15 results on '"Neves, Josiane Sabbadini"'
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2. Adenosine Diphosphate Improves Wound Healing in Diabetic Mice Through P2Y12 Receptor Activation
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Borges, Paula Alvarenga, primary, Waclawiak, Ingrid, additional, Georgii, Janaína Lima, additional, Fraga-Junior, Vanderlei da Silva, additional, Barros, Janaína Figueiredo, additional, Lemos, Felipe Simões, additional, Russo-Abrahão, Thaís, additional, Saraiva, Elvira Maria, additional, Takiya, Christina M., additional, Coutinho-Silva, Robson, additional, Penido, Carmen, additional, Mermelstein, Claudia, additional, Meyer-Fernandes, José Roberto, additional, Canto, Fábio B., additional, Neves, Josiane Sabbadini, additional, Melo, Paulo A., additional, Canetti, Claudio, additional, and Benjamim, Claudia Farias, additional
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- 2021
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3. Neutrophil and Eosinophil DNA Extracellular Trap Formation: Lessons From Pathogenic Fungi
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Silva, Juliana da Costa, primary, Thompson-Souza, Glaucia de Azevedo, additional, Barroso, Marina Valente, additional, Neves, Josiane Sabbadini, additional, and Figueiredo, Rodrigo Tinoco, additional
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- 2021
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4. Contributors
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Abraham, David, primary, Aceves, Seema S., additional, Ackerman, Steven J., additional, Adamko, Darryl, additional, Akashi, Koichi, additional, Akuthota, Praveen, additional, Alam, Rafeul, additional, Appleton, Judith A., additional, Arizmendi, Narcy, additional, Asosingh, Kewal, additional, Balla, Keir M., additional, Bandeira-Melo, Christianne, additional, Bartoli, Marc, additional, Benghiat, Fleur Samantha, additional, Berek, Claudia, additional, Bickham, Utibe, additional, Bivins-Smith, Elizabeth R., additional, Blanchard, Carine, additional, Bochner, Bruce S., additional, Bossios, Apostolos, additional, Bozza, Patricia T., additional, Broide, David, additional, Buitenhuis, Miranda, additional, Busse, William W., additional, Butterfield, Joseph H., additional, Cancelas, Jose A., additional, Capron, Monique, additional, Cardell, Lars Olaf, additional, Chu, Van T., additional, Comeau, Michael R., additional, Cook-Mills, Joan M., additional, Cools, Jan, additional, Cravetchi, Olga V., additional, Davis, Benjamin P., additional, Denburg, Judah A., additional, Domachowske, Joseph B., additional, Driss, Virginie, additional, Du, Jian, additional, Dvorak, Ann M., additional, Dyer, Kimberly D., additional, Elishmereni, Moran, additional, Eppihimer, Michael J., additional, Erzurum, Serpil C., additional, Falk, Gary W., additional, Fillon, Sophie, additional, Fiocchi, Claudio, additional, Foster, Paul S., additional, Fryer, Allison D., additional, Furuta, Glenn T., additional, Gauvreau, Gail M., additional, Gebreselassie, Nebiat G., additional, Gelfand, Erwin W., additional, Gentil, Katrin, additional, Gleich, Gerald J., additional, Haldar, Pranab, additional, Hirasawa, Noriyasu, additional, Hoerauf, Achim, additional, Hogan, Simon P., additional, Ilarraza, Ramses, additional, Irvin, Charles G., additional, Ishihara, Kenji, additional, Iwasaki, Hiromi, additional, Jacobsen, Elizabeth A., additional, Jacoby, David B., additional, Kariyawasam, Harsha H., additional, Kato, Atsushi, additional, Katz, Howard R., additional, Kay, A. Barry, additional, Kelly, Elizabeth A., additional, Kern, Robert, additional, Khoury, Paneez, additional, Kita, Hirohito, additional, Klion, Amy D., additional, Koenderman, Leo, additional, Kolbeck, Roland, additional, Krahn, Martin, additional, Lacy, Paige, additional, Lavigne, Mark C., additional, Layland, Laura E., additional, Moine, Alain Le, additional, Lee, James J., additional, Lee, Nancy A., additional, Legrand, Fanny, additional, Lemaitre, Philippe, additional, Letuve, Séverine, additional, Levi-Schaffer, Francesca, additional, Levy, Nicolas, additional, Lotfi, Ramin, additional, Lötvall, Jan, additional, Lotze, Michael Thomas, additional, McGarry, Michael P., additional, McNagny, Kelly M., additional, Mahmudi-Azer, Salahaddin, additional, Maltby, Steven, additional, Malter, James S., additional, Månsson Kvarnhammar, Anne M., additional, Massart, Annick, additional, Masterson, Joanne C., additional, Matsumoto, Kenji, additional, Mattes, Joerg, additional, Melo, Rossana C.N., additional, Molfino, Nestor A., additional, Moqbel, Redwan, additional, Mori, Yasuo, additional, Munitz, Ariel, additional, Nair, Parameswaran, additional, Neves, Josiane