Search

Chagas disease is caused by Trypanosoma cruzi, being considered a public health problem. An alternative to combat this pathogen is the use of natural products isolated from fruits such as Eugenia uniflora, a plant used by traditional communities as food and medicine due to its antimicrobial and biological activities. Ethanolic extract from E. uniflora was used to evaluate in vitro anti-epimastigote and cytotoxic activity. This is the first record of anti-Trypanosoma activity of E. uniflora, demonstrating that a concentration presenting 50% of activity (EC(50)) was 62.76 μg/mL. Minimum inhibitory concentration (MIC) was ≤ 1024 μg/mL. Our results indicate that E. uniflora could be a source of plant-derived natural products with anti-epimastigote activity with low toxicity.

[Indexed for MEDLINE], ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum chiloperone var. angustifolium Engl. (Rutaceae) stem bark is used traditionally in Paraguay for its antiparasitic properties. Canthin-6-one is main compound isolated from Zanthoxylum chiloperone var angustifolium with broad spectrum antifungal, leishmanicidal and trypanocidal activities. AIM OF THE STUDY: The qualitative and quantitative characterization and the isolation of main alkaloidal components of different organs of Zanthoxylum chiloperone are investigated by HPLC-UV-MS. The in vitro biological activity of each extract against trypomastigote and amastigote forms of Trypanosoma cruzi parasites were evaluated, then comparison the in vivo efficacy of the ethanolic leaves extract of Zanthoxylum chiloperone with reference drug, benznidazole, in acute Trypanosoma cruzi infected mice when administered by oral route. We have also evaluated the mutagenic and cytotoxic activity of the main component of Zanthoxylum chiloperone, i.e. canthin-6-one, by mouse bone marrow micronucleus test. MATERIALS AND METHODS: The compositions of the ethanol extracts obtained after the maceration process were studied by HPLC-UV-MS methods. The quantitation analysis was performed by external standard method, using a calibration curve constructed utilizing solutions containing different concentrations of the reference samples. The anti-trypomastigote activity was evaluated by the lysis effect on mouse blood trypomastigotes (Y strain Trypanosoma cruzi). The anti-amastigote Trypanosoma cruzi activity was evaluated by a modified colorimetric method with chlorophenol red-β-d-galactopyranoside (CPRG). The cytotoxicity of extracts and compounds was performed on NCTC 929 cells. The in vivo efficacy of the ethanolic leaves extract of Zanthoxylum chiloperone and benznidazole, in acute Trypanosoma cruzi (two different strains) was evaluated in Trypanosoma cruzi infected mice; the drugs were administered by oral route. The mortality rates were recorded and

Leishmaniasis is caused by parasites of the genus Leishmania. Recent reports about leishmaniasis show a few number of drugs available, indicating the necessity of new drugs. In this study, the ethanol extract and fractions of Pityrogramma calomelanos (L.) link. (Pteridaceae) were assayed to verify the cytotoxicity and in vitro leishmanicidal activity against promastigote forms of Leishmania brasiliensis. The cytotoxic assay was performed using fibroblasts NCTC929. The studies indicated a leishmanicidal effect of the ethanol extract and the ethyl-acetate fraction. However, a high cytotoxic effect was observed. The hexane and methanol fractions did not show leishmanicidal activity, nor cytotoxic effect. The phytochemical screening detected the presence of alkaloids, a class of secondary metabolites with a known leishmanicidal activity. This is the first study reporting an anti-Leishmania and cytotoxic effect of P. calomelanos, being an interesting approach in the search for drugs against this disease.

