Amantadine mitigates the cytotoxic and genotoxic effects of doxorubicin in SH-SY5Y cells and reduces its mutagenicity.

Amantadine (AMA) is a useful drug in neuronal disorders, but few studies have been performed to access its toxicological profile. Conversely, doxorubicin (Dox) is a well-known antineoplastic drug that has shown neurotoxic effects leading to cognitive impairment. The aims of this study are to evaluate the cytotoxic, genotoxic, and mutagenic effects of AMA, as well as its possible protective actions against deleterious effects of Dox. The Salmonella/microsome assay was performed to assess mutagenicity while cytotoxicity and genotoxicity were evaluated in SH-SY5Y cells using MTT and comet assays. Possible modulating effects of AMA on the cytotoxicity, genotoxicity, and mutagenicity induced by Dox were evaluated through cotreatment procedures. Amantadine did not induce mutations in the Salmonella/microsome assay and decreased Dox-induced mutagenicity in the TA98 strain. AMA reduced cell viability and induced DNA damage in SH-SY5Y cells. In cotreatment with Dox, AMA attenuated the cytotoxicity of Dox and showed an antigenotoxic effect. In conclusion, AMA does not induce gene mutations, although it has shown a genotoxic effect. Furthermore, AMA decreases frameshift mutations induced by Dox as well as the cytotoxic and genotoxic effects of Dox in SH-SY5Y cells, suggesting that AMA can interfere with Dox mutagenic activity and attenuate its neurotoxic effects.

Dry tobacco leaves: an in vivo and in silico approach to the consequences of occupational exposure.

Exposure of tobacco workers handling dried tobacco leaves has been linked to an increased risk of toxicity and respiratory illness due to the presence of nicotine and other chemicals. This study aimed to evaluate the DNA damage caused by the exposure of tobacco growers during the dry leaf classification process and the relation to cellular mechanisms. A total of 86 individuals participated in the study, divided into a group exposed to dry tobacco (n = 44) and a control group (n = 42). Genotoxicity was evaluated using the alkaline comet assay and lymphocyte micronucleus (MN) assay (CBMN-Cyt), and measurement of telomere length. The levels of oxidative and nitrosative stress were evaluated through the formation of thiobarbituric acid reactive species, and nitric oxide levels, respectively. The inorganic elements were measured in the samples using particle-induced X-ray emission method. The combination of variables was demonstrated through principal component analysis and the interactions were expanded through systems biology. Comet assay, MN, death cells, thiobarbituric acid reactive species, and nitrosative stress showed a significant increase for all exposed groups in relation to the control. Telomere length showed a significant decrease for exposed women and total exposed group in relation to men and control groups, respectively. Bromine (Br) and rubidium (Rb) in the exposed group presented higher levels than control groups. Correlations between nitrate and apoptosis; Br and MN and necrosis; and Rb and telomeres; besides age and DNA damage and death cells were observed. The systems biology analysis demonstrated that tobacco elements can increase the nuclear translocation of NFKB dimers inducing HDAC2 expression, which, associated with BRCA1 protein, can potentially repress transcription of genes that promote DNA repair. Dry tobacco workers exposed to dry leaves and their different agents showed DNA damage by different mechanisms, including redox imbalance.

Fluorosilicic acid and cotinine, separately and in combination, induce genotoxicity and telomeric reduction in human osteoblast cell line MG63.

Skeletal fluorosis is a severe case in which bone deformations and bone tissue weakening occur due to excessive fluorine deposition. Recently, data on smoking have been published that smoke constituents can indirectly influence bone mass and interfere in the metabolism of fluorides in humans. Thus, the present in vitro study aimed to assess the genetic instability in human osteoblast MG63 cells exposed to fluorosilicic acid (FA) and cotinine (COT), separately and in combination, in concentrations found in human plasma. For this, cell cytotoxicity was performed by MTT assay; DNA damage was performed by alkaline comet assay (CA), modified by repair endonucleases (+FPG); micronuclei test (MN) using CBMN-Cyt assay; and telomere length (TL) by qPCR in MG63 cells. No cytotoxicity was observed for all concentrations tested in this study. Alkaline CA results showed a significant increase in DNA damage at all FA concentrations (0.03125-0.300 mg/L), in the two highest concentrations of COT (125 and 250 ng/mL), and the highest concentration of FA+COT (0.300 mg/L+250 ng/mL). Alkaline CA+FPG test was used to detect oxidized nucleobases, which occurred at the two highest concentrations of FA, COT, and FA+COT. Micronuclei test showed an increase in the frequency of MN at all concentrations of FA (0.075-0.300 mg/L) except in the lowest concentration (0.03125 mg/L), in the two highest concentrations of COT (125 and 250 ng/mL), and all concentrations of FA+COT. There was no significant difference in nuclear division index, binucleated cells, nucleoplasmic bridge, and nuclear bud. A TL reduction was observed in cells treated with the highest concentrations of FA alone (0.300 mg/L) and FA+COT (0.300 mg/L+250 ng/mL). Finally, our study showed that FA and COT (mainly alone) at concentrations found in human plasma induced oxidative damage and genetic instability in human osteoblast cells.

