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Efeito protetor da flavana extra?da da esp?cie Brosimum acutifolium contra danos causados por hip?xia em c?lulas retinianas: um estudo in vitro

FONSECA, Susanne Suely Santos da
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Dissertação de Mestrado
POR
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O acidente vascular cerebral isqu?mico (AVCi) causa danos celulares por provocar intensa excitotoxicidade e estresse oxidativo ap?s priva??o de oxig?nio e glicose para uma regi?o do enc?falo. Neste trabalho, investigamos o potencial neuroprotetor da planta amaz?nica Brosimum acutifolium que ? rica em flavanas como a 4',7-diidroxi-8-(3,3-dimetilalil)flavana (brosimina b, aqui abreviada como Bb) que apresenta elevado potencial antioxidante. Utilizamos cultura de c?lulas retinianas de embri?o de galinha submetidas a hip?xia experimental, por priva??o de oxig?nio e glicose, para avaliarmos o potencial antioxidante da Bb atrav?s da an?lise do sequestro do radical 2,2-difenil-1-picril-hidrazil (DPPH). Al?m disso, avaliamos a viabilidade celular (VC) e o perfil oxidativo e antioxidativo ap?s 3, 6 e 24 horas de hip?xia, pela produ??o de oxig?nio reativo (O2-) e atividade antioxidante end?gena pela enzima catalase, respectivamente. Nossos resultados demonstram que nosso modelo experimental de hip?xia in vitro provoca redu??o tempo-dependente da VC, acompanhada por intenso estrese oxidativo, devido ? excessiva produ??o de oxig?nio reativo (O2-). O tratamento com Bb (10?M) protegeu significativamente a viabilidade celular durante 3 e 6 h de hip?xia experimental em c?lulas retiniana cultivadas in vitro...

Acta del Ayuntamiento de Valencia

Fernández, Emilio (Presidente Constitucional del Estado Carabobo)
Fonte: Ayuntamiento de Valencia Publicador: Ayuntamiento de Valencia
Tipo: Imagem Formato: 1-3
ES
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Valencia, Venezuela; Resolución mediante la cual, el Presidente Constitucional del Estado Carabobo, elimina el puesto de adjunto al Superintendente de Instrucción Pública del Estado; nombramiento de Juana Carlomagno de Bolívar, como Preceptora de la Escuela Mixta número 15 del estado; asignación mensual de 120 bolívares, a Rosa Rueda alumna del Colegio Nuestra Señora de Lourdes.; Alcaldia de Valencia - Universidad Simon Bolivar - Bolivarium

Tau deposition drives neuropathological, inflammatory and behavioral abnormalities independently of neuronal loss in a novel mouse model

Cook, Casey; Kang, Silvia S.; Carlomagno, Yari; Lin, Wen-Lang; Yue, Mei; Kurti, Aishe; Shinohara, Mitsuru; Jansen-West, Karen; Perkerson, Emilie; Castanedes-Casey, Monica; Rousseau, Linda; Phillips, Virginia; Bu, Guojun; Dickson, Dennis W.; Petrucelli, Le
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
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Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints of existing models of tauopathy. In order to generate a more versatile mouse model of tauopathy, somatic brain transgenesis was utilized to deliver adeno-associated virus serotype 1 (AAV1) encoding human mutant P301L-tau compared with GFP control. At 6 months of age, we observed widespread human tau expression with concomitant accumulation of hyperphosphorylated and abnormally folded proteinase K resistant tau. However, no overt neuronal loss was observed, though significant abnormalities were noted in the postsynaptic scaffolding protein PSD95. Neurofibrillary pathology was also detected with Gallyas silver stain and Thioflavin-S, and electron microscopy revealed the deposition of closely packed filaments. In addition to classic markers of tauopathy, significant neuroinflammation and extensive gliosis were detected in AAV1-TauP301L mice. This model also recapitulates the behavioral phenotype characteristic of mouse models of tauopathy, including abnormalities in exploration, anxiety, and learning and memory. These findings indicate that biochemical and neuropathological hallmarks of tauopathies are accurately conserved and are independent of cell death in this novel AAV-based model of tauopathy...

Heat Flux Sensors for Infrared Thermography in Convective Heat Transfer

Carlomagno, Giovanni Maria; de Luca, Luigi; Cardone, Gennaro; Astarita, Tommaso
Fonte: MDPI Publicador: MDPI
Tipo: Artigo de Revista Científica
Publicado em 07/11/2014 EN
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This paper reviews the most dependable heat flux sensors, which can be used with InfraRed (IR) thermography to measure convective heat transfer coefficient distributions, and some of their applications performed by the authors' research group at the University of Naples Federico II. After recalling the basic principles that make IR thermography work, the various heat flux sensors to be used with it are presented and discussed, describing their capability to investigate complex thermo-fluid-dynamic flows. Several applications to streams, which range from natural convection to hypersonic flows, are also described.

