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1.
Multidisciplinary Scientific Cruises for Environmental Characterization in the Santos Basin – Methods and Sampling Design
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Moreira, Daniel L.
; Dalto, Adriana G.
; Figueiredo JR, Alberto G.
; Valerio, Aline M.
; Detoni, Amalia M. S.
; Bonecker, Ana C. T.
; Signori, Camila N.
; Namiki, Cláudia
; Sasaki, Dalton K.
; Pupo, Daniel V.
; Silva, Danilo A.
; Kutner, Deborah S.
; Duque-Castaño, Diana C.
; Marcon, Eduardo H.
; Gallotta, Fabiana D. C.
; Paula, Fabiana S.
; Gallucci, Fabiane
; Roque, Gabriela C. F.
; Campos, Giulia S.
; Fonseca, Gustavo
; Mattos, Gustavo
; Lavrado, Helena P.
; Silveira, Ilson C. A. da
; Costa, Jessica O.
; Santos Filho, João R. dos
; Carneiro, Juliane C.
; Moreira, Julio C.F.
; Rozo, Laura
; Araujo, Leandro F.M.
; Lazzari, Letícia
; Silva, Letícia O. da
; Michelazzo, Luan S.
; Fernandes, Luciano F.
; Dottori, Marcelo
; Araújo Jr., Marcus A. G. de
; Chuqui, Mateus G.
; Ceccopieri, Milena
; Borges-Silva, Milton
; Kampel, Milton
; Bergo, Natascha M.
; Silva, Paulo V. M.
; Tura, Pedro M.
; Moura, Rafael B. de
; Romano, Renato G.
; Martins, Renato P.
; Carreira, Renato S.
; Toledo, Rodrigo G.A.
; Bonecker, Sérgio L.C.
; Disaró, Sibelle T.
; Rodrigues, Silvana V.
; Corbisier, Thais N.
; Vicente, Thaisa M.
; Paiva, Vitor G. de
; Pellizari, Vivian H.
; Belo, Wellington C.
; Brandini, Frederico P.
; Sousa, Silvia H.M
.
Abstract The Santos Basin (SB) is the main petroliferous basin in the Brazilian continental margin and one of the most studied marine areas in Brazil. However, historical data suggest that new efforts should be carried out to acquire quantitative biological data, especially in the deep sea, to establish the baseline of essential ocean variables in different ecosystems for future monitoring programs. The Brazilian energy company Petrobras planned and executed 24 oceanographic cruises over a period of 2 years to assess the benthic (SANSED cruise) and pelagic (SANAGU cruise) systems of the SB (356 days at sea in 2019 and 2021/2022). These efforts were part of the Santos Project, which comprised a comprehensive environmental study aimed at investigating benthic and pelagic variables to characterize ecology, biogeochemistry, thermohaline properties of water masses, and ocean circulation patterns, geomorphology, and sedimentology, as well as organic and inorganic chemistry. Here we present the detailed sampling designs and the field methods employed on board, during the SB scientific cruises. All sampling protocols were based on standardized approaches. For the benthos analyses, triplicate sediment samples were performed using a GOMEX-type box corer (0.25 m²) or a large modified Van Veen grab (0.75 m²) at 100 stations ranging from 25 to 2400 m depth. At each station, 25 geochemical and physico-chemical parameters were analyzed in addition to micro-, meio-, and macrofauna and living foraminifera samples. For the pelagic system, 60 stations were selected to investigate the plankton community, ranging in size from pico- to macroplankton, through vertical, horizontal, and oblique net hauls (20, 200, and 500 μm mesh size), as well as 25 biogeochemical parameters collected with an aid of a CTD-rosette sampler. Part of this scientific information also serves the Regional Environmental Characterization Project (PCR-BS) in support of Petrobras’ Santos Basin drilling licensing process led by the Brazilian Environmental Agency – IBAMA. This project contributes to the sustainable development of the SB, in line with the guidelines of the United Nations Decade of Ocean Science for Sustainable Development.
2.
Práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras: uma análise secundária do estudo Fluid-TRIPS
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Freitas, Flavio Geraldo Rezende de
; Hammond, Naomi
; Li, Yang
; Azevedo, Luciano Cesar Pontes de
; Cavalcanti, Alexandre Biasi
; Taniguchi, Leandro
; Gobatto, André
; Japiassú, André Miguel
; Bafi, Antonio Tonete
; Mazza, Bruno Franco
; Noritomi, Danilo Teixeira
; Dal-Pizzol, Felipe
; Bozza, Fernando
; Salluh, Jorge Ibrahin Figueira
; Westphal, Glauco Adrieno
; Soares, Márcio
; Assunção, Murillo Santucci César de
; Lisboa, Thiago
; Lobo, Suzana Margarete Ajeje
; Barbosa, Achilles Rohlfs
; Ventura, Adriana Fonseca
; Souza, Ailson Faria de
; Silva, Alexandre Francisco
; Toledo, Alexandre
; Reis, Aline
; Cembranel, Allan
; Rea Neto, Alvaro
; Gut, Ana Lúcia
; Justo, Ana Patricia Pierre
; Santos, Ana Paula
; Albuquerque, André Campos D. de
; Scazufka, André
; Rodrigues, Antonio Babo
; Fernandino, Bruno Bonaccorsi
; Silva, Bruno Goncalves
; Vidal, Bruno Sarno
; Pinheiro, Bruno Valle
; Pinto, Bruno Vilela Costa
; Feijo, Carlos Augusto Ramos
; Abreu Filho, Carlos de
; Bosso, Carlos Eduardo da Costa Nunes
; Moreira, Carlos Eduardo Nassif
; Ramos, Carlos Henrique Ferreira
; Tavares, Carmen
; Arantes, Cidamaiá
; Grion, Cintia
; Mendes, Ciro Leite
; Kmohan, Claudio
; Piras, Claudio
; Castro, Cristine Pilati Pileggi
; Lins, Cyntia
; Beraldo, Daniel
; Fontes, Daniel
; Boni, Daniela
; Castiglioni, Débora
; Paisani, Denise de Moraes
; Pedroso, Durval Ferreira Fonseca
; Mattos, Ederson Roberto
; Brito Sobrinho, Edgar de
; Troncoso, Edgar M. V.
; Rodrigues Filho, Edison Moraes
; Nogueira, Eduardo Enrico Ferrari
; Ferreira, Eduardo Leme
; Pacheco, Eduardo Souza
; Jodar, Euzebio
; Ferreira, Evandro L. A.
; Araujo, Fabiana Fernandes de
; Trevisol, Fabiana Schuelter
; Amorim, Fábio Ferreira
; Giannini, Fabio Poianas
; Santos, Fabrício Primitivo Matos
; Buarque, Fátima
; Lima, Felipe Gallego
; Costa, Fernando Antonio Alvares da
; Sad, Fernando Cesar dos Anjos
; Aranha, Fernando G.
; Ganem, Fernando
; Callil, Flavio
; Costa Filho, Francisco Flávio
; Dall´Arto, Frederico Toledo Campo
; Moreno, Geovani
; Friedman, Gilberto
; Moralez, Giulliana Martines
; Silva, Guilherme Abdalla da
; Costa, Guilherme
; Cavalcanti, Guilherme Silva
; Cavalcanti, Guilherme Silva
; Betônico, Gustavo Navarro
; Betônico, Gustavo Navarro
; Reis, Hélder
; Araujo, Helia Beatriz N.
; Hortiz Júnior, Helio Anjos
; Guimaraes, Helio Penna
; Urbano, Hugo
; Maia, Israel
; Santiago Filho, Ivan Lopes
; Farhat Júnior, Jamil
; Alvarez, Janu Rangel
; Passos, Joel Tavares
; Paranhos, Jorge Eduardo da Rocha
; Marques, José Aurelio
; Moreira Filho, José Gonçalves
; Andrade, Jose Neto
; Sobrinho, José Onofre de C
; Bezerra, Jose Terceiro de Paiva
; Alves, Juliana Apolônio
; Ferreira, Juliana
; Gomes, Jussara
; Sato, Karina Midori
; Gerent, Karine
; Teixeira, Kathia Margarida Costa
; Conde, Katia Aparecida Pessoa
; Martins, Laércia Ferreira
; Figueirêdo, Lanese
; Rezegue, Leila
; Tcherniacovsk, Leonardo
; Ferraz, Leone Oliveira
; Cavalcante, Liane
; Rabelo, Ligia
; Miilher, Lilian
; Garcia, Lisiane
; Tannous, Luana
; Hajjar, Ludhmila Abrahão
; Paciência, Luís Eduardo Miranda
; Cruz Neto, Luiz Monteiro da
; Bley, Macia Valeria
; Sousa, Marcelo Ferreira
; Puga, Marcelo Lourencini
; Romano, Marcelo Luz Pereira
; Nobrega, Marciano
; Arbex, Marcio
; Rodrigues, Márcio Leite
; Guerreiro, Márcio Osório
; Rocha, Marcone
; Alves, Maria Angela Pangoni
; Alves, Maria Angela Pangoni
; Rosa, Maria Doroti
; Dias, Mariza D’Agostino
; Martins, Miquéias
; Oliveira, Mirella de
; Moretti, Miriane Melo Silveira
; Matsui, Mirna
; Messender, Octavio
; Santarém, Orlando Luís de Andrade
; Silveira, Patricio Júnior Henrique da
; Vassallo, Paula Frizera
; Antoniazzi, Paulo
; Gottardo, Paulo César
; Correia, Paulo
; Ferreira, Paulo
; Torres, Paulo
; Silva, Pedro Gabrile M. de Barros e
; Foernges, Rafael
; Gomes, Rafael
; Moraes, Rafael
; Nonato filho, Raimundo
; Borba, Renato Luis
; Gomes, Renato V
; Cordioli, Ricardo
; Lima, Ricardo
; López, Ricardo Pérez
; Gargioni, Ricardo Rath de Oliveira
; Rosenblat, Richard
; Souza, Roberta Machado de
; Almeida, Roberto
; Narciso, Roberto Camargo
; Marco, Roberto
; waltrick, Roberto
; Biondi, Rodrigo
; Figueiredo, Rodrigo
; Dutra, Rodrigo Santana
; Batista, Roseane
; Felipe, Rouge
; Franco, Rubens Sergio da Silva
; Houly, Sandra
; Faria, Sara Socorro
; Pinto, Sergio Felix
; Luzzi, Sergio
; Sant’ana, Sergio
; Fernandes, Sergio Sonego
; Yamada, Sérgio
; Zajac, Sérgio
; Vaz, Sidiner Mesquita
; Bezerra, Silvia Aparecida Bezerra
; Farhat, Tatiana Bueno Tardivo
; Santos, Thiago Martins
; Smith, Tiago
; Silva, Ulysses V. A.
