Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
improving access to chagas disease diagnosis and etiologic treatment in remote rural communities of the argentine chaco through strengthened primary health care and broad social participation.rural populations in the gran chaco region have large prevalence rates of trypanosoma cruzi infection and very limited access to diagnosis and treatment. we implemented an innovative strategy to bridge these gaps in 13 rural villages of pampa del indio held under sustained vector surveillance and control.201728192425
phylogenomics of trypanosoma cruzi: few evidence of tci/tcii mosaicism in tciii challenges the hypothesis of an ancient tci/tcii hybridization.phylogenetic relationships among major lineages of trypanosoma cruzi are still debatable. particularly, it is controversial the origin of two main lineages: tciii and tciv. some authors proposed that these lineages have been the result of an ancient hybridization between tci and tcii, and this was one of the most accepted evolutionary models in the scientific community for several years. in the present paper we analyse several genomes of t. cruzi in order to examine if there is evidence supporti ...201728192210
synthesis and trypanocidal activity of a library of 4-substituted 2-(1h-pyrrolo[3,2-c]pyridin-2-yl)propan-2-ols.a library of 16 4-substituted 2-(1h-pyrrolo[3,2-c]pyridin-2-yl)propan-2-ols 17-32 has been synthesized for use in biological testing against trypanosoma cruzi, the protozoan parasite that causes chagas disease. the 4-substituted 2-(1h-pyrrolo[3,2-c]pyridin-2-yl)propan-2-ols 17-32 were subjected to biological testing to evaluate their efficacy against intracellular trypanosoma cruzi (y strain) amastigotes infecting u2os human cells, with benznidazole as a reference compound. the assay was perform ...201728189084
real-time pcr strategy for the identification of trypanosoma cruzi discrete typing units directly in chronically infected human blood.the protozoan trypanosoma cruzi is the causative agent of chagas disease, a major public health problem in latin america. this parasite has a complex population structure comprised by six or seven major evolutionary lineages (discrete typing units or dtus) tci-tcvi and tcbat, some of which have apparently resulted from ancient hybridization events. because of the existence of significant biological differences between these lineages, strain characterization methods have been essential to study t ...201728185987
chaetocin-a histone methyltransferase inhibitor-impairs proliferation, arrests cell cycle and induces nucleolar disassembly in trypanosoma cruzi.the trypanosomatidae family includes pathogenic species of medical and veterinary interest. chagas disease is endemic in latin america, and about 8 million people are infected worldwide. there is a need for more effective drugs for the acute, undetermined and chronic phases of the disease that, in addition, do not cause side effects, stimulating the search for identification of new drug targets, as well as new chemotherapeutic targets. trypanosomatids contain characteristic structures, such as t ...201728185826
a homolog of cyclophilin d is expressed in trypanosoma cruzi and is involved in the oxidative stress-damage response.mitochondria have an important role in energy production, homeostasis and cell death. the opening of the mitochondrial permeability transition pore (mptp) is considered one of the key events in apoptosis and necrosis, modulated by cyclophilin d (cypd), a crucial component of this protein complex. in trypanosoma cruzi, the protozoan parasite that causes chagas disease, we have previously described that mitochondrial permeability transition occurs after oxidative stress induction in a cyclosporin ...201728179991
kinetics, subcellular localization, and contribution to parasite virulence of a trypanosoma cruzi hybrid type a heme peroxidase (tcapx-ccp).the trypanosoma cruzi ascorbate peroxidase is, by sequence analysis, a hybrid type a member of class i heme peroxidases [tcapx-cytochrome c peroxidase (ccp)], suggesting both ascorbate (asc) and cytochrome c (cc) peroxidase activity. here, we show that the enzyme reacts fast with h2o2 (k = 2.9 × 10(7) m(-1)⋅s(-1)) and catalytically decomposes h2o2 using cc as the reducing substrate with higher efficiency than asc (kcat/km = 2.1 × 10(5) versus 3.5 × 10(4) m(-1)⋅s(-1), respectively). visible-absor ...201728179568
hosts and vectors of trypanosoma cruzi discrete typing units in the chagas disease endemic region of the paraguayan chaco.active trypanosoma cruzi transmission persists in the gran chaco region, which is considered hyperendemic for chagas disease. understanding domestic and sylvatic transmission cycles and therefore the relationship between vectors and mammalian hosts is crucial to designing and implementing improved effective control strategies. here we describe the species of triatomine vectors and the sylvatic mammal reservoirs of t. cruzi, in different localities of the paraguayan and bolivian chaco. we identif ...201728179034
trypanosoma cruzi high mobility group b (tchmgb) can act as an inflammatory mediator on mammalian cells.high mobility group b (hmgb) proteins are nuclear architectural factors involved in chromatin remodeling and important nuclear events. hmgbs also play key roles outside the cell acting as alarmins or damage-associated molecular patterns (damps). in response to a danger signal these proteins act as immune mediators in the extracellular milieu. moreover, these molecules play a central role in the pathogenesis of many autoimmune and both infectious and sterile inflammatory chronic diseases.201728178282
linalool, a piper aduncum essential oil component, has selective activity against trypanosoma cruzi trypomastigote forms at 4°c.recent studies showed that essential oils from different pepper species (piper spp.) have promising leishmanicidal and trypanocidal activities.201728177047