Prolactin receptor does not correlate with oestrogen and progesterone receptors in primary breast cancer and lacks prognostic significance. Ten year results of the Naples adjuvant (GUN) study.

De Placido, S.; Gallo, C.; Perrone, F.; Marinelli, A.; Pagliarulo, C.; Carlomagno, C.; Petrella, G.; D'Istria, M.; Delrio, G.; Bianco, A. R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1990 EN
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The correlation between prolactin (PRLR) and oestrogen (ER) or progesterone receptors (PgR) in breast cancer and a possible prognostic significance of PRLR at 10 year follow-up have been investigated in the Naples (GUN) adjuvant trial. A total of 308 pre- and post-menopausal patients with early breast cancer, who entered the trial from 1 February 1978 to 31 December 1983, received randomly Tamoxifen (TM), 30 mg per die for 2 years, or no therapy. PRLR status was known in 229 (74.3%) patients. Values of specific binding less than 1% were considered negative. PRLR was positive in 75/229 (32.8%). ER was assayed in 210/229 (91.7%) patients and PgR in 188/229 (82.1%). No significant correlation, by the Spearman test, was found between PRLR and ER or PgR, while ER status was highly interrelated with PgR status. By the Cox model no evidence of an independent prognostic role of PRLR on disease-free survival (DFS) was observed, nor an interaction between PRLR and adjuvant treatment with TM was found.

Congenital scoliosis associated with agenesis of the uterine cervix. Case report

Carlomagno, Giorgio; Di Blasi, Arturo; Monica, Matteo Della
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 30/06/2004 EN
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Simultaneous surgical treatment of liver metastases from colorectal cancer in the elderly through Habib's technique

Dumani, Xheseda; Rizzo, Gennaro; Grassia, Sebastiano; Tammaro, Vincenzo; Carlomagno, Nicola; Renda, Andrea
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 16/09/2013 EN
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Activity and safety of pegylated liposomal doxorubicin, 5-fluorouracil and folinic acid in inoperable hepatocellular carcinoma: A phase II study

Lorenzo, Giuseppe Di; Rea, Antonio; Carlomagno, Chiara; Pepe, Stefano; Palmieri, Giovannella; Labianca, Roberto; Chirianni, Antonio; Stefano, Alfonso De; Esposito, Vincenzo; Placido, Sabino De; Montesarchio, Vincenzo
Fonte: Baishideng Publishing Group Co., Limited Publicador: Baishideng Publishing Group Co., Limited
Tipo: Artigo de Revista Científica
EN
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AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase II study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA).

Features of the rho-dependent transcription termination polar element within the hisG cistron of Salmonella typhimurium.

Ciampi, M S; Alifano, P; Nappo, A G; Bruni, C B; Carlomagno, M S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1989 EN
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Previous genetic analysis showed that the polar effects of mutations in the hisG cistron of Salmonella typhimurium are dependent on the presence of a single putative transcription termination element within the hisG gene. In fact, all proximal mutations causing translation termination are strongly polar, whereas distal ones are not. The element was mapped by isolating mutations able to relieve the polar phenotype, and they were found to be small deletions in the region downstream of the translational stop codon (M. S. Ciampi and J. R. Roth, Genetics 118:193-202, 1988). In this study, we analyzed the his-specific RNAs synthesized in vivo in different strains harboring the polar frameshift hisG2148 mutation. The nature of the polarity effects is clearly transcriptional, since shorter RNA molecules were produced. When the hisG2148 mutation was transferred in a rho background or in strains harboring the small distal deletions, an increase in readthrough transcription was observed. The transcriptional termination element was characterized in more detail by performing high-resolution S1 nuclease mapping experiments. This analysis showed that (i) termination or exonucleolytic degradation following termination produced transcripts with heterogeneous 3' ends; (ii) this process is dependent on the transcription termination factor Rho...

