Perfil epidemiológico de doenças tropicais negligenciadas no nordeste brasileiro / Epidemiological profile of neglected tropical diseases in Northeast Brazil / Perfil epidemiológico de enfermedades tropicales desatendidas en el nordeste brasileño

As doenças tropicais negligenciadas são associadas às populações desfavorecidas socioeconomicamente e muitas delas apresentam alta prevalência no Nordeste brasileiro. Diante disso, o objetivo desta revisão de literatura foi descrever o perfil epidemiológico da leishmaniose, da esquistossomose e da doença de Chagas nessa região, bem como os determinantes sociais envolvidos na manutenção dessas doenças. Trata-se de uma revisão narrativa da literatura do tipo descritiva. Foram detectados cem artigos publicados entre 2012 e 2017 nas bases bibliográficas. Desses, 72 foram selecionados para leitura completa. Após leitura integral e aplicação dos critérios de seleção, restaram 39 artigos. Os resultados convergentes para as três doenças estudadas relacionaram-se às condições inadequadas de vida em sociedade, à baixa escolaridade e à organização falha da estrutura habitacional. A partir da descrição do perfil epidemiológico dessas enfermidades, foi possível ratificar que as variáveis sociais são determinantes para a manutenção dessas condições de saúde. Por fim, os fatores identificados neste estudo foram válidos visando a construção do mapeamento de áreas de risco, além de serem importantes para estudantes da área da saúde, uma vez que compõem o acervo de estudos disponíveis e necessários na capacitação de futuros profissionais no enfrentamento de tais problemas sociais.

Neglected Tropical Diseases are associated with socioeconomically disadvantaged populations, and many of them show high prevalence in Northeast Brazil. Hence, this descriptive narrative literature review describes the epidemiological profile of Leishmaniasis, Schistosomiasis and Chagas disease in the region, as well as the social determinants involved in their proliferation. The database search returned 100 articles published between 2012 and 2017, of which 72 were selected for full reading. After applying the selection criteria, 39 articles remained. The converging results for the three studied diseases were related to inadequate living conditions, low schooling levels, and poor housing infrastructure. From this epidemiological profile, the study confirmed that social variables are determinants for the proliferation of these diseases. Finally, the factors identified here were valid and useful for mapping risk areas, and proved important for healthcare students, since they make up the set of studies available for future professionals and necessary for addressing such social issues.

Las enfermedades tropicales desatendidas están asociadas a las poblaciones desfavorecidas socioeconómicamente y presentan, en la mayoría de los casos, alta prevalencia en el Nordeste brasileño. Con ello, el objetivo de esta revisión de literatura fue describir el perfil epidemiológico de la leishmaniasis, esquistosomiasis y enfermedad de Chagas en esa región, así como los determinantes sociales involucrados en su mantenimiento. Esta es una revisión narrativa de la literatura, de carácter descriptivo. En las bases bibliográficas se detectaron cien artículos publicados entre 2012 y 2017. De estos, setenta y dos fueron seleccionados para una lectura completa. Tras la lectura completa y aplicación de los criterios de selección, quedaron 39 artículos. Los resultados convergentes para las tres enfermedades estudiadas se relacionaron con las condiciones inadecuadas de vida en sociedad, a la baja escolaridad y a una inadecuada organización de la estructura habitacional. A partir de la descripción del perfil epidemiológico de esas enfermedades, fue posible ratificar que las variables sociales son determinantes para el mantenimiento de estas condiciones de salud. Los factores identificados en este estudio fueron válidos para elaborar un mapeo de áreas de riesgo, pero también son importantes para los estudiantes del área de la salud debido a que esta cuestión compone la temática disponible y necesaria a la formación de los futuros profesionales para enfrentar este tipo de problema social.

Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

ABSTRACT Introduction: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. Material and methods: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed. Results: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms. Conclusion: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity.

