Toxicity and Anti-promastigote Activity of Benzoxazinoid Analogs Against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum

Purpose: Here, we aim to evaluate the antileishmanial activity of compounds with a benzoxazinoid (BX) skeleton, previously synthesized by our group, against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum promastigotes. Methods: Anti-promastigote activity, as well as cytotoxicity, were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays. The selectivity index (SI) for each compound was calculated using a ratio of the cytotoxicity of compounds and the geometric mean (GM) of antileishmanial concentrations to each species tested. The comparisons between groups were carried out using a t test or analysis of variance (one-way ANOVA). A P value of less than 0.05 was considered significant. Results: All the compounds tested were active, with IC50 falling between 92 +/- 6.19 mu g/mL and 238 +/- 6.57 mu g/mL for L. braziliensis, and 89 +/- 6.43 mu g/mL and 188 +/- 3.58 mu g/mL against L. infantum. Bex2, Bex3, Pyr1, Pyr2, and Pyr4 were compounds that showed activity similar to the drug Glucantime (R), exhibited low cytotoxicity against splenic hamster cells (CC50 raging between >400 and 105.7 +/- 2.26 mu g/mL) and had favorable selectivity indices (SI 1.12 to 3.96). Conclusion: The analogs in question are promising prototypes for the pharmaceutical development of novel, safer and more effective leishmanicidal agents

Effects of Gender, Sterilization, and Environment on the Spatial Distribution of Free-Roaming Dogs: An Intervention Study in an Urban Setting.

Information concerning the factors affecting the circulation and distribution of free-roaming dogs is crucial in developing control actions and limiting the spread of zoonoses. The present study analyzes the influence of gender, sterilization, and environment on the spatial distribution of free-roaming dogs in urban settings. Animals were captured/recaptured in seven consecutive morning sampling efforts conducted at 2-monthly intervals in control and intervention areas in a medium-size town in southeastern Brazil. Capture locations were georeferenced and captured animals were microchipped before being released at their original capture sites. Dogs captured in the intervention area were subjected additionally to surgical sterilization prior to release. Home range (HR) areas were calculated by applying the minimum convex polygon method to dogs that had been captured at least three times. Land coverage zones were determined from satellite images and overlaid on maps of the study areas along with the locations of 22 commercial food outlets. HR areas showed a global mean of 448 m2 and a median of 28 m2, values that were smaller than those reported previously for dogs in rural regions. The median HR of females (64.m2) was higher than that of males (15 m2), while median HRs of animals in the control and intervention areas were similar (27 and 28.5 m2, respectively). Variability of HR was high, although animals with small HRs predominated. Free-roaming dogs grouped primarily in urbanized and transitional regions, and their spatial distribution was positively correlated with locations of commercial food outlets. While sterilization did not influence HR size, the search for food was a key factor in determining mobility and spatial aggregation of free-roaming dogs. Our findings are pertinent in understanding the ecology of free-roaming dogs in urban environments and will be applicable to strategies aimed at promoting animal welfare and preventing the dissemination of zoonoses

ATLANTIC EPIPHYTES: a data set of vascular and non-vascular epiphyte plants and lichens from the Atlantic Forest

Epiphytes are hyper-diverse and one of the frequently undervalued life forms in plant surveys and biodiversity inventories. Epiphytes of the Atlantic Forest, one of the most endangered ecosystems in the world, have high endemism and radiated recently in the Pliocene. We aimed to (1) compile an extensive Atlantic Forest data set on vascular, non-vascular plants (including hemiepiphytes), and lichen epiphyte species occurrence and abundance; (2) describe the epiphyte distribution in the Atlantic Forest, in order to indicate future sampling efforts. Our work presents the first epiphyte data set with information on abundance and occurrence of epiphyte phorophyte species. All data compiled here come from three main sources provided by the authors: published sources (comprising peer-reviewed articles, books, and theses), unpublished data, and herbarium data. We compiled a data set composed of 2,095 species, from 89,270 holo/hemiepiphyte records, in the Atlantic Forest of Brazil, Argentina, Paraguay, and Uruguay, recorded from 1824 to early 2018. Most of the records were from qualitative data (occurrence only, 88%), well distributed throughout the Atlantic Forest. For quantitative records, the most common sampling method was individual trees (71%), followed by plot sampling (19%), and transect sampling (10%). Angiosperms (81%) were the most frequently registered group, and Bromeliaceae and Orchidaceae were the families with the greatest number of records (27,272 and 21,945, respectively). Ferns and Lycophytes presented fewer records than Angiosperms, and Polypodiaceae were the most recorded family, and more concentrated in the Southern and Southeastern regions. Data on non-vascular plants and lichens were scarce, with a few disjunct records concentrated in the Northeastern region of the Atlantic Forest. For all non-vascular plant records, Lejeuneaceae, a family of liverworts, was the most recorded family. We hope that our effort to organize scattered epiphyte data help advance the knowledge of epiphyte ecology, as well as our understanding of macroecological and biogeographical patterns in the Atlantic Forest. No copyright restrictions are associated with the data set. Please cite this Ecology Data Paper if the data are used in publication and teaching events. © 2019 The Authors. Ecology © 2019 The Ecological Society of Americ

