPARAN-SULFATE STRUCTURE THROUGHOUT EVOLUTION - CHEMICAL and ENZYMIC DEGRADATION, and C-13 NMR-SPECTRAL EVIDENCE

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    IST CHIM & BIOCHIM G RONZONI,MILANO,ITALYESCOLA PAULISTA MED,DEPT BIOQUIM,BR-04034 São Paulo,SP,BRAZILESCOLA PAULISTA MED,DEPT BIOQUIM,BR-04034 São Paulo,SP,BRAZILESCOLA PAULISTA MED,DEPT BIOQUIM,BR-04034 São Paulo,SP,BRAZILWeb of Scienc

    Modulation of gamma globin genes expression by histone deacetylase Inhibitors : an in vitro study

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    Induction of fetal haemoglobin (HbF) is a promising therapeutic approach for the treatment of β-thalassaemia and sickle cell disease (SCD). Several pharmacological agents, such as hydroxycarbamide (HC) and butyrates, have been shown to induce the γ-globin genes (HBG1, HBG2). However, their therapeutic use is limited due to weak efficacy and an inhibitory effect on erythroid differentiation. Thus, more effective agents are needed. The histone deacetylase (HDAC) inhibitors are potential therapeutic haemoglobin (Hb) inducers able to modulate gene expression through pleiotropic mechanisms. We investigated the effects of a HDAC inhibitor, Givinostat (GVS), on erythropoiesis and haemoglobin synthesis and compared it with sodium butyrate and HC. We used an in vitro erythropoiesis model derived from peripheral CD34+ cells of healthy volunteers and SCD donors. GVS effects on erythroid proliferation and differentiation and on Hb synthesis were investigated. We found that GVS at high concentrations delayed erythroid differentiation with no specific effect on HBG1/2 transcription. At a low concentration (1 nmol/l), GVS induced Hb production with no effects on cells proliferation and differentiation. The efficacy of GVS 1 mol/l in Hb induction in vitro was comparable to that of HC and butyrate. Our results support the evaluation of GVS as a new candidate molecule for the treatment of the haemoglobinophathies due to its positive effects on haemoglobin production at low and non-toxic concentrations

    Cardiac development and remodelling in Magic-F1 transgenic mice

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    MAGIC-F1 (Met Activating Genetically Improved Chimeric Factor 1) is a human recombi- nant protein, derived from dimerization of the receptor-binding domain of hepatocyte growth factor (HGF). Previous experiments demonstrated that skeletal muscle specific expression of Magic-F1 can induce constitutive muscular hypertrophy, improve running performance and accelerate muscle regeneration after injury in hemizigous transgenic mice [1]. Furthermore, the microarray analysis of Magic-F1+/+ satellite cells showed transcriptomic changes in genes involved in the control of muscle growth, development and vascularisation [2]. In this study we demonstrate that Magic-F1 mice show an alteration of the heart morphol- ogy. Morphometric analysis and three-dimensional reconstruction of the hearth revealed that MAGIC-F1 paracrine effect is able to induce a robust remodelling of the left ventricle cham- ber in transgenic mice. Interestingly, we found in Magic-F1 hearts an alteration of Phd2 and HIF1 protein levels. These two oxygen sensors are found dysregulated in cardiac ischaemic conditions, where generalised hypoxia causes functional impairments in cardiomyocytes and structural tissue damage [3-4]. These preliminary results support the involvement of oxygen sensors in Magic-F1-induced cardiac hypertrophy and dilation. In addition, Magic-F1+/+ mice can be used as non-pressure overload model to further investigate the role of oxygen-sensors in ischaemic heart disease. To better understand the biological effects of MAGIC-F1 on the mor- phology and function of cardiac muscle, more detailed studies are required. It could be also interesting to have a longer follow-up of the homozygous animals, to investigate the progres- sion of the cardiac remodelling upon a double dose of MAGIC-F1

    Factors related to swallowing oral phase

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    Introduction: Efficacy of swallowing oral phase is often impaired in dysphagic patients and may impact on pharyngeal stage, meal consumption, nutritional status and quality of life. However, factors related to oral phase of swallowing have been little studied. Matherial & Methods: Thirty-nine adult patients with dysphagia of different etiology were enrolled. FEES and the Test of Mastication and Swallowing Solids (TOMASS) were performed. The Penetration-Aspiration scale, the Yale Pharyngeal Residue Severity Rating Scale and the Dysphagia Outcome and Severity Scale (DOSS) were used to assess the FEES. Tongue strength was assessed using the Iowa Oral Performance Instrument. Patients completed the Eating Assessment Tool-10. The time the patients needed to consume a meal, the Functional Oral Intake Scale score and the body mass index (BMI) were recorded. Correlations between the TOMASS and other variables were studied using Spearman’s correlation coefficient. TOMASS scores were compared between patients with complete denture and those with partial edentulism through Mann-Whitney test. Results: The number of discrete bites correlated only with the BMI (r=-0.38; p=0.01). Statistically significant correlations were found between the number of masticatory cycles and tongue strength (r=-0.47; p<0.01), pharyngeal residue (r=0.42; p<0.01), DOSS (r=-0.38; p=0.01). The total time of the TOMASS correlated with tongue strength (r=-0.45; p<0.01), pharyngeal residue (r=0.48; p<0.01), time needed to consume a meal (r=0.41; p=0.01) and DOSS (r=-0.36; p=0.02). A significant difference was found between patients with complete denture and patients with partial edentulism for the number of masticatory cycles (p=0.02) and total time (p=0.03). Conclusions: Swallowing oral phase seems to correlate with tongue strength, denture, pharyngeal residue, overall dysphagia severity, duration of meals and BMI. Further studies involving a larger sample size are necessary to confirm present data
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