Molluscicidal activity of polyvinylpyrrolidone (PVP)-functionalized silver nanoparticles to Biomphalaria glabrata: Implications for control of intermediate host snail of Schistosoma mansoni.

Silver nanoparticles (Ag NPs) have been applied in several commercial products due to their antimicrobial properties, while their molluscicide properties, mode of action and toxicity to snail species remain unclear. In this study, the comparative toxicity of polyvinylpyrrolidone (PVP)-functionalized Ag NPs and their dissolved counterpart (Ag ions) was analyzed during the early developmental stages of the freshwater snail Biomphalaria glabrata, intermediate host of Schistosoma mansoni. Ag NPs were synthesized and characterized by multiple techniques, and the snail embryotoxicity was analyzed in terms of mortality, hatching, developmental stages and morphological alterations, while the acute toxicity to newly-hatched snails was analyzed by mortality and behavioral impairments. Results showed that both Ag forms induced mortality, hatching delay and morphological alterations (especially hydropic abnormalities) in snail embryos in a concentration and exposure time dependent patterns. Ag NPs showed low embryotoxic effects and similar toxicity for newly-hatched snails when compared to their dissolved counterparts, indicating that the nanotoxicity was dependent of snail developmental stages. The knowledge about the Ag NP toxicity to different early development stages of B. glabrata contributes to its potential use as molluscicide and control of neglected tropical diseases, including schistosomiasis.

In silico repositioning of new drugs against Schistosoma mansoni

Schistosomiasis is a neglected tropical disease caused by parasites of the genus Schistosoma. In Brazil only Schistosoma mansoni causes this disease. The World Health Organization estimated in 2012 approximately 249 million people at risk of acquiring this disease around the world. The main strategy to control this disease is praziquantel treatment of individuals living in endemic areas. The drug praziquantel is used on a large scale in the treatment of schistosomiasis and currently there are reported cases of resistance, indicating the need to discover new drugs. In silico drug repositioning is a time and cost reducing strategy in the search for anti-Schistosoma agents. This work used bioinformatic tools to identify potential schistosomicidal drugs. A list was compiled of S. mansoni potential targets that are part of essential processes in the database TDR and the targets that are part of the tegument were obtained in the scientific literature. The file with S. mansoni targets contained 1,376 targets, and of these only 61 targets associated with 399 drugs had homology with drug targets. After removal of duplicate drugs, drugs found in previous studies and after the analysis of the conservation of the binding site, only 28 S. mansoni targets associated with 102 drugs had 60% or more of the active site conserved. Some of the drugs had activity and are interesting to validate this study such as: artemether, lumefantrine, meloxicam. Among the drugs found 18 drugs were selected to be tested in prospective experimental assays according to the following criteria: low toxicity in vivo, off-patent status, and logP <5.0.

Comprometimento organizacional de trabalhadores da vigilância sanitária em municípios do estado de Goiás / Organizational commitment of health surveillance workers in municipalities of the state of Goiás, Brazil / Compromiso organizacional de los trabajadores de la vigilancia sanitaria en municipios del estado de Goiás, Brasil

Trata-se de estudo de campo, com abordagem quantitativa, sobre o nível de comprometimento organizacional de fiscais da vigilância sanitária municipal. Foram analisadas possíveis diferenças entre os grupos amostrais, divididos de acordo com suas características sociodemográficas. Participaram do estudo 335 fiscais de 53 municípios de Goiás, que responderam à Escala de Bases do Comprometimento Organizacional em 2011. A escala aborda sete diferentes tipos de vínculo que os trabalhadores têm em relação à instituição onde trabalham, além de dados pessoais e profissionais. As análises realizadas foram: descritivas, de variância e testes qui-quadrado. Encontrou-se alto comprometimento afetivo e alto sentimento de obrigação pelo desempenho no trabalho, baixos níveis nos sentimentos de afiliação e de obrigação em permanecer trabalhando na vigilância sanitária municipal, bem como diferenças entre grupos quando levadas em conta as características individuais e profissionais. Os gestores públicos da área devem atentar para a importância dos recursos humanos no desenvolvimento das políticas públicas e priorizar ações que resultem em níveis elevados de comprometimento desses profissionais.

