Estudo in vitro dos efeitos da BMP-2 e do seu antagonista Noggin sobre a proliferação e migração celulares em carcinoma epidermóide de língua

Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in the oral cavity and reach a large number of individuals, has become an important public health problem. Studies have demonstrated changes in pathway components BMP in various types of cancers as prostate, colon, breast, gastric and OSCCs. Is the current knowledge that these proteins may exert pro-tumor effect in more advanced stages of neoplastic development coming to favor progression and invasion tumor. The inhibition of the signaling pathway BMP-2 through its antagonists, have shown positive results of antitumor activity and use of Noggin may be a novel therapeutic target for cancer. Given this evidence and the few studies with BMP-2, Noggin and OSCC, the objective of this research was to evaluate the effect of BMP-2 and its antagonist Noggin on proliferation and migration cell in line of cell cultures of human tongue squamous cell carcinoma (SCC25). The study was divided in three groups, a control group, where SCC25 cells suffered no treatment, a BMP-2 group, in which cells were treated with 100ng/ml of BMP-2 and a group of cells that were treated with 100ng/ml of Noggin. For the proliferation assay and cell cycle were established three time intervals (24, 48 and 72 hours). Proliferative activity was investigated by trypan blue and cell cycle analysis by staining with propidium iodide flow cytometry. The potential for migration / invasion of SCC25 cells was performing by a cell invasion assay using Matrigel in a 48-hour interval. The proliferation curve showed a higher proliferation in cells treated with BMP-2 in 72 hours (p < 0.05), and lower overgrowth and cell viability in Noggin group. Recombinant proteins favored a greater percentage of cells in cell cycle phase Go/G1 with a statistically significant difference in the interval of 24 hours (p < 0.05). BMP- 2 produced a greater invasion of cells studied as well as its antagonist Noggin inhibits invasion of cells (p < 0.05). Thus, these results indicate that BMP-2 promotes malignant phenotype, dues stimulates proliferation and invasion of SCC25 cells and, its antagonist Noggin may be an alternative treatment, due to inhibit the tumor progression

Steam reforming of ethanol for hydrogen production on Co/CeO²-ZRO² catalysts prepared by polymerization method

Catalysts containing 10%Co supported on CexZr1-xO2 (0 < x < 1) were applied to ethanol steam reforming reactions. The catalysts were characterized by Raman spectroscopy, XANES-H-2 and DRS-UV-Vis. The catalytic tests were conducted at 673, 773 and 873 K, with molar ratios of H2O:ethanol = 3:1. The ethanol conversion and H-2 selectivity were temperature dependent and the association of CeO2 with ZrO2 in the support led to show a low formation of CO, due to the higher mobility of oxygen. (C) 2012 Elsevier B.V. All rights reserved.

Avaliação da percepção sobre interdisciplinaridade nas unidades de saúde USF Paranapiacaba, US Vila Helena e CEO Vila Guilherme