Endocrine Alterations Are the Main Determinants of Cardiac Remodelling in Restrictive Anorexia Nervosa

Carlomagno, Guido; Mercurio, Valentina; Ruvolo, Antonio; Senatore, Ignazio; Halinskaya, Irina; Fazio, Valeria; Affuso, Flora; Fazio, Serafino
Fonte: International Scholarly Research Network Publicador: International Scholarly Research Network
Tipo: Artigo de Revista Científica
EN
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Objective. Anorexia nervosa is a condition of reduced hemodynamic load, characterized by varying degrees of cardiac remodelling, only in part related to reduced body mass; the mechanism for such variability, as well as its clinical significance, remains unknown. Aim of the study was to assess the possible influence of a great number of clinical, biochemical, and endocrine factors on cardiovascular parameters in restrictive anorexia nervosa. Method. Twenty-five female patients hospitalized for restrictive anorexia nervosa underwent extensive cardiovascular, clinical, and biochemical evaluation. Results. Height-adjusted and cardiac workload-matched left ventricular mass was significantly related to several endocrine parameters, blood pressure, and vasoreactivity. On multivariate analysis, IGF/GH ratio and systolic blood pressure were the only independent predictors of height-adjusted ventricular mass (adj-R2 = 0.585; P = 0.001); when matching for cardiac workload, left ventricular mass was independently predicted only by GH and FT3 levels. All effects were independent of patient's weight and BMI. Conclusions. Indices of endocrine impairment seem to be the most relevant determinants of left ventricular hypotrophy in anorectic patients...

Molecular heterogeneity of RET loss of function in Hirschsprung's disease.

Carlomagno, F; De Vita, G; Berlingieri, M T; de Franciscis, V; Melillo, R M; Colantuoni, V; Kraus, M H; Di Fiore, P P; Fusco, A; Santoro, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 03/06/1996 EN
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The RET proto-oncogene encodes a receptor with tyrosine kinase activity (RET) that is involved in several neoplastic and non-neoplastic diseases. Oncogenic activation of RET, achieved by different mechanisms, is detected in a sizeable fraction of human thyroid tumors, as well as in multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinoma tumoral syndromes. Germline mutations of RET have also been associated with a non-neoplastic disease, the congenital colonic aganglionosis, i.e. Hirschsprung's disease (HSCR). To analyse the impact of HSCR mutations on RET function, we have introduced into wild-type RET and activated RET(MEN2A) and RET(MEN2B) alleles three missense mutations associated with HSCR. Here we show that the three mutations caused a loss of function of RET when assayed in two model cell systems, NIH 3T3 and PC12 cells. The effect of different HSCR mutations was due to different molecular mechanisms. The HSCR972 (Arg972-->Gly) mutation, mapping in the intracytoplasmic region of RET, impaired its tyrosine kinase activity, while two extracellular mutations, HSCR32 (Ser32-->Leu) and HSCR393 (Phe393-->Leu), inhibited the biological activity of RET by impairing the correct maturation of the RET protein and its transport to the cell surface.

Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation

Cook, Casey; Gendron, Tania F.; Scheffel, Kristyn; Carlomagno, Yari; Dunmore, Judy; DeTure, Michael; Petrucelli, Leonard
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
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The abnormal accumulation of the microtubule-binding protein tau is associated with a number of neurodegenerative conditions, and correlates with cognitive decline in Alzheimer's disease. The ubiquitin ligase carboxy terminus of Hsp70-interacting protein (CHIP) and the molecular chaperone Hsp90 are implicated in protein triage decisions involving tau, and have consequently been targeted for therapeutic approaches aimed at decreasing tau burden. Here, we present evidence that CHIP binds, ubiquitinates and regulates expression of histone deacetylase 6 (HDAC6). As the deacetylase for Hsp90, HDAC6 modulates Hsp90 function and determines the favorability of refolding versus degradation of Hsp90 client proteins. Moreover, we demonstrate that HDAC6 levels positively correlate with tau burden, while a decrease in HDAC6 activity or expression promotes tau clearance. Consistent with previous research on Hsp90 clients in cancer, we provide evidence that a loss of HDAC6 activity augments the efficacy of an Hsp90 inhibitor and drives client degradation, in this case tau. Therefore, our current findings not only identify HDAC6 as a critical factor for the regulation of tau levels, but also indicate that a multi-faceted treatment approach could more effectively arrest tau accumulation in disease.