Análise espacial das leishmanioses no município de Divinópolis, Minas Gerais, Brasil

Submitted by Nuzia Santos ([email protected]) on 2015-04-15T12:20:48Z No. of bitstreams: 1 Tese_DIP_RafaelGoncalvesTeixeiraNeto.pdf: 9728378 bytes, checksum: 9aa64df9a24c4ed1f3ed10cd3eba51d5 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-04-15T12:20:58Z (GMT) No. of bitstreams: 1 Tese_DIP_RafaelGoncalvesTeixeiraNeto.pdf: 9728378 bytes, checksum: 9aa64df9a24c4ed1f3ed10cd3eba51d5 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-04-15T12:21:07Z (GMT) No. of bitstreams: 1 Tese_DIP_RafaelGoncalvesTeixeiraNeto.pdf: 9728378 bytes, checksum: 9aa64df9a24c4ed1f3ed10cd3eba51d5 (MD5)Made available in DSpace on 2015-04-15T12:21:07Z (GMT). No. of bitstreams: 1 Tese_DIP_RafaelGoncalvesTeixeiraNeto.pdf: 9728378 bytes, checksum: 9aa64df9a24c4ed1f3ed10cd3eba51d5 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.As Leishmanioses compreendem um grupo de doenças parasitárias, distribuídas em países tropicais e subtropicais, em ciclos zoonóticos e antroponóticos e constituem um grave problema de saúde pública. No Brasil, as leishmanioses eram caracterizadas como endemias rurais, no entanto, casos autóctones vêm sendo notificados em centros urbanos e sua distribuição vem se ampliando consideravelmente. O município de Divinópolis é considerado região endêmica para Leishmaniose Tegumentar Americana (LTA) e a ocorrência de Leishmaniose Visceral (LV) apesar de recente, vem se expandindo nos últimos anos. Com base neste cenário, o presente estudo objetivou ampliar o conhecimento sobre a situação epidemiológica da LV e da LTA no município de Divinópolis, enfatizando a distribuição espacial dos hospedeiros vertebrados e dos casos humanos na área urbana. Um total de 102 pequenos mamíferos foi capturado no período de um ano em cinco áreas de mata espalhadas na zona urbana do município e em 15 residências com casos de LTA ou LV notificados entre 2005 e 2010. Deste total, três exemplares foram identificados naturalmente infectados por Leishmania através da Reação em Cadeia da Polimerase (PCR). Também foi avaliada a distribuição espacial dos casos humanos de LTA notificados entre os anos de 2007 e fevereiro de 2013. A circulação de Leishmania infantum foi confirmada através do isolamento do parasito em cães soropositivos. Foi realizado um inquérito sorológico para Leishmaniose Visceral Canina (LVC) em toda a zona urbana do município utilizando uma amostragem estratificada e uma prevalência de 3%. Dos 3.652 cães avaliados distribuídos nos 11 estratos do município 169 apresentaram sorologia positiva, com prevalência estimada de 4,62% (3,95 – 5,31). Todas as quadras amostradas no inquérito da LVC e casos humanos de LV ocorridos no municipio foram georreferenciados. A análise de dependência espacial confirmou que existe uma correlação positiva entre a ocorrência de LVC e casos humanos de LV. Estes achados contribuem para a compreensão da epidemiologia da LTA e da LV no município de Divinópolis e podem auxiliar na definição de áreas prioritárias para a implementação de medidas de controle.The Leishmaniases comprise a group of parasitic diseases, distributed in tropical and subtropical countries in zoonotic and anthroponotic cycles and are a serious public health problem. In Brazil, leishmaniases were characterized as rural endemic diseases, however, autochthonous cases have been reported in urban centers and their distribution has expanded considerably. The municipality of Divinópolis is considered an endemic area for American Cutaneous Leishmaniasis (ACL) and the occurrence of Visceral Leishmaniasis (VL) although recent, has expanded in recent years. Based on this scenario, the present study aimed to increase knowledge of the epidemiological situation of VL and ACL in the municipality of Divinópolis, emphasizing the spatial distribution of vertebrate hosts and human cases in the urban area. A total of 102 small mammals were captured during one year in five forest areas scattered in the urban area and 15 residences with cases of ACL or VL reported between 2005 and 2010. From these, three specimens were identified naturally infected by Leishmania by Polymerase Chain Reaction (PCR). We also evaluated the spatial distribution of human cases of ACL reported between the years 2007 and February 2013. Leishmania infantum circulation has been confirmed by isolation of parasites in seropositive dogs. A serological for Canine Visceral Leishmaniasis (CVL) was conducted across the urban area using a stratified sampling and a prevalence of 3%. Among the 3,652 evaluated dogs distributed in 11 strata of the city 169 had a positive serology, with an estimated prevalence of 4.62% (3.95 to 5.31). All blocks sampled in the survey of CVL and human cases of VL occurring in the municipality were georeferenced. The spatial dependence analysis confirmed a positive correlation between the occurrence of CVL and human cases of VL. These findings contribute to the understanding of the epidemiology of ACL and VL in Divinópolis city and can assist in definition of priority areas for the implementation of control measures