trypanosoma cruzi (agent of chagas disease) in sympatric human and dog populations in "colonias" of the lower rio grande valley of texas.the zoonotic, vector-borne parasite trypanosoma cruzi causes chagas disease throughout the americas, but human and veterinary health burdens in the united states are unknown. we conducted a cross-sectional prevalence study in indigent, medically underserved human and cohabiting canine populations of seven south texas border communities, known as colonias. defining positivity as those samples that were positive on two or more independent tests, we found 1.3% seroprevalence in 233 humans, includin ...201728167589
antitrypanosomal activity of sterol 14α-demethylase (cyp51) inhibitors vni and vfv in the swiss mouse models of chagas disease induced by the trypanosoma cruzi y strain.chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite trypanosoma cruzi the current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (cyp51), the cytochrome p450 enzyme essential for the biosynthesis of sterols in eukaryotes and the major target of clinical and agricultural antifungals. here we performed a comparative investigation of two protozo ...201728167559
pharmacokinetics and tissue distribution of benznidazole after oral administration in mice.specific chemotherapy using benznidazole (bnz) for chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. although bnz has been used to treat chagas disease since the 1970s, few studies about the biodistribution of this drug exist. in this study, bnz tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. a bioanalytical high-performance liquid chromatography method with a uv detector (hplc-uv) was develo ...201728167558
pharmacokinetics of benznidazole in healthy volunteers and implications in future clinical trials.despite its toxicity and low efficacy in the chronic phase, benznidazole is the drug of choice in chagas disease. scarce information about pharmacokinetics and pharmacodynamics of benznidazole has been published. we performed a phase i, open-label, nonrandomized pharmacokinetic study of benznidazole (abarax) conducted with 8 healthy adult volunteers at the infectious diseases department of the vall d'hebron university hospital (barcelona, spain). the separation and detection of benznidazole were ...201728167552
purinergic enzymatic activities in lymphocytes and cardiomyocytes of mice acutely infected by trypanosoma cruzi modulating the inflammatory responses.the aim of this study was to evaluate the activity of purinergic enzymes in lymphocytes and cardiac tissue of mice experimentally infected by trypanosoma cruzi. twelve female mice were used, divided into two groups (n = 6): uninfected and infected. on day 12 post-infection (pi), the animals were anesthetized and after euthanized, and samples were collected for analyses. infected mice showed reduction in erythrocyte counts, hematocrit and hemoglobin concentration, as well as reduced number of tot ...201728167210
carbonic anhydrases from trypanosoma and leishmania as anti-protozoan drug targets.trypanosoma cruzi and leishmania spp. are protozoa of the trypanosomatidae family, being the etiological agents of two widespread parasitic diseases, chagas disease and leishmaniasis, respectively. both parasites are the focus of worldwide research with the aim to find effective and less toxic drugs than the few ones available so far, and for controlling the spread of the diseases. carbonic anhydrases (cas, ec 4.2.1.1) belonging to the α- and β-class were recently identified in these protozoans ...201728161253
antitrypanosomal activity and evaluation of the mechanism of action of dehydrodieugenol isolated from nectandra leucantha (lauraceae) and its methylated derivative against trypanosoma cruzi.from a previous screening of brazilian biodiversity for antiprotozoal activity, the hexane extract from leaves of nectandra leucantha (nees & mart.) (lauraceae) demonstrated activity against trypanosoma cruzi. chromatographic separation of this extract afforded bioactive dehydrodieugenol (1). furthermore, methylated derivative 2 (dehydrodieugenol dimethyl ether) was prepared and also tested against t. cruzi.201728160863
trypanocidal activity of quinoxaline 1,4 di-n-oxide derivatives as trypanothione reductase inhibitors.chagas disease or american trypanosomiasis is a worldwide public health problem. in this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-n-oxide derivatives as potential trypanocidal agents. additionally, molecular docking and enzymatic assays on trypanothione reductase (tr) were performed to provide a basis for their potential mechanism of action. seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displaye ...201728157150
organometallic gold(iii) complexes with hybrid sns-donating thiosemicarbazone ligands: cytotoxicity and anti-trypanosoma cruzi activity.stable organogold(iii) compounds of the composition [au(iii)(hdamp)(l1)]cl are formed from reactions of [aucl2(damp)] with h2l1 (damp(-) = dimethylaminomethylphenyl; h2l1 = n'-(diethylcarbamothioyl)benzimidothiosemicarbazides). the cationic complexes can be neutralized by reactions with weak bases under the formation of [au(iii)(damp)(l1)] compounds. the structures of the products show interesting features like relatively short auh contacts between the methylene protons of the hdamp ligand and t ...201728154849
commentary: systems biology approach to model the life cycle of trypanosoma cruzi. 201728149830
spatial and temporal distribution of house infestation by triatoma infestans in the toro toro municipality, potosi, bolivia.triatoma infestans is the main vector of trypanosoma cruzi in bolivia. the species is present both in domestic and peridomestic structures of rural areas, and in wild ecotopes of the andean valleys and the great chaco. the identification of areas persistently showing low and high house infestation by the vector is important for the management of vector control programs. this study aimed at analyzing the temporal and spatial distribution of house infestation by t. infestans in the toro toro munic ...201728148283