Isolated eye-lid ptosis as initial manifestation of pediatric Behcet's Disease (BD)

Alessio, M; Indaco, R; Carlomagno, R; Romano, A
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 15/09/2008 EN
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A gastrointestinal stromal tumor (GIST) masquerading as an ovarian mass

Carlomagno, Giorgio; Beneduce, Pasquale
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 13/05/2004 EN
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Sanger sequencing in routine KRAS testing: a review of 1720 cases from a pathologist's perspective

Malapelle, Umberto; Bellevicine, Claudio; Salatiello, Maria; de Luca, Caterina; Rispo, Elisabetta; Riccio, Palmira; Sparano, Lucianna; De Stefano, Alfonso; Carlomagno, Chiara; Maiello, Francesco Maria; Vita, Giulia; Nappi, Oscar; Troncone, Giancarlo
Fonte: BMJ Publishing Group Publicador: BMJ Publishing Group
Tipo: Artigo de Revista Científica
EN
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RNA structure determination by solid-state NMR spectroscopy

Marchanka, Alexander; Simon, Bernd; Althoff-Ospelt, Gerhard; Carlomagno, Teresa
Fonte: Nature Pub. Group Publicador: Nature Pub. Group
Tipo: Artigo de Revista Científica
Publicado em 11/05/2015 EN
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Knowledge of the RNA three-dimensional structure, either in isolation or as part of RNP complexes, is fundamental to understand the mechanism of numerous cellular processes. Because of its flexibility, RNA represents a challenge for crystallization, while the large size of cellular complexes brings solution-state NMR to its limits. Here, we demonstrate an alternative approach on the basis of solid-state NMR spectroscopy. We develop a suite of experiments and RNA labeling schemes and demonstrate for the first time that ssNMR can yield a RNA structure at high-resolution. This methodology allows structural analysis of segmentally labelled RNA stretches in high-molecular weight cellular machines—independent of their ability to crystallize— and opens the way to mechanistic studies of currently difficult-to-access RNA-protein assemblies.

A Reducing Milieu Renders Cofilin Insensitive to Phosphatidylinositol 4,5-Bisphosphate (PIP2) Inhibition*

Schulte, Bianca; John, Isabel; Simon, Bernd; Brockmann, Christoph; Oelmeier, Stefan A.; Jahraus, Beate; Kirchgessner, Henning; Riplinger, Selina; Carlomagno, Teresa; Wabnitz, Guido H.; Samstag, Yvonne
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
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Background: Cofilin is a key molecule for actin dynamics whose activity can be locally inhibited by PIP2.

Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance

Cook, Casey; Carlomagno, Yari; Gendron, Tania F.; Dunmore, Judy; Scheffel, Kristyn; Stetler, Caroline; Davis, Mary; Dickson, Dennis; Jarpe, Matthew; DeTure, Michael; Petrucelli, Leonard
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
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The accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is a neuropathological hallmark of tauopathies, including Alzheimer's disease (AD) and chronic traumatic encephalopathy, but effective therapies directly targeting the tau protein are currently lacking. Herein, we describe a novel mechanism in which the acetylation of tau on KXGS motifs inhibits phosphorylation on this same motif, and also prevents tau aggregation. Using a site-specific antibody to detect acetylation of KXGS motifs, we demonstrate that these sites are hypoacetylated in patients with AD, as well as a mouse model of tauopathy, suggesting that loss of acetylation on KXGS motifs renders tau vulnerable to pathogenic insults. Furthermore, we identify histone deacetylase 6 (HDAC6) as the enzyme responsible for the deacetylation of these residues, and provide proof of concept that acute treatment with a selective and blood–brain barrier-permeable HDAC6 inhibitor enhances acetylation and decreases phosphorylation on tau's KXGS motifs in vivo. As such, we have uncovered a novel therapeutic pathway that can be manipulated to block the formation of pathogenic tau species in disease.

Identification of two novel RET kinase inhibitors through MCR-based drug discovery: Design, synthesis and evaluation

Frett, Brendan; Moccia, Marialuisa; Carlomagno, Francesca; Santoro, Massimo; Li, Hong-yu
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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From an MCR fragment library, two novel chemical series have been developed as inhibitors of RET, which is a kinase involved in the pathology of medullary thyroid cancer (MTC). Structure activity relationship studies (SAR) identified two sub-micromolar tractable leads, 6g and 13g. 6g was confirmed to be a Type-II RET inhibitor. 13g and 6g inhibited RET in cells transformed by RET/C634. A RET DFG-out homology model was established and utilized to predict Type-II inhibitor binding modes.

Inhomogeneous phases in nonlocal chiral quark models

Carlomagno, J. P.; Dumm, D. Gomez; Scoccola, N. N.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 06/07/2015
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The presence of inhomogeneous phases in the QCD phase diagram is analyzed within chiral quark models that include nonlocal interactions. We work at the mean field level, assuming that the spatial dependence of scalar and pseudo-scalar condensates is given by a dual chiral density wave. Phase diagrams for Gaussian nonlocal form factors are studied in detail and compared with those obtained within the Nambu-Jona-Lasinio model and quark-meson approaches.; Comment: 14 pages, 3 figures