Metaflumizone é um novo inseticida, pertencente ao novo grupo químico semicarbazone, com excelente atividade no controle de várias espécies da Ordem Lepidoptera. O produto atua no sistema nervoso dos insetos bloqueando os canais de sódio sem a necessidade de ativação metabólica, ou seja, a molécula é tóxica em sua forma original. O mecanismo de ação de metaflumizone é distinto dos inseticidas piretróides que atuam como moduladores de canais de sódio. Para conhecer a atividade de metaflumizone sobre Spodoptera frugiperda (J.E. Smith) e estabelecer estratégias proativas de manejo da resistência para preservar a vida útil desse produto, os principais objetivos da dissertação foram: (a) estabelecer a linha-básica de suscetibilidade a metaflumizone em populações de S. frugiperda coletadas na cultura do milho em diferentes regiões do Brasil; (b) definir concentrações diagnósticas (CL95 e CL99) para o monitoramento da suscetibilidade das populações de S. frugiperda; (c) verificar a possibilidade de resistência cruzada entre metaflumizone e lambda-cyhalothrin; e (d) verificar a eficácia agronômica de metaflumizone no controle de S. frugiperda em condições de campo. O método de bioensaio adotado foi o de tratamento superficial da dieta artificial com inseticidas, utilizando-se lagartas de 3° ínstar. Para o monitoramento da suscetibilidade das populações de S. frugiperda a metaflumizone, foram definidas as concentrações diagnósticas de 32 e 100 µg de metaflumizone/mL de água destilada (ppm). Para as duas concentrações diagnósticas foram encontradas diferenças significativas na suscetibilidade das populações testadas, com sobrevivências de 5,3 a 16,73% na concentração diagnóstica de 32 ppm e de 0,42 a 10,37% na concentração de 100 ppm. Para verificar a presença de resistência cruzada entre metaflumizone e lambda-cyhalothrin, foi realizada a caracterização da curva de concentração-resposta a metaflumizone em uma população de S. frugiperda resistente (R) a esse inseticida e comparada com a resposta obtida com a população suscetível de referência (S), observando-se ausência de resistência cruzada. A eficácia agronômica de metaflumizone em condições de campo foi verificada por meio de 2 ensaios de campo na cultura de milho com infestações de S. frugiperda com alta freqüência de resistência a inseticidas piretróides (40%), realizando-se duas aplicações de inseticidas, espaçadas em sete dias. Os tratamentos foram: 1-testemunha; 2-metaflumizone 200 g I.A./ha, 3-metaflumizone 240 g I.A./ha; 4-indoxacarb 75 g I.A./ha; e 5-lambda-cyhalothrin 7,5 g I.A./ha. Os menores níveis de desfolha, aos 7 dias após a segunda aplicação de inseticida, foram obtidos com os tratamentos de indoxacarb a 75 g I.A./ha e metaflumizone a 240 g I.A./ha, comprovando a eficácia no controle de S. frugiperda. Portanto, metaflumizone pode ser utilizado como uma alternativa para o manejo da resistência de S. frugiperda a inseticidas. / Metaflumizone is a new insecticide, belonging to the new chemical group semicarbazone, with excellent activity against many species of Lepidoptera Order. The product acts in the nervous system of insects blocking the sodium channels without metabolic activation, in other words, the molecule is toxic on its original form. The mechanism of action of metaflumizone is distinguished to the pyrethroids that act as sodium channel modulators. To know the activity of metaflumizone against Spodoptera frugiperda (J.E. Smith) and to establish proactive strategies of resistance management to preserve the lifetime of that product, the main objectives of this work were: (a) to establish the baseline susceptibility of metaflumizone in populations of S. frugiperda collected in maize crop in different regions of Brazil; (b) to define diagnostic concentrations (LC95 e LC99) for the susceptibility monitoring of S. frugiperda populations; (c) to verify the possibility of cross-resistance between metaflumizone and lambda-cyhalothrin; and (d) to verify the agronomic efficacy of metaflumizone in the control of S. frugiperda under field conditions. The bioassay method was the surface treatment of an artificial diet with pesticides by using 3rd instar larvae. The diagnostic concentrations of 32 e 100 µg of metaflumizone/mL of distilled water (ppm) were defined for the susceptibility monitoring of S. frugiperda populations to metaflumizone. Significant differences in susceptibility to metaflumizone were found for the two diagnostic concentrations in the populations, with survival percentage from 5.3 to 16.73% in the concentration of 32 ppm and from 0.42 to 10.37% in the concentration of 100 ppm. To verify the cross-resistance between metaflumizone and lambda-cyhalothrin, the characterization of dose-mortality curve to metaflumizone was done in a lambda-cyhalothrin-resistant population of S. frugiperda (R) and the results were compared to the response of the susceptible population (S). The results suggested no existence of cross-resistance. The agronomic efficacy of metaflumizone under field conditions was verified in 2 field trials in maize crop infested with S. frugiperda at high level of pyrethroids resistance frequency (40%), with two applications of insecticides, at seven days interval. The treatments were: 1-untreated; 2-metaflumizone 200 g A.I./ha, 3-metaflumizone 240 g A.I./ha; 4-indoxacarb 75 g A.I./ha; and 5-lambda-cyhalothrin 7,5 g A.I./ha. The lower defoliation levels were achieved by the treatments of indoxacarb at 75 g A.I./ha and metaflumizone at 240 g A.I./ha, at 7 days after the second application of the insecticides, confirming its efficacy against S. frugiperda. Therefore, metaflumizone can be used as an alternative for the resistance management of S. frugiperda to insecticides.

