Perfil epidemiológico de parasitoses intestinais na microrregião de Itajaí/SC: Epidemiological profile of intestinal parasitosis in the microregion of Itajaí/SC

Introdução: As infecções parasitarias intestinais não são de caráter de notificação compulsória no Brasil o que resulta na falta do conhecimento epidemiológico, subdiagnóstico e dificulta a tomada de medidas terapêuticas efetivas. Objetivo: Determinar o perfil epidemiológico das enteroparasitoses da microrregião de Itajaí/SC, levando em consideração gênero e idade mais acometidos.  Materiais e Métodos: Trata-se de uma pesquisa do tipo descritiva analítica transversal não intervencionista a partir de análise dos dados de pacientes atendidos pelos laboratórios da microrregião de Itajaí no período de janeiro de 2015 à dezembro de 2017. Resultados: De 3016 laudos, 591 foram positivos para enteroparasitas e os agentes etiológicos mais prevalentes foram os protozoários: Giardia lamblia, Endolimax nana, Entamoeba coli e os helmintos: Ascaris lumbricoides seguido de Enterobius vermiculares. Discussão e Conclusão: Itajaí por ser um polo turístico que recebe um fluxo grande de pessoas é importante o engajamento de todos, como os órgãos governamentais, educadores, profissionais da saúde, pais ou responsáveis, bem como a comunidade em geral, buscando a melhoria das condições de saúde para a população. Como perspectiva, espera-se a continuação de estudos epidemiológicos que estimem a prevalência de parasitoses, buscando avaliar um maior número de pessoas e desenvolver ações de prevenção junto à comunidade

new pre clinical evidence of anti inflammatory effect and safety of a substituted fluorophenyl imidazole

Abstract Acute Respiratory Distress Syndrome (ARDS) is an inflammatory condition with high mortality rates, and there is still no pharmacological approach with proven effectiveness. In the past few years, several imidazole small molecules have been developed to treat conditions in which inflammation plays a central role. In the present work, we hypothesize that a novel substituted fluorophenyl imidazole synthetized by our research group would present in vivo anti-inflammatory effect in an ARDS murine model induced by LPS. Results shows that the fluorophenyl imidazole has the ability to inhibit leukocyte migration to the bronchoalveolar lavage fluid and lung tissue of animals challenged intranasally with LPS. Furthermore, this inhibition is followed with reduction in myeloperoxidase activity, nitric oxide metabolites generation and cytokines (TNF-α, IL-6, IL-17, IFN-γ and IL-10) secretion. This effect is at least partly related to the capacity of the fluorophenyl imidazole in inhibit p38 MAPK and NF-κB phosphorylation. Finally, fluorophenyl imidazole showed no signs of acute oral toxicity in the toxicological protocol suggested by OECD 423. Taken together, the results shows that fluorophenyl imidazole is a promising prototype for the development of a novel anti-inflammatory drug in which p38 MAPK and NF-κB plays a pivotal role

Efeito anti-inflamatório da N-antipirina-3,4-dicloromaleimida e seus derivados em modelo in vitro e revisão sistemática sobre o impacto da dexametasona na mortalidade de pacientes com sepse

