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Análise de níveis de preservação digital para repositórios institucionais
No full textTrabalho apresentado na sessão virtual de Comunicação Oral da 11ª ConfOA no dia 08/10/2020.Este vídeo tem como objetivo principal apresentar uma reflexão sobre a integridade dos acervos culturais e científicos em repositórios institucionais diante dos tipos de níveis de preservação digital, a partir da leitura e experiências na literatura e documentação como modelos. A partir desta questão central, propor uma discussão sobre a decisão para promoção das políticas de preservação digital. Neste trabalho, foram analisados quatro modelos encontrados na literatura e em documentação técnica de instituições estrangeiras que apresentam ferramentas, técnicas e modelos para a avaliação de níveis de preservação digital de acervos. Esse estudo se fundamenta na lacuna da produção acadêmica nacional sobre a temática, vinculada principalmente ao planejamento, organização e criação de um plano de preservação digital para o Repositório Institucional Arca, da Fundação Oswaldo Cruz, tendo em vista sua missão de guarda, memória, disseminação, preservação, acesso e uso da informação através das tecnologias abertas
Isolation of caryatin as an Antiplasmodial component of Symphyopappus casarettoi (Asteraceae)
No full textMalaria remains a serious public health problem, being lethal to near 400,000 people every year, mostly in Africa. Due to the resistance of Plasmodium falciparum to available antimalarials, including artemisinin derivatives, and P. vivax to chloroquine, new therapies are necessary, since drug treatment remains as the main method to control the disease. The medicinal plants are an important source of malaria treatment and remains as an important strategy in the field of drug discovery. This study aimed to identification the antimalarials bioactive compounds isolated from Symphyopappus casarettoi inflorescences. The extract was investigated using a bioassay-guided fractionation protocol based on the assay with P. falciparum, and the cytotoxicity using monkey kidney cells. A fraction derived from the crude extract was active against P. falciparum and showed low cytotoxicity. From this fraction we isolated the flavonoid caryatin, a compound with activity against P. falciparum in vitro. It was, however, not active in the experiments with animals infected with P. berghei. The present work is the first to report the presence of caryatin in the family Asteraceae and its antiplasmodial activity. Another finding was the isolation of a new labdane type diterpene with a rare hydroxylation pattern.2099-12-3
Immunostimulatory and antioxidant activities of a lignin isolated from Conocarpus erectus leaves
No full textCNPq
CAPES
FACEPEIn this work, we investigated the antioxidant and immunomodulatory activities of a lignin isolated from Conocarpus erectus leaves. The lignin was characterized by FTIR, 1H NMR, 13C NMR and gel permeation chromatography analysis as well as ultraviolet/visible absorption spectra. The lignin was evaluated for total antioxidant activity (TAA), DPPH and ABTS+ scavenging abilities, and by a lipid peroxidation inhibition assay. Immunomodulatory activity of the lignin (10 μg/mL) on human peripheral blood mononuclear cells (PBMCs) was determined. The C. erectus lignin was found to be of the guaiacyl-syringyl-p-hydroxyphenyl (G-S-H) type, with an average molecular weight of 2709 Da (polydispersity index: 2.1). It showed low TAA (17.92%) and moderate antioxidant activity against DPPH and ABTS+ (IC50: 231.16 and 356.03 μg/mL, respectively). It also inhibited lipid peroxidation by 42.14%. The lignin promoted an increase in mitochondrial ROS levels as well as cytosolic Ca2+ in PBMCs. In addition, it promoted the differentiation and activation of CD8+ T lymphocytes, differentiation of CD14+ monocytes, and stimulated the release of nitric oxide and cytokines, mainly those linked to a Th1 response. The results showed that the C. erectus lignin may be used in future studies in which the modulation of the immune response is a key factor.2025-04-0
Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni
No full textProdução científica do Laboratório de Malacologia.Author summary: Schistosomiasis mansoni is a chronic and debilitating tropical disease caused by the helminth Schistosoma mansoni. The control and treatment of the disease rely almost exclusively on praziquantel (PZQ). Thus, there is an urgent need to search for promising protein targets to develop new drugs. Drugs that inhibit enzymes that modify the chromatin structure have been developed for a number of diseases. We and others have shown that S. mansoni epigenetic enzymes are also potential therapeutic targets. Here we evaluated the potential of the S. mansoni histone demethylase LSD1 (SmLSD1) as a drug target. We reported the synthesis of a novel and potent LSD1 inhibitor, MC3935, and show that it selectively inhibited the enzymatic activity of SmLSD1. Treatment of juvenile or adult worms with MC3935 caused severe damage to the tegument of the parasites and compromised egg production. Importantly, MC3935 proved to be highly toxic to S. mansoni, culminating in the death of juvenile or adult worms within 96 h. Transcriptomic analysis of MC3935-treated parasites revealed changes in the gene expression of hundreds of genes involved in key biological processes. Importantly, SmLSD1 contains unique sequences within its polypeptide chain that could be explored to develop a S. mansoni selective drug.Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors
Comunicação popular e comunitária em tempos de Covid-19: o direito de se comunicar e o direito à saúde
No full textAs desigualdades existentes no Brasil têm imposto grandes dificuldades nas respostas à pandemia do coronavírus. O problema, que perpassa as condições de moradia, acesso à alimentação segura e à saúde, também está presente no tocante à comunicação. No lugar de uma construção da comunicação como um direito de todos, o que presenciamos por aqui é a uma grande concentração de veículos de mídia nas mãos de poucos empresários, que, com isso, determinam o conteúdo a ser veiculado, além da forma e da linguagem a ser utilizada. Isso tem efeitos no exercício da cidadania de toda a população, e em tempos de emergência de saúde e com a necessidade de cuidados específicos, como é o atual cenário com a Covid-19, a situação se agrava. Entretanto, a resistência de comunicadores e comunicadoras populares e comunitários se mantém no período de pandemia e supera as dificuldades para dialogar em diversos territórios. E a boa notícia é que, em muitos casos, contam com parcerias de instituições ligadas à área da saúde para realizar esse trabalho e passar adiante informações qualificadas
Mundo pós-pandemia terá valores feministas no vocabulário comum, diz antropóloga
No full textA antropóloga e professora da faculdade de direito da Universidade de Brasília (UnB), Debora Diniz, que também é integrante do Programa de Pós-Graduação em Bioética, Ética Aplicada e Saúde Coletiva, em artigo ao Jornal Folha de São Paulo, afirma que conceitos como cuidado, proteção social, interdependência e saúde terão que ser discutidos. Ela arrisca uma previsão para o mundo pós-pandemia do novo coronavírus: "será um mundo mais alinhado aos valores feministas". Ela fala sobre como o novo coronavírus atinge as mulheres ao gerar desamparo na sociedade, sobre a importância do luto e sobre as relações entre o que vivemos hoje e a zika
Judicialização por medicamentos antineoplásicos para o tratamento de câncer de mama no estado de Pernambuco
No full textA via judicial tem sido utilizada para tentar garantir o direito constitucional da saúde, onde o Estado seria o responsável pela efetivação deste. Este fenômeno, denominado de judicialização da saúde tem crescido em todo o Brasil. O objetivo da pesquisa é analisar a judicialização por Medicamentos Antineoplásicos para o Tratamento do Câncer de Mama (MATCAM), no Estado de Pernambuco, já que o câncer de mama é uma doença bastante presente no Estado. Realizou-se um estudo de caso de abordagem quantitativa utilizando como modelo teórico o ciclo de políticas públicas judicializado. Foram utilizados dados primários encontrados no Núcleo de ações Judiciais da Secretaria Estadual de Saúde de Pernambuco e no Núcleo de Apoio Técnico em Saúde do Tribunal de Justiça do Estado, sobre ações que solicitaram MATCAM entre os anos de 2015 e 2018, no âmbito do SUS. Os resultados demonstraram que esse tipo de ação teve um crescimento acumulado de 209% durante o período avaliado. A maioria dos autores era do sexo feminino, até 50 anos, residia na I Região de Saúde do Estado e se encontrava no estágio IV da doença, quando ingressaram com a ação. Quase a metade dos demandantes procurou a via administrativa anteriormente, os principais representantes jurídicos foram públicos, assim como a origem das unidades que prescreveram os medicamentos. Os medicamentos mais solicitados foram: Pertuzumabe, Trastuzumabe Entasina, Trastuzumabe, Everolimo e Lapatinibe. Dos quais, dois são incorporados ao SUS, mas a maioria não era fornecida pelo Poder Público. Uma pequena parcela desses medicamentos ainda foi prescrita offlabel, não tinha registro na ANVISA e não possuía evidência científica sobre a sua eficácia. Concluiu-se que, em Pernambuco, existe uma falha na rede de assistência oncológica para pacientes acometidos com o câncer de mama, além de uma ineficiente articulação entre o Poder Judiciário e o Executivo .The judicial system has been used to try guarantee the constitucional right of health, where the State would be responsible for its effectiveness. This phenomenon, called the judicialization of health has grown throughout Brail. The objective of the research is to analyse the judicialization by Antineoplastic Medicines for the treatment of Breast Cancer (MATCAM), in the State of Pernambuco, since breast cancer is a very present disease in the State. A quantitative approach case study was carried out using the judicialized cycle of public policies as a theoretical model. Primary data found in the Center for Legal Actions of the State Health Secretariat of Pernambuco and in the Center for Technical Support in Health of the State Court of Justice were used on actions that requested MATCAM between the years 2015 and 2018 under the SUS.The results showed that this type of action had an accumulated growth of 209% during the evaluated period. Most of the authors were female, up to 50 years old, residing in the I Health Region of the State and were in stage IV of the disease when they filed the lawsuit.Almost half of the plaintiffs had sought the administratie route previously, the main legal representatives were public, as well as the origin of the units that prescribed the medications. The most requested medications were: Pertuzumab, Trastuzumab Entasin, Trastuzumab, Everolimo and Lapatinibe. Of which, two werw incorporated into the SUS, but most were not provided by the government. A small portion of these medications were still prescribed offlabel, had no registration with ANVISA and had no scientific evidence. It was concluded that, in Pernambuco, there is a failure in the oncology care network for patients affected with breast cancer, in addition to an inefficient articulation between the Judiciary and the Executive
Dactylogyridae (Monogenoidea, Polyonchoinea) des branchies d’Auchenipterus nuchalis (Siluriformes, Auchenipteridae) de la rivière Tocantins au Brésil
No full textTwo species of Cosmetocleithrum Kritsky, Thatcher & Boeger, 1986 (both new) and two species of Demidospermus Suriano, 1983 (one new) are reported from the gills of the catfish Auchenipterus nuchalis, popularly known as “mapará”, from the Tocantins River and tributaries, North Region of Brazil. Cosmetocleithrum berecae n. sp. differs from all other species presently known in the genus by the morphology of the anchors presenting an elongate shaft and short recurved point, a coiled male copulatory organ (MCO) with three rings, and an elongate slender accessory piece with a bifurcated distal end. Cosmetocleithrum nunani n. sp. differs from its congeners by the combination of the following features: (1) Ventral and dorsal anchors with moderately long curved shaft and short point; (2) Hooks with poorly developed thumb; (3) Hook pairs 5 and 6 similar to each other, but morphologically distinct from remaining hook pairs; and (4) MCO coiled, with approximately 1.5 rings. Demidospermus tocantinensis n. sp. is easily distinguished from other species of the genus by presenting an inverted-G-shaped MCO with a median knee-like expansion. Demidospermus osteomystax Tavernari, Takemoto, Lacerda & Pavanelli, 2010 is redescribed based on paratypes and specimens from the gills of A. nuchalis from the Tocantins River, a new host and locality records for this species. The monotypic Paracosmetocleithrum Acosta, Scholz, Blasco-Costa, Alves & Silva, 2017, the only other Neotropical genus reported in siluriforms besides Cosmetocleithrum with species presenting two ribbon-like projections on the posterior margin of the dorsal bar, is considered a junior subjective synonym of Cosmetocleithrum.Deux espèces de Cosmetocleithrum Kritsky, Thatcher et Boeger, 1986 (toutes deux nouvelles) et deux espèces de Demidospermus Suriano, 1983 (une nouvelle) sont signalées des branchies du poisson-chat Auchenipterus nuchalis, communément appelé « mapará », de la rivière Tocantins et affluents, Région Nord