BACKGROUND: Vector control has substantially reduced Chagas disease (ChD) incidence. However, transmission by household-reinfesting triatomines persists, suggesting that entomological surveillance should play a crucial role in the long-term interruption of transmission. Yet, infestation foci become smaller and harder to detect as vector control proceeds, and highly sensitive surveillance methods are needed. Community participation (CP) and vector-detection devices (VDDs) are both thought to enhance surveillance, but this remains to be thoroughly assessed. METHODOLOGY/PRINCIPAL FINDINGS: We searched Medline, Web of Knowledge, Scopus, LILACS, SciELO, the bibliographies of retrieved studies, and our own records. Data from studies describing vector control and/or surveillance interventions were extracted by two reviewers. Outcomes of primary interest included changes in infestation rates and the detection of infestation/reinfestation foci. Most results likely depended on study- and site-specific conditions, precluding meta-analysis, but we re-analysed data from studies comparing vector control and detection methods whenever possible. Results confirm that professional, insecticide-based vector control is highly effective, but also show that reinfestation by native triatomines is common and widespread across Latin America. Bug notification by householders (the simplest CP-based strategy) significantly boosts vector detection probabilities; in comparison, both active searches and VDDs perform poorly, although they might in some cases complement each other. CONCLUSIONS/SIGNIFICANCE: CP should become a strategic component of ChD surveillance, but only professional insecticide spraying seems consistently effective at eliminating infestation foci. Involvement of stakeholders at all process stages, from planning to evaluation, would probably enhance such CP-based strategies., Author Summary. Blood-sucking triatomine bugs are the vectors of Chagas disease, a potentially fatal illness that affects millions in Latin America. With no vaccines available, prevention heavily depends on controlling household-infesting triatomines. Insecticide-spraying campaigns have effectively reduced incidence, but persistent household reinfestation can result in disease re-emergence. What, then, is the best strategy to keep houses free of triatomines and thus interrupt disease transmission in the long run? We reviewed published evidence to (i) assess the effectiveness of insecticide-based vector control, gauging the importance of reinfestation; (ii) compare the efficacy of programme-based (with households periodically visited by trained staff) and community-based (with residents reporting suspect vectors found in their homes) surveillance strategies; and (iii) evaluate the performance of alternative vector-detection methods. The results confirm that insecticide-based vector control is highly effective, but also that persistent house reinfestation is a general trend across Latin America. Surveillance systems are significantly more effective when householders report suspect bugs than when programme staff search houses, either manually or using vector-detection devices. Our results clearly support the view that long-term vector surveillance will be necessary for sustained Chagas disease control – and that community participation can substantially contribute to this aim.

In the Gran Chaco region, control of Triatoma infestans has been limited by persistent domestic infestations despite the efforts of the Vector Control Services. In Paraguay, this region is the highest endemic area in the country, showing high levels of indoor and outdoor infestation. Although sylvatic T. infestans have been found in the Bolivian and Argentine Chaco, similar searches for sylvatic populations of this species in Paraguay had been unsuccessful over the last 20 years. Here we present a new approach to detecting sylvatic Triatominae, using a trained dog, which has successfully confirmed sylvatic populations of T. infestans and other triatomine species in Paraguay. A total of 22 specimens corresponding to dark morph forms of T. infestans were collected, and 14 were confirmed as T. infestans by the mitochondrial cytochrome B gene analysis. Through this analysis, one of which were previously reported and a second that was a new haplotype. Triatomines were captured from amongst vegetation such as dry branches and hollows trees of different species such Aspidosperma quebracho-blanco, Bulnesia sarmientoi and Stetsonia coryne. The colonies found have been small and without apparent infection with Trypanosoma cruzi. During the study, Triatoma sordida and Triatoma guasayana have also been found in ecotopes close to those of T. infestans, Author Summary: Confirmation of sylvatic colonies of Triatoma infestans has a significant connotation for Paraguay. Prior to our findings, we believed this vector —unlike in other regions of the Gran Chaco—was living exclusively in domestic and peridomestic habitats. We never considered the possibility of sylvatic species re-infesting domiciliary dwellings. After this discovery, the frame of transmission dynamics of Trypanosoma cruzi in the Paraguayan Chaco proposes new research perspectives. This also opens the door to promote knowledge regarding potential genetic flows between different T. infestans populations, reservoirs associated with their colonies, as well as their impact over control actions. Fieldwork for wild species identification is difficult and often unsuccessful, we used several techniques and tools, proven by others such as light traps, and mouse-baited sticky traps however, the triatomine collection in our study area was scarce or null. Incorporating a trained dog – NERO – to our work team has been a highly successful and productive initiative. The surprising ability NERO has shown will enable us to provide specific data regarding the still unknown wild ecotopes of T. infestans, as well as the potential use of trained dogs as a community surveillance tool of triatomine species considered particularly important for public health.