Estudo das relações entre imunidade humoral e carga parasitária em cães naturalmente infectados por Leishmania (leishmania) infantum chagasi.

No presente estudo foi avaliado um grupo de 45 cães composto de animais não infectados e naturalmente infectados por L. infantum chagasi (identificação através da PCR-RFLP). Após avaliação clínica os animais foram divididos em três grupos: Cães controle (CC), cães assintomáticos (CA) e cães sintomáticos (CS). Foi avaliada a carga parasitária nas amostras de pele e baço destes animais através da técnica de quantificação “Leishman Donovan Units” (LDU). De acordo com densidade parasitária separamos os animais nos seguintes grupos: baixo parasitismo (BP), médio parasitismo (MP) e alto parasitismo (AP). Neste contexto estudamos o índice de positividade da PCR em diferentes amostras clínicas, o perfil da resposta humoral (IgG e suas subclasses IgG1 e IgG2) e a avidez de IgGtotal com relação à forma clínica e ao parasitismo apresentado pelo cão. A análise dos resultados da PCR mostrou que não houve diferença estatística na positividade da reação entre os grupos com diferentes formas clínicas. Os animais foram positivos em pelo menos dois tecidos avaliados e as amostras clínicas com melhor desempenho seguiram a seguinte ordem: baço, linfonodo, pele, medula óssea, fígado e sangue. Com relação ao parasitismo tecidual foi observada diferença estatística significante na carga parasitária das amostras de pele ao compararmos os grupos CA e CS (p=0,0011). Em ambos tecidos onde foi avaliada a carga parasitária observou-se que no grupo CA houve um maior número de animais com baixo parasitismo, já no grupo CS a maioria dos animais apresentava alto parasitismo. A avaliação do perfil de Ig mostrou que os níveis séricos de IgG1 apresentavam-se mais elevados nos animais assintomáticos, sugerindo uma possível associação com mecanismos imunoprotetores da infecção, por outro lado os níveis séricos de IgG2 parecem estar associados com a presença de sintomas na LVC. Correlacionando o perfil de Ig com a carga parasitária, foi constatado que à medida que aumentava a intensidade parasitária (baço e pele) os valores de IgG e IgG2 também subiam. Observamos também uma correlação negativa entre os valores de IgG1 e a densidade parasitária no baço. O índice de avidez (IA) de IgGtotal nos animais sintomáticos foi mais alto quando comparado ao IA dos animais assintomáticos. Além disso, animais mais parasitados tanto no baço quanto na pele possuem maior IA que os animais com baixo parasitismo. Com base nestes achados sugerimos que a LVC se inicia a partir de uma forma clínica assintomática, com baixo parasitismo, alta produção de IgG1 e baixa afinidade das moléculas de IgGtotal evoluindo para uma forma clínica sintomática, com maior densidade parasitária, níveis de IgG2 mais elevados e alta afinidade de IgGtotal. Além disso, confirmamos a eficácia da PCR como ferramenta no diagnóstico da LVC ressaltando sua importância do ponto de vista epidemiológico devido à sua capacidade na detecção de animais assintomáticos.In the present study, a group of 45 dogs composed of uninfected and naturally infected animals with L. infantum chagasi (identification by means of PCR-RFLP) was evaluated. Following clinical evaluation, the animals were divided into three groups: Uninfected dogs (UD), asymptomatic dogs (AD), and symptomatic dogs (SD). The parasitary burden was assessed taken into account samples of the skin and spleen of those animals, by using the quantification technique “Leishman Donovan Units” (LDU). According to the parasitary burden, the animals were separated into the following groups: low parasitism (LP), median parasitism (MP), and high parasitism (HP). In this context, we studied the positivity index of PCR using different clinical samples, the profile of the humoral response (IgG and its sub-classes IgG1 and IgG2), as well as the IgGtotal avidity in relation to the clinical form and the parasitism presented by the dog. Analysis of the results obtained by means of PCR showed that there was no significant statistical difference related to the reaction positivity among the groups with different clinical forms. The animals were found to be positive in at least two of the evaluated tissues, and the clinical samples showing the best results were as follows: spleen, lymph node, skin, bone marrow, liver and blood, respectively. In relation to the tecidual parasitism, a significant statistical difference could be observed in the parasitary burden of the skin samples, when the groups AD and SD were compared (p = 0.0011). In both tissues used to evaluate the parasitary burden, it could be observed that in the group AD there was a higher number of animals with low parasitism, whereas in the group SD the great majority of the animals presented high parasitism. Evaluation of the Ig profile showed that the seric levels of IgG1 were higher in the asymptomatic animals, suggesting a possible association with immunoprotector mechanisms of the infection. On the other hand, the seric levels of IgG2 seem to be associated with the presence of symptoms in the Canine Visceral Leishmaniasis (CVL). Correlating the Ig profile with the parasitary burden, it was observed that the more intense the parasitary burden was (spleen and skin), higher were the IgG and IgG2 values too. We also observed a negative correlation between the IgG1 values and the parasitary density in the spleen as well. The avidity index (AI) of IgGtotal in the symptomatic animals was higher, when compared with the AI of the asymptomatic animals. Moreover, the animals with a higher parasitary burden either in the spleen or skin showed a higher avidity index than the animals with lower parasitism. Based on these findings, we suggest that CVL commences with an asymptomatic clinical form with low parasitism, high production of IgG1 and low affinity of the IgGtotal molecules, evolving to a symptomatic clinical form, with higher parasitism intensity, higher IgG2 levels, and high affinity of IgGtotal. Furthermore, we confirmed the efficacy of PCR as a tool for the CVL diagnosis, emphasizing its importance under the epidemiological viewpoint, due to its performance concerning the detection of asymptomatic animals

