Publications

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dual role of monocyte-derived dendritic cells in trypanosoma cruzi infection.pathogens can cause inflammation when inoculated into the skin. the vector-transmitted protozoan parasite trypanosoma cruzi induces poor cellular-infiltration and disseminates, causing high mortality in the experimental model. here, we characterized the inflammatory foci at the parasite inoculation site and secondary lymphoid organs using a murine model. while no macrophages and few neutrophils and monocytes (mo) were recruited into the skin, t. cruzi infection elicited the mobilization of ly6c( ...201728748529
peptides selected using phage library variants, effectively inhibit trypanosoma cruzi infection.four peptide sequences characterized by high content of hydrophobic, charged, and polar amino acids were obtained from 23 clones of m13 phage. peptides p2 and p4 exhibited highest binding affinity for immobilized trypomastigotes. the inhibitory effects of peptides seemed to be due to blockade of certain epitopes on t. cruzi surface proteins responsible for interactions with the respective receptors of host cells.201728744646
role of inactive and active trypanosoma cruzi trans-sialidases on t cell homing and secretion of inflammatory cytokines.trans-sialidase from trypanosoma cruzi (tc-ts) belongs to a superfamily of proteins that may have enzymatic activity. while enzymatically active members (tc-ats) are able to transfer sialic acid from the host cell sialyl-glycoconjugates onto the parasite or to other molecules on the host cell surface, the inactive members (tc-its) are characterized by their lectinic properties. over the last 10 years, several papers demonstrated that, individually, tc-ats or tc-its is able to modulate several bi ...201728744279
3-hydroxykynurenine, a tryptophan metabolite generated during the infection, is active against trypanosoma cruzi.the antiparasitic activity of 3-hydroxykynurenine (3-hk), one of the major tryptophan catabolites of the kynurenine pathway, against both trypanosoma cruzi evolutive forms that are important for human infection, trypomastigotes (tps) and amastigotes (am), possible targets in the parasite and the drug toxicity to mammalian cells have been investigated. 3-hk showed a potent activity against am with ic50 values in the micromolar concentration range, while the ic50 values to cause tps death was ∼600 ...201728740612
therapeutic effects of sphingosine kinase inhibitor n,n-dimethylsphingosine (dms) in experimental chronic chagas disease cardiomyopathy.chagas disease cardiomyopathy is a parasite-driven inflammatory disease to which there are no effective treatments. here we evaluated the therapeutic potential of n,n-dimethylsphingosine(dms), which blocks the production of sphingosine-1-phosphate(s1p), a mediator of cellular events during inflammatory responses, in a model of chronic chagas disease cardiomyopathy. dms-treated, trypanosoma cruzi-infected mice had a marked reduction of cardiac inflammation, fibrosis and galectin-3 expression when ...201728733584
comparative study and analytical verification of pcr methods for the diagnosis of congenital chagas disease.congenital infection is currently the first cause of new cases of chagas disease in argentina and nonendemic areas worldwide. its diagnosis is of utmost importance to guarantee curative treatment. to improve such diagnosis, a transfer process of pcr tests to the national laboratory network has been initiated. we performed a comparative study of four pcr assays [two end-point pcr and two duplex real-time quantitative pcr (qpcr) procedures] to detect trypanosoma cruzi dna in blood samples. because ...201728727985
small subunit ribosomal metabarcoding reveals extraordinary trypanosomatid diversity in brazilian bats.bats are a highly successful, globally dispersed order of mammals that occupy a wide array of ecological niches. they are also intensely parasitized and implicated in multiple viral, bacterial and parasitic zoonoses. trypanosomes are thought to be especially abundant and diverse in bats. in this study, we used 18s ribosomal rna metabarcoding to probe bat trypanosome diversity in unprecedented detail.201728727769
study of infectious diseases in archaeological bone material - a dataset.bones of human and ground sloth remains were analyzed for presence of trypanosoma cruzi by conventional pcr using primers tc, tc1 and tc2. sequence results amplified a fragment with the same product size as the primers (300 and 350pb). amplified pcr product was sequenced and analyzed on genbank, using blast. although these sequences did not match with these parasites they showed high amplification with species of bacteria. this article presents the methodology used and the alignment of the seque ...201728725674
systemic insecticide treatment of the canine reservoir of trypanosoma cruzi induces high levels of lethality in triatoma infestans, a principal vector of chagas disease.despite large-scale reductions in chagas disease prevalence across central and south america, trypanosoma cruzi infection remains a considerable public health problem in the gran chaco region where vector-borne transmission persists. in these communities, peridomestic animals are major blood-meal sources for triatomines, and household presence of infected dogs increases t. cruzi transmission risk for humans. to address the pressing need for field-friendly, complementary methods to reduce triatom ...201728724448
comparative repeatome analysis on triatoma infestans andean and non-andean lineages, main vector of chagas disease.triatoma infestans is the most important chagas disease vector in south america. two main evolutionary lineages, named andean and non-andean, have been recognized by geographical distribution, phenetic and genetic characteristics. one of the main differences is the genomic size, varying over 30% in their haploid dna content. here we realize a genome wide analysis to compare the repetitive genome fraction (repeatome) between both lineages in order to identify the main repetitive dna changes occur ...201728723933
evolution of anti-trypanosoma cruzi antibody production in patients with chronic chagas disease: correlation between antibody titers and development of cardiac disease severity.chagas disease is one of the most important endemic infections in latin america affecting around 6-7 million people. about 30-50% of patients develop the cardiac form of the disease, which can lead to severe cardiac dysfunction and death. in this scenario, the identification of immunological markers of disease progression would be a valuable tool for early treatment and reduction of death rates. in this observational study, the production of anti-trypanosoma cruzi antibodies through a retrospect ...201728723905