altered bone marrow lymphopoiesis and interleukin-6-dependent inhibition of thymocyte differentiation contribute to thymic atrophy during trypanosoma cruzi infection.thymic atrophy occurs during infection being associated with apoptosis of double positive (dp) and premature exit of dp and double negative (dn) thymocytes. we observed for the first time that a significant bone marrow aplasia and a decrease in common lymphoid progenitors (clps) preceded thymic alterations in mice infected with trypanosoma cruzi. in addition, depletion of the dn2 stage was previous to the dn1, indicating an alteration in the differentiation from dn1 to dn2 thymocytes. interestin ...201728147332
chagas disease transmission by consumption of game meat: systematic review.to evaluate the influence of game meat consumption in chagas disease (cd) transmission, the conditions under which it occurs and the frequency of reports in the literature.201728146169
recent developments in trans-sialidase inhibitors of trypanosoma cruzi.chagas is a lethal chronic disease that currently affects 8 to 10 million people worldwide, primarily in south and central america. trypanosoma cruzi trans-sialidase is an enzyme that is of vital importance for the survival of the parasite due to its key role in the transfer of sialic acid from the host to the parasite surface and it also helps the parasite combat the host´s immune system. this enzyme has no equivalent human enzyme, thus it has become an interesting target for the development of ...201728140698
effective gene delivery to trypanosoma cruzi epimastigotes through nucleofection.new opportunities have raised to study the gene function approaches of trypanosoma cruzi after its genome sequencing in 2005. functional genomic approaches in trypanosoma cruzi are challenging due to the reduced tools available for genetic manipulation, as well as to the reduced efficiency of the transient transfection conducted through conventional methods. the amaxa nucleofector device was systematically tested in the present study in order to improve the electroporation conditions in the epim ...201728137669
effect of ionizing radiation exposure on trypanosoma cruzi ubiquitin-proteasome system.in recent years, proteasome involvement in the damage response induced by ionizing radiation (ir) became evident. however, whether proteasome plays a direct or indirect role in ir-induced damage response still unclear. trypanosoma cruzi is a human parasite capable of remarkable high tolerance to ir, suggesting a highly efficient damage response system. here, we investigate the role of t. cruzi proteasome in the damage response induced by ir. we exposed epimastigotes to high doses of gamma ray an ...201728137628
the type of trypanosoma cruzi strain (native or non-native) used as substrate for immunoassays influences the ability of screening asymptomatic blood donors.the origin (native or non-native) of trypanosoma cruzi strains used as substrate for immunoassays may influence their performance.201728134939
nonsteroidal anti-inflammatory is more effective than anti-oxidant therapy in counteracting oxidative/nitrosative stress and heart disease in t. cruzi-infected mice.we compared the relevance of ibuprofen, vitamins c and e to control oxidative/nitrosative stress and heart disease in mice infected by trypanosoma cruzi. swiss mice were randomized into five groups: control, uninfected; infected without treatment; and infected treated with vitamins c, e or ibuprofen. animals were inoculated with 2000 trypomastigote forms of t. cruzi. after 20 days, infected mice presented reduced vitamin c and e tissue levels, high cytokines (interferon gamma, tumour necrosis fa ...201728134069
long-term comparative pharmacovigilance of orally transmitted chagas disease: first report.two old drugs are the only choice against trypanosoma cruzi and little is known about their secondary effects in the acute stage of oral-transmitted chagas disease (chd).201728132566
inhibition of nfe2l2-are pathway by mitochondrial ros contributes to development of cardiomyopathy and left ventricular dysfunction in chagas disease.we investigated the effects of mitochondrial reactive oxygen species (mtros) on nfe2l2 transcription factor activity during trypanosoma cruzi (tc) infection, and determined if enhancing the mtros scavenging capacity preserved the heart function in chagas disease.201728132522
ageing is not associated with an altered immune response during trypanosoma cruzi infection: ageing and trypanosoma cruzi infection.the aims of this work were to evaluate the influence of ageing on the magnitude of the immune response in male wistar rats infected with the y strain of trypanosoma cruzi (t. cruzi). infected young animals displayed enhanced cd4(+) t cells as compared to uninfected counterparts. ageing also triggered a significant reduction in cd8(+) t cells compared to young and uninfected groups. the percentage of spleen nkt cells was reduced for all groups, regardless of the infection status. significant decr ...201728131881
biological activity of the azlactone derivative epa-35 against trypanosoma cruzi.chagas disease, caused by trypanosoma cruzi, affects six to seven million people worldwide. treatment is based on benznidazole, producing several side effects and debatable efficacy, highlighting the need for new alternative drugs. we investigated the activity of four c-4 functionalized azlactone derivatives (epa-27, epa-35, epa-63 and epa-91) as potential t. cruzi inhibitors. screening with epimastigotes indicated epa-35 as the best compound (ic50/24 h: 33 μm). this compound was 14.1 times more ...201728130370