Small Cell Lung Cancer (SCLC) is a highly aggressive neuroendocrine tumor with a 5% survival rate over 5 years. Though SCLC comprises 13% of all cases of lung cancer the median survival time of 14.5 months has seen little improvement over the last four decades. Standard treatment relies on DNA damaging agents such as Cisplatin/Etoposide (EP) which induce a high response rate of 60-70%. Despite this initial response, nearly all patients will relapse rendering first-line therapies ineffective. Furthermore, SCLC has been shown to develop chemotherapy cross-resistance in which resistance to first-line chemotherapies will confer resistance to additional DNA damaging agents thereby reducing treatment efficacy and duration of response. Cross-Resistance constitutes a major clinical issue whose underlying mechanisms remain a mystery. The modest improvements in SCLC patient outcomes over the decades may be partially explained by the existing systems of study. Current methodologies of SCLC study rely on cell lines, patient samples, and Genetically Engineered Mouse Models which have little functional correlation to clinical outcomes. While few sources have proposed Patient Derived Xenograft (PDX) systems as an improved alternative, significant data remains sparse. Without a robust model system which accurately recapitulates patient outcomes, molecular pathways driving resistance cannot be uncovered. Here we present the generation of 34 SCLC PDX models which maintain both genomic and functional fidelity. Furthermore, treatment of a 30-model subset with first-line chemotherapy EP and a novel chemotherapy Olaparib/Temozolomide (OT) allowed for functional and molecular comparison between groups. Our findings demonstrate incomplete independent resistance mechanisms between EP and OT treatment with a small overlap of 31 genes involved in glycolysis and xenobiotic metabolism.

Photodynamic therapy (PDT) for cancer utilizes the localised delivery of light to activate a photosensitizing drug (such as Photofrin) which is selectively retained by tumour tissues. Although this treatment modality is undergoing clinical trials, the mechanism of PDT cytotoxicity is not fully understood. One approach to understanding the mechanism of action of PDT is to study cell mutants showing alterations in their response to PDT. The capacity of mammalian cells to support virus replication has been used as an assay to compare cellular response to ultraviolet (UV) light and other cytotoxic agents. Cellular capacity has been previously employed to measure cellular recovery following UV irradiation and to predict the sensitivity of cells to several anticancer drugs. In this work, I have examined the use of the capacity assay to examine the sensitivity of cells to PDT treatment. RIF-1 mouse fibrosarcoma cells and a PDT resistant derivative, RIF-8A; as well as Chinese hamster ovary (CHO) cells and CHOMDR (multi-drug resistant) mutant cells were studied. Consistent with the clonogenic survival of these cells after PDT, the viral capacities of RIF-8A and CHO-MDR cells· were greater than those of RIF-1 and CHO cells respectively following PDT treatment. The capacity assay was also used to examine the relative ability of RIF cells to recover from PDT damage. These capacity experiments show that recovery from PDT damage is greater in RIF-SA cells compared to RIF-1 cells, suggesting that RIF-SA cells have an enhanced repair capacity for PDT damage compared to RIF-1 cells. The response of CHO cells and the RIF cells to ultraviolet (UV) light irradiation was also examined. No difference in the UV sensitivity of CHO-N and CHO-MDR cells was found. However, the RIF-SA cell line showed a cross-resistance to UV. The survival of viral DNA synthesis for UV-irradiated virus was also greater in RIF-SA cells compared to RIF-1 cells, suggesting that RIF-SA cells have an increased capacity for the repair of UV-induced DNA damage. It is possible that the increased resistance to PDT of RIF-SA may also result from an increased repair of POT-induced DNA damage in RIF-SA cells. The identification and characterization of a POT-sensitive cell mutant was also investigated. The CHO-AUXB1 cell mutant was found to show an increased sensitivity to PDT and UV compared to the CHO-PRO- parent line. This sensitivity of the CHO-AUXB1 mutant may also result from a deficiency in the repair mechanism of PDT-induced and UV-induced damage. / Thesis / Master of Science (MS)

Organic insecticides play a big role in reducing the usage of chemical insecticides and their negative impact on the environment. Bacillus thuringiensis (Bt) spays are the only tool that organic farmers are allowed to use for the control of pests. Genetic engineering and modification of crops have been made possible with scientific advances in cell and molecular biology. These advances are used to transfer some of the Bt Cry toxins into crops for control of target species to reduce yield loss. Bt maize were commercialised for the first time in South Africa in 1998 and the economic important stem borers, Busseola fusca (Fuller) (Lepidoptera: Noctuidae), Chilo partellus (Swinhoe) (Lepidoptera: Crambidae) and Sesamia calamistis (Hampson) (Lepidoptera: Noctuidae) were exposed to the Cry1Ab toxin that is found in Bt maize. Busseola fusca developed resistance to Cry1Ab under field conditions within eight years after it had been released. Eldana saccharina (Walker) (Lepidoptera: Pyralidae) is a major pest on sugarcane in South Africa and although it has not been recorded on maize in this country, is it known as a major pest of maize in other African countries. African armyworm, Spodoptera exempta (Walker) (Lepidoptera: Noctuidae) has a very wide distribution in Africa and is known to be an occasional pest on maize. The aims of this dissertation were to determine the efficacy of Bt spray applications for control of four lepidopteran pests and whether development of Cry1Ab resistance by B. fusca caused a loss in susceptibility to other Bt toxins (i.e. cross-resistance). Susceptibility bioassays with 10 day old larvae were conducted under laboratory conditions. Treatments included application of various dosage rates of Dipel® and deltamethrin as well as exposure to MON810 (maize leaves). Stemborer populations of C. partellus, E. saccharina, and B. fusca (Venda) as well as the S. exempta were effectively controlled by the Bt spray, Dipel®. Care should be taken not be interpret the percentage C. partellus, E. saccharina and S. exempta larvae that survived after exposure to MON810 and Bt spray treatments as development of resistance without verification of these experiments with earlier instars that are known to be more susceptible. Spodoptera exempta is active throughout a year in temperate zones of Africa. If S. exempta develop resistance to Cry toxins and Bt maize events would be released for commercial planting in these areas, S. exempta pose a threat added to their injuriousness. Busseola fusca larvae were sampled from Venda (susceptible population), Ventersdorp and the Vaalharts Irrigation Scheme (resistant population). The Ventersdorp B. fusca population was controlled by MON810 and MON89034 and Bt sprays, but the percentage larvae that survived showed reduced susceptibility within the population. Dipel® treatments, MON810 and MON89034 did not provide effective control of the Vaalharts B. fusca population reported to be resistant to Cry1Ab, in two experiments. The high survival rates indicate a reduction in susceptibility to Cry toxins other than Cry1Ab and therefore development of cross resistance in the Vaalharts B. fusca population. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2014