Sabbadini, additional, Nutman, Thomas B., additional, Ochkur, Sergei I., additional, (Wole) Odemuyiwa, S.O., additional, Ohuchi, Kazuo, additional, Orihara, Kanami, additional, Pavord, Ian D., additional, Percopo, Caroline M., additional, Plank, Maximilian, additional, Pretolani, Marina, additional, Prussin, Calman, additional, Ptaschinski, Catherine, additional, Rådinger, Madeleine, additional, Rao, Savita P., additional, Rieder, Florian, additional, Robinson, Douglas S., additional, Rosenberg, Helene F., additional, Rothenberg, Marc E., additional, Roufosse, Florence, additional, Schleimer, Robert P., additional, Schroeder, Shauna, additional, Scott, Gregory D., additional, Sexton, Darren W., additional, Shin, Mi-Kyung, additional, Simon, Dagmar, additional, Simon, Hans-Uwe, additional, Smith, Dirk E., additional, Spada, Neal, additional, Spencer, Lisa A., additional, Sriramarao, P., additional, Straumann, Alex, additional, Takatsu, Kiyoshi, additional, Teplinsky, Anastasya, additional, Thomas, Alex, additional, Traver, David, additional, Tulic, Meri K., additional, Venge, Per, additional, Waddell, Amanda, additional, Wagner, Lori A., additional, Walsh, Garry M., additional, Wang, Haibin, additional, Wardlaw, Andrew J., additional, Weller, Peter F., additional, Wennerås, Christine, additional, Xenakis, Jason J., additional, Yamada, Yoshiyuki, additional, Yousefi, Shida, additional, Zhu, Xiang, additional, and Zimmermann, Nives, additional
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- 2013
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5. Study of the Mechanisms Involved in Both Superoxide Anion Production and Dismutation in a Murine Model of Asthma: 124
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Valenca, Samuel Santos, Nesi, Renata Tiscoski, Lanzetti, Manuella, Pereira Pires, Karla Maria, Barroso, Marina Valente, Neves, Josiane Sabbadini, and Benjamim, Cláudia Farias
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- 2012
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6. Adenosine Diphosphate Improves Wound Healing in Diabetic Mice Through P2Y12 Receptor Activation.
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Borges, Paula Alvarenga, Waclawiak, Ingrid, Georgii, Janaína Lima, Fraga-Junior, Vanderlei da Silva, Barros, Janaína Figueiredo, Lemos, Felipe Simões, Russo-Abrahão, Thaís, Saraiva, Elvira Maria, Takiya, Christina M., Coutinho-Silva, Robson, Penido, Carmen, Mermelstein, Claudia, Meyer-Fernandes, José Roberto, Canto, Fábio B., Neves, Josiane Sabbadini, Melo, Paulo A., Canetti, Claudio, and Benjamim, Claudia Farias
- Subjects
ADENOSINE diphosphate ,ADENOSINES ,HEALING ,CHRONIC wounds & injuries ,SKIN injuries ,WOUND care ,WOUND nursing - Abstract
Chronic wounds are a public health problem worldwide, especially those related to diabetes. Besides being an enormous burden to patients, it challenges wound care professionals and causes a great financial cost to health system. Considering the absence of effective treatments for chronic wounds, our aim was to better understand the pathophysiology of tissue repair in diabetes in order to find alternative strategies to accelerate wound healing. Nucleotides have been described as extracellular signaling molecules in different inflammatory processes, including tissue repair. Adenosine-5'-diphosphate (ADP) plays important roles in vascular and cellular response and is immediately released after tissue injury, mainly from platelets. However, despite the well described effect on platelet aggregation during inflammation and injury, little is known about the role of ADP on the multiple steps of tissue repair, particularly in skin wounds. Therefore, we used the full-thickness excisional wound model to evaluate the effect of local ADP application in wounds of diabetic mice. ADP accelerated cutaneous wound healing, improved new tissue formation, and increased both collagen deposition and transforming growth factor-β (TGF-β) production in the wound. These effects were mediated by P2Y
12 receptor activation since they were inhibited by Clopidogrel (Clop) treatment, a P2Y12 receptor antagonist. Furthermore, P2Y1 receptor antagonist also blocked ADP-induced wound closure until day 7, suggesting its involvement early in repair process. Interestingly, ADP treatment increased the expression of P2Y12 and P2Y1 receptors in the wound. In parallel, ADP reduced reactive oxygen species (ROS) formation and tumor necrosis factor-α (TNF-α) levels, while increased IL-13 levels in the skin. Also, ADP increased the counts of neutrophils, eosinophils, mast cells, and gamma delta (γδ) T cells (Vγ4+ and Vγ5+ cells subtypes of γδ+ T cells), although reduced regulatory T (Tregs) cells in the lesion. In accordance, ADP increased fibroblast proliferation and migration, myofibroblast differentiation, and keratinocyte proliferation. In conclusion, we provide strong evidence that ADP acts as a pro-resolution mediator in diabetes-associated skin wounds and is a promising intervention target for this worldwide problem. [ABSTRACT FROM AUTHOR]- Published