; Damasceno, Valnei Bento
; Nobre, Vandack
; Dantas, Vicente Cés de Souza
; Irineu, Vivian Menezes
; Bogado, Viviane
; Nedel, Wagner
; Campos Filho, Walther
; Dantas, Weidson
; Viana, William
; Oliveira Filho, Wilson de
; Delgadinho, Wilson Martins
; Finfer, Simon
; Machado, Flavia Ribeiro
.
Revista Brasileira de Terapia Intensiva
- Métricas del periódico
RESUMO Objetivo: Descrever as práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras e compará-las com as de outros países participantes do estudo Fluid-TRIPS. Métodos: Este foi um estudo observacional transversal, prospectivo e internacional, de uma amostra de conveniência de unidades de terapia intensiva de 27 países (inclusive o Brasil), com utilização da base de dados Fluid-TRIPS compilada em 2014. Descrevemos os padrões de ressuscitação volêmica utilizados no Brasil em comparação com os de outros países e identificamos os fatores associados com a escolha dos fluidos. Resultados: No dia do estudo, foram incluídos 3.214 pacientes do Brasil e 3.493 pacientes de outros países, dos quais, respectivamente, 16,1% e 26,8% (p < 0,001) receberam fluidos. A principal indicação para ressuscitação volêmica foi comprometimento da perfusão e/ou baixo débito cardíaco (Brasil 71,7% versus outros países 56,4%; p < 0,001). No Brasil, a percentagem de pacientes que receberam soluções cristaloides foi mais elevada (97,7% versus 76,8%; p < 0,001), e solução de cloreto de sódio a 0,9% foi o cristaloide mais comumente utilizado (62,5% versus 27,1%; p < 0,001). A análise multivariada sugeriu que os níveis de albumina se associaram com o uso tanto de cristaloides quanto de coloides, enquanto o tipo de prescritor dos fluidos se associou apenas com o uso de cristaloides. Conclusão: Nossos resultados sugerem que cristaloides são usados mais frequentemente do que coloides para ressuscitação no Brasil, e essa discrepância, em termos de frequências, é mais elevada do que em outros países. A solução de cloreto de sódio 0,9% foi o cristaloide mais frequentemente prescrito. Os níveis de albumina sérica e o tipo de prescritor de fluidos foram os fatores associados com a escolha de cristaloides ou coloides para a prescrição de fluidos.
Abstract Objective: To describe fluid resuscitation practices in Brazilian intensive care units and to compare them with those of other countries participating in the Fluid-TRIPS. Methods: This was a prospective, international, cross-sectional, observational study in a convenience sample of intensive care units in 27 countries (including Brazil) using the Fluid-TRIPS database compiled in 2014. We described the patterns of fluid resuscitation use in Brazil compared with those in other countries and identified the factors associated with fluid choice. Results: On the study day, 3,214 patients in Brazil and 3,493 patients in other countries were included, of whom 16.1% and 26.8% (p < 0.001) received fluids, respectively. The main indication for fluid resuscitation was impaired perfusion and/or low cardiac output (Brazil: 71.7% versus other countries: 56.4%, p < 0.001). In Brazil, the percentage of patients receiving crystalloid solutions was higher (97.7% versus 76.8%, p < 0.001), and 0.9% sodium chloride was the most commonly used crystalloid (62.5% versus 27.1%, p < 0.001). The multivariable analysis suggested that the albumin levels were associated with the use of both crystalloids and colloids, whereas the type of fluid prescriber was associated with crystalloid use only. Conclusion: Our results suggest that crystalloids are more frequently used than colloids for fluid resuscitation in Brazil, and this discrepancy in frequencies is higher than that in other countries. Sodium chloride (0.9%) was the crystalloid most commonly prescribed. Serum albumin levels and the type of fluid prescriber were the factors associated with the choice of crystalloids or colloids for fluid resuscitation.
https://doi.org/10.5935/0103-507x.20210028
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3.
