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Alice Song Edson Abdala Daniel Waisberg Rodrigo Bronze Martino Ho Yeh Li Luiz Marcelo Sa Malbouisson Ryan Yukimatsu Tanigawa Amaro Duarte Neto Guilherme Marques Andrade Liliana Ducatti Andre Mario Doi João Renato Rebello Pinho Michele Gomes‐Gouvea Fernanda Malta Lecio Figueira Pinto Bruno Fukelmann Guedes Luciana Haddad Venancio Avancini F. Alves Luiz Augusto D. Albuquerque 《The Brazilian journal of infectious diseases》2018
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Rheumatoid arthritis (RA) and osteoarthritis (OA) are prevalent chronic health conditions. However, despite recent advances in medical therapeutics, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. Accordingly, there is an urgent need to develop and test new drugs for RA and OA that selectively target inflamed joints thereby mitigating damage to healthy tissues.Conceivably, biocompatible, biodegradable, disease-modifying antirheumatic nanomedicines (DMARNs) could represent a promising therapeutic approach for RA and OA. To this end, the unique physicochemical properties of drug-loaded nanocarriers coupled with pathophysiological characteristics of inflamed joints amplify bioavailability and bioactivity of DMARNs and promote their selective targeting to inflamed joints. This, in turn, minimizes the amount of drug required to control articular inflammation and circumvents collateral damage to healthy tissues. Thus, nanomedicine could provide selective control both in space and time of the inflammatory process in affected joints.However, bringing safe and efficacious DMARNs for RA and OA to the marketplace is challenging because regulatory agencies have no official definition of nanotechnology, and rules and definitions for nanomedicines are still being developed. Although existing toxicology tests may be adequate for most DMARNs, as new toxicity risks and adverse health effects derived from novel nanomaterials with intended use in humans are identified, additional toxicology tests would be required. Hence, we propose that detailed pre-clinical in vivo safety assessment of promising DMARNs leads for RA and OA, including risks to the general population, must be conducted before clinical trials begin. 相似文献
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Manoela Viar Fogaça Lucas Milanez Benicio Lara Martinelli Zapata Priscilla de Freitas Cardoso Marcelo Tempesta de Oliveira 《Pharmaceutical biology》2017,55(1):2005-2014
Context: Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood.Objective: We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN- and ISA-induced expression of ERCC1 or BAX genes.Materials and methods: HeLa and/or CHO-K1 cell lines were tested (3 or 24?h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72?h) tests after treatment with IRN (0.1 to 200?μM) or ISA (0.5 to 50?μM). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24?h) by gavage (50, 100 and 150?mg/kg determined from the LD50 – 1?g/kg b.w.) and submitted to comet assay in vivo.Results: IRN reduced the viability of CHO-K1 (24?h; 5 to 200?μM) and HeLa cells (10 to 200?μM), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10?μM; HeLa: 5 and 10?μM). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24?h) at all doses tested. IRN (100 and 150?mg/kg) also induced genotoxicity in vivo (4?h).Conclusion: IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations. 相似文献
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Marcello Fonseca Salgado‐Filho Samira Saady Morhy Henrique Doria de Vasconcelos Eric Benedet Lineburger Fabio de Vasconcelos Papa Eduardo Souza Leal Botelho Marcelo Ramalho Fernandes Maurício Daher David Le Bihan Chiara Scaglioni Tessmer Gatto Cláudio Henrique Fischer Alexander Alves da Silva Carlos Galhardo Júnior Carolina Baeta Neves Alexandre Fernandes Marcelo Luiz Campos Vieira 《Brazilian Journal of Anesthesiology》2018,68(1):1-32
Through the Life Cycle of Intraoperative Transesophageal Echocardiography (ETTI/SBA) the Brazilian Society of Anesthesiology, together with the Department of Cardiovascular Image of the Brazilian Society of Cardiology (DIC/SBC), createded a task force to standardize the use of intraoperative transesophageal echocardiography by Brazilian anesthesiologists and echocardiographers based on scientific evidence from the Society of Cardiovascular Anesthesiologists/American Society of Echocardiography (SCA/ASE) and the Brazilian Society of Cardiology. 相似文献
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