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2021.O processo inflamatório é uma resposta a estímulos nocivos que visa a destruição de agentes estranhos para posteriormente reparar o local afetado. Quando a inflamação é descontrolada ou não resolvida, pode levar a lesões teciduais significativas como os quadros de sepse. Muitos fármacos anti-inflamatórios têm sido utilizados para o tratamento de processos inflamatórios, como a dexametasona. No entanto, a demanda por novas moléculas mais eficazes com maiores margens de segurança permanece ativa. Assim, o objetivo do estudo foi avaliar o efeito anti-inflamatório in vitro dos compostos N-antipirina-3,4-dicloromaleimida e seus derivados e revisar sistematicamente a literatura para avaliar a mortalidade de pacientes com sepse ou choque séptico em uso de dexametasona. No estudo experimental desta tese, macrófagos RAW 264.7 foram utilizados para avaliar a citotoxicidade e a atividade anti-inflamatória por meio da mensuração de óxido nítrico, IL-1ß, IL-6, MCP-1 (CCL2), TNF-a, INF-?, IL-4 e IL-13 e ativação do NF-?B. Primeiramente, foi verificado que nenhum composto apresentou citotoxicidade significativa (CC50<100 µM). Posteriormente, foi avaliado o potencial de inibição do óxido nítrico como triagem e de todos os compostos testados, três mostraram um perfil promissor. Quando avaliado o efeito desses três compostos na produção de IL-1ß, IL-6, MCP-1 (CCL2), TNF-a e INF-?, apenas os compostos N-antipirina-3,4-dicloromaleimida e N-antipirina-3-cloro-4-(3,4-dicloroanilina)maleimida apresentaram um perfil de inibição significativo. Além disso, esses dois compostos também foram capazes de aumentar a produção de citocinas conhecidas pelo perfil anti-inflamatório (IL-4 e IL-13), e ainda inibiram significativamente a fosforilação da subunidade p-p65 NF-?B. A busca sistemática da literatura foi realizada em quatro bancos de dados eletrônicos e as avaliações de risco de viés foram realizadas usando a ferramenta Cochrane Collaboration e a qualidade da notificação foi avaliada usando a lista de verificação baseada no CONSORT. O protocolo de estudo da revisão sistemática foi registrado no banco de dados PROSPERO (CRD42018088150). Os três estudos selecionados incluíram oitenta pacientes adultos com sepse ou choque séptico que receberam dexametasona como intervenção. Dos três artigos, dois concluíram que o uso de dexametasona reduz significativamente a mortalidade em pacientes com sepse ou choque séptico. Os resultados de risco de viés da ferramenta Cochrane Collaboration mostraram que nenhum dos estudos estava completamente livre de viés e, por meio da lista de verificação CONSORT, verificou-se que nenhum dos estudos atendia a 50% ou mais dos requisitos aplicáveis. Em conclusão, fica claro a partir da revisão sistemática que mais ensaios clínicos randomizados comparando o uso de dexametasona com placebo em terapia adjuvante para pacientes com sepse são necessários. A partir dos resultados experimentais, dois compostos apresentam um efeito anti-inflamatório significativo com fortes indícios que seu mecanismo envolva imunomodulação dos macrófagos, qualificando-os como protótipos promissores para o desenvolvimento de novos anti-inflamatórios com características imunomoduladoras.Abstract: The inflammatory process is a response to harmful stimuli aimed at destroying foreign agents to later repair the affected site. When inflammation is uncontrolled or unresolved, it can lead to significant tissue damage such as sepsis. Many anti-inflammatory drugs have been used to treat inflammatory processes, such as dexamethasone. However, the demand for new, more effective molecules with greater safety margins remains active. Thus, the aim of the study was to evaluate the in vitro anti-inflammatory effect of N-antipyrine-3,4-dichloromaleimide compounds and their derivatives and to systematically review the literature to assess the mortality of patients with sepsis or septic shock using dexamethasone. In the experimental study of this thesis, RAW 264.7 macrophages were used to assess cytotoxicity and anti-inflammatory activity by measuring nitric oxide, IL-1ß, IL-6, MCP-1 (CCL2), TNF-a, INF- ?, IL-4, IL-13, and NF-?B activation. First, it was verified that no compound showed significant cytotoxicity (CC50 <100 µM). Subsequently, the potential for inhibition of nitric oxide was evaluated as a screening and of all tested compounds, three showed a promising profile. When evaluating the effect of these three compounds on the production of IL-1ß, IL-6, MCP-1 (CCL2), TNF-a and INF-?, only the compounds N-antipyrine-3,4-dichloromaleimide and N-antipyrine-3-chloro-4-(3,4-dichloroaniline)maleimide showed a significant inhibition profile. Furthermore, these two compounds were also able to increase the production of cytokines known for their anti-inflammatory profile (IL-4 and IL-13), and significantly inhibited the phosphorylation of the p-p65 NF-?B subunit. A systematic literature search was performed in four electronic databases and risk of bias assessments were performed using the Cochrane Collaboration tool and the quality of reporting was assessed using the CONSORT-based checklist. The study protocol of the systematic review was registered in the PROSPERO database (CRD42018088150). The three selected studies included eighty adult patients with sepsis or septic shock who received dexamethasone as an intervention. Of the three articles, two concluded that the use of dexamethasone significantly reduced mortality in patients with sepsis or septic shock. The risk of bias results from the Cochrane Collaboration tool showed that none of the studies was completely free of bias and, through the CONSORT checklist, none of the studies were found to meet 50% or more of the applicable requirements. In conclusion, it is clear from the systematic review that more randomized controlled trials comparing the use of dexamethasone with placebo in adjuvant therapy for patients with sepsis are needed. Based on the experimental results, two compounds have a significant anti-inflammatory effect with strong evidence that their mechanism involves macrophage immunomodulation, qualifying them as promising prototypes for the development of new anti-inflammatory drugs with immunomodulatory characteristics

Further Drimane Sesquiterpenes From Drimys Brasiliensis Stem Barks With Cytotoxic Potential