Organic insecticides play a big role in reducing the usage of chemical insecticides and their negative impact on the environment. Bacillus thuringiensis (Bt) spays are the only tool that organic farmers are allowed to use for the control of pests. Genetic engineering and modification of crops have been made possible with scientific advances in cell and molecular biology. These advances are used to transfer some of the Bt Cry toxins into crops for control of target species to reduce yield loss. Bt maize were commercialised for the first time in South Africa in 1998 and the economic important stem borers, Busseola fusca (Fuller) (Lepidoptera: Noctuidae), Chilo partellus (Swinhoe) (Lepidoptera: Crambidae) and Sesamia calamistis (Hampson) (Lepidoptera: Noctuidae) were exposed to the Cry1Ab toxin that is found in Bt maize. Busseola fusca developed resistance to Cry1Ab under field conditions within eight years after it had been released. Eldana saccharina (Walker) (Lepidoptera: Pyralidae) is a major pest on sugarcane in South Africa and although it has not been recorded on maize in this country, is it known as a major pest of maize in other African countries. African armyworm, Spodoptera exempta (Walker) (Lepidoptera: Noctuidae) has a very wide distribution in Africa and is known to be an occasional pest on maize. The aims of this dissertation were to determine the efficacy of Bt spray applications for control of four lepidopteran pests and whether development of Cry1Ab resistance by B. fusca caused a loss in susceptibility to other Bt toxins (i.e. cross-resistance). Susceptibility bioassays with 10 day old larvae were conducted under laboratory conditions. Treatments included application of various dosage rates of Dipel® and deltamethrin as well as exposure to MON810 (maize leaves). Stemborer populations of C. partellus, E. saccharina, and B. fusca (Venda) as well as the S. exempta were effectively controlled by the Bt spray, Dipel®. Care should be taken not be interpret the percentage C. partellus, E. saccharina and S. exempta larvae that survived after exposure to MON810 and Bt spray treatments as development of resistance without verification of these experiments with earlier instars that are known to be more susceptible. Spodoptera exempta is active throughout a year in temperate zones of Africa. If S. exempta develop resistance to Cry toxins and Bt maize events would be released for commercial planting in these areas, S. exempta pose a threat added to their injuriousness. Busseola fusca larvae were sampled from Venda (susceptible population), Ventersdorp and the Vaalharts Irrigation Scheme (resistant population). The Ventersdorp B. fusca population was controlled by MON810 and MON89034 and Bt sprays, but the percentage larvae that survived showed reduced susceptibility within the population. Dipel® treatments, MON810 and MON89034 did not provide effective control of the Vaalharts B. fusca population reported to be resistant to Cry1Ab, in two experiments. The high survival rates indicate a reduction in susceptibility to Cry toxins other than Cry1Ab and therefore development of cross resistance in the Vaalharts B. fusca population. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2014

Made available in DSpace on 2015-03-26T13:30:15Z (GMT). No. of bitstreams: 1 texto completo.pdf: 526506 bytes, checksum: 599838531677d80fdf541112b66fb2cd (MD5) Previous issue date: 2007-02-28 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The objectives of the present study were to evaluate the ozone toxicity to populations of Tribolium castaneum, Rhyzopertha dominica and Oryzaephilus surimanensis, to determine if there is cross resistance between ozone and phosphine; to verify if there is relationship between the ozone toxicity and respiratory metabolism of the insects; to determine the reproductive standards of the populations in the absence of selective pressure and provide evidence of adaptive costs associated with phosphine resistance. Sixteen Brazilian populations of T. castaneum, 11 of R. dominica and nine of O. surinamensis were collected from the states of Goiás, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Paraná and São Paulo. In the toxicity bioassays, the concentration of the ozone was fixed in 150 ppm (2 L min-1 flow). The lethal exposure time for 50 or 95% of mortality (TL50 and TL95) of each insect population was estimated through time-response bioassays and used to calculate respective resistance ratios (RRs). The respiratory and instantaneous growth rates (ri) of each population of three species were evaluated. In addition, the development and population growth rate of two phosphine resistant and two susceptible populations of each specie were evaluated. None of the tested populations showed ozone resistance. The resistance ratios at TL50 of the populations of T. castaneum, R. dominica and O. surinamensis ranged, respectively, from 1.00 to 1.76, 1.03 to 1.32, and 1.0 to 1.58- fold. In contrast, some of these populations showed high resistance to phosphine, indicating that there was no cross resistance between ozone and phosphine. Different respiratory standards were observed among the populations of each species, suggesting that ozone toxicity was not influenced by the respiratory metabolism of insects. Different reproductive standards were found in the development and populational growth rates, where some phosphine resistant populations showed adaptative costs in the absence of the insecticide. Since these populations did not show ozone resistance, independent of the resistance or susceptibility to phosphine, ozone can be one of the major eco-friendly alternative to phosphine for use in managing resistant pest populations. / Este trabalho teve por objetivos avaliar a toxicidade do ozônio a populações de Tribolium castaneum, Rhyzopertha dominica e Oryzaephilus surimanensis; determinar se existe resistência cruzada entre o ozônio e a fosfina; averiguar se há relação entre a toxicidade do ozônio e o metabolismo respiratório dos insetos; determinar os padrões reprodutivos das populações na ausência de pressão seletiva e prover evidências de custos adaptativos associados à resistência à fosfina. Foram utilizadas 16 populações brasileiras de T. castaneum, 11 de R. dominica e nove de O. surinamensis coletadas nos estados de