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identification of novel chemical scaffolds inhibiting trypanothione synthetase from pathogenic trypanosomatids.the search for novel chemical entities targeting essential and parasite-specific pathways is considered a priority for neglected diseases such as trypanosomiasis and leishmaniasis. the thiol-dependent redox metabolism of trypanosomatids relies on bis-glutathionylspermidine [trypanothione, t(sh)2], a low molecular mass cosubstrate absent in the host. in pathogenic trypanosomatids, a single enzyme, trypanothione synthetase (trys), catalyzes trypanothione biosynthesis, which is indispensable for pa ...201627070550
stairway to heaven or hell? perspectives and limitations of chagas disease chemotherapy.in this review, we intend to provide a general view of the evolution of experimental studies in the area of chemotherapy for chagas disease. we can follow the process of drug development through three phases. the first phase began almost at the same time as the discovery made by carlos chagas and proceeds to 1970, during which time an extensive list of compounds was subjected to preclinical and clinical trials. the second phase began with the introduction of nifurtimox and benznidazole into the ...201627072716
advances and progress in chagas disease drug discovery.chagas disease represents a serious burden for millions of people worldwide. transmitted by the protozoan parasite trypanosoma cruzi, this neglected tropical disease causes more than 10,000 deaths each year and is the main cause of heart failure in latin america, where it is endemic. although most cases are concentrated in latin american countries, chagas disease has been increasingly reported in non-endemic regions, where the low level of public awareness on the subject contributes to the growi ...201627072717
a 12-mer repetitive antigenic epitope from trypanosoma cruzi is a potential marker of therapeutic efficacy in chronic chagas' disease.the objective was to characterize a trypanosoma cruzi repetitive amino acid sequence that can be used as a marker of therapeutic drug efficacy in patients with chronic chagas' disease.201627073267
vaccination of dogs with trypanosoma rangeli induces antibodies against trypanosoma cruzi in a rural area of córdoba, argentina.dogs play a major role in the domestic cycle of trypanosoma cruzi, acting as reservoirs. in a previous work we have developed a model of vaccination of dogs in captivity with nonpathogenic trypanosoma rangeli epimastigotes, resulting in the production of protective antibodies against t. cruzi, with dramatic decrease of parasitaemia upon challenge with 100,000 virulent forms of this parasite. the aim of this work was to evaluate the immunogenicity of this vaccine in dogs living in a rural area. d ...201627074257
proceedings of the 2015 national toxicology program satellite symposium.the 2015 annual national toxicology program satellite symposium, entitled "pathology potpourri" was held in minneapolis, minnesota, at the american college of veterinary pathologists/american society for veterinary clinical pathology/society of toxicologic pathology combined meeting. the goal of this symposium is to present and discuss diagnostic pathology challenges or nomenclature issues. because of the combined meeting, both laboratory and domestic animal cases were presented. this article pr ...201627075180
attenuated salmonella sp. as a dna delivery system for trypanosoma cruzi antigens.chagas disease is an important neglected disease affecting thousands of people in the americas. novel strategies for prophylactic and therapeutic vaccines against the etiological agent, the intracellular protozoan trypanosoma cruzi, are urgently needed. vaccines based on attenuated virus and bacteria as a foreign dna delivery system represent a strong advantage over naked dna-based vaccines. here we describe the use of attenuated salmonella carrying a eukaryotic expression plasmid encoding a t. ...201627076330
molecular epidemiology of trypanosoma cruzi and triatoma dimidiata in costal ecuador.chagas disease is a neglected tropical disease caused by the protozoan parasite trypanosoma cruzi. in ecuador, triatoma dimidiata and rhodnius ecuadoriensis are the main vector species, responsible for over half of the cases of t. cruzi infection in the country. t. dimidiata is believed to have been introduced in ecuador during colonial times, and its elimination from the country is thus believed to be feasible. we investigated here the molecular ecology of t. dimidiata and t. cruzi in costal ec ...201627079265
histone epigenetic marks in heterochromatin and euchromatin of the chagas' disease vector, triatoma infestans.triatoma infestans, a vector of chagas' disease, shows several particular cell biology characteristics, including the presence of conspicuous heterochromatic bodies (chromocenters) where dna methylation has not been previously detected. whether histone modifications contribute to the condensed state of these bodies has not yet been studied. here, we investigated epigenetic modifications of histones h3 and h4 and presence of the non-histone heterochromatin protein (hp1-α) in the chromocenters and ...201627079857
antiparasitic evaluation of betulinic acid derivatives reveals effective and selective anti-trypanosoma cruzi inhibitors.betulinic acid is a pentacyclic triterpenoid with several biological properties already described, including antiparasitic activity. here, the anti-trypanosoma cruzi activity of betulinic acid and its semi-synthetic amide derivatives (ba1-ba8) was investigated. the anti-trypanosoma cruzi activity and selectivity were enhanced in semi-synthetic derivatives, specially on derivatives ba5, ba6 and ba8. to understand the mechanism of action underlying betulinic acid anti-t. cruzi activity, we investi ...201627080160
phenolic composition and antiparasitic activity of plants from the brazilian northeast "cerrado".this work describes the antiparasitic and cytotoxic activities of three plant species from the cerrado biome, northeastern brazil. significant antiparasitic inhibition was observed against trypanosoma cruzi (63.86%), leishmania brasiliensis (92.20%) and leishmania infantum (95.23%) when using ethanol extract from leaves of guazuma ulmifolia lam. (malvaceae), at a concentration of 500 μg/ml. however, low levels of inhibition were observed when assessing leishmanicidal and trypanocidal (clone cl-b ...201627081371
identification of trypanocidal activity for known clinical compounds using a new trypanosoma cruzi hit-discovery screening cascade.chagas disease is a significant health problem in latin america and the available treatments have significant issues in terms of toxicity and efficacy. there is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. a key first step is the identification of compounds with anti-trypanosoma cruzi activity from compound libraries. here we describe a hit discovery screening cascade designed to specifically identify hits th ...201627082760