du Brésil. Cosmetocleithrum berecae n. sp. diffère de toutes les autres espèces actuellement connues dans le genre par la morphologie des anchors présentant un manche allongé et une pointe recourbée courte, un organe copulateur mâle (OCM) enroulé avec trois anneaux et une pièce accessoire allongée et mince avec une extrémité distale bifurquée. Cosmetocleithrum nunani n. sp. diffère de ses congénères par la combinaison des caractéristiques suivantes: (1) Anchors ventrales et dorsales avec tige incurvée modérément longue et pointe courte; (2) Crochets avec pouce peu développé; (3) Paires de crochets 5 et 6 similaires les unes aux autres, mais morphologiquement distinctes des paires de crochets restantes; (4) OCM enroulé, avec environ 1,5 anneaux. Demidospermus tocantinensis n. sp. se distingue facilement des autres espèces du genre par un OCM en forme de G inversé avec une expansion médiane du genou. Demidospermus osteomystax Tavernari, Takemoto, Lacerda & Pavanelli, 2010 est redécrit sur la base de paratypes et de spécimens des branchies d’A. nuchalis de la rivière Tocantins, et représente un hôte nouveau et une localité nouvelle pour cette espèce. Le genre monotypique Paracosmetocleithrum Acosta, Scholz, Blasco-Costa, Alves & Silva, 2017, le seul autre genre néotropical signalé chez les Siluriformes en dehors de Cosmetocleithrum, avec des espèces présentant deux projections en forme de ruban sur la marge postérieure de la barre dorsale, est considéré comme synonyme subjectif junior de Cosmetocleithrum
High-density lipoprotein as a new target for leprosy therapy
No full textWith the increased number of new leprosy cases in many regions of the world [1], the search for new tools to improve leprosy control must become a priority. The disease is characterized by the presence of debilitating lesions in the skin and peripheral nerves triggered by Mycobacterium leprae infection. Patients can be divided into two groups: paucibacillary (Pb) and multibacillary (Mb). Pb presents a low bacillary load and an active cellular immune response, while Mb has a high bacillary load with a systemic infection, anti-inflammatory cytokines and humoral immune response. Multidrug therapy (MDT) was implemented by WHO in 1981, and its use dropped the incidence of leprosy worldwide. However, cases of relapse after drug discharge point to therapeutic resistance. Besides, the long treatment period and its side effects favor abandonment. Other complications, like erythema nodosum leprosum (ENL) or reversal reaction episodes before, during, or after MDT can accelerate permanent disabilities. Thus, it is important to invest in the identification of therapeutic targets that enhance MDT efficacy and shorten treatment time or avoid complications.2030-12-3
Evaluation of super-boosted lopinavir/ritonavir in combination with rifampicin in HIV-1-infected patients with tuberculosis
No full textRifampicin induces the metabolism of many drugs. To overcome the reduction in serum concentrations of lopinavir/ritonavir (LPV/r) when used in combination with rifampicin, 800/200 mg or 400/400 mg doses are used. This study evaluated super-boosted LPV/r (400/400 mg) in HIV/TB co-infected patients for adequate concentrations as well as short-term safety, tolerability and clinical response to therapy. This was an open-label, non-randomised pharmacokinetic (PK) study in HIV/TB patients. The primary objective was to determine the PK profile of super-boosted LPV/r when given with a rifampicin-based TB regimen. Secondary objectives were short-term safety, tolerability and clinical response. Primary endpoints were a lopinavir trough concentration (Cmin) >1.0 µg/mL and a rifampicin maximum concentration (Cmax) of 8-24 µg/mL. Secondary PK endpoints were a rifampicin area under the concentration-time curve from 0-24 h (AUC0-24) of 44-70 µg·h/mL, a lopinavir Cmax of 6-14 µg/mL and a lopinavir AUC0-12 of 56-130 µg·h/mL. Eleven patients (10 male, age 25-43 years) were enrolled. Two patients were discontinued due to non-compliance. A lopinavir Cmin of >1.0 µg/mL was achieved in a least one of the PK samplings in all nine subjects who completed treatment. All patients met lopinavir Cmax and AUC0-12 targets. Five patients achieved the primary endpoint of rifampicin Cmax (≥8 µg/mL) in at least one of the PK samplings, and five achieved the minimum rifampicin AUC0-24 (≥44 µg·h/mL). One grade 3 adverse event was reported. Super-boosted LPV/r was safe and effective in HIV/TB patients. [ClinicalTrials.gov ID NCT01700790.]