- 2021
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7. Pharmacological modulation of reactive oxygen species (ROS) improves the airway hyperresponsiveness by shifting the Th1 response in allergic inflammation induced by ovalbumin
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Nesi, Renata Tiscoski, primary, Barroso, Marina Valente, additional, Souza Muniz, Valdirene de, additional, de Arantes, Ana Carolina, additional, Martins, Marco Aurélio, additional, Brito Gitirana, Lycia de, additional, Neves, Josiane Sabbadini, additional, Benjamim, Cláudia Farias, additional, Lanzetti, Manuella, additional, and Valenca, Samuel Santos, additional
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- 2017
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8. Study of the Mechanisms Involved in Both Superoxide Anion Production and Dismutation in a Murine Model of Asthma
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Santos Valenca, Samuel, primary, Nesi, Renata Tiscoski, additional, Lanzetti, Manuella, additional, Pires, Karla Maria Pereira, additional, Barroso, Marina Valente, additional, Neves, Josiane Sabbadini, additional, and Benjamim, Cláudia Farias, additional
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- 2012
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9. Effects of acute exposure to particulate matter from burning diesel fuel and biodiesel from the buses of the city of Rio de Janeiro in mice lungs
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Cavalieri, Isabella Cattani Pinto, Souza, Bruna Romana de, Neves, Josiane Sabbadini, and Resende, Angela de Castro
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Inflammation ,Combustíveis diesel ,Pulmões Doenças ,Pulmão ,Air pollution ,Mistura de diesel/biodiesel ,CIENCIAS BIOLOGICAS::MORFOLOGIA [CNPQ] ,Diesel/biodiesel mixture ,Mice ,Inflamação ,Ar Poluição ,Poluição do ar ,Camundongos ,Dano oxidativo ,Oxidative damage ,Biodiesel ,Lung - Abstract
Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:12:35Z No. of bitstreams: 1 Isabella Cattani Pinto Cavalieri Dissertacao completa.pdf: 1933904 bytes, checksum: 6946d254e5caedb34b888d0360fcfdb8 (MD5) Made available in DSpace on 2021-01-05T18:12:35Z (GMT). No. of bitstreams: 1 Isabella Cattani Pinto Cavalieri Dissertacao completa.pdf: 1933904 bytes, checksum: 6946d254e5caedb34b888d0360fcfdb8 (MD5) Previous issue date: 2017-02-21 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior One of the main forms of air pollution in urban centers of Brazil comes from diesel combustion from bus and truck engines. Diesel in Brazil is composed of diesel fuel and biodiesel (BS) with the aim of reducing air pollution. Thus, our aim was to investigate the effect of BS particulate matter exposure from fuel burning by public transport of Rio de Janeiro City in mice lung. BS particulate matter was collected from the exhaust pipes of buses from the public transportation fleet of Rio de Janeiro City and dissolved in saline/dimethyl sulfoxide. Female C57BL/6 mice were treated with 250 μg or 1000 μg of BS particulate matter and the control group with vehicle by intranasal instillation along five consecutive days. After sixth day, 10 animals per group were euthanized and the lungs and broncoalveolar lavage were collected. Ten animals were separated only for pulmonary mechanic analysis. We demonstrated that BS particulate matter was able to penetrate into the lung in the BS 250 μg and BS 1000 μg groups. In addition, the agglomerate of BS particulate matter in pulmonary parenchyma was higher in the BS 250 μg and BS 1000 μg groups than in the control group. The instillation of BS particulate matter increased the static elastance (Est) and lung resistive pressure (ΔP1) in BS 250 μg and BS 1000 μg groups when compared to control group. Furthermore, the macrophage number and protein levels of tumor necrosis factor-α (TNF-α) were also increased in lung of the BS 250 and 1000 μg group when compared to control group. The BS particulate matter enhanced reactive oxygen species synthesis and the malondialdehyde levels in both treated groups when compared to control group. The expression of glutamate cysteine ligase modifier subunit was lower in the BS 250 μg group than in the control group. The protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB) and