bioactivity-guided isolation of laevicarpin, an antitrypanosomal and anticryptococcal lactam from piper laevicarpu (piperaceae).crude ch2cl2 extract from leaves of piper laevicarpu (piperaceae) displayed antitrypanosomal activity against trypomastigote forms of trypanosoma cruzi (y strain) and antimicrobial potential against cryptococcus gattii (strain-type wm 178). bioactivity-guided fractionation of crude extract afforded one new natural bioactive lactam derivative, named laevicarpin. the structure of isolated compound, which displayed a very rare ring system, was elucidated based on nmr, ir and ms spectral analysis. u ...201627083380
analysis of regional left ventricular strain in patients with chagas disease and normal left ventricular systolic function.chagas heart disease has a high socioeconomic burden, and any strategy to detect early myocardial damage is welcome. speckle-tracking echocardiography assesses global and segmental left ventricular (lv) systolic function, yielding values of two-dimensional strain (ε). the aim of this study was to determine if patients with chronic chagas disease and normal lv ejection fractions present abnormalities in global and segmental lv ε.201627086044
diagnosis of congenital chagas disease using an iron superoxide dismutase excreted as antigen, in mothers and their children during the first year of life.chagas disease caused by trypanosoma cruzi is endemic in latin america. human infection is mainly spread by triatominae insects. other forms of transmission are congenital, blood transfusion and organ transplantation.201627088584
blood meal sources of wild and domestic triatoma infestans (hemiptera: reduviidae) in bolivia: connectivity between cycles of transmission of trypanosoma cruzi.chagas disease is a major public health problem in latin america. its etiologic agent, trypanosoma cruzi, is mainly transmitted through the contaminated faeces of blood-sucking insects called triatomines. triatoma infestans is the main vector in various countries in south america and recently, several foci of wild populations of this species have been described in bolivia and other countries. these wild populations are suspected of affecting the success of insecticide control campaigns being car ...201627090297
new serological tools for improved diagnosis of human tegumentary leishmaniasis.human tegumentary leishmaniasis (htl), characterized by skin ulcers that may spread and cause dreadful and massive tissue destruction of the nose and mouth, is considered a neglected tropical disease, and it is a serious threat to global health due to its continuous expansion, favored by the lifecycle of its causative organism that is maintained in domestic animal reservoirs and anthropophilic sand fly species. serodiagnosis of htl is a great challenge due to many biological factors, including h ...201627090730
long-chain acyl-coa synthetase 2 knockdown leads to decreased fatty acid oxidation in fat body and reduced reproductive capacity in the insect rhodnius prolixus.long-chain acyl-coa esters are important intermediates in lipid metabolism and are synthesized from fatty acids by long-chain acyl-coa synthetases (acsl). the hematophagous insect rhodnius prolixus, a vector of chagas' disease, produces glycerolipids in the midgut after a blood meal, which are stored as triacylglycerol in the fat body and eggs. we identified twenty acyl-coa synthetase genes in r. prolixus, two encoding acsl isoforms (rhopracsl1 and rhopracsl2). rhopracsl1 transcripts increased i ...201627091636
antitrypanosomal activity of 5-nitro-2-aminothiazole-based compounds.a small series of 5-nitro-2-aminothiazole-based amides containing arylpiperazine-, biphenyl- or aryloxyphenyl groups in their core were synthesized and evaluated as antitrypanosomatid agents. all tested compounds were active or moderately active against trypanosoma cruzi amastigotes in infected l6 cells and trypanosoma brucei brucei, four of eleven compounds were moderately active against leishmania donovani axenic parasites while none were deemed active against t. brucei rhodesiense. for the mo ...201627092415
correction: first documented transmission of trypanosoma cruzi infection through blood transfusion in a child with sickle-cell disease in belgium. 201627096415
alkanediamide-linked bisbenzamidines are promising antiparasitic agents.a series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two trypanosoma brucei (t.b.) subspecies: t.b. brucei and t.b. rhodesiense, trypanosoma cruzi, leishmania donovani and two plasmodium falciparum subspecies: a chloroquine-sensitive strain (nf54) and a chloroquine-resistant strain (k1). the in vitro cytotoxicity was determined against rat myoblast cells (l6). seven compounds (5, 6, 10, 11, 12, 14, 15) showed high potency against bot ...201627104545
trypanosoma cruzi infection prevalence and bloodmeal analysis in triatomine vectors of chagas disease from rural peridomestic locations in texas, 2013-2014.protozoan pathogen trypanosoma cruzi (chagas, 1909) is the etiologic agent of chagas disease, which affects millions of people in latin america. recently, the disease has been gaining attention in texas and the southern united states. transmission cycle of the parasite involves alternating infection between insect vectors and vertebrate hosts (including humans, wildlife, and domestic animals). to evaluate vector t. cruzi parasite burden and feeding patterns, we tested triatomine vectors from 23 ...201627106934
chromatin proteomics reveals variable histone modifications during the life cycle of trypanosoma cruzi.histones are well-conserved proteins that form the basic structure of chromatin in eukaryotes and undergo several post-translational modifications, which are important for the control of transcription, replication, dna damage repair, and chromosome condensation. in early branched organisms, histones are less conserved and appear to contain alternative sites for modifications, which could reveal evolutionary unique functions of histone modifications in gene expression and other chromatin-based pr ...201627108550
fluctuations in trypanosoma cruzi discrete typing unit composition in two naturally infected triatomines: mepraia gajardoi and m. spinolai after laboratory feeding.mepraia species are hematophagous insects and the most important wild vectors of trypanosoma cruzi, the causative agent of chagas disease in southeastern south america. because the domestic triatoma infestans is already controlled, the transmission of different t. cruzi discrete typing units (dtus) by mepraia species deserves attention. our aim is to gather information on the diversity of t. cruzi dtus circulating in natural insect populations. two groups of naturally infected bugs 21 mepraia ga ...201627109041
post-transplantation infections in bolivia.over 26 years, we found 46 infectious episodes in 350 kidney transplant recipients. fifteen were urinary tract infections, recurrent in 4 patients. there were 8 cytomegalovirus infections, three of them fatal when intravenous (iv) ganciclovir was not available. seven patients had a reactivation of tuberculosis (tb) in the pleura, cervical spine, lumbar spine, knee, ankle, skin and peritoneum, respectively, and were all resolved satisfactorily with conventional anti-tb therapy. three patients tra ...201627110022