Living Labs model concentrate its effort to support actors, providing a neutral space in which stakeholders could know and co-develop innovations in real-world contexts and proposes five basic principles for the operations of the aforementioned living labs: courage, openness, realism, influence and sustainability. The objective of this paper is to propose and test a Living Lab and project management model from the actual stakeholders, following the perspective of the Stakeholder Theory and the Soft Systems Methodology (SSM). This perspective places the Research - Action model on the basis of the SSM model as an appropriate vehicle for the openness towards worldviews, problems and conflicts solving by the organizations, especially when it involves the formulation of possible cultural changes (structural, process, attitudinal) and "actions for improvement" are established. Therefore, we present the case of the Development Center for Scientific Research which brings together a multidisciplinary group of researchers and the project "Participatory approach with ethnic focus for Community Development of the Maskoy Diez Leguas ethnicity in the Central Chaco of Paraguay".

Two-dimensional bond-based bilinear indices and linear discriminant analysis are used in this report to perform a quantitative structure-activity relationship study to identify new trypanosomicidal compounds. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop the theoretical models. Two discriminant models, computed using bond-based bilinear indices, are developed and both show accuracies higher than 86% for training and test sets. The stochastic model correctly indentifies nine out of eleven compounds of a set of organic chemicals obtained from our synthetic collaborators. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Both models show a good agreement between theoretical predictions and experimental results. Three compounds showed IC50 values for epimastigote elimination (AE) lower than 50 ?M, while for the benznidazole the IC50=54.7 ?M which was used as reference compound. The value of IC50 for cytotoxicity of these compounds is at least 5 times greater than their value of IC50 for AE. Finally, we can say that, the present algorithm constitutes a step forward in the search for efficient ways of discovering new antitrypanosomal c

Leishmaniasis is among the neglected diseases that represent 90% of the world burden of morbidity. According to the WHO, there are 12 million people, mostly deeply impoverished who suffer from visceral leishmaniasis (VL). The drugs currently used for the treatment of human cutaneous and visceral leishmaniasis are toxic, have severe adverse reactions which limit their use, and have presented teratogenic and cardiotoxic effects and increasing resistance. Given this scenario, the search for new, accessible and effective drugs for the treatment of leishmaniasis is a priority. This review aims to provide an overview of selected phenolic compounds with antileishmanial activities that have been published from 2007 to the present. Natural source or efficient synthesis, biological assays and possible mechanisms of actions are also described. Five flavonoids, six chalcones and three polyphenols have shown a selective index (SI) equal or greater than 20 which places them with greater antileishmanial activity. Quercitrin (3), hispidulin (6), octa-acetylhyperoside (11a), biochanin A (13) and ageconyflavone C (14) showed a SI range between 19.5 and 100. Chalcones 31, 33, 41, 42 65 and 67 were the highest antileishmanial compounds. Polyphenols 74 and 85 showed an important selective index when tested on promastigotes (71.4) and amastigotes (36.5) of L major and axenic amastigotes of L. mexicana (20). Compound 83 has demonstrated a potent in vitro (19.7) and in vivo effect on Balb/c mice experimentally infected with L. amazonensis. A wide range of biological assays with several strains and different parasite forms, have identified promising compounds, but few of them are conducted to clinical trials. This restriction emphasizes the necessity to reach a consensus regarding in vitro and in vivo screening protocol to advance leading compounds to clinical trials.

