Aprensentação

A PROExC tem sido para mim uma atividade muito gratificante. Os resultados positivos que temos alcançado me animam e me envolvem cada vez mais nas ações de ligação entre a Universidade e a Sociedade. Como sabemos, extensão não se faz individualmente, mas sim com o resultado de uma construção coletiva e assim venho aprendendo desde meu ingresso nesta instituição (menos de 5 anos) com os colegas professores e técnicos, e com cada um que participou por um tempo ou de alguma maneira nos projetos e contribuiu para o seu sucesso. Embora para muitos, as vertentes acadêmico-científica, política e sócio-cultural sejam aparentemente distantes, não tenho dúvidas sobre a coerência interna entre elas, modulada pelos valores éticos e humanistas que nasceram e se nutrem a partir de minha vida familiar, profissional e social. A experiência política e a vivência cultural têm facilitado a capacidade de desenvolver o trabalho acadêmico-científico e extensionista, ampliando a minha visão e capacidade de resposta às questões que surgem na vida acadêmica

Genotoxicity of polycyclic aromatic hydrocarbons and nitro-derived in respirable airborne particulate matter collected from urban areas of Rio de Janeiro (Brazil)

Submitted by José Mazzei ([email protected]) on 2019-12-07T11:41:30Z No. of bitstreams: 1 (Rainho et al 2013) Genotoxicity of Polycyclic Aromatic Hydrocarbons.pdf: 1287100 bytes, checksum: 8308704287cfb9e5791bfa22853ca3bb (MD5)Approved for entry into archive by Michelle Lanzellote ([email protected]) on 2019-12-10T14:01:00Z (GMT) No. of bitstreams: 1 (Rainho et al 2013) Genotoxicity of Polycyclic Aromatic Hydrocarbons.pdf: 1287100 bytes, checksum: 8308704287cfb9e5791bfa22853ca3bb (MD5)Made available in DSpace on 2019-12-10T14:01:00Z (GMT). No. of bitstreams: 1 (Rainho et al 2013) Genotoxicity of Polycyclic Aromatic Hydrocarbons.pdf: 1287100 bytes, checksum: 8308704287cfb9e5791bfa22853ca3bb (MD5) Previous issue date: 2013Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcantara Gomes. Departamento de Biofísica e Biometria. Laboratório de Mutagênese Ambiental. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Tecnologia. Departamento de Química Ambiental. Resende, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Instituto Biomédico. Departamento de Genética e Biologia Molecular. Laboratório de Genotoxicidade. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcantara Gomes. Departamento de Biofísica e Biometria. Laboratório de Mutagênese Ambiental. Rio de Janeiro, RJ, Brasil.Air pollution toxic effects are mainly attributed to small inhalable particulates with an aerodynamic diameter of less than 2.5 µ m (PM 2.5). Our objective was to investigate mutagenic and clastogenic activity in PM samples collected in Rio de Janeiro. Samples were collected using a high-volume sampler at three sites: with low traffic and (2) and (3) with a heavy traffic. Six polycyclic aromatic hydrocarbons (PAHs) were quantified by gas chromatography/mass spectrometry (GC/MS). Salmonella typhimurium TA98 and the derivative strains YG1021 and YG1024 were used in mutagenicity assays in the presence of organic extracts (10-50 µ g/ plate) with and without exogenous metabolization. Allium cepa test was performed to evaluate possible cytotoxic and clastogenic activities. The highest PM 2.5 µ m (132.73 µ m/m(3)) and PAH values (1.22 ng/m(3) for benzo(a)pyrene) were detected at site 3. High mutagenic frameshift responses in absence and presence of metabolic activation were detected at site 3. The participation of nitroarenes and dinitroarenes was detected in the total mutagenicity of the extracts studied. The cytotoxic effect and the abnormalities detected by Allium cepa test can be attributed to the PAH nitroderivatives in the organic extracts. Evaluation of the genotoxicity of urban airborne particulate matter is important as a basis for decision making by regulatory authorities

Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group

Submitted by Alexandre Sousa ([email protected]) on 2015-07-02T18:25:31Z No. of bitstreams: 1 Mem_Inst_Oswaldo_Cruz_110_492-499.pdf: 731403 bytes, checksum: e3c80a885f8ca653823b2bbdf158f8c5 (MD5)Approved for entry into archive by Alexandre Sousa ([email protected]) on 2015-07-02T18:31:44Z (GMT) No. of bitstreams: 1 Mem_Inst_Oswaldo_Cruz_110_492-499.pdf: 731403 bytes, checksum: e3c80a885f8ca653823b2bbdf158f8c5 (MD5)Approved for entry into archive by Alexandre Sousa ([email protected]) on 2015-07-02T18:52:16Z (GMT) No. of bitstreams: 1 Mem_Inst_Oswaldo_Cruz_110_492-499.pdf: 731403 bytes, checksum: e3c80a885f8ca653823b2bbdf158f8c5 (MD5)Made available in DSpace on 2015-07-02T18:52:16Z (GMT). No. of bitstreams: 1 Mem_Inst_Oswaldo_Cruz_110_492-499.pdf: 731403 bytes, checksum: e3c80a885f8ca653823b2bbdf158f8c5 (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Departamento de Biofísica e Biometria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil.Westfälischen Wilhelms-Universität Münster. Organisch-Chemisches Institut. Münster, Germany.Westfälischen Wilhelms-Universität Münster. Organisch-Chemisches Institut. Münster, Germany.Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO 2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide

Antiplasmodial, Trypanocidal, and Genotoxicity <i>In Vitro</i> Assessment of New Hybrid α,α-Difluorophenylacetamide-statin Derivatives

Background: Statins present a plethora of pleiotropic effects including anti-inflammatory and antimicrobial responses. A,α-difluorophenylacetamides, analogs of diclofenac, are potent pre-clinical anti-inflammatory non-steroidal drugs. Molecular hybridization based on the combination of pharmacophoric moieties has emerged as a strategy for the development of new candidates aiming to obtain multitarget ligands. Methods: Considering the anti-inflammatory activity of phenylacetamides and the potential microbicidal action of statins against obligate intracellular parasites, the objective of this work was to synthesize eight new hybrid compounds of α,α-difluorophenylacetamides with the moiety of statins and assess their phenotypic activity against in vitro models of Plasmodium falciparum and Trypanosoma cruzi infection besides exploring their genotoxicity safety profile. Results: None of the sodium salt compounds presented antiparasitic activity and two acetated compounds displayed mild anti-P. falciparum effect. Against T. cruzi, the acetate halogenated hybrids showed moderate effect against both parasite forms relevant for human infection. Despite the considerable trypanosomicidal activity, the brominated compound revealed a genotoxic profile impairing future in vivo testing. Conclusions: However, the chlorinated derivative was the most promising compound with chemical and biological profitable characteristics, without presenting genotoxicity in vitro, being eligible for further in vivo experiments

In Vitro and In Vivo Studies of the Antiparasitic Activity of Sterol 14 -Demethylase (CYP51) Inhibitor VNI against Drug-Resistant Strains of Trypanosoma cruzi

Made available in DSpace on 2015-08-19T13:49:14Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) marianazare_soeiro_etal_IOC_2013.pdf: 2674692 bytes, checksum: 3a65a035a5e86d30da0b019f841bc6f9 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Vanderbilt University. Vanderbilt Institute of Chemical Biology Synthesis Core. Nashville, Tennesse, USA.Vanderbilt University. Vanderbilt Institute of Chemical Biology Synthesis Core. Nashville, Tennesse, USA.Vanderbilt University. Department of Biochemistry School of Medicine. Nashville, Tennessee, USA.Vanderbilt University. Department of Biochemistry School of Medicine. Nashville, Tennessee, USA.Vanderbilt University. Department of Biochemistry School of Medicine. Nashville, Tennessee, USA /Vanderbilt University. Vanderbilt Institute for Global Health. Nashville, Tennessee, USA.Chagas disease affects more than 10 million people worldwide, and yet, as it has historically been known as a disease of the poor, it remains highly neglected. Two currently available drugs exhibit severe toxicity and low effectiveness, especially in the chronic phase, while new drug discovery has been halted for years as a result of a lack of interest from pharmaceutical companies. Although attempts to repurpose the antifungal drugs posaconazole and ravuconazole (inhibitors of fungal sterol 14α-demethylase [CYP51]) are finally in progress, development of cheaper and more efficient, preferably Trypanosoma cruzi-specific, chemotherapies would be highly advantageous. We have recently reported that the experimental T. cruzi CYP51 inhibitor VNI cures with 100% survival and 100% parasitological clearance both acute and chronic murine infections with the Tulahuen strain of T. cruzi. In this work, we further explored the potential of VNI by assaying nitro-derivative-resistant T. cruzi strains, Y and Colombiana, in highly stringent protocols of acute infection. The data show high antiparasitic efficacy of VNI and its derivative (VNI/VNF) against both forms of T. cruzi that are relevant for mammalian host infection (bloodstream and amastigotes), with the in vivo potency, at 25 mg/kg twice a day (b.i.d.), similar to that of benznidazole (100 mg/kg/day). Transmission electron microscopy and reverse mutation tests were performed to explore cellular ultrastructural and mutagenic aspects of VNI, respectively. No mutagenic potential could be seen by the Ames test at up to 3.5 μM, and the main ultrastructural damage induced by VNI in T. cruzi was related to Golgi apparatus and endoplasmic reticulum organization, with membrane blebs presenting an autophagic phenotype. Thus, these preliminary studies confirm VNI as a very promising trypanocidal drug candidate for Chagas disease therapy