This is a field study, with a quantitative approach, on the level of organizational commitment among municipal health surveillance inspectors. An analysis was made of possible differences between the sample groups, which were divided according to their sociodemographic characteristic s. The study included 335 inspectors from 53 Goiás, Brazil, municipalities, who responded to the 2011 Organizational Commitment Scale Bases. The scale covers seven different types of ties that employees have with the institutions they work for, as well as personal and professional data. The analyses were descriptive, variance, and chi-square tests. Noted were a high affective commitment and high sense of obligation for job performance, low feelings of affiliation and obligation to continue working in municipal health surveillance, in addition to differences between groups when the individual and professional characteristics were taken into account. The area's public managers should pay attention to the importance of human resources in the development of public policies and prioritize actions that result in high levels of commitment among these professionals.

Se trata de un estudio de campo con un enfoque cuantitativo, sobre el nivel de compromiso organizacional de los fiscales de la vigilancia sanitaria municipal. Se analizaron las posibles diferencias entre los grupos de muestra, divididos en función de sus características sociodemográficas. El estudio incluyó a 335 fiscales de 53 municipios de Goiás (Brasil), que respondieron a la Escala de Bases del Compromiso Organizacional en 2011. La escala cubre siete tipos diferentes de vínculos que tienen los trabajadores en relación con la institución en la que trabajan, así como datos personales y profesionales. Los análisis realizados fueron: descriptivos, de varianza y pruebas de chi-cuadrado. Se encontró un alto compromiso afectivo y alto sentimiento de obligación por el desempeño en el trabajo, bajos niveles en los sentimientos de afiliación y de obligación de permanencia en el trabajo de la vigilancia sanitaria municipal, así como diferencias entre los grupos cuando se toman en cuenta las características individuales y profesionales. Los gestores públicos del área deben prestar atención a la importancia de los recursos humanos en el desarrollo de las políticas públicas y priorizar las acciones que resulten en altos niveles de compromiso de estos profesionales.

Experimental toxoplasmosis: evaluation of the hepatic damage in murines

Toxoplasma gondii é um dos protozoários mais ubíquos encontrado parasitando tanto animais quanto humanos sendo encontrado em diversos órgãos de seus hospedeiros, inclusive o fígado. Este estudo avaliou as lesões hepáticas causadas pela toxoplasmose experimental em duas cepas de T. gondii (RH e ME-49). Análises bioquímicas e histopatológicas foram realizadas. Foi possível detectas um aumento significativo nos níveis séricos de AST, ALT e LDH em ambas as infecções. A análise histopatológica demonstrou infiltrado inflamatório na infecção experimental com a cepa ME-49 e hiperemia e vasodilatação na infecção com a cepa RH. A infecção aguda (cepa RH) induziu falência hepática e morte do hospedeiro. A infecção crônica (cepa ME-49) levou a lesão hepática, mas não à morte do hospedeiro. Portanto este estudo valida a importância das análises bioquímicas para avaliação da infecção ressaltando o rigoroso exame clinico em indivíduos infectados com T. gondii.

Fatty acids oxidation and alternative energy sources detected in Taenia crassiceps cysticerci after host treatment with antihelminthic drugs.

Human cysticercosis caused by Taenia crassiceps is rare however it is considered of zoonotic risk. The treatment of the infected patients was successful when using albendazole or praziquantel. The active forms of albendazole inhibit the glucose uptake and the active forms of praziquantel alter glycogen levels and nutrients absorption. The aim of this study was to analyze the production of organic acids that indicate the oxidation of fatty acids and the use of alternative energy sources from T. crassiceps cysticerci removed from the peritoneal cavity of mice treated with low dosages of albendazole (5.75 and 11.5mg/kg) or praziquantel (3.83 and 7.67 mg/kg). The beta-hydroxibutyrate production was higher by the larval stage cysticerci in all treated groups and the propionate production was higher in final stage cysticerci treated with 11.5mg/kg of albendazole when compared to the control group. The larval stages of cysticerci from the groups treated with 5.75 mg/kg of albendazole and 3.83 mg/kg of praziquantel produced more urea than the initial and final stages which indicate amino acids breakdown. We conclude that it was possible to detect the fatty acid oxidation and amino acids breakdown which indicate the use of alternative energy production sources as the used dosages only cause a partial blockage of the glucose uptake and leads to metabolic alterations in the cysticerci. The metabolic behavior observed after host treatment was different from former descriptions of the in vitro one which indicates great host-parasite interaction.