2b-rad genotyping for population genomic studies of chagas disease vectors: rhodnius ecuadoriensis in ecuador.rhodnius ecuadoriensis is the main triatomine vector of chagas disease, american trypanosomiasis, in southern ecuador and northern peru. genomic approaches and next generation sequencing technologies have become powerful tools for investigating population diversity and structure which is a key consideration for vector control. here we assess the effectiveness of three different 2b restriction site-associated dna (2b-rad) genotyping strategies in r. ecuadoriensis to provide sufficient genomic res ...201728723901
silencing of two vitellogenin genes inhibits oviposition in the chagas disease vector triatoma infestans (hemiptera: reduviidae).rna interference caused by exogenous double-stranded rna (dsrna) is used to downregulate crucial genes to control insects. the reproductive success of all oviparous species depends on vitellogenin (vg) biosynthesis and its accumulation in the developing oocytes. adult females of triatoma infestans were independently injected with two vg dsrnas (vg1 dsrna or vg2 dsrna) or nuclease-free water (control) 24 hours before feeding, and a group of adult females not injected was also analyzed (control). ...201728722589
study of the salivary glands in triatominae (hemiptera, reduviidae, triatominae): their color and application to the chagas disease vector evolution.chagas disease is caused by trypanosoma cruzi and transmitted by feces of a triatomine that has the habit of defecating during blood feeding. the salivary glands of triatomines are important to hematophagy because their saliva is rich in anticoagulant and hemolytic proteins. the salivary glands of some rhodnius species analyzed are reddish due to the presence of nitrophorins (antihemostatic activity). the present study aimed to analyze the color pattern of the salivary glands of 67 triatomine sp ...201728722578
prevention of congenital chagas disease by benznidazole treatment in reproductive-age women. an observational study.since the decline in new cases of infection by insect/vector, congenital chagas disease has become more relevant in the transmission of chagas disease. treatment with benznidazole significantly reduces the parasitemia, which constitutes an important factor linked to vertical transmission. the objective of this study was to evaluate whether treatment with benznidazole previously administered to women of childbearing age can prevent or reduce the incidence of new cases of congenital chagas disease ...201728720492
the immunomodulatory effects of the enalapril in combination with benznidazole during acute and chronic phases of the experimental infection with trypanosoma cruzi.trypanosoma cruzi infection triggers a chronic inflammatory process responsible for the alterations in the extracellular matrix and functionality of the heart. the angiotensin converting enzyme (ace) inhibitors affects t. cruzi in vitro surveillance and modulates in vivo some inflammatory mediators. in this study, we investigated the treatment with an ace inhibitor (enalapril) and the benznidazole (bz) in a single and combination therapies (ct) in c57bl/6 mice infected with vl-10 strain of the t ...201728720491
simplified membrane feeding of bloodsucking triatomines (hemiptera: reduviidae).laboratory-reared hematophagous triatomines that are the main vectors of chagas disease are generally fed on small vertebrates or on blood-filled membrane devices. such devices allow a large-scale rearing of these vectors without sacrificing host animals but are almost always expensive, fragile, not easily purchased, and usually difficult to use because they need to be sterilized before and carefully cleaned after each feeding. we present here a simple device to feed triatomines that is composed ...201728720489
high triatoma brasiliensis densities and trypanosoma cruzi prevalence in domestic and peridomestic habitats in the state of rio grande do norte, brazil: the source for chagas disease outbreaks?abstracta total of 2,431 triatoma brasiliensis were collected from 39 populations of paraíba (pb) and rio grande do norte (rn) states, brazil. in pb, trypanosoma cruzi infection was not detected in either peridomestic or domestic vector populations. in contrast, in rn, t. brasiliensis was detected with high parasite prevalence in these ecotopes (30.7-40.0%). moreover, peridomicile insect population densities were more than double the average densities of all other settings evaluated (19.17 versu ...201728719275
cholinesterase inhibition reduces arrhythmias in asymptomatic chagas disease.parasympathetic dysfunction may play a role in the genesis of arrhythmias in chagas disease.201728715142
correction for ekanayake et al., "epigenetic regulation of transcription and virulence in trypanosoma cruzi by o-linked thymine glucosylation of dna". 201728710121
an infrequent cause of apical ventricular aneurysm in the united states.chronic chagas cardiomyopathy (ccc) is a late complication of chagas disease with various manifestations including arrhythmia, heart failure, thromboembolism, and stroke. in a patient with symptoms of heart failure and left ventricular apical aneurysm unexplained by structural heart or coronary vascular abnormalities, ccc should be strongly considered and inquiry made about exposure status. typical electrocardiographic findings of bundle branch block, complete heart blocks, and ventricular arrhy ...201728706597
prevalence of trypanosoma cruzi infection in dogs and small mammals in nuevo león, mexico.chagas disease, caused by the protozoan trypanosoma cruzi, is an important public health concern in areas extending from south america northward into the southern united states of america. although this hemoflagellate has many wild and domestic mammalians reported as reservoir hosts, studies on this subject are scarce in nuevo león state, a region located in northeastern mexico. this cross-sectional study showed that the general prevalence of t. cruzi infection in nuevo león state was 14.5% (35/ ...201728705488
modelling the influence of host community composition in a sylvatic trypanosoma cruzi system.species composition of wild reservoir hosts can influence the transmission and maintenance of multi-host vector borne pathogens. the 'pace of life' hypothesis proposes that the life history strategy of reservoir hosts can influence pathogen transmission of vector borne generalist pathogens. we use empirical data to parameterize a mathematical model that investigates the impacts of host life history traits on vector transmission dynamics of the vector-borne multi-host parasite trypanosoma cruzi i ...201728701240
taxonomic status of panstrongylus herreri wygodzinsky, 1948 and the number of chagas disease vectors. 201728700072