geographical variation of deltamethrin susceptibility of triatoma infestans (hemiptera: reduviidae) in argentina with emphasis on a resistant focus in the gran chaco.chagas disease is one of the most important parasitic infections in latin america. the main vector of the protozoan trypanosoma cruzi in america is triatoma infestans, a blood-sucking triatomine bug who is widely distributed in the gran chaco ecoregion. control programs in endemic countries are focused in the elimination of triatomine vectors with pyrethroid insecticides. however, chemical control has failed in the gran chaco over the last two decades because of several factors. previous studies ...201627113106
rhodnius prolixus intoxicated.rhodnius prolixus (hemiptera: reduviidae) is a hematophagous insect native from south america. by the end of the 20th century, it was one of the main vectors of chagas disease in venezuela, colombia, several central american countries and southern mexico. the aim of the present article is to review the literature regarding r. prolixus toxicology. british entomologist vincent b. wigglesworth carried out the first studies on this subject over seventy years ago. a wide bibliographical search allowe ...201727113321
unique behavior of trypanosoma cruzi mevalonate kinase: a conserved glycosomal enzyme involved in host cell invasion and signaling.mevalonate kinase (mvk) is an essential enzyme acting in early steps of sterol isoprenoids biosynthesis, such as cholesterol in humans or ergosterol in trypanosomatids. mvk is conserved from bacteria to mammals, and localizes to glycosomes in trypanosomatids. during the course of t. cruzi mvk characterization, we found that, in addition to glycosomes, this enzyme may be secreted and modulate cell invasion. to evaluate the role of tcmvk in parasite-host cell interactions, tcmvk recombinant protei ...201627113535
impact of helminth infection on the clinical and microbiological presentation of chagas diseases in chronically infected patients.helminth infections are highly prevalent in tropical and subtropical countries, coexisting in chagas disease endemic areas. helminth infections in humans may modulate the host immune system, changing the th1/th2 polarization. this immunological disturbance could modify the immune response to other infections. the aim of this study is to evaluate the relationship between clinical, microbiological and epidemiological characteristics of chagas disease patients, with the presence of helminth infecti ...201627115603
inflammation enhances the risks of stroke and death in chronic chagas disease patients.ischemic strokes have been implicated as a cause of death in chagas disease patients. inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. in this study, we evaluated the association between inflammatory markers and the death risk (dr) and stroke risk (sr) of patients with different clinical forms of chronic chagas disease. the mrna expression levels of cytokines, transcription ...201627115869
development and application of a sensitive, phenotypic, high-throughput image-based assay to identify compound activity against trypanosoma cruzi amastigotes.we have developed a high content 384-well, image-based assay to estimate the effect of compound treatment on trypanosoma cruzi amastigotes in 3t3 fibroblasts. in the same well, the effect of compound activity on host cells can also be determined, as an initial indicator of cytotoxicity. this assay has been used to identify active compounds from an in-house library of compounds with either known biological activity or that are fda approved, and separately, from the medicines for malaria venture m ...201527120069
rhodnius prolixus and r. robustus (hemiptera: reduviidae) nymphs show different locomotor patterns on an automated recording system.circadian rhythms of triatomines, vectors of the etiological agent trypanosoma cruzi responsible for chagas disease, have been extensively studied in adults of the two most epidemiologically relevant vector species, rhodnius prolixus and triatoma infestans. however, little attention has been dedicated to the activity patterns in earlier developmental stages, even though triatomine nymphs are equally capable of transmitting t. cruzi to humans. because circadian rhythms may differ even between clo ...201627121502
structure and ligand-binding mechanism of a cysteinyl leukotriene-binding protein from a blood-feeding disease vector.blood-feeding disease vectors mitigate the negative effects of hemostasis and inflammation through the binding of small-molecule agonists of these processes by salivary proteins. in this study, a lipocalin protein family member (ltbp1) from the saliva of rhodnius prolixus, a vector of the pathogen trypanosoma cruzi, is shown to sequester cysteinyl leukotrienes during feeding to inhibit immediate inflammatory responses. calorimetric binding experiments showed that ltbp1 binds leukotrienes c4 (ltc ...201627124118
analysis of association of foxo3 gene with trypanosoma cruzi infection and chronic chagasic cardiomyopathy.foxo3, a member of the forkhead family of proteins, plays a role in controlling immune response. foxo3 gene variant rs12212067 has been associated to differential severity of infectious diseases like malaria. in this study, we assessed whether this foxo3 gene polymorphism is related to susceptibility to infection by trypanosoma cruzi and/or chronic chagasic cardiomyopathy. a total of 1171 individuals from a colombian region endemic for chagas disease, classified as seronegative (n = 595), seropo ...201627125259
nucleologenesis in trypanosoma cruzi.nucleolar assembly is a cellular event that requires the synthesis and processing of ribosomal rna, in addition to the participation of pre-nucleolar bodies (pnbs) at the end of mitosis. in mammals and plants, nucleolar biogenesis has been described in detail, but in unicellular eukaryotes it is a poorly understood process. in this study, we used light and electron microscopy cytochemical techniques to investigate the distribution of nucleolar components in the pathway of nucleolus rebuilding du ...201627126372
endophytic actinobacteria from the brazilian medicinal plant lychnophora ericoides mart. and the biological potential of their secondary metabolites.endophytic actinobacteria from the brazilian medicinal plant lychnophora ericoides were isolated for the first time, and the biological potential of their secondary metabolites was evaluated. a phylogenic analysis of isolated actinobacteria was accomplished with 16s rrna gene sequencing, and the predominance of the genus streptomyces was observed. all strains were cultured on solid rice medium, and ethanol extracts were evaluated with antimicrobial and cytotoxic assays against cancer cell lines. ...201627128202
acute colonic complications in a patient with chagas disease.we present the case of a young bolivian woman who suffered two acute and impressive colonic complications due to a chagasic megacolon.201627128343
treatment success in trypanosoma cruzi infection is predicted by early changes in serially monitored parasite-specific t and b cell responses.chagas disease is the highest impact parasitic disease in latin america. we have proposed that changes in trypanosoma cruzi-specific immune responses might serve as surrogate indicators of treatment success. herein, we addressed in a long-term follow-up study whether cure achieved after treatment can be predicted by changes in non-conventional indexes of anti-parasite serological and t cell activities.201627128444