response surface methodology in drug design: a case study on docking analysis of a potent antifungal fluconazole.molecular docking is a valuable in silico technique for discovery/design of bioactive compounds. a current challenge within docking simulations is the incorporation of receptor flexibility. a useful strategy toward solving such problem would be the docking of a typical ligand into the multiple conformations of the target. in this study, a multifactor response surface model was constructed to estimate the autodock based binding free energy of fluconazole within multiple conformations of 14α-demet ...201728129567
trypanosoma cruzi: evaluation of pcr as a laboratory tool to follow up the evolution of parasite load.the study evaluated qualitative pcr, primers 121-122 as a tool to follow up evolution parasite load of trypanosoma cruzi.201728127346
design and synthesis of potent substrate-based inhibitors of the trypanosoma cruzi dihydroorotate dehydrogenase.chagas disease, caused by the parasitic protozoan trypanosoma cruzi, is the leading cause of heart disease in latin america. t. cruzi dihydroorotate dehydrogenase (dhodh), which catalyzes the production of orotate, was demonstrated to be essential for t. cruzi survival, and thus has been considered as a potential drug target to combat chagas disease. here we report the design and synthesis of 75 compounds based on the orotate structure. a comprehensive structure-activity relationship (sar) study ...201728118956
differential expression of matrix metalloproteinases 2, 9 and cytokines by neutrophils and monocytes in the clinical forms of chagas disease.dilated cardiomyopathy, the most severe manifestation in chronic phase of chagas disease, affects about 30% of patients and is characterized by myocardial dysfunction and interstitial fibrosis due to extracellular matrix (ecm) remodeling. ecm remodeling is regulated by proteolytic enzymes such as matrix metalloproteinases (mmps) and cytokines produced by immune cells, including phagocytes. we evaluated by flow cytometry the expression of mmp-2, mmp-9, il-1β, tnf-α, tgf-β and il-10 by neutrophils ...201728118356
grail and otubain-1 are related to t cell hyporesponsiveness during trypanosoma cruzi infection.trypanosoma cruzi infection is associated with severe t cell unresponsiveness to antigens and mitogens and is characterized by decreased il-2 synthesis. in addition, the acquisition of the anergic phenotype is correlated with upregulation of "gene related to anergy in lymphocytes" (grail) protein in cd4 t cells. we therefore sought to examine the role of grail in cd4 t cell proliferation during t. cruzi infection.201728114324
beta-adrenergic antagonist propranolol inhibits mammalian cell lysosome spreading and invasion by trypanosoma cruzi metacyclic forms.the involvement of β-adrenergic receptor (β-ar) in host cell invasion by trypanosoma cruzi metacyclic trypomastigote (mt) is not known. we examined whether isoproterenol, an agonist of β-ar, or nonselective β-blocker propranolol affected mt internalization mediated the stage-specific surface molecule gp82. treatment of hela cells with propranolol significantly inhibited mt invasion whereas isoproterenol had no effect. propranolol, but not isoproterenol, also inhibited the lysosome spreading requ ...201728111357
editing the trypanosoma cruzi genome with zinc finger nucleases.gene function studies in trypanosoma cruzi, the protozoan parasite that causes chagas disease, have been hindered by the lack of efficient genetic manipulation protocols. in most organisms, insertion and deletion of dna fragments in the genome are dependent on the generation of double-stranded dna break (dsb) and repair. by inducing a site-specific dsb, zinc finger nucleases (zfns) have proven to be useful to enhance gene editing in many cell types. using a pair of zfns targeted to the t. cruzi ...201728108186
ecology of trypanosoma cruzi i genotypes across rhodnius prolixus captured in attalea butyracea palms.trypanosoma cruzi, the agent of chagas disease exhibits significant genetic diversity. this parasite is divided into six discrete typing units (dtus) where t. cruzi i (tci) is the most widespread in the americas. tci genotypes have been associated to domestic and sylvatic cycles of transmission (tcidom and sylvatic tci). due to the importance of the enzootic transmission, we determined the frequency of tci genotypes present in rhodnius prolixus captured in different regions of the palm a. butyra ...201728104454
community-based entomological surveillance reveals urban foci of chagas disease vectors in sobral, state of ceará, northeastern brazil.the aim of this work was to explore the potential risk of vector-borne chagas disease in urban districts in northeastern brazil, by analyzing the spatiotemporal distributions and natural infection rates with trypanosoma cruzi of triatomine species captured in recent years. the main motivation of this work was an acute human case of chagas disease reported in 2008 in the municipality of sobral.201728103294
epidemiology and molecular typing of trypanosoma cruzi in naturally-infected hound dogs and associated triatomine vectors in texas, usa.trypanosoma cruzi is the etiologic agent of chagas disease throughout the americas. few population-level studies have examined the epidemiology of canine infection and strain types of t. cruzi that infect canines in the usa. we conducted a cross-sectional study of t. cruzi infection in working hound dogs in south central texas, including analysis of triatomine vectors collected within kennel environments.201728095511
molecular identification and genotyping of trypanosoma cruzi dna in autochthonous chagas disease patients from texas, usa.the parasitic protozoan trypanosoma cruzi, the causative agent of chagas disease, is widely distributed throughout the americas, from the southern united states (us) to northern argentina, and infects at least 6 million people in endemic areas. much remains unknown about the dynamics of t. cruzi transmission among mammals and triatomine vectors in sylvatic and peridomestic eco-epidemiological cycles, as well as of the risk of transmission to humans in the us. identification of t. cruzi dtus amon ...201728095298