Taenia crassiceps: host treatment alters glycolisis and tricarboxilic acid cycle in cysticerci.

Human cysticercosis by Taenia crassiceps is rare although it is considered of zoonotic risk, especially to immunocompromised individuals. Albendazole and praziquantel are widely used and effective in its treatment. Their active forms inhibit the glucose uptake by the parasite and induce muscle contractions that alter its glycogen levels interfering in the energetic metabolism of the parasite and leading to its death. The aim of this study was to evaluate alterations in glycolysis, the tricarboxylic acid cycle and glucose concentrations caused by low dosage treatments of the hosts with albendazole and praziquantel. Therefore, T. crassiceps intraperitoneally infected mice were treated by gavage feeding with 5.75 or 11.5 mg/kg of albendazole and 3.83 or 7.67 mg/kg of praziquantel. The treated mice were euthanized after 24 h and the cysticerci collected were morphologically classified into initial, larval or final phases. Concentrations of the organic acid produced and glucose were evaluated to detect alterations into the glycolysis and the tricarboxylic acid cycle pathways through chromatography and spectrophotometry. The low dosage treatment caused a partial blockage of the glucose uptake by the cysticerci in spite of the non significant difference between its concentrations. An activation of the tricarboxylic acid cycle was noted in the cysticerci that received the treatment due to an increase in the production of citrate, malate and α-ketoglutarate and the consumption of oxaloacetate, succinate and fumarate. The detection of α-ketoglutarate indicates that the cysticerci which were exposed to the drugs after host treatment present different metabolic pathways than the ones previously described after in vitro treatment.

Taenia crassiceps: fatty acids oxidation and alternative energy source in in vitro cysticerci exposed to anthelminthic drugs.

Cysticerci metabolic studies demonstrate alternative pathways responsible for its survival, such as energy sources, fatty acids oxidation and excretion of beta-hydroxybutyrate, which indicates the capability of energy production from proteins. The aim of this study was to detect alternative metabolic pathways for energy production and its end products in Taenia crassiceps cysticerci in vitro exposed to praziquantel and albendazole, in sub-lethal doses. Spectrophotometer and chromatographic analysis were performed to detect: propionate, acetate, beta-hydroxybutyrate, total proteins, urea and creatinine, SE by cysticerci in vitro exposed to praziquantel and albendazole. The drugs influenced the metabolism by inducing the creatinine phosphate phosphorylation as an alternative energy source, inhibiting the use of proteins and amino acids in the acid nucleic synthesis; and preventing the budding and replication of the cysticerci. This study also highlights the description of urea excretion, which is an important metabolic pathway to excrete toxic products such as ammonia, and the fatty acid oxidation as an alternative energy source in cysticerci exposed to anthelmintic drugs.

Activity of Stryphnodendron polyphyllum, a plant from the brazilian savannah, against hemocytes of Biomphalaria glabrata, an intermediate host of Schistosoma mansoni