Double Blind Peer Reviewed International Research Journal, El modelo de los Laboratorios Ciudadanos o Vivientes, concentran su esfuerzo por apoyar a los actores, ofreciendo un espacio neutral en el que los interesados puedan conocer y co-desarrollar innovaciones en contextos del mundo real. Para ello, autores como Etzkowitz (2003) e Irizar y MacLeod (2008) mencionan la concurrencia de la triple hélice: la administración, el sector universitario y la empresa. Esta experiencia que se presenta a continuación se basa en la vinculación de cuatro sectores y que constituye un cambio de modelo en los sistemas de innovación (Arnkil et al, 2010, Kaivo-oja, 2011 y Serra 2013), en los que interviene, además de los tres sectores anteriormente citados, la comunidad. El objetivo del este artículo es mostrar, una experiencia de vinculación y de gestión de proyectos a partir de los interesados reales, siguiendo las orientaciones del nuevo modelo de la cuádruple hélice, considerando al Centro de Desarrollo para la Investigación Científica CEDIC como núcleo propiciador de esta experiencia.

Double Blind Peer Reviewed International Research Journal, El modelo de los Laboratorios Ciudadanos o Vivientes, concentran su esfuerzo por apoyar a los actores, ofreciendo un espacio neutral en el que los interesados puedan conocer y co-desarrollar innovaciones en contextos del mundo real. Para ello, autores como Etzkowitz (2003) e Irizar y MacLeod (2008) mencionan la concurrencia de la triple hélice: la administración, el sector universitario y la empresa. Esta experiencia que se presenta a continuación se basa en la vinculación de cuatro sectores y que constituye un cambio de modelo en los sistemas de innovación (Arnkil et al, 2010, Kaivo-oja, 2011 y Serra 2013), en los que interviene, además de los tres sectores anteriormente citados, la comunidad. El objetivo del este artículo es mostrar, una experiencia de vinculación y de gestión de proyectos a partir de los interesados reales, siguiendo las orientaciones del nuevo modelo de la cuádruple hélice, considerando al Centro de Desarrollo para la Investigación Científica CEDIC como núcleo propiciador de esta experiencia.

BACKGROUND: Vector control has substantially reduced Chagas disease (ChD) incidence. However, transmission by household-reinfesting triatomines persists, suggesting that entomological surveillance should play a crucial role in the long-term interruption of transmission. Yet, infestation foci become smaller and harder to detect as vector control proceeds, and highly sensitive surveillance methods are needed. Community participation (CP) and vector-detection devices (VDDs) are both thought to enhance surveillance, but this remains to be thoroughly assessed. METHODOLOGY/PRINCIPAL FINDINGS: We searched Medline, Web of Knowledge, Scopus, LILACS, SciELO, the bibliographies of retrieved studies, and our own records. Data from studies describing vector control and/or surveillance interventions were extracted by two reviewers. Outcomes of primary interest included changes in infestation rates and the detection of infestation/reinfestation foci. Most results likely depended on study- and site-specific conditions, precluding meta-analysis, but we re-analysed data from studies comparing vector control and detection methods whenever possible. Results confirm that professional, insecticide-based vector control is highly effective, but also show that reinfestation by native triatomines is common and widespread across Latin America. Bug notification by householders (the simplest CP-based strategy) significantly boosts vector detection probabilities; in comparison, both active searches and VDDs perform poorly, although they might in some cases complement each other. CONCLUSIONS/SIGNIFICANCE: CP should become a strategic component of ChD surveillance, but only professional insecticide spraying seems consistently effective at eliminating infestation foci. Involvement of stakeholders at all process stages, from planning to evaluation, would probably enhance such CP-based strategies., Author Summary. Blood-sucking triatomine bugs are the vectors of Chagas disease, a potentially fatal illness that affects millions in Latin America. With no vaccines available, prevention heavily depends on controlling household-infesting triatomines. Insecticide-spraying campaigns have effectively reduced incidence, but persistent household reinfestation can result in disease re-emergence. What, then, is the best strategy to keep houses free of triatomines and thus interrupt disease transmission in the long run? We reviewed published evidence to (i) assess the effectiveness of insecticide-based vector control, gauging the importance of reinfestation; (ii) compare the efficacy of programme-based (with households periodically visited by trained staff) and community-based (with residents reporting suspect vectors found in their homes) surveillance strategies; and (iii) evaluate the performance of alternative vector-detection methods. The results confirm that insecticide-based vector control is highly effective, but also that persistent house reinfestation is a general trend across Latin America. Surveillance systems are significantly more effective when householders report suspect bugs than when programme staff search houses, either manually or using vector-detection devices. Our results clearly support the view that long-term vector surveillance will be necessary for sustained Chagas disease control – and that community participation can substantially contribute to this aim.