the combined deficiency of immunoproteasome subunits affects both the magnitude and quality of pathogen- and genetic vaccination-induced cd8+ t cell responses to the human protozoan parasite trypanosoma cruzi.the β1i, β2i and β5i immunoproteasome subunits have an important role in defining the repertoire of mhc class i-restricted epitopes. however, the impact of combined deficiency of the three immunoproteasome subunits in the development of protective immunity to intracellular pathogens has not been investigated. here, we demonstrate that immunoproteasomes play a key role in host resistance and genetic vaccination-induced protection against the human pathogen trypanosoma cruzi (the causative agent o ...201627128676
validation of n-myristoyltransferase as potential chemotherapeutic target in mammal-dwelling stages of trypanosoma cruzi.trypanosoma cruzi causes chagas disease, an endemic and debilitating illness in latin america. lately, owing to extensive population movements, this neglected tropical disease has become a global health concern. the two clinically available drugs for the chemotherapy of chagas disease have rather high toxicity and limited efficacy in the chronic phase of the disease, and may induce parasite resistance. the development of new anti-t. cruzi agents is therefore imperative. the enzyme n-myristoyltra ...201627128971
a deep insight into the sialome of rhodnius neglectus, a vector of chagas disease.triatomines are hematophagous insects that act as vectors of chagas disease. rhodnius neglectus is one of these kissing bugs found, contributing to the transmission of this american trypanosomiasis. the saliva of hematophagous arthropods contains bioactive molecules responsible for counteracting host haemostatic, inflammatory, and immune responses.201627129103
life cycle, feeding, and defecation patterns of panstrongylus chinai (hemiptera: reduviidae: triatominae) under laboratory conditions.chagas disease is caused by the protozoan trypanosoma cruzi panstrongylus chinai (del ponte) is highly domiciliated in the peruvian and ecuadorian andes and has been found naturally infected with t. cruzi the objective of this study was to describe the life cycle, feeding, and defecation patterns of p. chinai in the loja province within southern ecuador. to characterize its life cycle, a cohort of 70 individuals was followed from egg to adult. at each stage of development, prefeeding time, feedi ...201627131311
chemogenetic characterization of inositol phosphate metabolic pathway reveals druggable enzymes for targeting kinetoplastid parasites.kinetoplastids cause chagas disease, human african trypanosomiasis, and leishmaniases. current treatments for these diseases are toxic and inefficient, and our limited knowledge of drug targets and inhibitors has dramatically hindered the development of new drugs. here we used a chemogenetic approach to identify new kinetoplastid drug targets and inhibitors. we conditionally knocked down trypanosoma brucei inositol phosphate (ip) pathway genes and showed that almost every pathway step is essenti ...201627133314
immunoregulatory mechanisms in chagas disease: modulation of apoptosis in t-cell mediated immune responses.chronic chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. previous results have shown that the immune response plays an important role, although no all mechanisms are understood. immunoregulatory mechanisms such as apoptosis are important for the control of chagas disease, possibly affecting the morbidity in chronic clinical forms. apoptosis has been suggested to be an important mechanism of cellular res ...201627138039
detection and quantification of viable and nonviable trypanosoma cruzi parasites by a propidium monoazide real-time polymerase chain reaction assay.molecular techniques based on real-time polymerase chain reaction (qpcr) allow the detection and quantification of dna but are unable to distinguish between signals from dead or live cells. because of the lack of simple techniques to differentiate between viable and nonviable cells, the aim of this study was to optimize and evaluate a straightforward test based on propidium monoazide (pma) dye action combined with a qpcr assay (pma-qpcr) for the selective quantification of viable/nonviable epima ...201627139452
assessing the mitochondrial dna diversity of the chagas disease vector triatoma sordida (hemiptera: reduviidae).triatoma sordida is a species that transmits trypanosoma cruzi to humans. in brazil, t. sordida currently deserves special attention because of its wide distribution, tendency to invade domestic environments and vectorial competence. for the planning and execution of control protocols to be effective against triatominae, they must consider its population structure. in this context, this study aimed to characterise the genetic variability of t. sordida populations collected in areas with persiste ...201627143491
crystal structures of five new substituted tetrahydro-1-benzazepines with potential antiparasitic activity.tetrahydro-1-benzazepines have been described as potential antiparasitic drugs for the treatment of chagas disease and leishmaniasis, two of the most important so-called `forgotten tropical diseases' affecting south and central america, caused by trypanosoma cruzi and leishmania chagasi parasites, respectively. continuing our extensive work describing the structural characteristics of some related compounds with interesting biological properties, the crystallographic features of three epoxy-1-be ...201627146563
transmission capacity of trypanosoma cruzi (trypanosomatida: trypanosomatidae) by three subspecies of meccus phyllosomus (heteroptera: reduviidae) and their hybrids.three behaviors of epidemiological importance: the time lapse for the onset of feeding, actual feeding, and defecation time for meccus phyllosomus pallidipennis (stål), meccus phyllosomus longipennis (usinger), meccus phyllosomus picturatus (usinger), and their laboratory hybrids were evaluated in this study. the mean time lapse for the beginning of feeding was between 0.5 and 8.3 min considering all instars in each cohort, with highly significant differences only among fifth-instar nymphs, fema ...201627146680
longitudinal study of patients with chronic chagas cardiomyopathy in brazil (sami-trop project): a cohort profile.we have established a prospective cohort of 1959 patients with chronic chagas cardiomyopathy to evaluate if a clinical prediction rule based on ecg, brain natriuretic peptide (bnp) levels, and other biomarkers can be useful in clinical practice. this paper outlines the study and baseline characteristics of the participants.201627147390
synthesis, cytotoxic activity on leukemia cell lines and quantitative structure-activity relationships (qsar) studies of morita-baylis-hillman adducts.the morita-baylis-hillman reaction is an organocatalyzed chemical transformation that allows access to small poly-functionalized molecules and has considerable synthetic potential and promising biological profiles. the morita-baylis-hillman adducts (mbha) are a new class of bioactive compounds and highlight its potentialities to the discovery of new cheaper and efficient drugs, e.g. as anti-leishmania chagasi and leishmania amazonensis, anti- trypanosoma cruzi, anti-plasmodium falciparum and pla ...201627150963