cross-sectional, descriptive study of chagas disease among citizens of bolivian origin living in munich, germany.chagas disease (cd) has become a global health issue mainly due to migration. germany lacks surveillance data and is home to a large latin american immigrant population. recognising that bolivia is the country with the highest cd prevalence in latin america, this cross-sectional, descriptive pilot study investigated cd and associated factors among citizens of bolivian origin living in munich, germany.201728093440
the prevalence of trypanosoma cruzi, the causal agent of chagas disease, in texas rodent populations.rodent species were assessed as potential hosts of trypanosoma cruzi, the etiologic agent of chagas disease, from five sites throughout texas in sylvan and disturbed habitats. a total of 592 rodents were captured, resulting in a wide taxonomic representation of 11 genera and 15 species. heart samples of 543 individuals were successfully analyzed by sybrgreen-based quantitative pcr (qpcr) targeting a 166 bp fragment of satellite dna of t. cruzi. eight rodents representing six species from six gen ...201728091763
il-6 promotes m2 macrophage polarization by modulating purinergic signaling and regulates the lethal release of nitric oxide during trypanosoma cruzi infection.the production of nitric oxide (no) is a key defense mechanism against intracellular pathogens but it must be tightly controlled in order to avoid excessive detrimental oxidative stress. in this study we described a novel mechanism through which interleukin (il)-6 mediates the regulation of no release induced in response to trypanosoma cruzi infection. using a murine model of chagas disease, we found that, in contrast to c57bl/6 wild type (wt) mice, il-6-deficient (il6ko) mice exhibited a dramat ...201728087471
a new development in trypanosoma cruzi detection.chagas disease is caused by the parasite trypanosoma cruzi and is an important cause of morbidity and mortality in areas of latin america where chagas disease is endemic and among infected individuals who have migrated to nonendemic areas of north america and europe. there are many diagnostic tests that are employed in the serological diagnosis of this infection. in this issue of the journal of clinical microbiology, bautista-lópez et al. provide characterization of excretory vesicles (evs) from ...201728077696
lysosome-like compartments of trypanosoma cruzi trypomastigotes may originate directly from epimastigote reservosomes.trypanosoma cruzi epimastigote reservosomes store nutrients taken up during the intense endocytic activity exhibited by this developmental form. reservosomes were classified as pre-lysosomal compartments. in contrast, trypomastigote forms are not able to take up nutrients from the medium. interestingly, trypomastigotes also have acidic organelles with the same proteases contained in epimastigote reservosomes. nevertheless, the origin and function of these organelles have not been disclosed so fa ...201728077187
understanding transmissibility patterns of chagas disease through complex vector-host networks.chagas disease is one of the most important vector-borne zoonotic diseases in latin america. control strategies could be improved if transmissibility patterns of its aetiologic agent, trypanosoma cruzi, were better understood. to understand transmissibility patterns of chagas disease in mexico, we inferred potential vectors and hosts of t. cruzi from geographic distributions of nine species of triatominae and 396 wild mammal species, respectively. the most probable vectors and hosts of t. cruzi ...201728077180
post-translational modifications of trypanosoma cruzi canonical and variant histones.chagas disease, caused by trypanosoma cruzi, still affects millions of people around the world. no vaccines nor treatment for chronic chagas disease are available, and chemotherapy for the acute phase is hindered by limited efficacy and severe side effects. the processes by which the parasite acquires infectivity and survives in different hosts involve tight regulation of gene expression, mainly post-transcriptionally. nevertheless, chromatin structure/organization of trypanosomatids is similar ...201728076955
new imidazole-based compounds active against trypanosoma cruzi.current drugs available for the treatment of chagas disease are fraught with several challenges including severe toxicity and limited efficacy. these factors coupled with the absence of effective drugs for treating the chronic stage of the disease have rendered the development of new drugs against chagas disease a priority. this study screened several imidazole-based compounds for anti-trypanosoma potential. using in vitro experimental infection model, several imidazole-based compounds were scre ...201728071587
likely autochthonous transmission of trypanosoma cruzi to humans, south central texas, usa.chagas disease, caused by trypanosoma cruzi, is a major neglected tropical disease affecting the americas. the epidemiology of this disease in the united states is incomplete. we report evidence of likely autochthonous vectorborne transmission of t. cruzi and health outcomes in t. cruzi-seropositive blood donors in south central texas, usa.201728221110
synthesis and biological evaluation of potential inhibitors of the cysteine proteases cruzain and rhodesain designed by molecular simplification.analogues of 8-chloro-n-(3-morpholinopropyl)-5h-pyrimido[5,4-b]indol-4-amine 1, a known cruzain inhibitor, were synthesized using a molecular simplification strategy. five series of analogues were obtained: indole, pyrimidine, quinoline, aniline and pyrrole derivatives. the activity of the compounds was evaluated against the enzymes cruzain and rhodesain as well as against trypanosoma cruzi amastigote and trypomastigote forms. the 4-aminoquinoline derivatives showed promising activity against bo ...201728215783