É necessário compreender que o indivíduo, no processo saúde-doença, precisa receber atenção completa, que envolva várias disciplinas atuando de forma conjunta, numa visão que envolve integralidade de ações (Saupe et al., 2007; Salvador et al., 2011). Uma das principais características dos serviços de saúde hoje em dia no país é o atendimento feito por equipes multiprofissionais, cujo entrosamento, entendimento e troca de saberes entre seus membros levam à interdisciplinaridade (Salvador et al., 2011), tema central deste trabalho de pesquisa. Atendimento interdisciplinar envolve trabalho recíproco, criando relações sociais horizontais, contrariamente ao que ocorre no modelo de assistência tradicional, hegemônico. Exige que o saber do outro seja ouvido e pensado, inclusive dos indivíduos e das comunidades assistidos (Leite; Veloso, 2008). Este estudo, do tipo quali-quantitativo, tem por objetivo analisar as percepções que trabalhadores e usuários de três unidades de saúde, com estratégias distintas de atendimento, apresentam sobre interdisciplinaridade. Busca-se destacar dificuldades e possíveis meios facilitadores para sua prática diária na perspectiva de profissionais de saúde e usuários dessas três unidades de saúde. Foram aplicados questionários com perguntas fechadas semiestruturadas e abertas, cujos resultados foram submetidos à análise quantitativa, pela técnica descritiva de análise de frequência, e análise qualitativa pela técnica hermenêutica dialética, conforme preconizada por Minayo (2004). À luz dessa modalidade qualitativa de pesquisa aplicada aos profissionais surgiram três categorias: Meios para aumento da interdisciplinaridade; Fatores que afetam a interdisciplinaridade, subdivididos em Incentivadores, Desmotivadores e Ambíguos; e Resultados da interdisciplinaridade. Em relação aos usuários, as categorias emergentes foram: Desinteresse; Visão assistencial individualista e Vantagens da interdisciplinaridade. Os resultados encontrados foram: todas as categorias profissionais sentiram falta de outros profissionais em grupos educativos. A ausência mais sentida foi assistente social (18,75%). A estratégia interdisciplinar mais lembrada foi \"reuniões\" (38,6%). Falta noção de que é necessário trocar informações de forma efetiva, compreensível e satisfatória para todos. Mostrou-se importante aproveitar esses momentos para discutir protocolos e rotinas. Instrumento relevante para aumentar as trocas entre os profissionais foi a capacitação (13,6%) que melhora o relacionamento em equipe ao diminuir inseguranças. Trocas de informações em equipe multidisciplinar podem transformála em interdisciplinar. Pertencimento foi fato importante para a interdisciplinaridade, assim como dialogar, tolerar, respeitar, ouvir, ser flexível e enxergar o que está além de si, com interação social, horizontal. Número reduzido de profissionais, tomar conhecimento dos resultados das decisões em equipe e corresponsabilidade também foram fatores de destaque. Mais de 70% dos usuários relatou não participar de grupos educativos, evidenciando o curativismo. Os usuários valorizaram o atendimento por mais de um profissional. Acolhimento prescinde da ação interdisciplinar. Nenhum modo de atendimento foi sugerido pelos usuários. A interdisciplinaridade favorece a relação entre a equipe e o usuário, diminui espera e aumenta resolução. Na US Vila Helena, a interdisciplinaridade prescindiu de reuniões de equipe para acontecer.

Estrella Dominica novamente descuberta no ceo da Igreja : Historia panegyrica, ornada com todo o genero de erudiça? divina, & humana /

Mode of access: Internet.

Estrella Dominica novamente descuberta no ceo da Igreja : Historia panegyrica, ornada com todo o genero de erudiça? divina, & humana ... /

Mode of access: Internet.

CEO power, government monitoring, and bank dividends

We investigate the role of CEO power and government monitoring on bank dividend policy for a sample of 109 European listed banks for the period 2005-2013. We employ three main proxies for CEO power: CEO ownership, CEO tenure, and unforced CEO turnover. We show that CEO power has a negative impact on dividend payout ratios and on performance, suggesting that entrenched CEOs do not have the incentive to increase payout ratios to discourage monitoring from minority shareholders. Stronger internal monitoring by board of directors, as proxied by larger ownership stakes of the board members, increases performance but decreases payout ratios. These findings are contrary to those from the entrenchment literature for non-financial firms. Government ownership and the presence of a government official on the board of directors of the bank, also reduces payout ratios, in line with the view that government is incentivized to favor the interest of bank creditors before the interest of minority shareholders. These results show that government regulators are mainly concerned about bank safety and this allows powerful CEOs to distribute low payouts at the expense of minority shareholders.

Cambios de CEO y presidentes de directorio en el Perú : un enfoque para las empresas peruanas con mayor frecuencia de negociación en la BVL de 1992 al 2014

Esta investigación tiene como objetivo determinar si los anuncios de cambios de CEO y presidentes de Directorio de las empresas listadas en la Bolsa de Valores de Lima (BVL) afectan el valor de la firma en los días cercanos al anuncio. Fue la pronta salida de Steve Jobs como CEO de Apple Inc., a causa de una enfermedad mortal, lo que nos generó el cuestionamiento respecto a cuál sería el desempeño que tienen las acciones cuyas compañías pasan por eventos similares. Como se sabe, el mercado castigó la acción de Apple el día de la muerte de Steve Jobs, con caídas superiores al 2% el día del anuncio. ¿Tendrían los mercados desarrollados y emergentes el mismo comportamiento?, ¿los eventos de cambio de CEO generan las mismas reacciones en los países emergentes? Grande fue nuestra sorpresa al observar, a nivel local, cambios en la gerencia general como en Backus & Johnston (3/9/2013) sin un efecto significativo en el mercado, pues incluso el mercado no negoció dicho valor hasta el 19/9/2013. Con el objetivo de obtener una respuesta a las consultas inicialmente planteadas, se aplicó la metodología denominada Event Analysis, la cual ya ha sido utilizada para evaluar la existencia de retornos anormales ante cambios en CEO y presidentes de Directorio en mercados desarrollados como EE. UU., Países Bajos, Australia, España, etc., y también en mercados emergentes como Colombia, Chile y México. Nuestro estudio para el mercado peruano consistió en una muestra conformada por las cincuenta empresas cuyas acciones son las de mayor frecuencia de negociación en la BVL. Se tomó en consideración todos los eventos de cambio de CEO y presidentes de Directorio entre 1992 y el 2014. De acuerdo con los resultados de la investigación realizada, la existencia de retornos anormales en los cambios de CEO y presidentes de Directorio no son estadísticamente significativos, por lo que no podrían ser usado para generar estrategias del tipo Event-driven por parte de los hedge funds. La razón predominante es la alta volatilidad de los resultados y la poca profundidad del mercado que cuenta con poca liquidez; asimismo, el hecho de tener eventos relevantes que no son tomados en cuenta por el mercado.