heme oxygenase-1 (HO-1) enzyme was higher in BS 250 μg group, but lower in BS 1000 μg group, than in control group. In conclusion, the BS particulate matter instillation promotes inflammatory response and oxidative damage in mice lung activating Nrf2/HO-1 and NF-κB/TNF-α pathways. Uma das principais formas de poluição atmosférica nos centros urbanos do Brasil provém da combustão de diesel dos motores de ônibus e caminhões. O diesel no Brasil é composto por combustível diesel e biodiesel (BS) com o objetivo de reduzir a poluição do ar. Assim, nosso objetivo foi investigar o efeito da exposição ao material particulado BS proveniente da queima de combustível do transporte público da cidade do Rio de Janeiro em pulmões de camundongos. O material particulado BS foi coletado dos canos de descarga dos ônibus da frota do transporte público da cidade do Rio de Janeiro e foi dissolvido em uma mistura de solução salina e dimetilsulfóxido. Camundongos fêmeas C57BL/6 foram tratados com 250 μg ou 1000 μg de material particulado BS e o animais controle com veículo por instilação intranasal ao longo de cinco dias consecutivos. No 6° dia, 10 animais por grupo foram sacrificados, os pulmões e lavado broncoalveolar foram coletados. Dez animais por grupo foram reservados apenas para a análise da mecânica pulmonar. Foi demonstrado que o material particulado BS foi capaz de penetrar no parênquima pulmonar dos grupos BS 250 μg e BS 1000 μg. Além disso, o aglomerado de partículas BS no parênquima pulmonar foi maior nos grupos BS 250 μg e BS 1000 μg do que nos camundongos controle. A instilação do material particulado BS aumentou a elasticidade estática (Est) e a pressão resistiva pulmonar (ΔP1) nos grupos BS 250 μg e BS 1000 μg quando comparado ao grupo controle. O número de macrófagos e os níveis proteicos de proteína do fator de necrose tumoral-α (TNF-α) também estavam aumentados nos pulmões dos grupos BS 250 e 100 μg. O material particulado BS aumentou a produção de espécies reativas de oxigênio e os níveis de malondialdeído nos grupos tratados quando comparado ao grupo controle. A expressão proteica da glutamato cisteína ligase subunidade modificada foi menor no grupo BS 250 μg do que no grupo controle. A expressão proteica do fator nuclear relacionado à eritróide 2 (Nrf2), e do fator nuclear kappa B (NF-κB) e da enzima heme oxigenase-1 (HO-1) foi maior no grupo BS 250 μg, mas menor no grupo BS 1000 μg, quando comparado ao grupo controle. Em conclusão, a instilação do material particulado BS promove a resposta inflamatória e o dano oxidativo no pulmão de camundongos ativando as vias Nrf2/HO-1 e NF-κB/TNF-α.
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- 2017
10. Óleo de peixe (fonte de ácidos graxos n-3) atenua inflamação das vias aéreas e hiper-reatividade pulmonar induzida por alérgeno em camundongos
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Bargut, Thereza Cristina Lonzetti, Lacerda, Márcia Barbosa Águila Mandarim de, Martins, Patricia Machado Rodrigues e Silva, Neves, Josiane Sabbadini, and Matsuura, Cristiane
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Lung inflammation ,Pulmões Doenças Tratamento ,Inflamação pulmonar ,respiratory system ,Fish oil ,CIENCIAS BIOLOGICAS::MORFOLOGIA [CNPQ] ,GATA-3 ,Asthma ,n-3 PUFA ,Fator nuclear (NFκB) ,Óleo de peixe ,Receptor ativador de proliferação peroxissomal gama (PPARγ) ,Peroxisome proliferator-activated receptor gamma (PPARγ) ,Pulmões Inflamação ,Nuclear factor kappa B (NFκB) ,Asma - Abstract
Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:13:26Z No. of bitstreams: 1 Dissertacao Final Thereza Cristina Lonzetti BBargut.pdf: 1784354 bytes, checksum: 126282d05cf08b4a6720d421a397177e (MD5) Made available in DSpace on 2021-01-05T18:13:26Z (GMT). No. of bitstreams: 1 Dissertacao Final Thereza Cristina Lonzetti BBargut.pdf: 1784354 bytes, checksum: 126282d05cf08b4a6720d421a397177e (MD5) Previous issue date: 2013-03-07 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Fish oil (FO) is rich in n-3 polyunsaturated fatty acids (PUFA), which have been suggested to be anti-inflammatory and are associated with improvement of several inflammatory diseases. In this study, we investigated the influence of FO on allergen-induced lung inflammation and airway hyperreactivity in mice. Male A/J mice were fed either a standard-chow (SC) or a FO diet (FO) for 8 weeks. After 4 weeks, each group was further randomized for ovalbumin (SC-OVA and FO-OVA) or saline (SC-SAL and FO-SAL) challenge. Resistance and elastance were measured at baseline and after aerosolized methacholine, 24h after the last challenge. Bronchoalveolar lavage (BAL) was performed for leukocyte counts