Diretrizes Brasileiras de Hipertensão Arterial – 2020
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Barroso, Weimar Kunz Sebba
; Rodrigues, Cibele Isaac Saad
; Bortolotto, Luiz Aparecido
; Mota-Gomes, Marco Antônio
; Brandão, Andréa Araujo
; Feitosa, Audes Diógenes de Magalhães
; Machado, Carlos Alberto
; Poli-de-Figueiredo, Carlos Eduardo
; Amodeo, Celso
; Mion Júnior, Décio
; Barbosa, Eduardo Costa Duarte
; Nobre, Fernando
; Guimarães, Isabel Cristina Britto
; Vilela-Martin, José Fernando
; Yugar-Toledo, Juan Carlos
; Magalhães, Maria Eliane Campos
; Neves, Mário Fritsch Toros
; Jardim, Paulo César Brandão Veiga
; Miranda, Roberto Dischinger
; Póvoa, Rui Manuel dos Santos
; Fuchs, Sandra C
; Alessi, Alexandre
; Lucena, Alexandre Jorge Gomes de
; Avezum, Alvaro
; Sousa, Ana Luiza Lima
; Pio-Abreu, Andrea
; Sposito, Andrei Carvalho
; Pierin, Angela Maria Geraldo
; Paiva, Annelise Machado Gomes de
; Spinelli, Antonio Carlos de Souza
; Nogueira, Armando da Rocha
; Dinamarco, Nelson
; Eibel, Bruna
; Forjaz, Cláudia Lúcia de Moraes
; Zanini, Claudia Regina de Oliveira
; Souza, Cristiane Bueno de
; Souza, Dilma do Socorro Moraes de
; Nilson, Eduardo Augusto Fernandes
; Costa, Elisa Franco de Assis
; Freitas, Elizabete Viana de
; Duarte, Elizabeth da Rosa
; Muxfeldt, Elizabeth Silaid
; Lima Júnior, Emilton
; Campana, Erika Maria Gonçalves
; Cesarino, Evandro José
; Marques, Fabiana
; Argenta, Fábio
; Consolim-Colombo, Fernanda Marciano
; Baptista, Fernanda Spadotto
; Almeida, Fernando Antonio de
; Borelli, Flávio Antonio de Oliveira
; Fuchs, Flávio Danni
; Plavnik, Frida Liane
; Salles, Gil Fernando
; Feitosa, Gilson Soares
; Silva, Giovanio Vieira da
; Guerra, Grazia Maria
; Moreno Júnior, Heitor
; Finimundi, Helius Carlos
; Back, Isabela de Carlos
; Oliveira Filho, João Bosco de
; Gemelli, João Roberto
; Mill, José Geraldo
; Ribeiro, José Marcio
; Lotaif, Leda A. Daud
; Costa, Lilian Soares da
; Magalhães, Lucélia Batista Neves Cunha
; Drager, Luciano Ferreira
; Martin, Luis Cuadrado
; Scala, Luiz César Nazário
; Almeida, Madson Q.
; Gowdak, Marcia Maria Godoy
; Klein, Marcia Regina Simas Torres
; Malachias, Marcus Vinícius Bolívar
; Kuschnir, Maria Cristina Caetano
; Pinheiro, Maria Eliete
; Borba, Mario Henrique Elesbão de
; Moreira Filho, Osni
; Passarelli Júnior, Oswaldo
; Coelho, Otavio Rizzi
; Vitorino, Priscila Valverde de Oliveira
; Ribeiro Junior, Renault Mattos
; Esporcatte, Roberto
; Franco, Roberto
; Pedrosa, Rodrigo
; Mulinari, Rogerio Andrade
; Paula, Rogério Baumgratz de
; Okawa, Rogério Toshiro Passos
; Rosa, Ronaldo Fernandes
; Amaral, Sandra Lia do
; Ferreira-Filho, Sebastião R.
; Kaiser, Sergio Emanuel
; Jardim, Thiago de Souza Veiga
; Guimarães, Vanildo
; Koch, Vera H.
; Oigman, Wille
; Nadruz, Wilson
.
Arquivos Brasileiros de Cardiologia
- Métricas del periódico
https://doi.org/10.36660/abc.20201238
10948 descargas
4.