influence of environmental enrichment on the behavior and physiology of mice infected by trypanosoma cruzi.enriched environments normally increase behavioral repertoires and diminish the expression of abnormal behaviors and stress-related physiological problems in animals. although it has been shown that experimental animals infected with microorganisms can modify their behaviors and physiology, few studies have evaluated how environmental enrichment affects these parameters. this study aimed to evaluate the effects of environmental enrichment on the behavior and physiology of confined mice infected ...201728700052
pharmacotherapeutic follow-up of patients with chagas disease using benznidazole: drug-related problems and pharmaceutical interventions.benznidazole (bnz) is a drug available for the etiological treatment of chagas disease. however, this drug is toxic and has a limited effectiveness on the chronic phase of this disease, often leading to poor treatment adherence.201728700051
chagas disease: review of needs, neglect, and obstacles to treatment access in latin america.after more than one century since its discovery, chagas disease is still extremely prevalent in 21 latin american countries. chagas disease is one of the most concerning public health problems in latin america; the overall cost of cd treatment is approximately 7 billion united states dollars per year and it has a strong social impact on populations. little progress has been made regarding the access to diagnosis and treatment at the primary health care level, calling into question the current po ...201728700045
facing chagas disease. 201728700043
pacemaker implants in children and adolescents with chagas disease in brazil: 18-year incidence.chagas disease continues to be a serious public health problem, and accounts for 25-30% of the indications for cardiac stimulation in brazil.201728699977
avian antibodies (igy) against trypanosoma cruzi: purification and characterization studies.trypanosoma cruzi is a flagellated protozoan belonging to the trypanosomatidae family, the etiologic agent of chagas disease. currently, there is neither a licensed vaccine nor effective treatment, characterizing an unmet clinical need. the igy refers to the egg yolk immunoglobulin (y=yolk) and its production and use are subjects of many studies due to the diversity of its diagnostic and therapeutic applications. several researchers have shown that the use of specific igy may prevent and/or cont ...201728697990
the involvement of rhopr-crf/dh in feeding and reproduction in the blood-gorging insect rhodnius prolixus.rhodnius prolixus is a blood-gorging insect and a vector for human chagas disease. the insect transmits the disease following feeding, when it excretes urine and feces contaminated with the trypanosoma cruzi parasite. a corticotropin-releasing factor-like peptide acts as a diuretic hormone in r. prolixus (rhopr-crf/dh); however, its distribution throughout the insect's central nervous system (cns) and the expression of its receptor in feeding-related tissue as well as the female reproductive sys ...201728694056
betulinic acid induces cell death by necrosis in trypanosoma cruzi.chagas' disease is a neglected disease caused by the protozoan parasite trypanosoma cruzi and constitutes a serious health problem worldwide. the treatment is limited, with variable efficacy of benznidazole and nifurtimox. betulinic acid (ba), a triterpene, can be found in medicinal herbs and has a wide variety of biological and pharmacological activities. the objective was to evaluate betulinic acid effects on the cell death mechanism in trypanosoma cruzi strain y. ba inhibited the growth of ep ...201728690148
salivary gland transcripts of the kissing bug, panstrongylus chinai, a vector of chagas disease.the saliva of hematophagous arthropods injected during blood feeding contains potent pharmacologically active components to counteract the host hemostatic and inflammatory systems. in the present study, dominant salivary gland transcripts of panstrongylus chinai, a vector of chagas disease, were analyzed by sequencing randomly selected clones of the salivary gland cdna library. this analysis showed that 56.5% of the isolated transcripts coded for putative secreted proteins, of which 73.7% coded ...201728690145
extended screening of trypanosoma cruzi among the offspring of infected women. barcelona north metropolitan area, catalonia (spain), 2005-2016.to date, very little data is available on the extensive, familiar, serological screening of trypanosoma cruzi from infected-index cases. as it is a parasite with possibility of mother-to-child fetal transmission, the study of the offspring of chronically infected women has a special relevance.201728689672
in vitro and in vivo assessment of newer quinoxaline-oxadiazole hybrids as antimicrobial and antiprotozoal agents.a new series of n-(substituted-phenyl)-2-[5-(quinoxalin-2-yloxymethyl)-[1,3,4] oxadiazol-2-ylsulfanyl]-acetamides (5a-o) was designed and synthesised from the parent compound 2-hydroxy quinoxaline (1) through a multistep reaction sequence and was characterised by spectral and elemental analyses. all of the compounds synthesised were evaluated for their antimicrobial and antiprotozoal activities. the results revealed that quinoxaline-based 1,3,4-oxadiazoles displayed promising antibacterial, anti ...201728687457
complete mitochondrial genome of triatoma infestans (hemiptera, reduviidae, triatominae), main vector of chagas disease.the complete mitogenome of triatoma infestans, the main vector of chagas disease in south america, was obtained by combining illumina and sanger sequencing sequence data. the 17,301bp long genome contains 13 protein-coding genes, 22 transfer rnas, 2 ribosomal rnas, and a control region. the number, order and orientation of mitochondrial genes are the same as in t. dimidiata, the only triatominae mt genome published so far. the main differences between both mitogenomes are found in the control re ...201728684375
pharmacodynamics and follow-up period in the treatment of human trypanosoma cruzi infections with posaconazole. 201728683978
early clinics of the cardiac forms of chagas' disease: discovery and study of original medical files (1909-1915).we have uncovered 80 medical files corresponding to original cases of chagas' disease used for the classical description of the acute and cardiac forms of the disease. sixty of them were diagnosed cardiac forms of the disease. the detailed clinical description of these 60 files is in excellent agreement with the nosography of progressive heart disease given by chagas in his original 1922 paper. the reports we had access to, characterize a novel form of cardiac disease, dominated by progressive a ...201728676242