ULTRASTRUCTURAL CHANGES IN Schistosoma mansoni MALE WORMS AFTER in vitro INCUBATION WITH THE ESSENTIAL OIL OF Mentha x villosa Huds

Introduction: The essential oil Mentha x villosa (MVEO) has a wide range of actions, including antibacterial, antifungal, antiprotozoal and schistosomicidal actions. The present study aimed to investigate the ultrastructural changes of MVEO on the tegument of adult Schistosoma mansoni. Materials and Methods: Different concentrations of MVEO were tested on S. mansoni adult worms in vitro. Ultrastructural changes on the tegument of these adult worms were evaluated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: The MVEO caused the death of all worms at 500 μg mL-1 after 24 h. After 24h of 500 μg mL-1 MVEO treatment, bubble lesions were observed over the entire body of worms and they presented loss of tubercles in some regions of the ventral portion. In the evaluation by TEM, S. mansoni adult worms treated with MVEO, 500 μg mL-1, presented changes in the tegument and vacuoles in the syncytial matrix region. Glycogen granules close to the muscle fibers were visible. Conclusion: The ability of MVEO to cause extensive ultrastructural damage to S. mansoni adult worms correlates with its schistosomicidal effects and confirms earlier findings with S. mansoni.

Tegumental Changes in Adult Schistosoma mansoni Induced by a New Imidazolidinic Derivative.

Aims: Verify the potential of the schistosomicidal imidazolidine derivative (5Z)-3-(4- bromo-benzyl)-5-(4-chloro-benzylidene)-4-thioxo-imidazolidin-2-one. Study Design: In this study, we tested the imidazolidinic derivative 3 through in vitro evaluations, cytotoxicity assay and analysis of Scanning Electron Microscopy to verify its therapeutic potential in the treatment of schistosomiasis. Place and Duration of Study: Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Fundação Oswaldo Cruz (FIOCRUZ)/PE and (FIOCRUZ)/BA between January 2013 and march 2014. Methodology: This study was approved by the Ethics Committee on Animal Use Research Center Aggeu Magalhães/Oswaldo Cruz Fundação (CPqAM/FIOCRUZ) authorized by the license No. 21/2011. Male albino Swiss mice were used Mus musculus 25 days old weighing 50 grams. Compound 3 was assayed for its cytotoxicity through cell J774 macrophage lineage. The amount of inhibitory concentration (LC50) was determined by nonlinear regression using the Graph Pad Prism version 5.01. Then the compound was evaluated against adult worms of S. mansoni by performing the activity in vitro at doses 100-20μg/mL and ultrastructural investigation by Scanning Electron Microscopy (SEM) at doses of 100 and 60μg/ml. The PZQ was the positive control of the experiment. Results: The derivative 3 showed LC50 of 29.7±3.9mM. Compound 3 was able to have decreased motility of S. mansoni culminating with a mortality rate of 100% at doses of 60 and 100μg/mL on the fourth day of observation of the experiment. In the SEM, the compound caused various soft tissue changes of S. mansoni parasites such as blistering, destruction of the integument with loss of spines and tubercles, body contraction and windy. Conclusion: The derivative imidazolidine 3 showed a promising schistosomicidal activity in vitro. However, conducting further studies with the completion of work in front of the live schistosomiasis is required.

Activity Anti-Inflammatory and in silico Study of New Thiazolidinedione Derivatives.

Aims: Evaluation of the anti-inflammatory properties of new thiazolidine-2,4-diones derivatives. Study Design: Study the effects of new thiazolidine-2,4-diones derivatives on the inflammatory process. Place and Duration of Study: Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), between June 2011 and July 2012. Methodology: Compounds thiazolidine-2,4-diones were tested for anti-inflammatory activity by air pouch model. Swiss albino mice were used for the study. Air cavities were produced by subcutaneous injection of 2.5 mL of sterile air into the intrascapular area of the back. An additional 2.5 mL of air was injected into the cavity every 3 days to keep the space open. Seven days after the initial air injection, 1 mL of a 1% solution of carrageenan dissolved in saline was injected directly into the pouch to produce an inflammatory response. The compoundsthiazolidine-2,4-diones and standard piroxicam were tested at doses of 3 mg/kg body weight. The total number of polymorphonuclear leukocytes (PMNL) was countedusing an improved. Results: The results support the use of these derivatives in inflammatory process. Among the compounds tested the ones that showed a greater effect in inhibiting the migration of neutrophils were the 3a, 3b, 3c, 3d and 3e. The anti-inflammatory effects showed by 3a-j were promising, probably due to the duality of action on PPAR alpha and gamma. Conclusion: In conclusion, this study has shown that the thiazolidine derivatives do possess significant anti-inflammatory effects in laboratory animals. The exact mechanism and the bioactive principles responsible for these actions remain to be explained.

Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.