evidence of the presence of a calmodulin-sensitive plasma membrane ca(2+)-atpase in trypanosoma equiperdum.trypanosoma equiperdum belongs to the subgenus trypanozoon, which has a significant socio-economic impact by limiting animal protein productivity worldwide. proteins involved in the intracellular ca(2+) regulation are prospective chemotherapeutic targets since several drugs used in experimental treatment against trypanosomatids exert their action through the disruption of the parasite intracellular ca(2+) homeostasis. therefore, the plasma membrane ca(2+)-atpase (pmca) is considered as a potenti ...201728213174
polymorphisms of blood forms and in vitro metacyclogenesis of trypanosoma cruzi i, ii, and iv.trypanosoma cruzi is the etiologic agent of american trypanosomiasis has broad biological and genetic diversity. remaining to be studied are polymorphisms of the blood forms and metacyclogenesis of different t. cruzi discrete typing units (dtus). our goal was to evaluate the relationship between t. cruzi dtus, the morphology of blood trypomastigotes, and in vitro metacyclogenesis. t. cruzi strains that pertained to dtus tci, tcii, and tciv from different brazilian states were used. parameters th ...201728212811
structure, kinetic characterization and subcellular localization of the two ribulose 5-phosphate epimerase isoenzymes from trypanosoma cruzi.the enzyme of the pentose phosphate pathway (ppp) ribulose-5-phosphate-epimerase (rpe) is encoded by two genes present in the genome of trypanosoma cruzi cl brener clone: tcrpe1 and tcrpe2. despite high sequence similarity at the amino acid residue level, the recombinant isoenzymes show a strikingly different kinetics. whereas tcrpe2 follows a typical michaelian behavior, tcrpe1 shows a complex kinetic pattern, displaying a biphasic curve, suggesting the coexistence of -at least- two kinetically ...201728207833
chagas disease research and development: is there light at the end of the tunnel?chagas disease, or american trypanosomiasis, is the result of infection by the parasite trypanosoma cruzi. it is endemic in latin america, and spreading around the globe due to human migration. although it was first identified more than a century ago, only two old drugs are available for treatment and a lot of questions related to the disease progression, its pathologies, and not to mention the assessment of treatment efficacy, are subject to debate and remain to be answered. indeed, the current ...201728066534
evaluation of p2x7 receptor expression in peripheral lymphocytes and immune profile from patients with indeterminate form of chagas disease.chagas disease (cd) is caused by trypanosoma cruzi, an intracellular protozoan which is a potent stimulator of cell-mediated immunity. in the indeterminate form of cd (ifcd) a modulation between pro- and anti-inflammatory responses establishes a host-parasite adaptation. it was previously demonstrated that purinergic ecto-enzymes regulates extracellular atp and adenosine levels, influencing immune and inflammatory processes during ifcd. in inflammatory sites atp, as well as its degradation produ ...201728062289
prevalence of chagas disease in a u.s. population of latin american immigrants with conduction abnormalities on electrocardiogram.chagas disease (cd) affects over six million people and is a leading cause of cardiomyopathy in latin america. given recent migration trends, there is a large population at risk in the united states (us). early stage cardiac involvement from cd usually presents with conduction abnormalities on electrocardiogram (ecg) including right bundle branch block (rbbb), left anterior or posterior fascicular block (lafb or lpfb, respectively), and rarely, left bundle branch block (lbbb). identification of ...201728056014
comparative effects of histone deacetylases inhibitors and resveratrol on trypanosoma cruzi replication, differentiation, infectivity and gene expression.histone post-translational modification, mediated by histone acetyltransferases and deacetylases, is one of the most studied factors affecting gene expression. recent data showing differential histone acetylation states during the trypanosoma cruzi cell cycle suggest a role for epigenetics in the control of this process. as a starting point to study the role of histone deacetylases in the control of gene expression and the consequences of their inhibition and activation in the biology of t. cruz ...201728038431
alterations in pancreatic β cell function and trypanosoma cruzi infection: evidence from human and animal studies.the parasite trypanosoma cruzi causes a persistent infection, chagas disease, affecting millions of persons in endemic areas of latin america. as a result of immigration, this disease has now been diagnosed in non-endemic areas worldwide. although, the heart and gastrointestinal tract are the most studied, the insulin-secreting β cell of the endocrine pancreas is also a target of infection. in this review, we summarize available clinical and laboratory evidence to determine whether t. cruzi-infe ...201728013375
antiprotozoal drug nitazoxanide enhances parasitemia, tissue lesions and mortality caused by trypanosoma cruzi in murine model.chagas' disease is caused by unicellular parasite trypanosoma cruzi (t. cruzi). it is endemic throughout latin america, but nowadays has become a global challenge due to tourism and migration. non-treated infection may result in health-threatening complications and lead to death. current medications for this infection are nifurtimox (nft) and benznidazol. both drugs may cause side effects and are ineffective in the chronic phase. therefore, new antichagasic compounds are urgently required. nitaz ...201728011170
blood gene signatures of chagas cardiomyopathy with or without ventricular dysfunction.chagas disease, caused by the protozoan parasite trypanosoma cruzi, affects 7 million people in latin american areas of endemicity. about 30% of infected patients will develop chronic chagas cardiomyopathy (ccc), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. further studies are necessary to understand the molecular mechanisms of disease progression. transcriptome analysis has been increasingly used to identify molecular changes associated with disease ou ...201728003350