antiprotozoal activity of major constituents from the bioactive fraction of verbesina encelioides.the bioactive petroleum ether fraction of verbesina encelioides, previously studied by the authors, was chosen for the isolation of antiprotozoal metabolites. pseudotaraxasterol-3β-acetate (1), benzyl 2,6-dimethoxy benzoate (2), 16β-hydroxy-pseudotaraxasterol-3β-palmitate (3) and pseudotaraxasterol (4), in addition to β-sitosterol glucoside (5) and β-sitosterol galactoside (6) were isolated and identified based on one-dimensional and two-dimensional spectral analysis. this is the first report de ...201727154232
enhanced target-specific signal detection using an escherichia coli lysate in multiplex microbead immunoassays with e. coli-derived recombinant antigens.diverse techniques have been developed to analyze antibody-mediated responses to infections. however, the most common tests, i.e., enzyme-linked immunosorbent assays, require separate reactions for each antigen and consequently necessitate large sample volumes. luminex technology allows the detection of multiple antibodies in a single experiment, but nonspecific binding can impair the results. therefore, we examined the use of escherichia coli lysates to reduce nonspecific binding and improve th ...201627156997
electrocardiographic abnormalities and treatment with benznidazole among children with chronic infection by trypanosoma cruzi: a retrospective cohort study.chronic infection by trypanosoma cruzi could cause heart conduction disturbances. we sought to analyze electrocardiographic abnormalities among children with chronic t. cruzi infection with and without trypanocidal treatment with benznidazole.201627158908
combination chemotherapy with suboptimal doses of benznidazole and pentoxifylline sustains partial reversion of experimental chagas' heart disease.chronic chagasic cardiomyopathy (ccc) progresses with parasite persistence, fibrosis, and electrical alterations associated with an unbalanced immune response such as high plasma levels of tumor necrosis factor (tnf) and nitric oxide (no). presently, the available treatments only mitigate the symptoms of ccc. to improve ccc prognosis, we interfered with the parasite load and unbalanced immune response using the trypanocidal drug benznidazole (bz) and the immunoregulator pentoxifylline (ptx). c57 ...201627161638
giant fecaloma causing small bowel obstruction: case report and review of the literature.fecaloma is a mass of hardened feces being impacted mostly in rectum and sigmoid. the most common sites of the fecaloma is the sigmoid colon and the rectum. there are several causes of fecaloma and have been described in association with hirschsprung's disease, psychiatric patients, chagas disease, both inflammatory and neoplastic, and in patients suffering with chronic constipation. up to now several cases of giant fecaloma has been reported in the literature most of them presenting with megaco ...201527162906
characteristics of triatomine infestation and natural trypanosoma cruzi infection in the state of rio grande do norte, brazil.introduction natural and artificial ecotope infestation by the kissing bug triatomines and their colonization and infection by trypanosoma cruzi , the chagas disease agent, were evaluated in nine municipalities of the state of rio grande do norte, brazil. methods following identification, triatomine intestinal contents were analyzed by direct microscopic examination, xenoculture, and polymerase chain reaction (pcr) for parasite detection. trypanosoma cruzi isolates were genotyped using three dif ...201627163565
prevalence of chronic infections and susceptibility to measles and varicella-zoster virus in latin american immigrants.large numbers of latin american immigrants recently arrived in western europe. curative and preventive programmes need to take account of their risk of suffering and transmitting imported chronic infections and of their susceptibility to cosmopolitan infections. we aimed to assess the prevalence and co-occurrence of imported chronic infections among latin american immigrants, and their susceptibility to highly prevalent cosmopolitan infections.201627164954
socioeconomic inequalities in neglected tropical diseases: a systematic review.neglected tropical diseases (ntds) are generally assumed to be concentrated in poor populations, but evidence on this remains scattered. we describe within-country socioeconomic inequalities in nine ntds listed in the london declaration for intensified control and/or elimination: lymphatic filariasis (lf), onchocerciasis, schistosomiasis, soil-transmitted helminthiasis (sth), trachoma, chagas' disease, human african trypanosomiasis (hat), leprosy, and visceral leishmaniasis (vl).201627171166
between-country inequalities in the neglected tropical disease burden in 1990 and 2010, with projections for 2020.the world health organization (who) has set ambitious time-bound targets for the control and elimination of neglected tropical diseases (ntds). investing in ntds is not only seen as good value for money, but is also advocated as a pro-poor policy since it would improve population health in the poorest populations. we studied the extent to which the disease burden from nine ntds (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, trachoma, chagas disease, human afr ...201627171193
presence of chromatoid bodies in the rhodnius genus detected by cytochemical analysis.in addition to the epidemiological importance regarding the transmission of chagas disease, triatomines are also important biological models for cellular studies, because they have holocentric chromosomes, post-reductional meiosis for sex chromosomes, and nucleolar persistence. although the nucleolus is present during spermiogenesis, it was suggested that it is inactivated and all transcriptional activity necessary for cell differentiation is supported by the chromatoid body (cb). thus, consider ...201627173249
the tctasv proteins are novel promising antigens to detect active trypanosoma cruzi infection in dogs.in regions where chagas disease is endemic, canine trypanosoma cruzi infection is highly correlated with the risk of transmission of the parasite to humans. herein we evaluated the novel tctasv protein family (subfamilies a, b, c), differentially expressed in bloodstream trypomastigotes, for the detection of naturally infected dogs. a gene of each tctasv subfamily was cloned and expressed. indirect enzyme-linked immunosorbent assays (elisa) were developed using recombinant antigens individually ...201627173912
the pentose phosphate pathway in parasitic trypanosomatids.parasitic trypanosomatids cause important diseases. dissecting the biochemistry of these organisms offers a means of discovering targets against which inhibitors may be designed and developed as drugs. the pentose phosphate pathway is a key route of glucose metabolism in most organisms, providing nadph for use as a cellular reductant and various carbohydrate intermediates used in cellular metabolism. the pathway and its enzymes have been studied in trypanosoma brucei, trypanosoma cruzi, and vari ...201627174163