screening the medicines for malaria venture pathogen box across multiple pathogens reclassifies starting points for open-source drug discovery.open-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. the open-access pathogen box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. the supply of this resource by the medicines for malaria venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery ...201728674055
genetic adjuvantation of a cell-based therapeutic vaccine for amelioration of chagasic cardiomyopathy.chagas disease, caused by infection with the protozoan parasite trypanosoma cruzi, is a leading cause of heart disease ("chagasic cardiomyopathy") in latin america, disproportionately affecting people in resource-poor areas. the efficacy of currently approved pharmaceutical treatments is limited mainly to acute infection, and there are no effective treatments for the chronic phase of the disease. preclinical models of chagas disease have demonstrated that antigen-specific cd8(+) gamma interferon ...201728674032
chagas disease.chagas disease is an anthropozoonosis from the american continent that has spread from its original boundaries through migration. it is caused by the protozoan trypanosoma cruzi, which was identified in the first decade of the 20th century. once acute infection resolves, patients can develop chronic disease, which in up to 30-40% of cases is characterised by cardiomyopathy, arrhythmias, megaviscera, and, more rarely, polyneuropathy and stroke. even after more than a century, many challenges rema ...201728673423
targeting the active sites of malarial proteases for antimalarial drug discovery: approaches, progress and challenges.malaria is an infectious disease causing vast mortality and morbidity worldwide. although antimalarial drugs are effective in several parts of the world, there is a serious threat to malaria control as malaria parasites are continuously developing widespread resistance against currently available antimalarial drugs, including artemisinin. such widespread antimalarial drug resistance confirms the need to improve the efficacy of existing or new drugs as well as to develop alternative treatments th ...201728668681
death of adrenocortical cells during murine acute t. cruzi infection is not associated with tnf-r1 signaling but mostly with the type ii pathway of fas-mediated apoptosis.earlier studies from our laboratory demonstrated that acute experimental trypanosoma cruzi infection promotes an intense inflammation along with a sepsis-like dysregulated adrenal response characterized by normal levels of acth with raised glucocorticoid secretion. inflammation was also known to result in adrenal cell apoptosis, which in turn may influence hpa axis uncoupling. to explore factors and pathways which may be involved in the apoptosis of adrenal cells, together with its impact on the ...201728666938
development and assessment of a new cage-like particle adjuvant.to obtain and assess stable cage-like particles with low surface charge density, which can be prepared using a standardized, economic and scalable method.201728664569
identification of potential trypanothione reductase inhibitors among commercially available [formula: see text]-carboline derivatives using chemical space, lead-like and drug-like filters, pharmacophore models and molecular docking.american trypanosomiasis or chagas disease caused by the protozoan trypanosoma cruzi (t. cruzi) is an important endemic trypanosomiasis in central and south america. this disease was considered to be a priority in the global plan to combat neglected tropical diseases, 2008-2015, which indicates that there is an urgent need to develop more effective drugs. the development of new chemotherapeutic agents against chagas disease can be related to an important biochemical feature of t. cruzi: its redo ...201728656524
a brief view of the surface membrane proteins from trypanosoma cruzi.trypanosoma cruzi is the causal agent of chagas' disease which affects millions of people around the world mostly in central and south america. t. cruzi expresses a wide variety of proteins on its surface membrane which has an important role in the biology of these parasites. surface molecules of the parasites are the result of the environment to which the parasites are exposed during their life cycle. hence, t. cruzi displays several modifications when they move from one host to another. due to ...201728656101
catalase expression impairs oxidative stress-mediated signalling in trypanosoma cruzi.trypanosoma cruzi is exposed to oxidative stresses during its life cycle, and amongst the strategies employed by this parasite to deal with these situations sits a peculiar trypanothione-dependent antioxidant system. remarkably, t. cruzi's antioxidant repertoire does not include catalase. in an attempt to shed light on what are the reasons by which this parasite lacks this enzyme, a t. cruzi cell line stably expressing catalase showed an increased resistance to hydrogen peroxide (h2o2) when comp ...201728653592
synthesis and biological evaluation of 2-methyl-1h-benzimidazole-5-carbohydrazides derivatives as modifiers of redox homeostasis of trypanosoma cruzi.twelve novel benzimidazole derivatives were synthesized and their in vitro activities against epimastigotes of trypanosoma cruzi were evaluated. two derivatives (6 and 7), which have 4-hydroxy-3-methoxyphenyl moiety in their structures, proved to be the most active in inhibiting the parasite growth. compound 6 showed a trypanocidal activity higher than benznidazole (ic50=5µm and 7.5µm, respectively) and less than nifurtimox (ic50=3.6µm). in addition, the ability of 6 and 7 to modify the redox ho ...201728648464
increased of the hepatocytes and splenocytes apoptosis accompanies clinical improvement and higher survival in mice infected with trypanosoma cruzi and treated with highly diluted lycopodium clavatum.recent evidence includes apoptosis as a defense against trypanosoma cruzi infection, which promotes an immune response in the host induced by t cells, type 1, 2 and 17. currently, there is no medicine completely preventing the progression of this disease. we investigated the immunological and apoptotic effects, morbidity and survival of mice infected with t. cruzi and treated with dynamized homeopathic compounds 13c: kalium causticum (gcaus), conium maculatum, (gcon), lycopodium clavatum (gly) a ...201728645772
benznidazole treatment safety: the médecins sans frontières experience in a large cohort of bolivian patients with chagas' disease.up to half of patients with chagas' disease under benznidazole treatment present adverse drug reactions (adrs) and up to one-third do not complete standard treatment.201728645201
[on site-screening for chagas disease supported by a community intervention: can it improve accessibility for diagnosis and treatment?] 201728641864