Goiás, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Paraná e São Paulo. Nos bioensaios de toxicidade, fixou-se a concentração do ozônio em 150 ppm, em fluxo contínuo de 2 L min-1. Os tempos letais para causar 50 e 95% de mortalidade (TL50 e TL95) de cada população foram estimados por meio de bioensaios de tempo-resposta e usados para calcular as respectivas razões de resistência (RRs). Os padrões da taxa respiratória e do crescimento instantâneo (ri) de cada população das três espécies foram avaliados. Adicionalmente, foram avaliadas as taxas de desenvolvimento e de crescimento populacional de duas populações resistentes à fosfina e duas susceptíveis de cada espécie. Nenhuma das populações estudadas mostrou resistência ao ozônio. A razão de resistência para os TL50 das populações de T. castaneum, R. dominica e O. surinamensis variou, respectivamente, de 1,00 a 1,76; 1,03 a 1,32; e 1,0 a 1,58 vezes da população de maior para a de menor susceptibilidade. Por outro lado, algumas destas populações apresentam elevada resistência à fosfina, indicando que não há resistência cruzada entre o ozônio e a fosfina. Foram observados diferentes padrões respiratórios entre as populações de cada espécie, indicando que a toxicidade do ozônio não teve relação com o metabolismo respiratório dos insetos. Diferentes padrões reprodutivos foram verificados nas taxas de desenvolvimento e de crescimento populacional, onde algumas populações resistentes à fosfina apresentaram custo adaptativo na ausência do inseticida. Como essas populações não mostraram resistência ao ozônio, independentemente de serem resistentes ou susceptíveis à fosfina, é possível que o ozônio venha a se tornar uma alternativa ao uso da fosfina nos programas de manejo de resistência a esse fumigante.

Made available in DSpace on 2015-03-26T13:30:23Z (GMT). No. of bitstreams: 1 texto completo.pdf: 819713 bytes, checksum: bc07208206271366ce40b847926f6f9c (MD5) Previous issue date: 2009-02-13 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The maize weevil, Sitophilus zeamais Motschulsky, 1855 (Coleoptera: Curculionidae) is considered the main pest of stored maize in Brazil and its control is achieved mainly by insecticides. The massive and intensive use of these compounds may lead to selection of resistant populations and consequently compromise the control efficacy of this insect pest in Brazilian storage facilities. This work was a survey of physiological and behavioral resistance to the insecticides esfenvalerate, permethrin and the insecticide mixture esfenvalerate + fenitrothion in 27 populations of S. zeamais collected in several Brazilian counties and Paraguay, and also investigated possible costs associated with this phenomenon. The insects were subjected to concentration-mortality bioassays to determine the lethal concentrations LC50 and CL95. The populations were also subjected to two walking trials on surfaces treated and untreated with dried insecticide residues for detection of behavioral resistance. We also determined the instantaneous rate of population increase (ri), maize consumption and body mass of individuals of each population. We also determined the respiration rate, as well as amylase and lipase activity of the insects from each population as an indication of their metabolic rate. The concentrationmortality bioassays indicated resistance ratios ranging from 0.63 to 66.65x for esfenvalerate, 1.00 to 5.02x for the insecticide mixture esfenvalerate + fenitrothion from 0.79 to 69.59x for permethrin compared with the susceptible standard population (Sete Lagoas). These results indicate a decrease in pyrethroid resistance in Brazilian populations of maize weevil compared with previous studies. The behavioral characteristics of walking in treated area varied among populations and sex. There was avoidance to permethrin- and esfenvalerate- treated surfaces by females from different populations. There was no correlation between physiological and behavioral resistance, indicating that physiological resistance is independent of behavioral resistance in the populations tested. There was no significant difference in the instantaneous rate of increase (ri), body mass and respiration rate among the insects. In contrast, there were significant differences in food consumption and amylase and lipase activity among populations. Therefore, we conclude that there was no fitness cost associated with levels of resistance observed in the populations studied. / O caruncho do milho, Sitophilus zeamais Motschulsky, 1855 (Coleoptera: Curculionidae) é considerado a principal praga do milho armazenado no Brasil, sendo o seu controle realizado principalmente por inseticidas. A utilização maciça e intensa destes compostos pode levar à seleção de populações resistentes e, conseqüentemente, à diminuição da eficiência do controle deste inseto-praga em armazéns brasileiros. Neste trabalho foi realizado um levantamento da resistência fisiológica e comportamental aos inseticidas esfenvalerato, permetrina e a mistura esfenvalerato + fenitrotiona em 27 populações de S. zeamais coletadas em várias cidades brasileiras e no Paraguai, investigando também, possíveis custos adaptativos relacionados ao fenômeno. Os insetos foram submetidos a bioensaios de concentração-mortalidade com determinação das concentrações letais CL50 e CL95. As populações foram também submetidas a dois ensaios de caminhamento em superfície tratada e não-tratada com resíduo seco de inseticida para detecção de resistência comportamental. Foram também determinados a taxa instantânea de crescimento populacional (ri), o consumo de grão de milho e massa corporal dos indivíduos de cada população estudada. Determinou-se ainda a taxa respiratória, a atividade de amilase e de lipase como indicativo da taxa metabólica dos insetos. Os resultados dos bioensaios de mortalidade indicaram variação da razão de resistência de 0,63 a 66,65 vezes para esfenvalerato, de 1,00 a 5,02 vezes para a mistura esfenvalerato + fenitrotiona e de 0,79 a 69,59 vezes para permetrina em relação à população padrão de suscetibilidade (Sete Lagoas). Estes resultados indicam uma diminuição da resistência a piretróides em populações brasileiras de caruncho do milho em relação a estudos anteriores. As características comportamentais de caminhamento na área tratada variaram entre as populações e sexo. Houve repelência de fêmeas para permetrina e esfenvalerato quando comparado entre as populações. Não foi detectada correlação entre a resistência fisiológica e a resistência comportamental, evidenciando que a resistência fisiológica é independente da resistência comportamental nas populações testadas. Não se detectou diferença significativa na taxa instantânea de crescimento (ri), na massa corpórea e na taxa respiratória dos insetos. Detectou-se diferenças no consumo alimentar e na atividade de amilase e atividade de lipase entre as populações testadas. Assim, podemos concluir que não houve custo adaptativo associado aos níveis de resistência verificados nas populações estudadas.