trypanosoma cruzi seroprevalence and associated risk factors in cancer patients from southern brazil.the aim of this study was to investigate the prevalence of chagas disease in patients treated at a public oncology service in the city of pelotas, southern brazil.201728001226
high seroconversion rates in trypanosoma cruzi chronic infection treated with benznidazole in people under 16 years in guatemala.geographical, epidemiological, and environmental differences associated with therapeutic response to chagas etiological treatment have been previously discussed. this study describes high seroconversion rates 72 months after benznidazole treatment in patients under 16 years from a project implemented by doctors without borders in guatemala.201728001219
benznidazole therapy for chagas disease in asymptomatic trypanosoma cruzi -seropositive former blood donors: evaluation of the efficacy of different treatment regimens.chagas disease currently affects 5.7 million people in latin america and is emerging in non-endemic countries. there is no consensus concerning the efficacy of trypanocidal therapy for patients with the chronic form of the disease. we evaluated cardiac function and sociodemographic, clinical, and serologic characteristics of a group of asymptomatic trypanosoma cruzi-seropositive former blood donors, and compared the effects of benznidazole treatment applied for different lengths of time.201728001218
simvastatin attenuates endothelial activation through 15-epi-lipoxin a4 production in murine chronic chagas cardiomyopathy.current treatments for chronic chagas cardiomyopathy, a disease with high mortality rates and caused by the protozoan trypanosoma cruzi, are unsatisfactory. myocardial inflammation, including endothelial activation, is responsible for the structural and functional damage seen in the chronic phase. the clinical efficacy of benznidazole could be improved by decreasing chronic inflammation. statins, which have anti-inflammatory properties, may improve the action of benznidazole. here, the action of ...201727993857
myocarditis in different experimental models infected by trypanosoma cruzi is correlated with the production of igg1 isotype.this study was designed to verify the relationship between igg antibodies isotypes and myocarditis in trypanosoma cruzi infection using mice and dogs infected with different t. cruzi strains. the animals were infected with benznidazole-susceptible berenice-78 and benznidazole-resistant aas and vl-10 strains. the igg subtypes were measured in serum samples from dogs (igg, igg1, and igg2) and mice (igg, igg1, igg2a, and igg2b). the infection of dogs with vl-10 strain induced the highest levels of ...201727993495
orally-transmitted chagas disease.chagas disease is a zoonosis caused by protozoan parasite trypanosoma cruzi, which is most frequently associated with a vectorial transmission. however, in recent years we have observed a significant increase in the oral transmission of the disease, associated mainly with the consumption of drinks made from fruit or other vegetables contaminated with triatomine faeces or secretions from infected mammals. after a latency period of 3 to 22 days after ingestion, the oral infection is characterized ...201727993415
host epac1 is required for camp-mediated invasion by trypanosoma cruzi.mechanistic details of the modulation by camp of trypanosoma cruzi host cell invasion remain ill-defined. here we report that activation of host's epac1 stimulated invasion, whereas specific pharmacological inhibition or maneuvers that alter epac1 subcellular localization significantly reduced invasion. furthermore, while specific activation of host cell pka showed no effect, its inhibition resulted in an increased invasion, revealing a crosstalk between the pka and epac signaling pathways durin ...201727984073
characterization and diagnostic application of trypanosoma cruzi trypomastigote excreted-secreted antigens shed in extracellular vesicles released from infected mammalian cells.chagas disease, caused by trypanosoma cruzi, although endemic in many parts of central and south america, is emerging as a global health threat through the potential contamination of blood supplies. consequently, in the absence of a gold standard assay for the diagnosis of chagas disease, additional antigens or strategies are needed. a proteomic analysis of the trypomastigote excreted-secreted antigens (tesa) associated with exosomal vesicles shed by t. cruzi identified ∼80 parasite proteins, wi ...201727974541
expression and production of cardiac angiogenic mediators depend on the trypanosoma cruzi-genetic population in experimental c57bl/6 mice infection.mammalian cardiac cells are important targets to the protozoan trypanosoma cruzi. the inflammatory reaction in the host aims at eliminating this parasite, can lead to cell destruction, fibrosis and hypoxia. local hypoxia is well-defined stimulus to the production of angiogenesis mediators. assuming that different genetic t. cruzi populations induce distinct inflammation and disease patterns, the current study aims to investigate whether the production of inflammatory and angiogenic mediators is ...201727956355
identification of trypanosoma cruzi discrete typing units (dtus) in latin-american migrants in barcelona (spain).trypanosoma cruzi, the causative agent of chagas disease, is divided into six discrete typing units (dtus): tci-tcvi. we aimed to identify t. cruzi dtus in latin-american migrants in the barcelona area (spain) and to assess different molecular typing approaches for the characterization of t. cruzi genotypes. seventy-five peripheral blood samples were analyzed by two real-time pcr methods (qpcr) based on satellite dna (satdna) and kinetoplastid dna (kdna). the 20 samples testing positive in both ...201727940065