The Program for Biodiversity Research in Brazil: The role of regional networks for biodiversity knowledge, dissemination, and conservation
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ROSA, CLARISSA
; BACCARO, FABRICIO
; CRONEMBERGER, CECILIA
; HIPÓLITO, JULIANA
; BARROS, CLAUDIA FRANCA
; RODRIGUES, DOMINGOS DE JESUS
; NECKEL-OLIVEIRA, SELVINO
; OVERBECK, GERHARD E.
; DRECHSLER-SANTOS, ELISANDRO RICARDO
; ANJOS, MARCELO RODRIGUES DOS
; FERREGUETTI, ÁTILLA C.
; AKAMA, ALBERTO
; MARTINS, MARLÚCIA BONIFÁCIO
; TOMAS, WALFRIDO MORAES
; SANTOS, SANDRA APARECIDA
; FERREIRA, VANDA LÚCIA
; CUNHA, CATIA NUNES DA
; PENHA, JERRY
; PINHO, JOÃO BATISTA DE
; SALIS, SUZANA MARIA
; DORIA, CAROLINA RODRIGUES DA COSTA
; PILLAR, VALÉRIO D.
; PODGAISKI, LUCIANA R.
; MENIN, MARCELO
; BÍGIO, NARCÍSIO COSTA
; ARAGÓN, SUSAN
; MANZATTO, ANGELO GILBERTO
; VÉLEZ-MARTIN, EDUARDO
; SILVA, ANA CAROLINA BORGES LINS E
; IZZO, THIAGO JUNQUEIRA
; MORTATI, AMANDA FREDERICO
; GIACOMIN, LEANDRO LACERDA
; ALMEIDA, THAÍS ELIAS
; ANDRÉ, THIAGO
; SILVEIRA, MARIA AUREA PINHEIRO DE ALMEIDA
; SILVEIRA, ANTÔNIO LAFFAYETE PIRES DA
; MESSIAS, MARILUCE REZENDE
; MARQUES, MARCIA C.M.
; PADIAL, ANDRE ANDRIAN
; MARQUES, RENATO
; BITAR, YOUSZEF O.C.
; SILVEIRA, MARCOS
; MORATO, ELDER FERREIRA
; PAGOTTO, RUBIANI DE CÁSSIA
; STRUSSMANN, CHRISTINE
; MACHADO, RICARDO BOMFIM
; AGUIAR, LUDMILLA MOURA DE SOUZA
; FERNANDES, GERALDO WILSON
; OKI, YUMI
; NOVAIS, SAMUEL
; FERREIRA, GUILHERME BRAGA
; BARBOSA, FLÁVIA RODRIGUES
; OCHOA, ANA C.
; MANGIONE, ANTONIO M.
; GATICA, AILIN
; CARRIZO, MARÍA CELINA
; RETTA, LUCÍA MARTINEZ
; JOFRÉ, LAURA E.
; CASTILLO, LUCIANA L.
; NEME, ANDREA M.
; RUEDA, CARLA
; TOLEDO, JOSÉ JULIO DE
; GRELLE, CARLOS EDUARDO VIVEIROS
; VALE, MARIANA M.
; VIEIRA, MARCUS VINICIUS
; CERQUEIRA, RUI
; HIGASHIKAWA, EMÍLIO MANABU
; MENDONÇA, FERNANDO PEREIRA DE
; GUERREIRO, QUÊZIA LEANDRO DE MOURA
; BANHOS, AUREO
; HERO, JEAN-MARC
; KOBLITZ, RODRIGO
; COLLEVATTI, ROSANE GARCIA
; SILVEIRA, LUÍS FÁBIO
; VASCONCELOS, HERALDO L.
; VIEIRA, CECÍLIA RODRIGUES
; COLLI, GUARINO RINALDI
; CECHIN, SONIA ZANINI
; SANTOS, TIAGO GOMES DOS
; FONTANA, CARLA S.
; JARENKOW, JOÃO A.
; MALABARBA, LUIZ R.
; RUEDA, MARTA P.
; ARAUJO, PUBLIO A.
; PALOMO, LUCAS
; ITURRE, MARTA C.
; BERGALLO, HELENA GODOY
; MAGNUSSON, WILLIAM E.
.
Anais da Academia Brasileira de Ciências
- Métricas del periódico
Abstract The Program for Biodiversity Research (PPBio) is an innovative program designed to integrate all biodiversity research stakeholders. Operating since 2004, it has installed long-term ecological research sites throughout Brazil and its logic has been applied in some other southern-hemisphere countries. The program supports all aspects of research necessary to understand biodiversity and the processes that affect it. There are presently 161 sampling sites (see some of them at Supplementary Appendix), most of which use a standardized methodology that allows comparisons across biomes and through time. To date, there are about 1200 publications associated with PPBio that cover topics ranging from natural history to genetics and species distributions. Most of the field data and metadata are available through PPBio web sites or DataONE. Metadata is available for researchers that intend to explore the different faces of Brazilian biodiversity spatio-temporal variation, as well as for managers intending to improve conservation strategies. The Program also fostered, directly and indirectly, local technical capacity building, and supported the training of hundreds of undergraduate and graduate students. The main challenge is maintaining the long-term funding necessary to understand biodiversity patterns and processes under pressure from global environmental changes.
https://doi.org/10.1590/0001-3765202120201604
1034 descargas
5.