[what do the numbers tell us about the temporal evolution of chagas' disease?]chagas disease remains highly prevalent in chile, especially between the regions of arica and parinacota, and coquimbo. since 1999 it is considered that in chile the vector transmission was interrupted. under this premise, the epidemiological dynamics should be changing. we analyzed the evolution of the prevalence of chagas' disease analyzing 64,995 xenodiagnosis performed in the laboratory of parasitology of the faculty of medicine of the university of chile between 1949 and 2014. the evolution ...201728632825
repositioning fda drugs as potential cruzain inhibitors from trypanosoma cruzi: virtual screening, in vitro and in vivo studies.chagas disease (cd) is a neglected disease caused by the parasite trypanosoma cruzi, which affects underdeveloped countries. the current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. a computer-guided drug repositioning method was applied to identify potential fda drugs (approved and withdrawn) as cruzain (cz) inhibitors and trypanocidal effects were confirm ...201728629155
effects of (1e,4e)-2-methyl-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one on trypanosoma cruzi and its combinational effect with benznidazole, ketoconazole, or fluconazole.this study reports the activity induced by (1e,4e)-2-methyl-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one (a3k2a3) against trypanosoma cruzi. this compound showed trypanocidal activity against the multiplicative epimastigote and amastigote forms of this protozoan, with ic50 values of 1.99 ± 0.17 and 1.20 ± 0.16 μm, respectively, and ec50 value of 15.57 ± 0.34 μm against trypomastigotes. the combination of a3k2a3 with benznidazole or ketoconazole demonstrated strong synergism, increasing effectivene ...201728620619
canine macrophage dh82 cell line as a model to study susceptibility to trypanosoma cruzi infection.trypanosoma cruzi is an obligatory intracellular protozoan parasite, and it is the etiological agent of chagas' disease that is endemic in the americas. in addition to humans, a wide spectrum of mammals can be infected by t. cruzi, including dogs. dogs develop acute and chronic disease, similar to human infection. t. cruzi can infect almost all cell types and after cell invasion, the metacyclics trypomastigotes localize in the cytoplasm, where they transform into amastigotes, the replicative for ...201728620374
the non-canonical substrates of trypanosoma cruzi tyrosine and aspartate aminotransferases: branched-chain amino acids.trypanosoma cruzi, the etiological agent of chagas disease, lacks genes that encode canonical branched-chain aminotransferases. however, early studies showed that when epimastigotes were grown in the presence of (14) c1 -dl-leucine, the label was incorporated into various intermediates. more recently, our studies provided evidence that t. cruzi epimastigotes display a single atp-dependent and saturable transport system that enables epimastigotes to uptake branched-chain amino acids (bcaas) from ...201728618210
[estimating demand for anti-chagas drugs: a contribution for access in latin america].describe a tool to estimate demand for benznidazole and nifurtimox to treat chagas disease, and report on its implementation in a group of latin american countries.201728614468
functional characterization of aquaporin-like genes in the human bed bug cimex lectularius.the bed bug cimex lectularius is a blood-feeding re-emerging annoyance pest insect that has the ability to transmit trypanosoma cruzi under experimental laboratory conditions. aquaporins (aqps) are water channel proteins that are essential in biological organisms. c. lectularius are constantly exposed to water-related stress, suggesting that aqps may offer novel control avenues. we identified and cloned four aqps from c. lectularius, assessed tissue and lifestage-specific expression, and charact ...201728607409
inhibition of host cell lysosome spreading by trypanosoma cruzi metacyclic stage-specific surface molecule gp90 downregulates parasite invasion.successful infection by trypanosoma cruzi, the agent of chagas' disease, is critically dependent on host cell invasion by metacyclic trypomastigote (mt) forms. two main metacyclic stage-specific surface molecules, gp82 and gp90, play determinant roles in target cell invasion in vitro and in oral t. cruzi infection in mice. the structure and properties of gp82, which is highly conserved among t. cruzi strains, are well known. information on gp90 is still rather sparse. here, we attempted to fill ...201728607099
proteomic analysis of the kissing bug rhodnius prolixus antenna.reception of odorants is essential in insects' life since the chemical signals in the environment (=semiochemicals) convey information about availability of hosts for a blood meal, mates for reproduction, sites for oviposition and other relevant information for fitness in the environment. once they reach the antennae, these semiochemicals bind to odorant-binding proteins and are transported through the sensillar lymph until reach the odorant receptors. such perireceptor events, particularly the ...201728606853
the mechanisms of ventricular arrhythmia in chagas disease. 201728606682
triatokey: a web and mobile tool for biodiversity identification of brazilian triatomine species.triatomines are blood-sucking insects that transmit the causative agent of chagas disease, trypanosoma cruzi. despite being recognized as a difficult task, the correct taxonomic identification of triatomine species is crucial for vector control in latin america, where the disease is endemic. in this context, we have developed a web and mobile tool based on postgresql database to help healthcare technicians to overcome the difficulties to identify triatomine vectors when the technical expertise i ...201728605769
seasonality and temperature-dependent flight dispersal of triatoma infestans (hemiptera: reduviidae) and other vectors of chagas disease in western argentina.flight dispersal of triatominae is affected by climatic conditions and determines the spatiotemporal patterns of house invasion and transmission of trypanosoma cruzi chagas (kinetoplastida: trypanosomatidae). we investigated the detailed time structure and temperature dependencies of flight occurrence of triatoma infestans klug (hemiptera: reduviidae) and other triatomine species in a rural village of western argentina by taking advantage of the attraction of adult triatomines to artificial ligh ...201728605522