O Staphylococcus aureus é bactéria espécie não específica que, além de potencial patogenicidade, evoluiu em mecanismos de resistência a antimicrobianos. O S. aureus meticilina resistente (MRSA) antes restrito a infecções nosocomiais, dispersou-se na comunidade e nos animais de companhia e para produção de alimento. Na conduta para o controle da transmissão, além do uso de antibióticos, a ação sobre os agentes causais nas fontes de contaminação exige atenção, sendo decisiva e crítica a escolha de desinfetantes e antisépticos. A busca por recursos frente a agentes patogênicos resistentes a antimicrobianos convencionais e a demanda por insumos sanitários aplicáveis em modelos sustentáveis de produção agropecuária, motivam a investigação de extrações vegetais que apresentem atividade antibacteriana. O objetivo deste estudo foi avaliar a atividade bactericida de desinfetantes convencionais sobre isolados MRSA, testar a hipótese da possibilidade de resistência cruzada entre grupos químicos antibióticos (beta-lactâmicos) e desinfetantes e também avaliar a atividade bactericida de extrações das inflorescências de Achyrocline satureioides (Lam.) DC. (Asteraceae) (“macela”), planta medicinal, de uso popular e tradicional, nativa na região sul do Brasil, sobre os mesmos inóculos. A técnica de referência foi o “Teste de Suspensão na Avaliação Quantitativa da Atividade Bactericida de Desinfetantes e Antissépticos Químicos”. Nos testes com os desinfetantes hipoclorito de sódio (HS), iodofór (I) e quaternário de amônio (QAC - cloreto de cetil trimetilamônio), quatro concentrações de cada grupo químico foram confrontadas com 21 MRSA, em tempos de contato de cinco, 15 e 30 minutos e densidade populacional inicial dos inóculos de 107UFC/mL. Observou-se que os grupos químicos nas menores concentrações HS 25 ppm, I 12,5 ppm e QAC 125 ppm, apresentaram atividade bactericida frente a todos os isolados no menor tempo de contato. A proporção usada da A. satureioides foi de 5 g:100 mL de solvente e as densidades iniciais dos inóculos confrontados foram 107, 106 e 105 UFC/mL. A atividade da forma decocto foi verificada frente a 51 isolados MRSA, em tempos de contato de uma, oito e 24 h. Vinte e um deles também foram submetidos ao extrato hidroetanólico hidratado (EH), obtido de maceração hidroetanólica 70º GL, desalcoolizada e hidratada ao volume inicial, nos tempos de contato de cinco e 30 minutos e de uma até quatro horas. Por Cromatografia Liquida de Alta Eficiência (CLAE) foi confirmada, no acesso da planta, a presença dos marcadores fitoquímicos quercetina, luteolina e 3-Ometilquercetina. As extrações da A. satureioides apresentaram atividade antibacteriana frente a todos os isolados MRSA. O EH mostrou atividade de inativação em menor tempo. Tomando como exemplo a 1 h de contato, na maior densidade do inóculo, 19% dos isolados estavam inativados, enquanto que no decocto não foi observada inativação. Em 4 horas de contato com o EH 85,7% dos isolados, na maior densidade desafio, estavam inativados e 100% dos isolados sofreram redução da densidade populacional. O decocto demonstrou maior atividade bactericida entre 8h e 24 horas, inativando 100% dos isolados até as 24 h. Concluiu-se que, controlados os conhecidos fatores limitantes da atividade bactericida, o hipoclorito de sódio o iodofor e o quaternário de amônio são adequados para controlar os MRSA nas fontes de contaminação em ambientes de saúde humana ou nos de saúde e de produção animal. Para os isolados resistentes aos antibióticos beta-lactâmicos confrontados não foi observada relação de resistência com os desinfetantes. A atividade bactericida das soluções de Achyrocline satureioides frente aos isolados MRSA e ao microrganismo de referência Staphylococcus aureus ATCC 6538 sugere seu potencial uso, diretamente nas formas avaliadas ou em formulações, em procedimentos de higiene, tanto nas fontes de infecção de ambientes de saúde humana quanto nos de saúde e de produção animal. / The bacterium Staphylococcus aureus is a speciea not specific and potential pathogenicity, which has evolved mechanisms for antimicrobial resistance. S. aureus methicillin resistant (MRSA) once restricted to nosocomial infections, dispersed in the community and in companion animals and production. In order to control the transmission, besides the use of antibiotics, the action on the causative agents in the sources of contamination requires attention, being decisive and critical the choice of disinfectants and antiseptics. The search for resources against pathogens resistant to conventional antibiotics and the demand for health inputs applicable in sustainable agriculture production motivated the investigation of plant extractions that have antibacterial activity. The aim of this study was to evaluate the bactericidal activity of conventional disinfectants on MRSA isolates, testing the hypothesis of the possibility of cross-resistance between chemical groups antibiotics (beta-lactams) and disinfectants and also assess the bactericidal activity of extractions of inflorescences Achyrocline satureioides (Lam.) Dc. (Asteraceae) ("macela"), a medicinal plant with a popular and traditional use, native from southern Brazil on the