Quality of bevacizumab (Avastin®) repacked in single-use glass vials for intravitreal administration
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Sugimoto, Michelle A. A.
; Toledo, Vicente de Paulo Coelho Peixoto de
; Cunha, Mariem Rodrigues Ribeiro
; Carregal, Virginia M.
; Jorge, Rodrigo
; Leão, Pedro
; Fialho, Sílvia Ligorio
; Silva-Cunha, Armando
.
Arquivos Brasileiros de Oftalmologia
- Métricas del periódico
RESUMO Objetivos: Avastin® (bevacizumabe) é um anticorpo monoclonal inibidor do fator de crescimento endotelial de vasos (VEGF) utilizado "off-label" por meio de administração intravítrea para o tratamento de doenças oculares. A sua aplicação clínica associada ao custo-benefício do medicamento gerou uma demanda para seu fracionamento em frascos de dose única para utilização pela via intraocular. No entanto, a segurança do fracionamento do anticorpo em frascos de dose única ainda é alvo de discussão. Neste trabalho, a estabilidade e a eficácia do Avastin® fracionado em frascos ou ampolas de vidro de dose unitária por farmácias de manipulação do mercado foram avaliadas. Métodos: As técnicas de eletroforese em gel de poliacrilamida (PAGE), cromatografia por exclusão de tamanho (SEC), espalhamento dinâmico da luz (DLS) e turbidimetria foram empregadas para avaliar a formação de agregados de diferentes tamanhos. Alterações na atividade biológica do bevacizumabe foram estudadas utilizando ELISA. Resultados: Amostras referência e do bevacizumabe fracionado apresentaram resultados semelhantes quando analisado por gel de poliacrilamida. Por cromatografia por exclusão de tamanho, um pequeno aumento na quantidade de agregados de alta massa molar seguido de uma redução nos monômeros do bevacizumabe foram observados para as amostras das três farmácias de manipulação quando comparado ao referência. A comparação dos cromatogramas mostrou uma quantidade de redução do monômero inferior a 1% para todas as amostras fracionadas. Por espalhamento dinâmico da luz e turbidimetria, não foram detectados agregados de proteína na faixa de tamanho de micrômetro e nanômetro. No ensaio de eficácia, o bevacizumabe fracionado preservou sua função biológica pois apresentou menos de 3% de perda na capacidade de ligação ao VEGF quando comparado ao referência. Conclusão: Este estudo sugere que o bevacizumabe se mantem estável após fracionamento em ampolas e frascos de vidro de dose unitária pois não foram observadas agregação e/ou fragmentação de proteínas e perda de atividade biológica em quan tidades significativas.
ABSTRACT Purpose: Avastin® (bevacizumab) is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody given as an off-label drug by intravitreal administration for treatment of ocular diseases. The drug's clinical application and its cost-benefit profile has generated demand for its division into single-use vials to meet the low volume and low-cost doses necessary for intraocular administration. However, the safety of compounding the drug in single-use vials is still under discussion. In this study, the stability and efficacy of Avastin® repacked in individual single-use glass vials and glass ampoules by external compounding pharmacies were evaluated. Methods: Polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC), dynamic light scattering (DLS), and turbidimetry were selected to detect the formation of aggregates of various sizes. Changes in bevacizumab biological efficacy were investigated by using an enzyme-linked immunosorbent assay (ELISA). Results: Repacked and reference bevacizumab showed similar results when analyzed by PAGE. By SEC, a slight increase in high molecular weight aggregates and a reduction in bevacizumab monomers were observed in the products of the three compounding pharmacies relative to those in the reference bevacizumab. A comparison of repacked and reference SEC chromatograms showed that the mean monomer loss was ≤1% for all compounding pharmacies. Protein aggregates in the nanometer- and micrometer-size ranges were not detected by DLS and turbidimetry. In the efficacy assay, the biological function of repacked bevacizumab was preserved, with <3% loss of VEGF binding capacity relative to that of the reference. Conclusion: The results showed that bevacizumab remained stable after compounding in ampoules and single-use glass vials; no significant aggregation, fragmentation, or loss of biological activity was observed.
https://doi.org/10.5935/0004-2749.20170026
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6.
RET Y791F: alone or accompanied?
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Toledo, Rodrigo A.
; Loureço Jr, Delmar M
; Camacho, Cleber
; Lindsey, Susan
; Cerutti, Janete
; Maciel, Rui M. B.