trypanosoma cruzi-trypanosoma rangeli co-infection ameliorates negative effects of single trypanosome infections in experimentally infected rhodnius prolixus.trypanosoma cruzi, causative agent of chagas disease, co-infects its triatomine vector with its sister species trypanosoma rangeli, which shares 60% of its antigens with t. cruzi. additionally, t. rangeli has been observed to be pathogenic in some of its vector species. although t. cruzi-t. rangeli co-infections are common, their effect on the vector has rarely been investigated. therefore, we measured the fitness (survival and reproduction) of triatomine species rhodnius prolixus infected with ...201627174360
a prime-boost immunization with tc52 n-terminal domain dna and the recombinant protein expressed in pichia pastoris protects against trypanosoma cruzi infection.we have previously reported that the n-terminal domain of the antigen tc52 (ntc52) is the section of the protein that confers the strongest protection against trypanosoma cruzi infection. to improve vaccine efficacy, we conducted here a prime-boost strategy (ntc52pb) by inoculating two doses of pcdna3.1 encoding the ntc52 dna carried by attenuated salmonella (sntc52), followed by two doses of recombinant ntc52 expressed in picchia pastoris plus odn-cpg as adjuvant. this strategy was comparativel ...201627177947
the trypanocidal benznidazole promotes adaptive response to oxidative injury: involvement of the nuclear factor-erythroid 2-related factor-2 (nrf2) and multidrug resistance associated protein 2 (mrp2).oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. benznidazole (bzl) is the only trypanocidal agent available for treatment of chagas disease in endemic areas. its use is associated with side effects, including increases in biomarkers of hepatotoxicity. however, bzl potential to cause oxidative stress has been poorly investigated. here, we evaluated the effect of a pharmacologically relevant bzl concentration (200μm) at different time points on redox status and the cou ...201627180241
phylogenetic analysis of the trypanosoma genus based on the heat-shock protein 70 gene.trypanosome evolution was so far essentially studied on the basis of phylogenetic analyses of small subunit ribosomal rna (ssu-rrna) and glycosomal glyceraldehyde-3-phosphate dehydrogenase (ggapdh) genes. we used for the first time the 70kda heat-shock protein gene (hsp70) to investigate the phylogenetic relationships among 11 trypanosoma species on the basis of 1380 nucleotides from 76 sequences corresponding to 65 strains. we also constructed a phylogeny based on combined datasets of ssu-rdna, ...201627180897
genomic african and native american ancestry and chagas disease: the bambui (brazil) epigen cohort study of aging.the influence of genetic ancestry on trypanosoma cruzi infection and chagas disease outcomes is unknown.201627182885
serum cytokines as biomarkers of early trypanosoma cruzi infection by congenital exposure.trypanosoma cruzi, the causing agent of chagas disease, leads to an activation of the immune system in congenitally infected infants. in this study, we measured a set of cytokines/chemokines and the levels of parasitemia by quantitative pcr in the circulation of neonates born to t. cruzi-infected mothers to evaluate the predictive value of these mediators as biomarkers of congenital transmission. we conducted a retrospective cohort study of 35 infants with congenital t. cruzi infection, of which ...201627183607
ecdysis period of rhodnius prolixus head investigated using phase contrast synchrotron microtomography.microtomography using synchrotron sources is a useful tool in biological imaging research since the phase coherence of synchrotron beams can be exploited to obtain images with high contrast resolution. this work is part of a series of works using phase contrast synchrotron microtomography in the study of rhodnius prolixus head, the insect vector of chagas' disease, responsible for about 12,000 deaths per year. the control of insect vector is the most efficient method to prevent this disease and ...201627184550
leishmania major and trypanosoma cruzi present distinct dna damage responses.leishmania major and trypanosoma cruzi are medically relevant parasites and interesting model organisms, as they present unique biological processes. despite increasing data regarding the mechanisms of gene expression regulation, there is little information on how the dna damage response (ddr) occurs in trypanosomatids. we found that l. major presented a higher radiosensitivity than t. cruzi. l. major showed g1 arrest and displayed high mortality in response to ionizing radiation as a result of ...201627188657
to spray or not to spray? understanding participation in an indoor residual spray campaign in arequipa, peru.current low participation rates in vector control programmes in arequipa, peru complicate the control of chagas disease. using focus groups (n = 17 participants) and semi-structured interviews (n = 71) conducted in march and may 2013, respectively, we examined barriers to and motivators of household participation in an indoor residual spray (irs) campaign that had taken place one year prior in arequipa. the most common reported barriers to participation were inconvenient spray times due to work ...201627189446
gold(iii) complexes with ons-tridentate thiosemicarbazones: toward selective trypanocidal drugs.tridentate thiosemicarbazone ligands with an ons donor set, h2l(r) (r = me and et) were prepared by reactions of 1-phenyl-1,3-butanedione with 4-r-3-thiosemicarbazides. h2l(r) reacts with na[aucl4]·2h2o in meoh in a 1:1 m ratio under formation of green gold(iii) complexes of composition [aucl(l(r))]. these compounds represent the first examples of gold(iii) complexes with ons chelate-bonded thiosemicarbazones. the in vitro anti-trypanosoma cruzi activity against both trypomastigote and amastigot ...201627191616
trypanosoma cruzi isolated from a triatomine found in one of the biggest metropolitan areas of latin america.to characterize trypanosoma cruzi (tci) isolated from a panstrongylus megistus specimen found in one of the biggest metropolitan areas of latin america, the relationship between the tci group of t. cruzi and the transmission cycle in the urban environment was studied.201627192587
extraction of trypanosoma cruzi dna from food: a contribution to the elucidation of acute chagas disease outbreaks.before 2004, the occurrence of acute chagas disease (acd) by oral transmission associated with food was scarcely known or investigated. originally sporadic and circumstantial, acd occurrences have now become frequent in the amazon region, with recently related outbreaks spreading to several brazilian states. these cases are associated with the consumption of açai juice by waste reservoir animals or insect vectors infected with trypanosoma cruzi in endemic areas. although guidelines for processin ...201627192588