same isolates. The reference technique was the "Suspension Test in Quantitative Evaluation of Bactericidal Activity of Chemical Disinfectants and Antiseptics." In tests with disinfectant sodium hypochlorite (HS), iodophor (I) and quaternary ammonium (QAC-cetyl trimethylammonium chloride), four concentrations of each chemical group were confronted with 21 MRSA on contact time of five, 15 and 30 minutes. The population density of the initial inoculum was 107UFC/mL. It was observed that the chemical groups at lower concentrations HS 25 ppm, and 12.5 ppm I 125 ppm QAC showed bactericidal activity against all isolates in less contact time. The proportion used of A. satureioides was 5 g: 100 mL of solvent and the initial densities of the inocula confronted were 107, 106 and 105 CFU / mL. The activity of decoction form was checked against 51 MRSA isolates, in times of a contact, eight and 24 h. Twenty-one of them also underwent hydroethanolic extract hydrate (EH) obtained by maceration hydroethanol 70 º GL, dealcoholised hydrated and the initial volume, the contact time of five and 30 minutes and one to four hours. By High performance liquid chromatography (HPLC) was confirmed in the access plan, the presence of markers phytochemicals quercetin, luteolin and 3-O-methylquercetin. The extractions of A. satureioides showed antibacterial activity against all MRSA isolates. The EH showed activity inactivation in less time. Taking as an example the 1 hr of contact, the greater density of the inoculum, 19% of the isolates were inactive, whereas the decoction did not show inactivation. In 4 hours of contact with the EH 85.7% of isolates in higher density challenge were inactivated and 100% of isolates reduced population density. The decoction showed greater bactericidal activity between 8 and 24 hours, inactivating 100% of isolates until 24 h. It was concluded that, controlling for known factors affecting the bactericidal activity, the sodium hypochlorite and quaternary ammonium iodophor are suitable for controlling MRSA in the sources of contamination in healthcare environments or in human health and animal production. For the isolates resistant to beta-lactam antibiotics confronted no relationship was observed resistance to disinfectants. The bactericidal activity of solutions Achyrocline satureioides against of MRSA isolates and reference microorganism Staphylococcus aureus ATCC 6538 suggests its potential use, directly into forms or formulations evaluated in hygiene procedures, both in the sources of infection in healthcare environments as in human health and animal production.

O Staphylococcus aureus é bactéria espécie não específica que, além de potencial patogenicidade, evoluiu em mecanismos de resistência a antimicrobianos. O S. aureus meticilina resistente (MRSA) antes restrito a infecções nosocomiais, dispersou-se na comunidade e nos animais de companhia e para produção de alimento. Na conduta para o controle da transmissão, além do uso de antibióticos, a ação sobre os agentes causais nas fontes de contaminação exige atenção, sendo decisiva e crítica a escolha de desinfetantes e antisépticos. A busca por recursos frente a agentes patogênicos resistentes a antimicrobianos convencionais e a demanda por insumos sanitários aplicáveis em modelos sustentáveis de produção agropecuária, motivam a investigação de extrações vegetais que apresentem atividade antibacteriana. O objetivo deste estudo foi avaliar a atividade bactericida de desinfetantes convencionais sobre isolados MRSA, testar a hipótese da possibilidade de resistência cruzada entre grupos químicos antibióticos (beta-lactâmicos) e desinfetantes e também avaliar a atividade bactericida de extrações das inflorescências de Achyrocline satureioides (Lam.) DC. (Asteraceae) (“macela”), planta medicinal, de uso popular e tradicional, nativa na região sul do Brasil, sobre os mesmos inóculos. A técnica de referência foi o “Teste de Suspensão na Avaliação Quantitativa da Atividade Bactericida de Desinfetantes e Antissépticos Químicos”. Nos testes com os desinfetantes hipoclorito de sódio (HS), iodofór (I) e quaternário de amônio (QAC - cloreto de cetil trimetilamônio), quatro concentrações de cada grupo químico foram confrontadas com 21 MRSA, em tempos de contato de cinco, 15 e 30 minutos e densidade populacional inicial dos inóculos de 107UFC/mL. Observou-se que os grupos químicos nas menores concentrações HS 25 ppm, I 12,5 ppm e QAC 125 ppm, apresentaram atividade bactericida frente a todos os isolados no menor tempo de contato. A proporção usada da A. satureioides foi de 5 g:100 mL de solvente e as densidades iniciais dos inóculos confrontados foram 107, 106 e 105 UFC/mL. A atividade da forma decocto foi verificada frente a 51 isolados MRSA, em tempos de contato de uma, oito e 24 h. Vinte e um deles também foram submetidos ao extrato hidroetanólico hidratado (EH), obtido de maceração hidroetanólica 70º GL, desalcoolizada e hidratada ao volume inicial, nos tempos de contato de cinco e 30 minutos e de uma até quatro horas. Por Cromatografia Liquida de Alta Eficiência (CLAE) foi confirmada, no acesso da planta, a presença dos marcadores fitoquímicos quercetina, luteolina e 3-Ometilquercetina. As