Living Labs model concentrate its effort to support actors, providing a neutral space in which stakeholders could know and co-develop innovations in real-world contexts and proposes five basic principles for the operations of the aforementioned living labs: courage, openness, realism, influence and sustainability. The objective of this paper is to propose and test a Living Lab and project management model from the actual stakeholders, following the perspective of the Stakeholder Theory and the Soft Systems Methodology (SSM). This perspective places the Research - Action model on the basis of the SSM model as an appropriate vehicle for the openness towards worldviews, problems and conflicts solving by the organizations, especially when it involves the formulation of possible cultural changes (structural, process, attitudinal) and "actions for improvement" are established. Therefore, we present the case of the Development Center for Scientific Research which brings together a multidisciplinary group of researchers and the project "Participatory approach with ethnic focus for Community Development of the Maskoy Diez Leguas ethnicity in the Central Chaco of Paraguay".

In the Gran Chaco region, control of Triatoma infestans has been limited by persistent domestic infestations despite the efforts of the Vector Control Services. In Paraguay, this region is the highest endemic area in the country, showing high levels of indoor and outdoor infestation. Although sylvatic T. infestans have been found in the Bolivian and Argentine Chaco, similar searches for sylvatic populations of this species in Paraguay had been unsuccessful over the last 20 years. Here we present a new approach to detecting sylvatic Triatominae, using a trained dog, which has successfully confirmed sylvatic populations of T. infestans and other triatomine species in Paraguay. A total of 22 specimens corresponding to dark morph forms of T. infestans were collected, and 14 were confirmed as T. infestans by the mitochondrial cytochrome B gene analysis. Through this analysis, one of which were previously reported and a second that was a new haplotype. Triatomines were captured from amongst vegetation such as dry branches and hollows trees of different species such Aspidosperma quebracho-blanco, Bulnesia sarmientoi and Stetsonia coryne. The colonies found have been small and without apparent infection with Trypanosoma cruzi. During the study, Triatoma sordida and Triatoma guasayana have also been found in ecotopes close to those of T. infestans, Author Summary: Confirmation of sylvatic colonies of Triatoma infestans has a significant connotation for Paraguay. Prior to our findings, we believed this vector —unlike in other regions of the Gran Chaco—was living exclusively in domestic and peridomestic habitats. We never considered the possibility of sylvatic species re-infesting domiciliary dwellings. After this discovery, the frame of transmission dynamics of Trypanosoma cruzi in the Paraguayan Chaco proposes new research perspectives. This also opens the door to promote knowledge regarding potential genetic flows between different T. infestans populations, reservoirs associated with their colonies, as well as their impact over control actions. Fieldwork for wild species identification is difficult and often unsuccessful, we used several techniques and tools, proven by others such as light traps, and mouse-baited sticky traps however, the triatomine collection in our study area was scarce or null. Incorporating a trained dog – NERO – to our work team has been a highly successful and productive initiative. The surprising ability NERO has shown will enable us to provide specific data regarding the still unknown wild ecotopes of T. infestans, as well as the potential use of trained dogs as a community surveillance tool of triatomine species considered particularly important for public health.