evaluation of human t-lymphotropic virus prevalence/co-infection rates for a four-year period in a non-metropolitan blood center in southeast brazil.human t-lymphotropic virus types 1/2 (htlv-1/2) are distributed worldwide and are endemic in specific regions.201627192594
new cases of chagas disease in a rural area of northeast brazilian.chagas disease is considered one of the 17 most neglected tropical diseases in the world, with the most common form of vector transmission.201627192597
apoptotic cd8 t-lymphocytes disable macrophage-mediated immunity to trypanosoma cruzi infection.chagas disease is caused by infection with the protozoan trypanosoma cruzi. cd8 t-lymphocytes help to control infection, but apoptosis of cd8 t cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. here, we investigate how apoptosis of activated cd8 t cells affects m1 and m2 macrophage phenotypes. first, we found that cd8 t-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute t. cruzi infection. we show that treatment with a ...201627195678
is the infectiousness of dogs naturally infected with trypanosoma cruzi associated with poly-parasitism?interactions among different species of parasites co-infecting the same host could be synergistic or antagonistic. these interactions may modify both the frequency of infected hosts and their infectiousness, and therefore impact on transmission dynamics. this study determined the infectiousness of trypanosoma cruzi-seropositive dogs (using xenodiagnosis) and their parasite load (quantified by qpcr), and tested the association between both variables and the presence of concomitant endoparasites. ...201627198799
trypanosoma teixeirae: a new species belonging to the t. cruzi clade causing trypanosomosis in an australian little red flying fox (pteropus scapulatus).little is known about the genetic diversity and pathogenicity of trypanosomes in australian bats. recently a novel trypanosome species was identified in an adult female little red flying fox (pteropus scapulatus) with clinical and pathological evidence of trypanosomosis. the present study used morphology and molecular methods to demonstrate that this trypanosome is a distinct species and we propose the name trypanosoma teixeirae sp. n. morphological comparison showed that its circulating trypoma ...201627198803
experimental infection of rhodnius prolixus (hemiptera, triatominae) with mycobacterium leprae indicates potential for leprosy transmission.leprosy is a chronic dermato-neurological disease caused by infection with mycobacterium leprae. in 2013 almost 200,000 new cases of leprosy were detected around the world. since the first symptoms take from years to decades to appear, the total number of asymptomatic patients is impossible to predict. although leprosy is one of the oldest records of human disease, the mechanisms involved with its transmission and epidemiology are still not completely understood. in the present work, we experime ...201627203082
simple methodology to directly genotype trypanosoma cruzi discrete typing units in single and mixed infections from human blood samples.different dna markers to genotype trypanosoma cruzi are now available. however, due to the low quantity of parasites present in biological samples, dna markers with high copy number like kinetoplast minicircles are needed. the aim of this study was to complete a dna assay called minicircle lineage specific-pcr (mls-pcr) previously developed to genotype the t. cruzi dtus tcv and tcvi, in order to genotype dtus tci and tcii and to improve tcvi detection. we screened kinetoplast minicircle hypervar ...201627208806
new sex-determination system in the genus  panstrongylus (hemiptera: reduviidae) revealed by chromosomal analysis of panstrongylus lutzi.panstrongylus lutzi (neiva & pinto, 1923) is a triatomine species native to caatinga habitats in north-eastern brazil. it is considered an important vector of chagas disease in this region, presenting high rates of natural infection with trypanosoma cruzi chagas, 1909, and readily invading houses by flight. this study describes a previously unknown chromosomal sex system in the genus panstrongylus based on p. lutzi.201627209318
neuropeptides in the regulation of rhodnius prolixus physiology.in the kissing bug rhodnius prolixus, events such as diuresis, antidiuresis, development and reproduction are triggered by blood feeding. hence, these events can be accurately timed, facilitating physiological experiments. this, combined with its relatively big size, makes r. prolixus an excellent model in insect neuroendocrinological studies. the importance of r. prolixus as a chagas' disease vector as much as an insect model has motivated the sequencing of its genome in recent years, facilitat ...201727210592
highly diluted medication reduces tissue parasitism and inflammation in mice infected by trypanosoma cruzi.to evaluate the effects of kalium causticum, conium maculatum, and lycopodium clavatum 13ch in mice infected by trypanosoma cruzi.201627211326
chagas cardiomyopathy: the potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogs chronically infected with trypanosoma cruzi.cardiac involvement represents the main cause of mortality among patients with chagas disease, and the relevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. in the present study, we used a canine model infected with the benznidazole-sensitive berenice-78 trypanosoma cruzi strain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiac muscle tissue damage and left ventricular diastolic dysfunction in the chronic p ...201627215760
phenotypic screening in vitro of novel aromatic amidines against trypanosoma cruzi.the current treatment of chagas disease (cd), based on nifurtimox and benznidazole (bz), is unsatisfactory. in this context, we performed the phenotypic in vitro screening of novel mono- and diamidines and drug interaction assays with selected compounds. ten novel amidines were tested for their activities against bloodstream trypomastigote (bt) and amastigote forms of trypanosoma cruzi (y and tulahuen strains) and their toxicities for mammalian host cells (l929 cells and cardiac cells). seven of ...201627216059
novel cruzipain inhibitors for the chemotherapy of chronic chagas disease.despite current efforts worldwide to develop new medications against chagas disease, only two drugs are available, nifurtimox and benznidazole. both drugs require prolonged treatment and have multiple side effects and limited efficacy on adult patients chronically infected with trypanosoma cruzi. recently, computer-guided drug repositioning led to the discovery of the trypanocidal effects of clofazimine and benidipine. these compounds showed inhibitory effects on cruzipain, the major cysteine pr ...201627216381
first finding of trypanosoma cruzi ii in vampire bats from a district free of domestic vector-borne transmission in northeastern argentina.establishing the putative links between sylvatic and domestic transmission cycles of trypanosoma cruzi, the etiological agent of chagas disease, is of public health relevance. we conducted three surveys to assess t. cruzi infection in wild mammals from a rural and a preserved area in misiones province, northeastern argentina, which had recently been declared free of vector- and blood-borne transmission of human t. cruzi infection. a total of 200 wild mammals were examined by xenodiagnosis (xd) a ...201627220254