O caramujo Biomphalaria glabrata atua como hospedeiro intermediário de Schistosoma mansoni, um parasito endêmico em vários países. Os hemócitos de B. glabrata estão relacionados à sua defesa contra infecções por trematódeos como S. mansoni. No presente artigo, avaliou-se pela primeira vez o efeito de substancias moluscicidas como o extrato tânico de Stryphnodendron polyphyllum, uma planta do cerrado brasileiro, sobre a morfologia e número de hemócitos de B. glabrata. Os extratos da casca e das folhas de S. polyphyllum foram diluídos em água desclorada. Os grupos de caramujos foram expostos a concentrações de 25 e 50 mg.l dos extratos e de ácido tânico por um período de 24h. E, posteriormente, a hemolinfa foi retirada da região pericárdica. As subpopulações de hemócitos foram detectadas e classificadas como pequenas (5,0 - 6,9 (Miu)m), de tamanho médio (7,0 - 8,9(Miu)m), grandes (9,0 - 12,0(Miu)m) e gigantes (mais que 12(Miu)m), sendo a última ainda não descrita na literatura. Os extratos estimularam um aumento no número de hemócitos na hemolinfa, o que é entendido como um mecanismo de defesa contra substancias tóxicas como o ácido tânicos, presente em altos níveis em ambos os extratos testados. Os hemócitos apresentaram vacúolos no citoplasma devido à presença de tais substancias indicando sinais de morte celular pr apoptose. Concluímos que os extratos são altamente eficazes contra B. glabrata e recomendamos maiores estudos para seu uso como moluscicida natural.

Taenia crassiceps: energetic and respiratory metabolism from cysticerci exposed to praziquantel and albendazole in vitro.

Praziquantel prevents glucose uptake, influencing energy metabolism, while albendazole selectively inhibits the uptake of glucose, leading to glycogen storage depletion in the parasite. The objective of this study was to determine the concentrations of glucose and organic acids related to energy and respiratory metabolisms in in vitro Taenia crassiceps cysticerci in the initial, larval and final stages exposed to sub lethal dosages of anti-helminthic drugs. Spectrophotometric and chromatographic analysis were performed to detect glucose, lactate, oxaloacetate, citrate, malate, fumarate and succinate secreted/excreted by in vitro cysticerci with 0.03 and 0.06 microg/mL of praziquantel and 0.05 and 0.075 microg/mL of albendazole. The anti-helminthic drugs decreased the excretion of lactate and induced aerobic energy pathways. Concentrations of glucose remained unaltered confirming blockage of its uptake.

Reproductive activity alterations on the Biomphalaria glabrata exposed to Euphorbia splendens var. hislopii latex

The reproductive activity of Biomphalaria glabrata exposed to Euphorbia splendens var. hislopii latex was evaluated. Parameters related to fecundity and fertility were observed. The snails were exposed to the LD50 (1 mg/l) of crude latex. At the first week post exposure (p.e.), the egg laying was reduced. After the fourth week p.e., an increase of the number of eggs/snail occurred. The results showed a marked reduction in the hatching of the snails, revealing an interference of latex exposure with the reproductive process of B. glabrata of E. splendens var. hislopii. The LD50 of the latex may be used as an alternative method to control the size of the populations of B. glabrata in field.

Taenia crassiceps organic acids detected in cysticerci.

Taenia crassiceps cysticerci is used as an experimental model to cysticercosis studies; however there are subcutaneous cases of cysticercosis caused by these cysticerci. It remains unclear in the literature the energetic and fatty acid metabolism in cestodes. Its metabolic study may provide knowledge of pathways that may serve as potential anti-helminthic drugs sites of action. In this work we studied the citric acid cycle organic acids and the fatty acid oxidation in cysticerci removed from mice with 21 and 42 days of infection in two different evolutive stages: growing and final. The organic acids were extracted using perchloric acid and analyzed by HPLC methodology. We found significant statistically differences in oxalate, malate, lactate, and beta-hydroxybutirate concentrations between cysticerci. These results indicate the aerobic metabolism in vivo in spite of the low oxygen concentration of its habitat, and also indicate the presence of fatty acid oxidation as an alternative energetic source.