extrações da A. satureioides apresentaram atividade antibacteriana frente a todos os isolados MRSA. O EH mostrou atividade de inativação em menor tempo. Tomando como exemplo a 1 h de contato, na maior densidade do inóculo, 19% dos isolados estavam inativados, enquanto que no decocto não foi observada inativação. Em 4 horas de contato com o EH 85,7% dos isolados, na maior densidade desafio, estavam inativados e 100% dos isolados sofreram redução da densidade populacional. O decocto demonstrou maior atividade bactericida entre 8h e 24 horas, inativando 100% dos isolados até as 24 h. Concluiu-se que, controlados os conhecidos fatores limitantes da atividade bactericida, o hipoclorito de sódio o iodofor e o quaternário de amônio são adequados para controlar os MRSA nas fontes de contaminação em ambientes de saúde humana ou nos de saúde e de produção animal. Para os isolados resistentes aos antibióticos beta-lactâmicos confrontados não foi observada relação de resistência com os desinfetantes. A atividade bactericida das soluções de Achyrocline satureioides frente aos isolados MRSA e ao microrganismo de referência Staphylococcus aureus ATCC 6538 sugere seu potencial uso, diretamente nas formas avaliadas ou em formulações, em procedimentos de higiene, tanto nas fontes de infecção de ambientes de saúde humana quanto nos de saúde e de produção animal. / The bacterium Staphylococcus aureus is a speciea not specific and potential pathogenicity, which has evolved mechanisms for antimicrobial resistance. S. aureus methicillin resistant (MRSA) once restricted to nosocomial infections, dispersed in the community and in companion animals and production. In order to control the transmission, besides the use of antibiotics, the action on the causative agents in the sources of contamination requires attention, being decisive and critical the choice of disinfectants and antiseptics. The search for resources against pathogens resistant to conventional antibiotics and the demand for health inputs applicable in sustainable agriculture production motivated the investigation of plant extractions that have antibacterial activity. The aim of this study was to evaluate the bactericidal activity of conventional disinfectants on MRSA isolates, testing the hypothesis of the possibility of cross-resistance between chemical groups antibiotics (beta-lactams) and disinfectants and also assess the bactericidal activity of extractions of inflorescences Achyrocline satureioides (Lam.) Dc. (Asteraceae) ("macela"), a medicinal plant with a popular and traditional use, native from southern Brazil on the same isolates. The reference technique was the "Suspension Test in Quantitative Evaluation of Bactericidal Activity of Chemical Disinfectants and Antiseptics." In tests with disinfectant sodium hypochlorite (HS), iodophor (I) and quaternary ammonium (QAC-cetyl trimethylammonium chloride), four concentrations of each chemical group were confronted with 21 MRSA on contact time of five, 15 and 30 minutes. The population density of the initial inoculum was 107UFC/mL. It was observed that the chemical groups at lower concentrations HS 25 ppm, and 12.5 ppm I 125 ppm QAC showed bactericidal activity against all isolates in less contact time. The proportion used of A. satureioides was 5 g: 100 mL of solvent and the initial densities of the inocula confronted were 107, 106 and 105 CFU / mL. The activity of decoction form was checked against 51 MRSA isolates, in times of a contact, eight and 24 h. Twenty-one of them also underwent hydroethanolic extract hydrate (EH) obtained by maceration hydroethanol 70 º GL, dealcoholised hydrated and the initial volume, the contact time of five and 30 minutes and one to four hours. By High performance liquid chromatography (HPLC) was confirmed in the access plan, the presence of markers phytochemicals quercetin, luteolin and 3-O-methylquercetin. The extractions of A. satureioides showed antibacterial activity against all MRSA isolates. The EH showed activity inactivation in less time. Taking as an example the 1 hr of contact, the greater density of the inoculum, 19% of the isolates were inactive, whereas the decoction did not show inactivation. In 4 hours of contact with the EH 85.7% of isolates in higher density challenge were inactivated and 100% of isolates reduced population density. The decoction showed greater bactericidal activity between 8 and 24 hours, inactivating 100% of isolates until 24 h. It was concluded that, controlling for known factors affecting the bactericidal activity, the sodium hypochlorite and quaternary ammonium iodophor are suitable for controlling MRSA in the sources of contamination in healthcare environments or in human health and animal production. For the isolates resistant to beta-lactam antibiotics confronted no relationship was observed resistance to disinfectants. The bactericidal activity of solutions Achyrocline satureioides against of MRSA isolates and reference microorganism Staphylococcus aureus ATCC 6538 suggests its potential use, directly into forms or formulations evaluated in hygiene procedures, both in the sources of infection in healthcare environments as in human health and animal production.