An Asp49 Phospholipase A2 From Snake Venom Induces Cyclooxygenase-2 Expression And Prostaglandin E2 Production Via Activation Of Nf-κb, P38mapk, And Pkc In Macrophages.

Phospholipases A2 (PLA2) are key enzymes for production of lipid mediators. We previously demonstrated that a snake venom sPLA2 named MT-III leads to prostaglandin (PG)E2 biosynthesis in macrophages by inducing the expression of cyclooxygenase-2 (COX-2). Herein, we explored the molecular mechanisms and signaling pathways leading to these MT-III-induced effects. Results demonstrated that MT-III induced activation of the transcription factor NF-κB in isolated macrophages. By using NF-κB selective inhibitors, the involvement of this factor in MT-III-induced COX-2 expression and PGE2 production was demonstrated. Moreover, MT-III-induced COX-2 protein expression and PGE2 release were attenuated by pretreatment of macrophages with SB202190, and Ly294002, and H-7-dihydro compounds, indicating the involvement of p38MAPK, PI3K, and PKC pathways, respectively. Consistent with this, MT-III triggered early phosphorylation of p38MAPK, PI3K, and PKC. Furthermore, SB202190, H-7-dihydro, but not Ly294002 treatment, abrogated activation of NF-κB induced by MT-III. Altogether, these results show for the first time that the induction of COX-2 protein expression and PGE2 release, which occur via NF-κB activation induced by the sPLA2-MT-III in macrophages, are modulated by p38MAPK and PKC, but not by PI3K signaling proteins.

Prognostic Value Of Dna And Mrna E6/e7 Of Human Papillomavirus In The Evolution Of Cervical Intraepithelial Neoplasia Grade 2.

This study aimed at evaluating whether human papillomavirus (HPV) groups and E6/E7 mRNA of HPV 16, 18, 31, 33, and 45 are prognostic of cervical intraepithelial neoplasia (CIN) 2 outcome in women with a cervical smear showing a low-grade squamous intraepithelial lesion (LSIL). This cohort study included women with biopsy-confirmed CIN 2 who were followed up for 12 months, with cervical smear and colposcopy performed every three months. Women with a negative or low-risk HPV status showed 100% CIN 2 regression. The CIN 2 regression rates at the 12-month follow-up were 69.4% for women with alpha-9 HPV versus 91.7% for other HPV species or HPV-negative status (P < 0.05). For women with HPV 16, the CIN 2 regression rate at the 12-month follow-up was 61.4% versus 89.5% for other HPV types or HPV-negative status (P < 0.05). The CIN 2 regression rate was 68.3% for women who tested positive for HPV E6/E7 mRNA versus 82.0% for the negative results, but this difference was not statistically significant. The expectant management for women with biopsy-confirmed CIN 2 and previous cytological tests showing LSIL exhibited a very high rate of spontaneous regression. HPV 16 is associated with a higher CIN 2 progression rate than other HPV infections. HPV E6/E7 mRNA is not a prognostic marker of the CIN 2 clinical outcome, although this analysis cannot be considered conclusive. Given the small sample size, this study could be considered a pilot for future larger studies on the role of predictive markers of CIN 2 evolution.

Solid Lipid Nanoparticles For Hydrophilic Biotech Drugs: Optimization And Cell Viability Studies (caco-2 & Hepg-2 Cell Lines).

Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens.

Microbial Evaluation Of Traumatized Teeth Treated With Triple Antibiotic Paste Or Calcium Hydroxide With 2% Chlorhexidine Gel In Pulp Revascularization.