Análise do direito humano à alimentação adequada: um direito social e político / Analysis of the right to adequate food: A social and political human right

Neste artigo, analisa-se a distinção aceita pela Organização das Nações Unidas entre os direitos humanos estabelecidos na Declaração Universal dos Direitos Humanos, da qual resultaram dois pactos internacionais de direitos humanos. Assim sendo, o Pacto Internacional de Direitos Econômicos, Sociais e Culturais reconhece o direito humano à alimentação adequada como um direito social e não como um direito político, assumindo que sua realização deve se dar de modo progressivo e não imediato. Para verificar a pertinência de superar a tese da progressividade, resgatam-se inicialmente suas origens, a partir do exame de documentos das Nações Unidas; em seguida, com base em referências que denunciam a hierarquização dos direitos, faz-se uma análise crítica das obrigações dos Estados indicadas pela Organização das Nações Unidas para a garantia do direito humano à alimentação adequada. Para expor a dificuldade em conciliar a indivisibilidade dos direitos humanos, reafirmada na Conferência Internacional de Direitos Humanos (Teerã, 1968), com a progressividade defendida no Pacto Internacional de Direitos Econômicos, Sociais e Culturais para a realização do direito à alimentação, apresenta-se como exemplo o caso concreto do perfil nutricional da população brasileira. Reconhece-se o múltiplo aspecto do direito humano à alimentação adequada, seja como direito social, seja como direito político; que não é possível tolerar a realização do direito de estar livre da fome sem respeitar o direito de acesso a alimentos adequados; e que é preciso reivindicar sua imediata efetivação. O fundamento para esta defesa não pode ser outro senão aquele afirmado na Declaração Universal dos Direitos Humanos: a dignidade da pessoa humana, princípio este que não admite gradação nem pode ser dividido.

This article analyzes the United Nations accepted distinction of human rights proclaimed by the Universal Declaration of Human Rights, which resulted in two international covenants on human rights. The International Covenant on Economic, Social and Cultural Rights recognizes the right to adequate food as a social and not a political right, assuming that it must occur progressively rather than immediately. In order to verify the pertinence of overcoming the thesis of progressiveness we initially rescue its origins, starting from the analysis of United Nations documents; we proceed with a critical analysis of State obligations, under the United Nations, to guarantee the right to adequate food, based on references that denounce the hierarchization of rights. To expose the difficulty in reconciling human rights indivisibility, reinforced at the International Conference of Human Rights (Teheran 1968), with International Covenant on Economic, Social and Cultural Rights advocating for the progressiveness for the fulfillment of the right to adequate food, we took as example the concrete case of the Brazilian population nutritional profile. The double aspect of the right to adequate food is recognized, both as a social right and a political right; the right to be free from hunger depends on respecting the right of access to adequate food; and it is necessary to claim its immediate fulfillment. The foundation for this defense can be no other than human dignity affirmed in Universal Declaration of Human Rights, a principle that admits no gradation and cannot be divided.

N-terminal amino acid sequences of the major outer membrane proteins from a Neisseria meningitidis group B strain isolated in Brazil

The four dominant outer membrane proteins (46, 38 33 and 28 kDa) were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in a semi-purified preparation of vesicle membranes of a Neisseria meningitidis (N44/89, B:4:P1.15:P5.5,7) strain isolated in Brazil. The N-terminal amino acid sequence for the 46 kDa and 28 kDa proteins matched that reported by others for class 1 and 5 proteins respectively, whereas the sequence (25 amino acids) for the 38 kDa (class 3) protein was similar to class 1 meningococcal proteins. The sequence for the 33 kDa (class 4) was unique and not homologous to any known protein.

Alcoolismo entre motoristas de caminhao de carga pesada liquida inflamavel e carga pesada solida em empresas de transporte

Estudo exploratorio com dados obtidos em uma amostra de 40 motoristas, com idade entre 25 a 60 anos, em duas empresas de transporte de carga: uma de carga pesada liquida inflamavel e outra de carga pesada solida do municipio de Canoas-RS, no periodo de novembro de 1988 a janeiro de 1989. Inicialmente foram aplicados questionarios CAGE, SADD e tese visomotor Bender e no segundo momento entrevista psicologica individual. Os resultados apontaram 65 por cento com suspeita de alcoolismo com a expressiva prevalencia para os motoristas de carga pesada com percentual de 75 por cento e, 55 por cento para os motoristas de carga pesada liquida inflamavel. Houve associacao significativa entre idade e suspeita de alcoolismo concentrados na faixa de 35 a 44 anos de idade, ficando a idade media de maior prevalencia 40 anos. Em relacao aos antecedentes familiares, os motoristas com suspeita de alcoolismo apresentaram: pai 42 por cento, desconhecido 39 por cento, avo 15 por cento, tio 4 por cento. Quanto aos acidentes de transito os portadores de suspeita de alcoolismo cometeram 71 por cento destes. As caracteristicas instrucao, estado civil e situacao socio-economica nao se correlacionam significativamente com a classificacao suspeita de alcoolismo.