jaburetox-induced toxic effects on the hemocytes of rhodnius prolixus (hemiptera: reduviidae).jaburetox is a recombinant peptide derived from a canavalia ensiformis urease that presents toxic effects upon several species of insects, phytopathogenic fungi and yeasts of medical importance. so far, no toxicity of jaburetox to mammals has been shown. previous reports have identified biochemical targets of this toxic peptide in insect models, although its mechanism of action is not completely understood. in this work, we aimed to characterize the effects of jaburetox in hemolymphatic insect c ...201728602911
qpcr for the detection of foodborne trypanosoma cruzi.here we presented a potential real-time pcr (qpcr) method with public health importance and relevance for detection of trypanosoma cruzi in açai pulp. there is not a current process to identify t. cruzi in açai, that ensures innocuity of this food concerning oral transmission. first, six new primers were designed using the dna sequences of t. cruzi y152 and emerald strains obtained from genbank. for primers evaluation and titration they were validated regarding the amplification and not with the ...201728602861
an elisa immunoassay employing a conserved leishmania hypothetical protein for the serodiagnosis of visceral and tegumentary leishmaniasis in dogs and humans.in the present study, a conserved leishmania hypothetical protein, namely lihypa, was evaluated for the serodiagnosis of visceral and tegumentary leishmaniasis in dogs and humans. this protein showed a high amino acid sequence homology between viscerotropic and cutaneotropic leishmania species. an enzyme-linked immunosorbent assay (elisa) was developed using the recombinant antigen (rlihypa), in addition to the a2 protein and two parasite antigenic preparations, which were used as controls. rega ...201728602279
omega-3 supplementation on inflammatory markers in patients with chronic chagas cardiomyopathy: a randomized clinical study.several studies have been focusing on the effect of omega-3 polyunsaturated fatty acids on modulation of inflammatory markers in several cardiopathies. although immunoregulatory dysfunction has been associated to the chronic cardiac involvement in chagas disease, there is no study examining the effects of omega-3 supplementation in these patients. we investigated the effects of omega-3 pufas on markers of inflammation and lipid profile in chronic chagas cardiomyopathy patients.201728599665
trans-sialidase overcomes many antigens to be used as a vaccine candidate against trypanosoma cruzi.the development of vaccines against trypanosoma cruzi remains in an exploratory stage. despite several antigen candidates have been evaluated, a comparison among the performance of the immunogens cannot be carried out because the available reports differ in formulations and infection model. in this work, we compared the protective capacity of seven t. cruzi antigens in the same model of five new antigens and two well-established candidates. materials & methods: we evaluated highly immunogenic pr ...201728595515
insights from tissue-specific transcriptome sequencing analysis of triatoma infestans.triatoma infestans is an insect of subfamily triatominae (hemiptera: reduviidae) and an important vector of trypanosoma cruzi, the etiologic agent of human chagas disease. in this work we reported a transcriptome assembly and annotation of t. infestans heads obtained by next generation sequencing (ngs) technologies.201728591407
sexual transmission of american trypanosomiasis in humans: a new potential pandemic route for chagas parasites.the trypanosoma cruzi infection endemic in latin america has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. we hypothesised that the sexual transmission of t. cruzi contributes to the ongoing spread of chagas disease.201728591404
[strategy to improve access to etiological treatment of chagas disease at the first level of care in argentina].improve distribution of etiological treatment of chagas disease by identifying barriers to the decentralization of treatment to the first level of care in argentina.201728591327
prediction models for decision-making on chagas disease. 201728591323
entomological survey in the state of piauí, northeastern brazil, reveals intradomiciliary colonization of triatoma brasiliensis macromelasoma.this survey aimed to assess the presence of triatomine vectors of chagas disease within the rural communities of são joão do piauí, northeast brazil. intradomiciliary and peridomiciliary collection strategies were implemented wherein 279 specimens of triatoma brasiliensis macromelasoma, both nymph and adult were found in 15 (50%) of the studied homes. of the intradomiciliary insects, 73 (67.6%) were identified as nymph instars (1st instar [n1]= 6, n2= 14, n3= 28, n4= 7 and n5= 18). in the studie ...201728591255
repurposing of human kinase inhibitors in neglected protozoan diseases.human african trypanosomiasis (hat), chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. drugs in current use have several limitations, and therefore new candidate drugs are required. the majority of current therapeutic trypanosomatid targets are enzymes or cell-surface receptors. among these, eukaryotic protein kinases are a major group of protein targets whos ...201728590590
heme a synthesis and cco activity are essential for trypanosoma cruzi infectivity and replication.trypanosoma cruzi, the causative agent of chagas disease, presents a complex life cycle and adapts its metabolism to nutrients' availability. although t. cruzi is an aerobic organism, it does not produce heme. this cofactor is acquired from the host and is distributed and inserted into different heme-proteins such as respiratory complexes in the parasite's mitochondrion. it has been proposed that t. cruzi's energy metabolism relies on a branched respiratory chain with a cytochrome c oxidase-type ...201728588043
pheophorbide a, a compound isolated from the leaves of arrabidaea chica, induces photodynamic inactivation of trypanosoma cruzi.approximately 6-7 million people are infected with trypanosoma cruzi, the etiological agent of chagas' disease. only two therapeutic compounds have been found to be useful against this disease: nifurtimox and benznidazole. these drugs have been effective in the acute phase of the disease but less effective in the chronic phase; they also have many side effects. thus, the search for new compounds with trypanocidal action is necessary. natural products can be the source of many important substance ...201728587855
lamp-2 absence interferes with plasma membrane repair and decreases t. cruzi host cell invasion.trypanosoma cruzi enters host cells by subverting the mechanism of cell membrane repair. in this process, the parasite induces small injuries in the host cell membrane leading to calcium entry and lysosomal exocytosis, which are followed by compensatory endocytosis events that drive parasites into host cells. we have previously shown that absence of both lamp-1 and 2, major components of lysosomal membranes, decreases invasion of t. cruzi into host cells, but the mechanism by which they interfer ...201728586379