O Staphylococcus aureus é bactéria espécie não específica que, além de potencial patogenicidade, evoluiu em mecanismos de resistência a antimicrobianos. O S. aureus meticilina resistente (MRSA) antes restrito a infecções nosocomiais, dispersou-se na comunidade e nos animais de companhia e para produção de alimento. Na conduta para o controle da transmissão, além do uso de antibióticos, a ação sobre os agentes causais nas fontes de contaminação exige atenção, sendo decisiva e crítica a escolha de desinfetantes e antisépticos. A busca por recursos frente a agentes patogênicos resistentes a antimicrobianos convencionais e a demanda por insumos sanitários aplicáveis em modelos sustentáveis de produção agropecuária, motivam a investigação de extrações vegetais que apresentem atividade antibacteriana. O objetivo deste estudo foi avaliar a atividade bactericida de desinfetantes convencionais sobre isolados MRSA, testar a hipótese da possibilidade de resistência cruzada entre grupos químicos antibióticos (beta-lactâmicos) e desinfetantes e também avaliar a atividade bactericida de extrações das inflorescências de Achyrocline satureioides (Lam.) DC. (Asteraceae) (“macela”), planta medicinal, de uso popular e tradicional, nativa na região sul do Brasil, sobre os mesmos inóculos. A técnica de referência foi o “Teste de Suspensão na Avaliação Quantitativa da Atividade Bactericida de Desinfetantes e Antissépticos Químicos”. Nos testes com os desinfetantes hipoclorito de sódio (HS), iodofór (I) e quaternário de amônio (QAC - cloreto de cetil trimetilamônio), quatro concentrações de cada grupo químico foram confrontadas com 21 MRSA, em tempos de contato de cinco, 15 e 30 minutos e densidade populacional inicial dos inóculos de 107UFC/mL. Observou-se que os grupos químicos nas menores concentrações HS 25 ppm, I 12,5 ppm e QAC 125 ppm, apresentaram atividade bactericida frente a todos os isolados no menor tempo de contato. A proporção usada da A. satureioides foi de 5 g:100 mL de solvente e as densidades iniciais dos inóculos confrontados foram 107, 106 e 105 UFC/mL. A atividade da forma decocto foi verificada frente a 51 isolados MRSA, em tempos de contato de uma, oito e 24 h. Vinte e um deles também foram submetidos ao extrato hidroetanólico hidratado (EH), obtido de maceração hidroetanólica 70º GL, desalcoolizada e hidratada ao volume inicial, nos tempos de contato de cinco e 30 minutos e de uma até quatro horas. Por Cromatografia Liquida de Alta Eficiência (CLAE) foi confirmada, no acesso da planta, a presença dos marcadores fitoquímicos quercetina, luteolina e 3-Ometilquercetina. As extrações da A. satureioides apresentaram atividade antibacteriana frente a todos os isolados MRSA. O EH mostrou atividade de inativação em menor tempo. Tomando como exemplo a 1 h de contato, na maior densidade do inóculo, 19% dos isolados estavam inativados, enquanto que no decocto não foi observada inativação. Em 4 horas de contato com o EH 85,7% dos isolados, na maior densidade desafio, estavam inativados e 100% dos isolados sofreram redução da densidade populacional. O decocto demonstrou maior atividade bactericida entre 8h e 24 horas, inativando 100% dos isolados até as 24 h. Concluiu-se que, controlados os conhecidos fatores limitantes da atividade bactericida, o hipoclorito de sódio o iodofor e o quaternário de amônio são adequados para controlar os MRSA nas fontes de contaminação em ambientes de saúde humana ou nos de saúde e de produção animal. Para os isolados resistentes aos antibióticos beta-lactâmicos confrontados não foi observada relação de resistência com os desinfetantes. A atividade bactericida das soluções de Achyrocline satureioides frente aos isolados MRSA e ao microrganismo de referência Staphylococcus aureus ATCC 6538 sugere seu potencial uso, diretamente nas formas avaliadas ou em formulações, em procedimentos de higiene, tanto nas fontes de infecção de ambientes de saúde humana quanto nos de saúde e de produção animal. / The bacterium Staphylococcus aureus is a speciea not specific and potential pathogenicity, which has evolved mechanisms for antimicrobial resistance. S. aureus methicillin resistant (MRSA) once restricted to nosocomial infections, dispersed in the community and in companion animals and production. In order to control the transmission, besides the use of antibiotics, the action on the causative agents in the sources of contamination requires attention, being decisive and critical the choice of disinfectants and antiseptics. The search for resources against pathogens resistant to conventional antibiotics and the demand for health inputs applicable in sustainable agriculture production motivated the investigation of plant extractions that have antibacterial activity. The aim of this study was to evaluate the bactericidal activity of conventional disinfectants on MRSA isolates, testing the hypothesis of the possibility of cross-resistance between chemical groups antibiotics (beta-lactams) and disinfectants and also assess the bactericidal activity of extractions of inflorescences Achyrocline satureioides (Lam.) Dc. (Asteraceae) ("macela"), a medicinal plant with a popular and traditional use, native from southern Brazil on the same isolates. The reference technique was the "Suspension Test in Quantitative Evaluation of Bactericidal Activity of Chemical Disinfectants and Antiseptics." In tests with disinfectant sodium hypochlorite (HS), iodophor (I) and quaternary ammonium (QAC-cetyl trimethylammonium chloride), four concentrations of each chemical group were confronted with 21 MRSA on contact time of five, 15 and 30 minutes. The population density of the initial inoculum was 107UFC/mL. It was observed that the chemical groups at lower concentrations HS 25 ppm, and 12.5 ppm I 125 ppm QAC showed bactericidal activity against all isolates in less contact time. The proportion used of A. satureioides was 5 g: 100 mL of solvent and the initial densities of the inocula confronted were 107, 106 and 105 CFU / mL. The activity of decoction form was checked against 51 MRSA isolates, in times of a contact, eight and 24 h. Twenty-one of them also underwent hydroethanolic extract hydrate (EH) obtained by maceration hydroethanol 70 º GL, dealcoholised hydrated and the initial volume, the contact time of five and 30 minutes and one to four hours. By High performance liquid chromatography (HPLC) was confirmed in the access plan, the presence of markers phytochemicals quercetin, luteolin and 3-O-methylquercetin. The extractions of A. satureioides showed antibacterial activity against all MRSA isolates. The EH showed activity inactivation in less time. Taking as an example the 1 hr of contact, the greater density of the inoculum, 19% of the isolates were inactive, whereas the decoction did not show inactivation. In 4 hours of contact with the EH 85.7% of isolates in higher density challenge were inactivated and 100% of isolates reduced population density. The decoction showed greater bactericidal activity between 8 and 24 hours, inactivating 100% of isolates until 24 h. It was concluded that, controlling for known factors affecting the bactericidal activity, the sodium hypochlorite and quaternary ammonium iodophor are suitable for controlling MRSA in the sources of contamination in healthcare environments or in human health and animal production. For the isolates resistant to beta-lactam antibiotics confronted no relationship was observed resistance to disinfectants. The bactericidal activity of solutions Achyrocline satureioides against of MRSA isolates and reference microorganism Staphylococcus aureus ATCC 6538 suggests its potential use, directly into forms or formulations evaluated in hygiene procedures, both in the sources of infection in healthcare environments as in human health and animal production.