and eotaxin-2 quantification. Lung tissue mucus deposition, peribronchiolar matrix deposition and eosinophil infiltration were quantified. Interleukin-13 expression was evaluated by immunohistochemistry and nuclear factor kappa B (NFκB), GATA-3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression was measured by Western blot. OVA challenge resulted in increased eosinophil infiltration, increased inflammatory cytokine production, peribronchiolar matrix and mucus deposition and airway hyperreactivity to aerosolized methacholine. Elevated lung NFκB and GATA-3 expression was noted in OVA-challenged mice, which was attenuated in FO diet-fed mice. Higher PPARγ expression was also detected in the lungs from the FO-fed groups. In conclusion, FO intake attenuated classical asthma features by reducing inflammatory mediator production via GATA-3 and NFκB down-regulation and PPARγ up-regulation. Thus, FO might be an alternative therapy for asthma prevention and control. O óleo de peixe é rico em ácidos graxos poli-insaturados (AGPI) n-3 e vem sendo apontado como anti-inflamatório associado à melhora de diversas doenças de natureza inflamatória. No presente estudo, objetivou-se avaliar a influência do óleo de peixe sobre a inflamação pulmonar e hiper-reatividade em camundongos ativamente sensibilizados desafiados com ovoalbumina (OVA). Camundongos A/J machos foram alimentados com dieta standard-chow (SC) ou dieta rica em óleo de peixe (Px) durante 8 semanas. Após 4 semanas do início da dieta, cada grupo foi subdividido aleatoriamente para ser desafiado com salina (SC-SAL e PX-SAL) ou ovoalbumina (SC-OVA e PX-OVA). A função pulmonar (resistência e elastância) foi avaliada através de pletismografia invasiva, na condição de aerolização ou não com metacolina 24 horas após o último desafio antigênico. Foi realizado lavado broncoalveolar (LBA) para contagem de leucócitos e quantificação de eotaxina-2. A deposição de muco e de matriz peribronquiolar e o infiltrado de eosinófilos foram quantificados no tecido pulmonar. Foram avaliados interleucina (IL)-13 através de imunohistoquímica e NFκB, GATA-3 e PPARγ, por western-blotting. O desafio com OVA resultou em aumento da infiltração de eosinófilos, elevada produção de citocinas inflamatórias, remodelamento pulmonar, produção de muco e hiper-reatividade das vias aéreas. Detectou-se aumento na expressão dos fatores de transcrição NFκB e GATA-3 nos camundongos do grupo sensibilizado e desafiado com OVA em comparação aos controles. Todas essas alterações foram atenuadas nos camundongos que receberam dieta com óleo de peixe. Expressão elevada de PPARγ foi detectada nos pulmões dos camundongos dos grupos alimentados com óleo de peixe. Em conclusão, nossos resultados mostram que a ingestão de óleo de peixe atenuou as características clássicas do quadro asmático através da modulação da síntese de mediadores inflamatórios, via regulação negativa de NFκB e GATA-3 e regulação positiva de PPARγ. O óleo de peixe parece ser uma terapia alternativa para o controle e tratamento da asma.
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- 2013
11. Síntese de novos derivados de éteres de oximas e avaliação farmacológica de suas propriedades anti-inflamatórias
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VEIGA, Fabiano, VELOSO, Márcia Paranho, CARVALHO, Diogo Teixeira, and NEVES, Josiane Sabbadini
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Anti-Inflamatórios ,SINTESE ORGANICA [QUIMICA ORGANICA] ,Química farmacêutica ,Sintese organica - Abstract
O processo inflamatório consiste em uma resposta biológica de um organismo vivo contra algum tipo de agressão física, biológica ou química. A resposta inflamatória é mediada por substâncias denominada mediadores químicos, um dos mediadores é o ácido araquidônico e seus metabólitos são responsáveis pelo processo inflamatório. A cascata do ácido araquidônico produz os principais mediadores da inflamação como leucotrienos, tromboxanas e prostaglandinas. Os anti-inflamatórios não esteroidais atuam na inibição da prostaglandina endoperóxido sintase ou ciclo-oxigenase que são enzimas responsáveis pela oxidação do ácido araquidônico que apresentam duas isoformas: a PGHS-1, também conhecida como ciclo-oxigenase 1 (COX 1), configura-se uma enzima constitutiva por estar presente nos processos fisiológicos e a PGHS-2, também conhecida por ciclo-oxigenase 2 (COX 2) e pode ser induzida através do processo inflamatório. Anti-inflamatórios altamente seletivos para PGHS-2 foram desenvolvidos, entretanto, alguns deles apresentaram efeitos adversos e foram retirados do mercado, tendo como exemplos os seguintes: lumiracoxibe (Prexige®), etoricoxibe (Arcoxia®), parecoxibe (Bextra®), por entender que seus perfis de segurança, incluindo as reações adversas cardíacas, hepáticas e renais graves, superam a relação risco-benefício no tratamento das indicações estudadas. Novos protótipos de fármacos anti-inflamatórios menos seletivos passaram a ser desenvolvidos. Compostos contendo o grupo funcional éter de oxima foram sintetizados em nosso grupo de pesquisa e seus perfis de atividade anti-inflamatória foram avaliados, apresentado resultados positivos que levaram à continuidade destes estudos com o objetivo de confirmar e complementar as atividades anti-inflamatórias já identificadas. Depois de sintetizados e identificados os éteres de oxima foram submetidos a novos ensaios in vivo confirmando suas propriedades anti-inflamatórias, analgésicas e também foram identificadas atividades na inibição de agregação plaquetária. Os ensaios corroboraram para confirmar a eficácia farmacológica dos compostos sintetizados pelo nosso grupo de estudo. Neste trabalho também foi realizada a síntese de inéditos derivados de éteres de oxima, que foram submetidos à analise por RMN1H e RMN13C confirmando suas estruturas e sua rota sintética. The inflammatory process consists is a biological response in a living organism against some kind of physical, biological or chemical attack. The inflammatory response is mediated by substances called chemical mediators. One of the mediators is arachidonic acid and its metabolites are responsible for the inflammatory process. The arachidonic acid cascade produces the main inflammatory mediators such as leukotrienes, prostaglandins and thromboxanes. Non-steroidal anti-inflammatory drugs act by inhibiting prostaglandin endoperoxide synthase or cyclooxygenase enzymes that are responsible for oxidation of arachidonic acid and which have two isoforms: a PGHS-1, also known as cyclooxygenase 1 (COX-1) which is a constitutive enzyme because of its presence in physiological processes and PGHS-2, also known as cyclooxygenase 2 (COX-2) which can be induced by the inflammatory process. Anti-inflammatory drugs highly selective for PGHS 2 have been developed. However, some of them showed adverse effects and were withdrawn from the market, the following being examples: lumiracoxib (Prexige ®), etoricoxib (Arcoxia ®), parecoxib (Bextra ®), as it was thought that their safety profiles, including serious adverse cardiac, hepatic and renal disease, outweighed the risk-benefit in their intended applications. New prototype of less selective anti-inflammatory drugs have been developed. Compounds containing the functional group oxime ether were synthesized in our research group and their profiles of anti-inflammatory activity were evaluated, and positive results were present leading to continuation of these studies in order to confirm and complement the anti-inflammatory activities already identified. Once synthesized and identified the oxime ethers were subjected to further tests in vivo confirming their anti-inflammatory and analgesic activities, and inhibiting actions on platelet aggregation have also been identified. The tests corroborated to confirm the effectiveness of the pharmacological compounds synthesized by our study group. In this work the synthesis of new derivatives of oxime ethers was also carried out, which were subjective to analysis by RMN 1H and RMN 13C, confirming their structures and their synthetic route. Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
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- 2013
12. The lung remodeling in mouse emphysema is independent of nitric oxide modulation
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Barroso, Carlos Romualdo Rueff, Pôrto, Luís Cristóvão de Moraes Sobrino, Valença, Samuel dos Santos, Resende, Angela de Castro, Moura, Roberto Soares de, Neves, Josiane Sabbadini, and Soares, Raquel Moraes
- Subjects
Inflammation ,Mice ,Inflamação ,Óxido Nítrico ,CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::FISIOLOGIA DA DIGESTAO [CNPQ] ,Oxidative stress ,Camundongos ,Estresse oxidativo ,Cigarette smoke ,Nitric oxide ,Fumaça de cigarro - Abstract
Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T18:07:35Z No. of bitstreams: 1 2010, Rueff-Barroso - TESE.pdf: 3021259 bytes, checksum: 6dc84074a960db97270af8537647c529 (MD5) Made available in DSpace on 2021-01-05T18:07:35Z (GMT). No. of bitstreams: 1 2010, Rueff-Barroso - TESE.pdf: 3021259 bytes, checksum: 6dc84074a960db97270af8537647c529 (MD5) Previous issue date: 2010-04-26 Nitric oxide (NO) represents one of the most important intra and extracellular mediators/messengers. It takes part in both biologic and pathologic processes. This study aimed to verify NO role in pulmonary emphysema induced by cigarette smoke (CS) in mice. So L-NAME (LN) (a NOinhibitor) and L-arginine (LA) (a substract for NO formation) were analyzed and compared to N-acetylcysteine (NAC) (which is used in COPD treatment). A total of 65 C57BL/6 male mice were used. Fifty of them were divided in control, cigarette smoke (CS), cigarette smoke + L-NAME (CS+LN), cigarette smoke + L-arginin (CS+LA) and cigarette smoke + N-acetylcysteine (CS+NAC) groups (n = 10, each group). Forty animals were exposed to 12 commercial cigarettes 3 times a day for sixty days. Control and CS groups were submitted to orogastric gavages with saline. FC+LN, FC+LA, FC+NAC groups received daily gavages with L-NAME (60 mg/kg), L-arginine (120 mg/kg) and NAC (200 mg/kg) respectively. Fifteen animals (n=5, each group) were exposed to ambient air and treated with L-NAME, L-arginine and NAC alone. Cell profile of bronchoalveolar lavage was analyzed and the right lung was removed in order to perform histological analysis of air space enlargement. This was done measuring median alveolar diameter (Lm) and total alveolar septal volume (Sv) of alveolar septa. Left lungs were removed and homogenized to perform enzymatic activity (SOD, CAT and MPO) and glutathione ratio analysis (GSH/GSSG). Besides it, nitrite values and the expression of 4-HNE, MMP-12, NE, TIMP-1 and TIMP2 were also performed. L-arginine administration favored NOproduction and release, while L-NAME use inhibited. Briefly, we suggest L-NAME action to be directed to extracellular matrix (via proteinase-antiproteinase), while L-arginine action is directed to oxidants, similar to NAC. Our results showed that NAC acts raising glutathione levels which interfere directly with oxidants (via oxidant-antioxidant) while L-arginine acts raising oxidative burden at the same time it raises oxidants time of action. This also increases inflammatory cell numbers, but decreases their time of action, allowing a longer remodeling period. In conclusion, NOand both effects were efficient in lung protection/remodeling, although this remodeling was not as effective as when NAC was administrated. O óxido nítrico (NO) constitui um dos mais importantes mediadores intra e extracelulares e tem sido descrita sua participação tanto em processos biológicos como patológicos. Nosso objetivo foi verificar se o aumento ou a diminuição do óxido nítrico apresenta um efeito benéfico na proteção do tecido pulmonar no enfisema pulmonar induzido por fumaça de cigarro em camundongos. Para tanto, utilizamos o L-NAME (inibidor do NO), a L-arginina (substrato para a formação do NO) e os comparamos com a N-acetilcisteína (utilizada no tratamento da DPOC). Foram utilizados 65 camundongos C57BL/6 machos. Cinquenta animais foram divididos em grupos controle, fumaça de cigarro (FC), fumaça de cigarro + L-NAME (FC+LN), fumaça de cigarro + L-arginina (FC+LA), fumaça de cigarro + N-acetilcisteína (FC+NAC) (n=10, por grupo). Durante sessenta dias 40 animais foram expostos a 12 cigarros comerciais por dia, 3 vezes ao dia. Os grupos controle e FC foram submetidos à gavagens orogástricas com o veículo. Os grupos FC+LN, FC+LA, FC+NAC receberam gavagens diárias de L-NAME (60 mg/kg), L-arginina (120 mg/kg) ou NAC (200 mg/kg) respectivamente. Quinze animais (n = 5, por grupo) foram expostos ao ar ambiente e tratados apenas com L-NAME, L-arginina e NAC. Realizamos a análise do perfil das células do lavado broncoalveolar após o sacrifício. O pulmão direito foi removido para as análises histológicas do alargamento dos espaços aéreos determinado pela medida do diâmetro alveolar médio (Lm) e da densidade de superfície (Sv) dos septos alveolares. Os pulmões esquerdos foram removidos e homogeneizados para a as análises da atividade enzimática (SOD, CAT e MPO) e do sistema glutationa (GSH/GSSG), para a análise dos valores de nitrito e da expressão de 4-HNE, MMP-12, NE, TIMP-1, TIMP-2. Nossos resultados apontam que o L-NAME tem uma ação voltada para a matriz extracelular (via protease-antiprotease), enquanto que a L-arginina possui uma ação voltada para os oxidantes, assim como a NAC. Porém a NAC atua aumentando os níveis de glutationa, o que interfere diretamente nos oxidantes (via oxidante-antioxidante), enquanto a L-arginina interfere aumentando o burden oxidativo concomitante a um aumento da velocidade de ação dos oxidantes o que aumenta as células inflamatórias, mas diminui seu tempo de ação permitindo uma maior proteção. Concluímos que tanto o favorecimento para a produção e liberação do NOatravés da administração da L-arginina quanto a inibição do NOpela utilização do L-NAME foi eficiente na proteção do pulmão, apesar de não terem alcançado um resultado tão bom quanto a NAC.