Bioatividade de Stryphnodendron adstringens, S. Polyphyllum, Caryocar brasiliense, plantas do cerrado brasileiro, sobre Trypanosoma cruzi in vivo / Bioactivity of Stryphnodendron adstringens, S. Polyphyllum, Caryocar brasiliense, plants from brazilian’s savannah on the Trypanosoma cruzi in vivo

O presente trabalho verificou a ação do extrato bruto etanólico da casca do Stryphnodendron adstringens, S. polyphyllum e Caryocar brasiliense, plantas do cerrado brasileiro, sobre a parasitemia de camundongos inoculados com a cepa Y de Trypanosoma cruzi na fase aguda da infecção, avaliando a interferência na agudização ou inibição do processo infeccioso. Os camundongos (Balb/C) foram infectados por via intraperitoneal com 1 x 104 formas tripomastigotas e, após 24 horas, inoculados por via intragástrica com dose diária de 400 micro grama/ml dos extratos durante 10 dias. A avaliação da parasitemia foi realizada em intervalos de dois dias até a morte dos animais. Durante o estudo, observou-se que o extrato do S. adstringens e S. polyphyllum apresentou aumento da atividade tripanocida no sexto e oitavo dias, ocorrendo maior inibição de crescimento no oitavo dia, quando comparado ao grupo controle. O extrato bruto de C. brasiliense apresentou atividade tripanocida com inibição de crescimento apenas no oitavo dia. Os resultados demonstraram que os extratos das plantas testadas apresentaram uma significativa interferência na curva de parasitemia do T. cruzi, reduzindo o número de parasitos no sangue dos camundongos.

The present work verified the action of the crude extract of the Stryphnodendron adstringens, S. polyphyllum and of the Caryocar brasiliense barks, on the parasitemia of mice inoculated with cepa Y of Trypanosoma cruzi in the acute phase of the infection, evaluating its interference on the agudization or inhibition of the infectious process. Mice (Balb/C) had been infected by intraperitoneal route with 1x 104 tripomastigotes forms, after 24 hours inoculated by intragastric route with daily doses of 400 micron gram/ml extracts for ten days. The evaluation of the parasitemia was achieved in intervals of 2 days until the death of the animals. During the study, it was observed that the extracts of S. adstringens and S. polyphyllum had presented a higher trypanomicidal activity after the sixth and eighth days, occurring a higher growth inhibition in the 8 th day, when it was compared to the control group. The crude extract of C. brasiliense presented a trypanocidal activity with growth inhibition only in the eighth day. The results demonstrated that the extracts of the tested plants presented a significant interference on the parasitemia growth of T. cruzi, reducing the number of parasites in the mice blood.

Avaliação da atividade larvicida de plantas fitoterápicas do cerrado do gênero Stryphnodendron spp. sobre miracídios e cercárias de Schistosoma mansoni / Evaluation of the larvicidal activity of phytotherapic brazilian savannah plants of the genus Stryphnodendron spp. on Schistosoma mansoni miracidia and cercariae

A esquistossomíase é uma doença endêmica causada por parasitos do gênero Schistosoma, sendo somente Schistosoma mansoni observado no Brasil. No presente trabalho, o potencial das plantas do Cerrado brasileiro. Stryphnodendron polyphyllum e Stryphnodendron adstringens, foi testado como fonte alternativa de produtos naturais utilizados contra miracídios e cercárias, as formas infectantes de S. mansoni. A partir dos extratos brutos EAA (extração acetona: água) das cascas dos caules preparam-se soluções-mãe de 400 ppm, que foram diluídas até se obterem as concentrações de 100 e 200 ppm para os bioensaios com miracídios, e de 20, 50, 100 e 200 ppm para os bioensaios com cercárias. Nos testes com miracídios, estas plantas demonstraram atividade somente 5 horas e 30 minutos após o contato inicial com os extratos, enquanto o grupo-controle sobreviveu por oito horas nas mesmas condições. A mortalidade das cercárias ocorreu apenas uma hora após o início dos experimentos em todas as concentrações testadas para as duas espécies vegetais. O grupo-controle sobreviveu, em água, por 36 horas após o início dos experimentos. Estes dados confirmam a presença, no Cerrado brasileiro, de plantas com potencial bioativo no combate às cercárias, forma infectante de S. mansoni para mamíferos.