OS IMPACTOS DO AMOR À MARCA, DO VALOR DA MARCA NA LEALDADE DO CONSUMIDOR E DAS INTENÇÕES DE COMPRA DO CLIENTE: O DESENVOLVIMENTO E TESTE DE MODELOS ALTERNATIVOS NO SETOR AUTOMOTIVO

O desenvolvimento de pesquisas sobre Valor das Marcas vem crescendo devido à importância do tema no desempenho na área de marketing. Por outro lado, o Amor à Marca é um conceito novo que vem sendo explorado mais recentemente em marketing, como uma das forças capazes de gerar lealdade e comportamento de compra. Com o objetivo de verificar os impactos do Amor à Marca e do Valor da Marca na lealdade dos consumidores e nas suas intenções de compra, foi conduzido um levantamento do tipo survey envolvendo 314 respondentes. Após os procedimentos de validação das medidas do instrumento, recorreu-se à técnica de Modelagem de Equações Estruturais com o objetivo de testar dois modelos concorrentes. No primeiro modelo, o Valor da Marca foi colocado como antecedente do Amor à Marca, enquanto que, no segundo modelo o Amor à Marca foi colocado como antecedente do Valor da Marca. Os resultados revelam que o segundo modelo é mais razoável e atinge uma maior acurácia preditiva. Isso sugere importantes implicações para a teoria e a prática na literatura sobre Valor da Marca. Sob o prisma teórico, esse estudo mostra que em um contexto de construção de marcas, avaliações emocionais (Amor à Marca) aparentemente são fontes naturais de julgamentos cognitivos (Valor da Marca). O modelo sugere ainda que benefícios funcionais e sociais percebidos nas marcas são reforçados por avaliações não racionais que transcendem os atributos do produto. Esse resultado reforça que consumidores são mais emocionais do que racionais quando estão avaliando marcas. Do ponto de vista prático, esse estudo torna notório que os aspectos afetivos relacionados à marca são realmente necessários para criar o Amor à Marca e, por conseqüência, o Valor da Marca