- Published
- 2010
13. Adenosine Diphosphate Improves Wound Healing in Diabetic Mice Through P2Y 12 Receptor Activation.
- Author
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Borges PA, Waclawiak I, Georgii JL, Fraga-Junior VDS, Barros JF, Lemos FS, Russo-Abrahão T, Saraiva EM, Takiya CM, Coutinho-Silva R, Penido C, Mermelstein C, Meyer-Fernandes JR, Canto FB, Neves JS, Melo PA, Canetti C, and Benjamim CF
- Subjects
- Adenosine Diphosphate therapeutic use, Administration, Cutaneous, Alloxan administration & dosage, Alloxan toxicity, Animals, Diabetes Mellitus, Experimental chemically induced, Humans, Male, Mice, Purinergic P2Y Receptor Agonists therapeutic use, Skin drug effects, Skin injuries, Skin pathology, Adenosine Diphosphate pharmacology, Diabetes Mellitus, Experimental complications, Purinergic P2Y Receptor Agonists pharmacology, Receptors, Purinergic P2Y12 metabolism, Wound Healing drug effects
- Abstract
Chronic wounds are a public health problem worldwide, especially those related to diabetes. Besides being an enormous burden to patients, it challenges wound care professionals and causes a great financial cost to health system. Considering the absence of effective treatments for chronic wounds, our aim was to better understand the pathophysiology of tissue repair in diabetes in order to find alternative strategies to accelerate wound healing. Nucleotides have been described as extracellular signaling molecules in different inflammatory processes, including tissue repair. Adenosine-5'-diphosphate (ADP) plays important roles in vascular and cellular response and is immediately released after tissue injury, mainly from platelets. However, despite the well described effect on platelet aggregation during inflammation and injury, little is known about the role of ADP on the multiple steps of tissue repair, particularly in skin wounds. Therefore, we used the full-thickness excisional wound model to evaluate the effect of local ADP application in wounds of diabetic mice. ADP accelerated cutaneous wound healing, improved new tissue formation, and increased both collagen deposition and transforming growth factor-β (TGF-β) production in the wound. These effects were mediated by P2Y
12 receptor activation since they were inhibited by Clopidogrel (Clop) treatment, a P2Y12 receptor antagonist. Furthermore, P2Y1 receptor antagonist also blocked ADP-induced wound closure until day 7, suggesting its involvement early in repair process. Interestingly, ADP treatment increased the expression of P2Y12 and P2Y1 receptors in the wound. In parallel, ADP reduced reactive oxygen species (ROS) formation and tumor necrosis factor-α (TNF-α) levels, while increased IL-13 levels in the skin. Also, ADP increased the counts of neutrophils, eosinophils, mast cells, and gamma delta (γδ) T cells (Vγ4+ and Vγ5+ cells subtypes of γδ+ T cells), although reduced regulatory T (Tregs) cells in the lesion. In accordance, ADP increased fibroblast proliferation and migration, myofibroblast differentiation, and keratinocyte proliferation. In conclusion, we provide strong evidence that ADP acts as a pro-resolution mediator in diabetes-associated skin wounds and is a promising intervention target for this worldwide problem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Borges, Waclawiak, Georgii, Fraga-Junior, Barros, Lemos, Russo-Abrahão, Saraiva, Takiya, Coutinho-Silva, Penido, Mermelstein, Meyer-Fernandes, Canto, Neves, Melo, Canetti and Benjamim.)- Published
- 2021
- Full Text
- View/download PDF
14. Detection of Eosinophil Extracellular DNA Traps.
- Author
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Barroso MV and Neves JS
- Subjects
- Eosinophils physiology, Extracellular Traps immunology, Humans, Leukocytes, Neutrophils immunology, Eosinophils metabolism, Extracellular Traps metabolism, Microscopy, Fluorescence methods
- Abstract
The process of extracellular DNA trap release by leukocytes, including eosinophils, has been considered as an important cell-mediated immune response to different inflammatory stimuli helping to understand the physiopathology of many diseases. Here we describe in detail two useful and simple protocols for a semiquantitative and a qualitative analysis of extracellular DNA traps released by human eosinophils, based on fluorimetry and fluorescence microscopy, respectively. These methods can also be applied to detect the DNA trap release by other leukocytes such as neutrophils and even other cell types.
- Published
- 2021
- Full Text
- View/download PDF
15. Antianaphylactic properties of 7-epiclusianone, a tetraprenylated benzophenone isolated from Garcinia brasiliensis.
- Author
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Neves JS, Coelho LP, Cordeiro RS, Veloso MP, Rodrigues e Silva PM, dos Santos MH, and Martins MA
- Subjects
- Allergens, Animals, Anti-Allergic Agents administration & dosage, Anti-Allergic Agents therapeutic use, Benzophenones administration & dosage, Benzophenones therapeutic use, Benzoquinones administration & dosage, Benzoquinones therapeutic use, Dose-Response Relationship, Drug, Female, Fruit, Guinea Pigs, Inhibitory Concentration 50, Male, Phthalazines pharmacology, Plant Extracts administration & dosage, Plant Extracts pharmacology, Plant Extracts therapeutic use, Anti-Allergic Agents pharmacology, Benzophenones pharmacology, Benzoquinones pharmacology, Garcinia, Ileum drug effects, Muscle Contraction drug effects, Phytotherapy, Trachea drug effects
- Abstract
Prior studies have emphasized the anti-inflammatory and antioxidant properties of polyisoprenylated benzophenone derivatives, but their putative effect on allergic conditions has not yet been addressed. In the current study, the naturally occurring 7-epiclusianone, isolated from Garcinia brasiliensis, was investigated to check its effectiveness on allergen-evoked intestinal spasm. The standard antiallergic azelastine was used for comparison. We found that 7-epiclusianone and azelastine inhibited antigen-induced contractions of guinea pig ileum with similar IC (50) values (2.3 +/- 1.1 microM and 3.3 +/- 1.2 microM, respectively). A similar blockade of anaphylactic histamine release from the ileum was also noted. In contrast, azelastine was more potent than 7-epiclusianone to prevent spasms induced by histamine (IC (50) = 6.3 +/- 0.2 nM and 3.7 +/- 0.1 microM, respectively). These findings reveal that 7-epiclusianone is clearly active against the anaphylactic response and should be considered as a molecular template in drug discovery for allergic syndromes.
- Published
- 2007
- Full Text
- View/download PDF
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