Profile of organic acid concentrations in the digestive gland and hemolymph of Biomphalaria glabrata under estivation

Using high performance liquid chromatography (HPLC) analysis it was possible to determine simultaneously the concentration of organic acids (pyruvate, lactate, succinate, fumarate, malate, acetate, propionate, acetoacetate, and ß-hydroxybutyrate) in the digestive gland and the extracellular concentration of these same acids in the hemolymph of estivating Biomphalaria glabrata, the intermediate host of Schistosoma mansoni. After a 7 day period of estivation, there was a significant increase in the tissue levels of lactate, succinate, malate and acetate compared to non-estivating snails. After 14 days of estivation, the levels of lactate and acetate were also significantly elevated. The hemolymph concentrations of pyruvate and acetate increased significantly after 7 days and acetate concentrations continued to be significantly increased up to 14 days of estivation. The other organic acids studied, such as ketone body acetoacetate and ß-hydroxybutyrate or the volatile acid propionate, did not accumulate. Their tissue concentrations, however, increased on the 7th day of estivation and reached normal levels within two weeks of estivation for some of them. One should take into consideration how the reduction in metabolism can be handled under aerobic conditions, and what role anaerobic pathways may play in both energy formation and redox balance processes

A comparative study of the organic acid content of the hemolymph of Schistosoma mansoni-resistant and susceptible strains of Biomphalaria glabrata

The freshwater snail Biomphalaria glabrata is an intermediate host of the trematode Schistosoma mansoni. However, some strains of B. glabrata are resistant to successful infection by S. mansoni larvae. The present work examines the profile of organic acids present in S. mansoni-resistant and susceptible strains of B. glabrata, in order to determine whether the type of organic acid present is related to susceptibility. The organic acids were extracted from the hemolymph of two susceptible B. glabrata strains (PR, Puerto Rico and Ba, Jacobina-Bahia from Brazil), and from the resistant strains 13-16-R1 and 10R2, using solid phase extraction procedures followed by high performance liquid chromatography. The organic acids obtained were analyzed and identified by comparison with known standards. Pyruvate, lactate, succinate, malate, fumarate, acetate, propionate, ß-hydroxybutyrate and acetoacetate were detected in all hemolymph samples. Under standard conditions, the concentration of each of these substances varied among the strains tested and appeared to be specific for each strain. An interesting variation was the low concentration of pyruvate in the hemolymph of PR-snails. Only the concentration of fumarate was consistently different (pó0.05) between resistant and susceptible strains.

Infecçäo por Toxoplasma gondii em pacientes com síndrome da imunodeficiência adquirida (SIDA/AIDS) do Hospital de Referência Estadual para Doenças Infecciosas em Goiás / Toxoplasma gondii infection in patients with the immunodeficiency syndrom (AIDS) from th Goiás State Reference Infecctious Diseases Hospital

Neste trabalho avaliou-se a ocorrência de infecçäo por Toxoplasma gondii em pacientes com SIDA/AIDS no Hospital de Doenças Tropicais de Goiás, através da reaçäo de imunofluorescência indireta (IFI). Foram utilizados dados obtidos de 337 prontuários de internaçäo hospitalar de pacientes com SIDA, que foram a óbito entre 1986 a 1994. Observou-se que a pesquisa de anticorpos específicos anti-toxoplasma (IgG e IgM), foi realizada no soro de 123(36,5(pôr cento)) pacientes sendoreagente em 80(65,0(pôr cento)-IC95(pôr cento)55,9 - 73,4). A reação de IFI, também, foi efetuada no liquor de 70 pacientes (20,8(pôr cento)) e 34 apresentaram-se liquor reagente (48,6(pôr cento) - IC95(pôr cento) 36,4 - 60,8). Em 37 pacientes foi executada simultaneamente a pesquisa de anticorpos no soro e liquor e 18 apresentaram concomitância de reatividade (48,6(pôr cento) - IC95(pôr cento)31,9 - 65,6). A IgM näo se apresentou reativa em qualquer dos resultados