Leishmaniasis is among the neglected diseases that represent 90% of the world burden of morbidity. According to the WHO, there are 12 million people, mostly deeply impoverished who suffer from visceral leishmaniasis (VL). The drugs currently used for the treatment of human cutaneous and visceral leishmaniasis are toxic, have severe adverse reactions which limit their use, and have presented teratogenic and cardiotoxic effects and increasing resistance. Given this scenario, the search for new, accessible and effective drugs for the treatment of leishmaniasis is a priority. This review aims to provide an overview of selected phenolic compounds with antileishmanial activities that have been published from 2007 to the present. Natural source or efficient synthesis, biological assays and possible mechanisms of actions are also described. Five flavonoids, six chalcones and three polyphenols have shown a selective index (SI) equal or greater than 20 which places them with greater antileishmanial activity. Quercitrin (3), hispidulin (6), octa-acetylhyperoside (11a), biochanin A (13) and ageconyflavone C (14) showed a SI range between 19.5 and 100. Chalcones 31, 33, 41, 42 65 and 67 were the highest antileishmanial compounds. Polyphenols 74 and 85 showed an important selective index when tested on promastigotes (71.4) and amastigotes (36.5) of L major and axenic amastigotes of L. mexicana (20). Compound 83 has demonstrated a potent in vitro (19.7) and in vivo effect on Balb/c mice experimentally infected with L. amazonensis. A wide range of biological assays with several strains and different parasite forms, have identified promising compounds, but few of them are conducted to clinical trials. This restriction emphasizes the necessity to reach a consensus regarding in vitro and in vivo screening protocol to advance leading compounds to clinical trials.

Two-dimensional bond-based bilinear indices and linear discriminant analysis are used in this report to perform a quantitative structure-activity relationship study to identify new trypanosomicidal compounds. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop the theoretical models. Two discriminant models, computed using bond-based bilinear indices, are developed and both show accuracies higher than 86% for training and test sets. The stochastic model correctly indentifies nine out of eleven compounds of a set of organic chemicals obtained from our synthetic collaborators. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Both models show a good agreement between theoretical predictions and experimental results. Three compounds showed IC50 values for epimastigote elimination (AE) lower than 50 ?M, while for the benznidazole the IC50=54.7 ?M which was used as reference compound. The value of IC50 for cytotoxicity of these compounds is at least 5 times greater than their value of IC50 for AE. Finally, we can say that, the present algorithm constitutes a step forward in the search for efficient ways of discovering new antitrypanosomal c

Leishmaniasis is caused by parasites of the genus Leishmania. Recent reports about leishmaniasis show a few number of drugs available, indicating the necessity of new drugs. In this study, the ethanol extract and fractions of Pityrogramma calomelanos (L.) link. (Pteridaceae) were assayed to verify the cytotoxicity and in vitro leishmanicidal activity against promastigote forms of Leishmania brasiliensis. The cytotoxic assay was performed using fibroblasts NCTC929. The studies indicated a leishmanicidal effect of the ethanol extract and the ethyl-acetate fraction. However, a high cytotoxic effect was observed. The hexane and methanol fractions did not show leishmanicidal activity, nor cytotoxic effect. The phytochemical screening detected the presence of alkaloids, a class of secondary metabolites with a known leishmanicidal activity. This is the first study reporting an anti-Leishmania and cytotoxic effect of P. calomelanos, being an interesting approach in the search for drugs against this disease.

Living Labs model concentrate its effort to support actors, providing a neutral space in which stakeholders could know and co-develop innovations in real-world contexts and proposes five basic principles for the operations of the aforementioned living labs: courage, openness, realism, influence and sustainability. The objective of this paper is to propose and test a Living Lab and project management model from the actual stakeholders, following the perspective of the Stakeholder Theory and the Soft Systems Methodology (SSM). This perspective places the Research - Action model on the basis of the SSM model as an appropriate vehicle for the openness towards worldviews, problems and conflicts solving by the organizations, especially when it involves the formulation of possible cultural changes (structural, process, attitudinal) and "actions for improvement" are established. Therefore, we present the case of the Development Center for Scientific Research which brings together a multidisciplinary group of researchers and the project "Participatory approach with ethnic focus for Community Development of the Maskoy Diez Leguas ethnicity in the Central Chaco of Paraguay".