; Toledo, Sergio P. A.
.
Archives of Endocrinology and Metabolism
- Métricas del periódico
https://doi.org/10.1590/2359-3997000000060
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7.
A differential diagnosis of inherited endocrine tumors and their tumor counterparts
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Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed.
https://doi.org/10.6061/clinics/2013(07)24
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8.
Biochemical, bone and renal patterns in hyperparathyroidism associated with multiple endocrine neoplasia type 1
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Lourenço Jr., Delmar M.
; Coutinho, Flavia L.
; Toledo, Rodrigo A.
; Gonçalves, Tatiana Denck
; Montenegro, Fabio L. M.
; Toledo, Sergio P. A.
.
Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.
https://doi.org/10.6061/clinics/2012(Sup01)17
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9.
Narrowing the gap of personalized medicine in emerging countries: the case of multiple endocrine neoplasias in Brazil
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Toledo, Rodrigo A.
; Sekiya, Tomoko
; Longuini, Viviane C.
; Coutinho, Flavia L.
; Lourenço Jr., Delmar M.
; Toledo, Sergio P. A.
.
The finished version of the human genome sequence was completed in 2003, and this event initiated a revolution in medical practice, which is usually referred to as the age of genomic or personalized medicine. Genomic medicine aims to be predictive, personalized, preventive, and also participative (4Ps). It offers a new approach to several pathological conditions, although its impact so far has been more evident in mendelian diseases. This article briefly reviews the potential advantages of this approach, and also some issues that may arise in the attempt to apply the accumulated knowledge from genomic medicine to clinical practice in emerging countries. The advantages of applying genomic medicine into clinical practice are obvious, enabling prediction, prevention, and early diagnosis and treatment of several genetic disorders. However, there are also some issues, such as those related to: (a) the need for approval of a law equivalent to the Genetic Information Nondiscrimination Act, which was approved in 2008 in the USA; (b) the need for private and public funding for genetics and genomics; (c) the need for development of innovative healthcare systems that may substantially cut costs (e.g. costs of periodic medical followup); (d) the need for new graduate and postgraduate curricula in which genomic medicine is emphasized; and (e) the need to adequately inform the population and possible consumers of genetic testing, with reference to the basic aspects of genomic medicine.
https://doi.org/10.6061/clinics/2012(Sup01)02
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10.
Surgical approach to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2
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Tavares, Marcos R.
; Toledo, Sérgio P. A.
; Montenegro, Fábio L. M.
; Moyses, Raquel A.
; Toledo, Rodrigo A.
; Sekyia, Tomoko
; Cernea, Claudio R.
; Brandão, Lenine G.
.
We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2-6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure.
https://doi.org/10.6061/clinics/2012(Sup01)25
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11.
Pituitary tumors in patients with MEN1 syndrome
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Syro, Luis V.
; Scheithauer, Bernd W.
; Kovacs, Kalman
; Toledo, Rodrigo A.
; Londoño, Francisco J.
; Ortiz, Leon D.
; Rotondo, Fabio
; Horvath, Eva
; Uribe, Humberto
.
We briefly review the characteristics of pituitary tumors associated with multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 is an autosomal-dominant disorder most commonly characterized by tumors of the pituitary, parathyroid, endocrine-gastrointestinal tract, and pancreas. A MEDLINE search for all available publications regarding multiple endocrine neoplasia type 1 and pituitary adenomas was undertaken. The prevalence of pituitary tumors in multiple endocrine neoplasia type 1 may vary from 10% to 60% depending on the studied series, and such tumors may occur as the first clinical manifestation of multiple endocrine neoplasia type 1 in 25% of sporadic and 10% of familial cases. Patients were younger and the time between initial and subsequent multiple endocrine neoplasia type 1 endocrine lesions was significantly longer when pituitary disease was the initial manifestation of multiple endocrine neoplasia type 1. Tumors were larger and more invasive and clinical manifestations related to the size of the pituitary adenoma were significantly more frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Normalization of pituitary hypersecretion was much less frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Pituitary tumors in patients with multiple endocrine neoplasia type 1 syndrome tend to be larger, invasive and more symptomatic, and they tend to occur in younger patients when they are the initial presentation of multiple endocrine neoplasia type 1.
https://doi.org/10.6061/clinics/2012(Sup01)09
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12.
Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1
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Coutinho, Flavia L.
; Lourenco Jr., Delmar M.
; Toledo, Rodrigo A.
; Montenegro, Fabio L. M.
; Toledo, Sergio P. A.
.