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Drimys brasiliensis Miers (Winteraceae) is used in folk medicine for the treatment of cancer. Its anti-tumor activity has been demonstrated in vitro models using extracts and isolated compounds. This study investigates the cytotoxic effects of stem bark extracts of D. brasiliensis as well as isolated compounds that may be responsible for the activitys and evaluates them in leukemia cells. The stem bark extract were subjected to column chromatography, and the structures of compounds were elucidated based on spectroscopic methods by using NMR and infrared spectroscopy and GC/MS. The cytotoxicity of the isolated compounds was evaluated in chronic myeloid (K562) and acute B lymphoblastic (Nalm6) leukemia cells using tetrazolium assay (MTT). Two new compounds were isolated 1 beta-O-p-methoxy-E-cinnamoyl-5 alpha-keto-11 alpha-enol-albicanol (1a) and the isomer 1 beta-O-p-methoxy-E-cinnamoyl-5 alpha-keto-11 beta-enol-albicanol (1b) and 1 beta-O-p-methoxy-E-cinnamoyl-isodrimeninol (2). The known compounds polygonal acid (3a) and the isomer isopolygonal acid (3b), fuegin (4a) and the isomer epifuegin (4b), the mixture drimanial (5) and 1 beta-O-(p-methoxy-E-cinnamoyl)-6 alpha-hydroxypolygodial (6) were also isolated. The drimanes (1-4) and drimanial (5), 1 beta-(p-coumaroyloxy)-polygodial (7), 1 beta-(p-methoxycinnamoyl)-polygodial (8), and polygodial (9) isolated previously were assessed in tumor cells. The IC50 values were between 3.56 and 128.91 mu M. 1-beta-(p-cumaroiloxi)-polygodial showed the best result with IC50 8.18 and 3.56 mu M by K562 and Nalm6, respectively. The chloroform extract of the stem bark of D. brasiliensis is a great source of drimane sesquiterpenes. Our experimental data suggest that drimanes are responsible for cytotoxicity activity demonstrated by this species, especially those with the aldehyde group linked to carbons C-11 and C-12.3897791797Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao de Apoio a Pesquisa Cientifica e Tecnologica do Estado de Santa Catarina (FAPESC)Programa Iberoamericano de Ciencia y Tecnologia para el Desarrollo (CYTED) [Red 0464 RIBECANCER]University of Vale do Itajai (UNIVALI)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Further drimane sesquiterpenes from Drimys brasiliensis stem barks with cytotoxic potential

Drimys brasiliensis Miers (Winteraceae) is used in folk medicine for the treatment of cancer. Its anti-tumor activity has been demonstrated in vitro models using extracts and isolated compounds. This study investigates the cytotoxic effects of stem bark extracts of D. brasiliensis as well as isolated compounds that may be responsible for the activitys and evaluates them in leukemia cells. The stem bark extract were subjected to column chromatography, and the structures of compounds were elucidated based on spectroscopic methods by using NMR and infrared spectroscopy and GC/MS. The cytotoxicity of the isolated compounds was evaluated in chronic myeloid (K562) and acute B lymphoblastic (Nalm6) leukemia cells using tetrazolium assay (MTT). Two new compounds were isolated 1 beta-O-p-methoxy-E-cinnamoyl-5 alpha-keto-11 alpha-enol-albicanol (1a) and the isomer 1 beta-O-p-methoxy-E-cinnamoyl-5 alpha-keto-11 beta-enol-albicanol (1b) and 1 beta-O-p-methoxy-E-cinnamoyl-isodrimeninol (2). The known compounds polygonal acid (3a) and the isomer isopolygonal acid (3b), fuegin (4a) and the isomer epifuegin (4b), the mixture drimanial (5) and 1 beta-O-(p-methoxy-E-cinnamoyl)-6 alpha-hydroxypolygodial (6) were also isolated. The drimanes (1-4) and drimanial (5), 1 beta-(p-coumaroyloxy)-polygodial (7), 1 beta-(p-methoxycinnamoyl)-polygodial (8), and polygodial (9) isolated previously were assessed in tumor cells. The IC50 values were between 3.56 and 128.91 mu M. 1-beta-(p-cumaroiloxi)-polygodial showed the best result with IC50 8.18 and 3.56 mu M by K562 and Nalm6, respectively. The chloroform extract of the stem bark of D. brasiliensis is a great source of drimane sesquiterpenes. Our experimental data suggest that drimanes are responsible for cytotoxicity activity demonstrated by this species, especially those with the aldehyde group linked to carbons C-11 and C-123897791797CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA E INOVAÇÃO DO ESTADO DE SANTA CATARINA - FAPESCsem informaçã