the active transport of histidine and its role in atp production in trypanosoma cruzi.trypanosoma cruzi, the aetiological agent of chagas's disease, metabolizes glucose, and after its exhaustion, degrades amino acids as energy source. here, we investigate histidine uptake and its participation in energy metabolism. no putative genes for the histidine biosynthetic pathway have been identified in genome databases of t. cruzi, suggesting that its uptake from extracellular medium is a requirement for the viability of the parasite. from this assumption, we characterized the uptake of ...201627222029
proteomic profile of circulating immune complexes in chronic chagas disease.immune complexes (ics) are the direct and real-time products of humoral immune responses. the identification of constituent foreign or autoantigens within ics might bring new insights into the pathology of infectious diseases. we applied immune complexome analysis of plasma to the study of chagas disease caused by trypanosoma cruzi. twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegativ ...201627223052
carlos chagas discoveries as a drop back to scientific construction of chronic chagas heart disease.the scientific construction of chronic chagas heart disease (cchd) started in 1910 when carlos chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. he described sudden cardiac death associated with arrhythmias in 1911, and its association with complete av block detected by jacquet's polygraph as chagas reported in 1 ...201627223644
serological based monitoring of a cohort of patients with chronic chagas disease treated with benznidazole in a highly endemic area of northern argentina.this study aimed to evaluate well-documented diagnostic antigens, named b13, 1f8 and jl7 recombinant proteins, as potential markers of seroconversion in treated chagasic patients. prospective study, involving 203 patients treated with benznidazole, was conducted from endemic areas of northern argentina. follow-up was possible in 107 out of them and blood samples were taken for serology and pcr assays before and 2, 3, 6, 12, 24 and 36 months after treatment initiation. reactivity against trypanos ...201627223650
innate immunomodulation to trypanosomatid parasite infections.the recognition of invading pathogens by the innate immune system is essential for host protection against human parasites and the initiation of an effective adaptive immune response. innate immune cells such as macrophages and dendritic cells (dcs) are involved in the first line of defense against protozoan parasites via sensing the invaders through pattern recognition receptors (prrs), such as toll-like receptors (tlrs). activation of macrophages and dendritic cells starts with the interaction ...201627223816
survey of feral swine ( sus scrofa ) infection with the agent of chagas disease ( trypanosoma cruzi ) in texas, 2013-14.: feral swine ( sus scrofa ) are an invasive species and reservoir of numerous zoonotic pathogens in the us, and texas leads the nation in the estimated population size of feral hogs. texas also harbors enzootic transmission cycles of the protozoan parasite trypanosoma cruzi , agent of chagas disease. given previous evidence that swine can serve as reservoirs of t. cruzi in latin america and new evidence of triatomines (kissing bugs) feeding on swine in texas, we measured the prevalence of t. cr ...201627224214
comprehensive left ventricular mechanics analysis by speckle tracking echocardiography in chagas disease.chagas disease (cd) is a frequent cause of dilated cardiomyopathy (cmp) in developing countries, leading to clinical heart failure and worse prognosis. therefore, the development and evolution of this cmp has always been a major topic in numbers of previous studies. a comprehensive echocardiographic study of left ventricular (lv) mechanics, fully assessing myocardial contraction, has never been done before. this could help characterize and improve the understanding of the evolution of this preva ...201627229468
what is the 'true' effect of trypanosoma rangeli on its triatomine bug vector?the phrase, "t. rangeli is pathogenic to its insect vector," is commonly found in peer-reviewed publications on the matter, such that it has become the orthodox view of this interaction. in a literature survey, we identified over 20 papers with almost the exact phrase and several others alluding to it. the idea is of particular importance in triatomine population dynamics and the study of vector-borne t. cruzi transmission, as it could mean that triatomines infected with t. rangeli have lower fi ...201627232121
vector capacity of members of triatoma brasiliensis species complex: the need to extend chagas disease surveillance to triatoma melanica.we conducted a lab-based comparative study on vector capacity features of two species of triatomines: triatoma brasiliensis and t. melanica. both are members of the t. brasiliensis species complex. the former is the most important chagas disease vector in the northeastern region of brazil. to date, no transmission via t. melanica has been recorded. immature insects exhibited distinct intermoult periods without a direct relationship to a given species. females of t. brasiliensis consumed an avera ...201627232124
population differentiation of the chagas disease vector triatoma maculata (erichson, 1848) from colombia and venezuela.the emerging vector of chagas disease, triatoma maculata (hemiptera, reduviidae), is one of the most widely distributed triatoma species in northern south america. despite its increasing relevance as a vector, no consistent picture of the magnitude of genetic and phenetic diversity has yet been developed. here, several populations of t. maculata from eleven colombia and venezuela localities were analyzed based on the morphometry of wings and the mitochondrial nadh dehydrogenase subunit 4 (nd4) g ...201627232127
active dispersal of triatoma infestans and other triatomines in the argentinean arid chaco before and after vector control interventions.peridomestic structures are considered the main sites where triatoma infestans (hemiptera: reduviidae) remain and disperse, representing the first risk factor for intradomestic invasion, even after vector control activities. this study analyzed t. infestans dispersal during vector control interventions in six rural houses of the arid chaco (la rioja, argentina). flying and walking dispersers were captured during five months of two consecutive warm seasons after insecticide spraying of intra- and ...201627232129
invasion of rural houses by wild triatominae in the arid chaco.triatomines are the vectors of trypanosoma cruzi, the etiologic agent of chagas disease, the main endemic disease affecting five to seven million people in latin america. besides triatoma infestans, the most important t. cruzi vector in the gran chaco region, other triatomine species associated with sylvatic birds and mammals are responsible for the maintenance of the wild cycle of t. cruzi. the present study aimed at evaluating the house invasion by sylvatic triatomine species in rural communit ...201627232130
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