The bone mineral density increments in patients with sporadic primary hyperparathyroidism after parathyroidectomy have been studied by several investigators, but few have investigated this topic in primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Further, as far as we know, only two studies have consistently evaluated bone mineral density values after parathyroidectomy in cases of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Here we revised the impact of parathyroidectomy (particularly total parathyroidectomy followed by autologous parathyroid implant into the forearm) on bone mineral density values in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Significant increases in bone mineral density in the lumbar spine and femoral neck values were found, although no short-term (15 months) improvement in bone mineral density at the proximal third of the distal radius was observed. Additionally, short-term and medium-term calcium and parathyroid hormone values after parathyroidectomy in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 are discussed. In most cases, this surgical approach was able to restore normal calcium/parathyroid hormone levels and ultimately lead to discontinuation of calcium and calcitriol supplementation.
https://doi.org/10.6061/clinics/2012(Sup01)28
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13.
RET haplotype, not linked to the C620R activating mutation, associated with Hirschsprung disease in a novel MEN2 family
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Quedas, Elisangela P. S.
; Longuini, Viviane C.
; Sekiya, Tomoko
; Coutinho, Flavia L.
; Toledo, Sergio P. A.
; Tannuri, Uenis
; Toledo, Rodrigo A.
.
Hirschsprung disease is a congenital form of aganglionic megacolon that results from cristopathy. Hirschsprung disease usually occurs as a sporadic disease, although it may be associated with several inherited conditions, such as multiple endocrine neoplasia type 2. The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease. The prevalence of Hirschsprung disease in multiple endocrine neoplasia type 2 cases was recently determined to be 7.5% and the cooccurrence of Hirschsprung disease and multiple endocrine neoplasia type 2 has been reported in at least 22 families so far. It was initially thought that Hirschsprung disease could be due to disturbances in apoptosis or due to a tendency of the mutated RET receptor to be retained in the Golgi apparatus. Presently, there is strong evidence favoring the hypothesis that specific inactivating haplotypes play a key role in the fetal development of congenital megacolon/Hirschsprung disease. In the present study, we report the genetic findings in a novel family with multiple endocrine neoplasia type 2: a specific RET haplotype was documented in patients with Hirschsprung disease associated with medullary thyroid carcinoma, but it was absent in patients with only medullary thyroid carcinoma. Despite the limited number of cases, the present data favor the hypothesis that specific haplotypes not linked to RET germline mutations are the genetic causes of Hirschsprung disease.
https://doi.org/10.6061/clinics/2012(Sup01)11
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14.
Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice
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Peroni, Cibele N.
; Hayashida, Cesar Y.
; Nascimento, Nancy
; Longuini, Viviane C.
; Toledo, Rodrigo A.
; Bartolini, Paolo
; Bowers, Cyril Y.
; Toledo, Sergio P.A.
.
OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormonereleasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormonereceptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a.
https://doi.org/10.6061/clinics/2012(03)11
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15.
Isolated familial somatotropinoma: 11Q13-LOH and gene/protein expression analysis suggests a possible involvement of aip also in non-pituitary tumorigenesis
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Toledo, Rodrigo A.
; Mendonca, Berenice B.
; Fragoso, Maria Candida B. V.
; Soares, Iberê C.
; Almeida, Madson Q.
; Moraes, Michelle B.
; Lourenço-Jr, Delmar M.
; Alves, Venâncio A. F.
; Bronstein, Marcello D.
; Toledo, Sergio P. A.
.
OBJECTIVE: Non-pituitary tumors have been reported in a subset of patients harboring germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. However, no detailed investigations of non-pituitary tumors of AIP-mutated patients have been reported so far. PATIENTS: We examined a MEN1- and p53-negative mother-daughter pair with acromegaly due to somatotropinoma. Subsequently, the mother developed a large virilizing adrenocortical carcinoma and a grade II B-cell non-Hodgkin's lymphoma. DESIGN: Mutational analysis was performed by automated sequencing. Loss-of-heterozygosity (LOH) analysis was carried out by sequencing and microsatellite analysis. AIP expression was assessed through quantitative PCR (qPCR) and immunohistochemistry. RESULTS: The functional inactivating mutation c.241C>T (R81X), which blocks the AIP protein from interacting with phosphodiesterase 4A (PDE4A), was identified in the heterozygous state in the leukocyte DNA of both patients. Analyzing the tumoral DNA revealed that the AIP wild-type allele was lost in the daughter's somatotropinoma and the mother's adrenocortical carcinoma. Both tumors displayed low AIP protein expression levels. Low AIP gene expression was confirmed by qPCR in the adrenocortical carcinoma. No evidence of LOH was observed in the DNA sample from the mother's B-cell lymphoma, and this tumor displayed normal AIP immunostaining. CONCLUSIONS: Our study presents the first molecular analysis of non-pituitary tumors in AIP-mutated patients. The finding of AIP inactivation in the adrenocortical tumor suggests that further investigation of the potential role of this recently identified tumor suppressor gene in non-pituitary tumors, mainly in those tumors in which the cAMP and the 11q13 locus are implicated, is likely to be worthwhile.
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