molecular diagnostics for chagas disease: up to date and novel methodologies.chagas disease is caused by the parasite trypanosoma cruzi. it affects 7 million people, mainly in latin america. diagnosis is usually made serologically, but at some clinical scenarios serology cannot be used. then, molecular detection is required for early detection of congenital transmission, treatment response follow up, and diagnosis of immune-suppression reactivation. however, present tests are technically demanding and require well-equipped laboratories which make them unfeasible in low-r ...201728582629
mutations to cysteine residues in the trypanosoma cruzi b-cell superantigen tc24 diminish susceptibility to igm-mediated hydrolysis.b-cell superantigens (bc-sags) are immunoevasins that have evolved in response to innate catalytic igm antibodies; germ-line encoded immunoglobulins present in the preimmune repertoire independent of prior antigen exposure. catalysis is the result of a 2-step process that involves the formation of a non-covalent bond between the bc-sag and the immunoglobulin first followed by covalent bond formation at the catalytic site resulting in target hydrolysis. tc24 is a recently described trypanosoma cr ...201728581897
whole genome cardiac dna methylation fingerprint and gene expression analysis provide new insights in the pathogenesis of chronic chagas disease cardiomyopathy.chagas disease, caused by the protozoan trypanosoma cruzi, is endemic in latin america and affects 10 million people worldwide. approximately 12,000 deaths attributable to chagas disease occur annually due to chagas disease cardiomyopathy (ccc), an inflammatory cardiomyopathy presenting with heart failure and arrythmia; 30% of infected subjects develop ccc years after infection. genetic mechanisms play a role in differential progression to ccc, but little is known about the role of epigenetic mo ...201728575239
ergosterol isolated from the basidiomycete pleurotus salmoneostramineus affects trypanosoma cruzi plasma membrane and mitochondria.major drawbacks of the available treatment against chagas disease (american trypanosomiasis) include its toxicity and therapeutic inefficiency in the chronic phase of the infection, which makes it a concern among neglected diseases. therefore, the discovery of alternative drugs for treating chronic chagas disease requires immediate action. in this work, we evaluated the mushroom pleurotus salmoneostramineus in the search for potential antiparasitic compounds.201728572816
moderate treadmill exercise training improves cardiovascular and nitrergic response and resistance to trypanosoma cruzi infection in mice.there is evidence suggesting that exercise training (et) acts as a factor toward resistance to trypanosoma cruzi infection. however, the effects of mean arterial pressure (map), heart rate (hr), and nitric oxide (no) during the acute phase of infection has not been elucidated yet. swiss mice were randomly assigned into four groups: sedentary control (sc, n = 30), trained control (tc, n = 30), sedentary infected (si, n = 30), and trained infected (ti, n = 30). et was performed on the treadmill fo ...201728572772
chagas disease knowledge and risk behaviors of the homeless population in houston, tx.chagas disease is a parasitic infection, caused by trypanosoma cruzi, endemic in latin america. sylvatic t. cruzi-infected triatomine vectors are present in rural and urban areas in the southern usa and may transmit t. cruzi infection to at-risk populations, such as homeless individuals. our study aimed to evaluate chagas disease knowledge and behaviors potentially associated with transmission risk of chagas disease among houston, texas' homeless population by performing interviews with 212 home ...201728567616
evaluating respiratory musculature, quality of life, anxiety, and depression among patients with indeterminate chronic chagas disease and symptoms of pulmonary hypertension.chagas disease (cd) is progressive and incapacitating, especially when cardiopulmonary function is affected. for example, respiratory muscle weakness can cause dyspnea upon exertion and fatigue, which may be exacerbated when it is associated with pulmonary hypertension (ph). the present study aimed to evaluate respiratory musculature, quality of life, anxiety, and depression among patients with indeterminate chronic cd and symptoms of ph.201728562755
evaluation of antioxidant therapy in experimental chagas disease.stimulation of inflammatory mediators such as cytokines and chemokines may cause oxidative stress in chagas disease. in this study, we evaluated the merit of vitamins c and e as antioxidant therapy to minimize the oxidative stress-induced damage in an experimental model of chagas disease.201728562754
effects of astaxanthin in mice acutely infected with trypanosoma cruzi.during trypanosoma cruzi infection, oxidative stress is considered a contributing factor for dilated cardiomyopathy development. in this study, the effects of astaxanthin (astx) were evaluated as an alternative drug treatment for chagas disease in a mouse model during the acute infection phase, given its anti-inflammatory, immunomodulating, and anti-oxidative properties. astx was tested in vitro in parasites grown axenically and in co-culture with vero cells. in vivo tests were performed in balb ...201728560955
the anti-protozoan drug nifurtimox preferentially inhibits clonogenic tumor cells under hypoxic conditions.tumor hypoxia is an independent prognostic indicator of tumor malignant progression and poor patient survival. therefore, eradication of hypoxic tumor cells is of paramount importance for successful disease control. in this study, we have made a new discovery that nifurtimox, a clinically approved drug to treat chagas disease caused by the parasitic protozoan trypanosomes, can function as a hypoxia-activated cytotoxin. we have found that nifurtimox preferentially kill clonogenic tumor cells espe ...201728560059
corrigendum: the contemporary distribution of trypanosoma cruzi infection in humans, alternative hosts and vectors.this corrects the article doi: 10.1038/sdata.2017.50.201728556826
evaluation of the immunohistochemical expression of gal-1, gal-3 and gal-9 in the colon of chronic chagasic patients.the aim of the present study was to evaluate the immunohistochemical expression of gal-1, gal-3 and gal-9 in the colon of chronic chagasic patients compared to biopsied non-chagasic patients.201728554765