Revascularization outcome depends on microbial elimination because apical repair will not happen in the presence of infected tissues. This study evaluated the microbial composition of traumatized immature teeth and assessed their reduction during different stages of the revascularization procedures performed with 2 intracanal medicaments. Fifteen patients (7-17 years old) with immature teeth were submitted to the revascularization procedures; they were divided into 2 groups according to the intracanal medicament used: TAP group (n = 7), medicated with a triple antibiotic paste, and CHP group (n = 8), dressed with calcium hydroxide + 2% chlorhexidine gel. Samples were taken before any treatment (S1), after irrigation with 6% NaOCl (S2), after irrigation with 2% chlorhexidine (S3), after intracanal dressing (S4), and after 17% EDTA irrigation (S5). Cultivable bacteria recovered from the 5 stages were counted and identified by means of polymerase chain reaction assay (16S rRNA). Both groups had colony-forming unit counts significantly reduced after S2 (P < .05); however, no significant difference was found between the irrigants (S2 and S3, P = .99). No difference in bacteria counts was found between the intracanal medicaments used (P = .95). The most prevalent bacteria detected were Actinomyces naeslundii (66.67%), followed by Porphyromonas endodontalis, Parvimonas micra, and Fusobacterium nucleatum, which were detected in 33.34% of the root canals. An average of 2.13 species per canal was found, and no statistical correlation was observed between bacterial species and clinical/radiographic features. The microbial profile of infected immature teeth is similar to that of primarily infected permanent teeth. The greatest bacterial reduction was promoted by the irrigation solutions. The revascularization protocols that used the tested intracanal medicaments were efficient in reducing viable bacteria in necrotic immature teeth.

What Is The Best Indication For Single-incision Ophira Mini Sling? Insights From A 2-year Follow-up International Multicentric Study.

The Ophira Mini Sling System involves anchoring a midurethral, low-tension tape to the obturator internus muscles bilaterally at the level of the tendinous arc. Success rates in different subsets of patients are still to be defined. This work aims to identify which factors influence the 2-year outcomes of this treatment. Analysis was based on data from a multicenter study. Endpoints for analysis included objective measurements: 1-h pad-weight (PWT), and cough stress test (CST), and questionnaires: International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Urinary Distress Inventory (UDI)-6. A logistic regression analysis evaluated possible risk factors for failure. In all, 124 female patients with stress urinary incontinence (SUI) underwent treatment with the Ophira procedure. All patients completed 1 year of follow-up, and 95 complied with the 2-year evaluation. Longitudinal analysis showed no significant differences between results at 1 and 2 years. The 2-year overall objective results were 81 (85.3%) patients dry, six (6.3%) improved, and eight (8.4%) incontinent. A multivariate analysis revealed that previous anti-incontinence surgery was the only factor that significantly influenced surgical outcomes. Two years after treatment, women with previous failed surgeries had an odds ratio (OR) for treatment failure (based on PWT) of 4.0 [95% confidence interval (CI) 1.02-15.57). The Ophira procedure is an effective option for SUI treatment, with durable good results. Previous surgeries were identified as the only significant risk factor, though previously operated patients showed an acceptable success rate.

Quantitative Proteomic Analysis Reveals Metabolic Alterations, Calcium Dysregulation, And Increased Expression Of Extracellular Matrix Proteins In Laminin α2 Chain-deficient Muscle.

Congenital muscular dystrophy with laminin α2 chain deficiency (MDC1A) is one of the most severe forms of muscular disease and is characterized by severe muscle weakness and delayed motor milestones. The genetic basis of MDC1A is well known, yet the secondary mechanisms ultimately leading to muscle degeneration and subsequent connective tissue infiltration are not fully understood. In order to obtain new insights into the molecular mechanisms underlying MDC1A, we performed a comparative proteomic analysis of affected muscles (diaphragm and gastrocnemius) from laminin α2 chain-deficient dy(3K)/dy(3K) mice, using multidimensional protein identification technology combined with tandem mass tags. Out of the approximately 700 identified proteins, 113 and 101 proteins, respectively, were differentially expressed in the diseased gastrocnemius and diaphragm muscles compared with normal muscles. A large portion of these proteins are involved in different metabolic processes, bind calcium, or are expressed in the extracellular matrix. Our findings suggest that metabolic alterations and calcium dysregulation could be novel mechanisms that underlie MDC1A and might be targets that should be explored for therapy. Also, detailed knowledge of the composition of fibrotic tissue, rich in extracellular matrix proteins, in laminin α2 chain-deficient muscle might help in the design of future anti-fibrotic treatments. All MS data have been deposited in the ProteomeXchange with identifier PXD000978 (http://proteomecentral.proteomexchange.org/dataset/PXD000978).

Icatibant, An Inhibitor Of Bradykinin Receptor 2, For Hereditary Angioedema Attacks: Prospective Experimental Single-cohort Study.

Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.