Leishmaniose visceral canina autóctone em área indene no Centro Oeste de Minas Gerais, Brasil

Objetivou-se relatar o primeiro caso autóctone de leishmaniose visceral canina no município de Cláudio-MG, Brasil. Com base no exame clínico foram constatados sinais sugestivos da doença em um cão macho, sem raça definida de aproximadamente sete anos. O animal foi submetido à colheita de sangue para realização dos testes imunológicos de imunocromatografia rápida (DPP®) e ensaio imunoenzimático (ELISA), obtendo-se resultados positivos para leishmaniose canina em ambos os testes. Após autorização do tutor foi obtida amostra de medula óssea do animal e posteriormente realizou-se a eutanásia e o exame necroscópico obtendo-se fragmentos de baço, linfonodos e pele. Amostras de medula óssea e tecidos foram utilizadas para realização dos exames parasitológicos, os quais demonstraram a presença do agente etiológico na forma amastigota. O fragmento de baço obtido na necropsia foi utilizado para identificação da espécie de Leishmania por meio da reação em cadeia da polimerase (PCR). Foi demostrado pela PCR-RFLP a presença de Leishmania infantum, confirmando a infecção do animal pela espécie responsável pelo desenvolvimento da forma visceral da doença. Conclui-se com este resultado que a implantação de estratégias de prevenção e controle epidemiológico da leishmaniose visceral canina no município é importante, a fim de evitar a propagação da doença entre a população canina, bem como a transmissão a população humana

Spatial distribution of tuberculosis from 2002 to 2012 in a midsize city in Brazil

Abstract Background Tuberculosis (TB) remains a major public health problem in many developing countries. Exploratory spatial analysis is a powerful instrument in spatial health research by virtue of its capacity to map disease distribution and associated risk factors at the population level. The aim of the present study was to describe the epidemiologic characteristics and spatial distribution of new cases of TB reported during the period 2002–2012 in Divinopolis, a midsized city located in the state of Minas Gerais, southeastern Brazil. Methods Sociodemographic and clinical data relating to the study cases were retrieved from the national Brazilian database and geocoded according to residential address. Choropleth and kernel density maps were constructed and a spatial-temporal analysis was performed. Tracts defined by the 2010 national census were classified as sectors with higher or lower densities of new TB cases based on the kernel density map. Multivariate logistic analysis was used to compare the two types of sectors according to income, level of literacy and population density. Results A total of 326 new cases of TB were reported during the study period. Residential addresses relating to 309 (94.8 %) of these were available in the SINAN database and the locations were geocoded and mapped. The average incidence of TB during the study period was 14.5/100,000 inhabitants. Pulmonary TB was the most predominant form (73.6 %) and 74.5 % of patients had been cured. The percentage of cases was highest in males (67.8 %) and individuals aged 25–44 years (41.1 %), and lowest in children aged less than 15 years (4.6 %). The disease was spatially distributed throughout the urban district. The incidence rate among urban census tracts ranged from 0.06 to 1.1 %, and the disease occurred predominantly in the downtown area (99.3 %). Higher population density was associated significantly with increased odds of living in a sector with a “higher density of cases”, even after adjusting for income and education (odds ratio = 13.7). Conclusions The highest density of cases was strongly associated with higher population density but not with lower income or level of literacy

Leishmania infection in a population of dogs: an epidemiological investigation relating to visceral leishmaniasis control

Identification of factors associated with Leishmania infection in dogs is essential for targeting visceral leishmaniasis control actions. Thus, the present study analyzed some of these factors in a population of dogs in a Brazilian municipality, along with the limitations of control strategies implemented there. The association between the exposure variables and occurrences of infection was analyzed through logistic regression models. The disease control interventions were treated qualitatively. Out of the 755 animals examined, 13.6% (103/755) were seropositive. Of these, 23.3% (24/103) were asymptomatic and 76.7% (79/103) presented at least one clinical sign possibly associated with visceral leishmaniasis. With weak associations, purebred, shorthaired, over 5 years of age, male and large dogs were more prone to infection. The latter two variables formed the final regression model and the association with dog size was statistically significant. The control strategies developed presented limitations and a great number of seronegative dogs was culled. The data presented contribute towards better understanding of the dynamics of infection in canine visceral leishmaniasis and indicate that actions aimed towards adequate implementation of Visceral Leishmaniasis control program in Brazilian endemic areas should be prioritized