ravuconazole self-emulsifying delivery system: in vitro activity against trypanosoma cruzi amastigotes and in vivo toxicity.self-emulsifying drug delivery systems (seddss) are lipid-based anhydrous formulations composed of an isotropic mixture of oil, surfactant, and cosurfactants usually presented in gelatin capsules. ravuconazole (biopharmaceutics classification system [bcs] class ii) is a poorly water-soluble drug, and a sedds type iiia was designed to deliver it in a predissolved state, improving dissolution in gastrointestinal fluids. after emulsification, the droplets had mean hydrodynamic diameters <250 nm, ze ...201728553114
pioneer study of population genetics of rhodnius ecuadoriensis (hemiptera: reduviidae) from the central coastand southern andean regions of ecuador.effective control of chagas disease vector populations requires a good understanding of the epidemiological components, including a reliable analysis of the genetic structure of vector populations. rhodnius ecuadoriensis is the most widespread vector of chagas disease in ecuador, occupying domestic, peridomestic and sylvatic habitats. it is widely distributed in the central coast and southern highlands regions of ecuador, two very different regions in terms of bio-geographical characteristics. t ...201728546079
mortality among blood donors seropositive and seronegative for chagas disease (1996-2000) in são paulo, brazil: a death certificate linkage study.individuals in the indeterminate phase of chagas disease are considered to have mortality rates similar to those of the overall population. this study compares mortality rates among blood donors seropositive for chagas disease and negative controls in the city of são paulo, brazil.201728545053
synergic and antagonistic relationship between mmp-2 and mmp-9 with fibrosis and inflammation in chagas' cardiomyopathy.cardiomyopathy is the most important clinical manifestation in the chronic phase of chagas' disease because of its frequency, severity and impact on morbidity and mortality. the extracellular matrix degradation during cardiac remodeling in trypanosoma cruzi infection is driven by matrix metalloproteinases (mmps), primarily the mmp-2 and mmp-9 gelatinases. mmps also regulate some molecules related to inflammation, such as growth factors, cytokines and chemokines. the involvement of mmp-2 and mmp- ...201728543409
specific activation of cd4(-) cd8(-) double-negative t cells by trypanosoma cruzi-derived glycolipids induces a proinflammatory profile associated with cardiomyopathy in chagas patients.cardiomyopathy is the most severe outcome of chagas disease, causing more than 12 000 deaths/year. immune cells participate in cardiomyopathy development either by direct tissue destruction, or by driving inflammation. we have shown that cd4(-) cd8(-) [double-negative (dn)] t cells are major sources of inflammatory and anti-inflammatory cytokines, associated with the cardiac (card) and indeterminate (ind) forms of chagas disease, respectively. here, we sought to identify trypanosoma cruzi-derive ...201728543170
implication of apoptosis for the pathogenesis of trypanosoma cruzi infection.apoptosis is induced during the course of immune response to different infectious agents, and the ultimate fate is the recognition and uptake of apoptotic bodies by neighboring cells or by professional phagocytes. apoptotic cells expose specific ligands to a set of conserved receptors expressed on macrophage cellular surface, which are the main cells involved in the clearance of the dying cells. these scavenger receptors, besides triggering the production of anti-inflammatory factors, also block ...201728536576
toxicity, repellency and flushing out in triatoma infestans (hemiptera: reduviidae) exposed to the repellents deet and ir3535.deet and ir3535 are insect repellents present worldwide in commercial products; their efficacy has been mainly evaluated in mosquitoes. this study compares the toxicological effects and the behavioral responses induced by both repellents on the blood-sucking bug triatoma infestans klug (hemiptera: reduviidae), one of the main vectors of chagas disease. when applied topically, the median lethal dose (72 h) for deet was 220.8 µg/insect. using ir3535, topical application of 500 µg/insect killed no ...201728533956
molecular and serological detection of trypanosoma cruzi in dogs (canis lupus familiaris) suggests potential transmission risk in areas of recent acute chagas disease outbreaks in colombia.chagas disease is a zoonotic infection widely distributed in tropical and subtropical regions of america, including more than 50% of the colombian territory. in the last years, an increase of outbreaks of acute chagas disease has been observed in the east of the country due to environmental changes and mammal movements toward human settlements. given the importance of dogs (canis lupus familiaris) as reservoir hosts and sentinels of trypanosoma cruzi infection across different regions of america ...201728532988
insecticide-treated durable wall lining (itwl): future prospects for control of malaria and other vector-borne diseases.while long-lasting insecticidal nets (llins) and indoor residual spraying (irs) are the cornerstones of malaria vector control throughout sub-saharan africa, there is an urgent need for the development of novel insecticide delivery mechanisms to sustain and consolidate gains in disease reduction and to transition towards malaria elimination and eradication. insecticide-treated durable wall lining (itwl) may represent a new paradigm for malaria control as a potential complementary or alternate lo ...201728532494
poly-epsilon-caprolactone nanoparticles enhance ursolic acid in vivo efficacy against trypanosoma cruzi infection.despite affecting millions of people worldwide, chagas disease is still neglected by the academia and industry and the therapeutic option available, benznidazole, presents limited efficacy and side effects. within this context, ursolic acid may serve as an option for treatment, however has low bioavailability, which can be enhanced through the encapsulation in polymeric nanoparticles. therefore, herein we developed ursolic acid-loaded nanoparticles with poly-ε-caprolactone by the nanoprecipitati ...201728531996
temporal variation in the abundance and timing of daily activity of chagas disease vector triatoma gerstaeckeri (stål, 1859) in a natural habitat in the lower rio grande valley, south texas.chagas disease caused by trypanosoma cruzi is a burden to millions of people in south and central america. a sylvatic life cycle of the parasite exists in the southern united states, but recent studies indicate an active peri-domestic life cycle of t. cruzi in texas. the usa-mexico border region in texas displays areas of high poverty and sub-standard housing conditions which are important risk factors for a potential spill-over transmission to a domestic life cycle including humans. the objecti ...201728530845
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