trypanosoma cruzi induces cellular proliferation in the trophoblastic cell line bewo.congenital transmission of trypanosoma cruzi (t. cruzi) is partially responsible for the progressive globalization of chagas disease. during congenital transmission the parasite must cross the placental barrier where the trophoblast, a continuous renewing epithelium, is the first tissue in contact with the parasite. the trophoblast turnover implies cellular proliferation, differentiation and apoptotic cell death. the epithelial turnover is considered part of innate immunity. we previously demons ...201727939813
ribosome assembly in trypanosomatids: a novel therapeutic target.in liu et al., the authors present a 2.5-å structure of the trypanosoma cruzi 60s ribosomal subunit and propose a model for the stepwise assembly of the large-subunit ribosomal rna (rrna). based on this study, we discuss how the unique features of trypanosomatid ribosome assembly offer potential drug targets.201727988096
diet regulates liver autophagy differentially in murine acute trypanosoma cruzi infection.chagas disease is a tropical parasitic disease caused by the protozoan trypanosoma cruzi, which affects about ten million people in its endemic regions of latin america. after the initial acute stage of infection, 60-80% of infected individuals remain asymptomatic for several years to a lifetime; however, the rest develop the debilitating symptomatic stage, which affects the nervous system, digestive system, and heart. the challenges of chagas disease have become global due to immigration. despi ...201727987056
involvement of an rna binding protein containing alba domain in the stage-specific regulation of beta-amastin expression in trypanosoma cruzi.amastins are surface glycoproteins, first identified in amastigotes of t. cruzi but later found to be expressed in several leishmania species, as well as in t. cruzi epimastigotes. amastins are encoded by a diverse gene family that can be grouped into four subfamilies named α, β, γ, and δ amastins. differential expression of amastin genes results from regulatory mechanisms involving changes in mrna stability and/or translational control. although distinct regulatory elements were identified in t ...201727986451
differential expression on mitochondrial tryparedoxin peroxidase (mtctxnpx) in trypanosoma cruzi after ferrocenyl diamine hydrochlorides treatments.resistance to benznidazole in certain strains of trypanosoma cruzi may be caused by the increased production of enzymes that act on the oxidative metabolism, such as mitochondrial tryparedoxin peroxidase which catalyses the reduction of peroxides. this work presents cytotoxicity assays performed with ferrocenyl diamine hydrochlorides in six different strains of t. cruzi epimastigote forms (y, bolivia, si1, si8, qmii, and sigr3). the last four strains have been recently isolated from triatominae ...201727918890
prevalence of trypanosoma cruzi/hiv coinfection in southern brazil.chagas disease reactivation has been a defining condition for acquired immune deficiency syndrome in brazil for individuals coinfected with trypanosoma cruzi and hiv since 2004. although the first coinfection case was reported in the 1980s, its prevalence has not been firmly established. in order to know coinfection prevalence, a cross-sectional study of 200 hiv patients was performed between january and july 2013 in the city of pelotas, in southern rio grande do sul, an endemic area for chagas ...201727914221
tci, tcii and tcvi trypanosoma cruzi samples from chagas disease patients with distinct clinical forms and critical analysis of in vitro and in vivo behavior, response to treatment and infection evolution in murine model.the clonal evolution of trypanosoma cruzi sustains scientifically the hypothesis of association between parasite's genetic, biological behavior and possibly the clinical aspects of chagas disease in patients from whom they were isolated. this study intended to characterize a range of biological properties of tci, tcii and tcvi t. cruzi samples in order to verify the existence of these associations. several biological features were evaluated, including in vitro epimastigote-growth, "vero"cells in ...201727908747
gene expression profiling and functional characterization of macrophages in response to circulatory microparticles produced during trypanosoma cruzi infection and chagas disease.chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (ccm). in this study, we determined if microparticles (mps) generated during trypanosoma cruzi (tc) infection carry the host's signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease.201727902980
benznidazole, the trypanocidal drug used for chagas disease, induces hepatic nrf2 activation and attenuates the inflammatory response in a murine model of sepsis.molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ros) production and cellular antioxidant capacity. previous studies demonstrated that benznidazole (bzl), known for its antiparasitic action on trypanosoma cruzi, has immunomodulatory effects, increasing survival in c57bl/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (clp). the mechanism by which bzl inhibits inflammatory response in sepsis is poorly understo ...201727899278
triatoma infestans calreticulin: gene cloning and expression of a main domain that interacts with the host complement system.triatoma infestans is an important hematophagous vector of chagas disease, a neglected chronic illness affecting approximately 6 million people in latin america. hematophagous insects possess several molecules in their saliva that counteract host defensive responses. calreticulin (crt), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. human crt (hucrt) and trypanosoma cruzi crt (tccrt) inhibit the classical pathway of complement activation, mainly ...201727895277
outcome of oral infection in mice inoculated with trypanosoma cruzi iv of the western brazilian amazon.a new epidemiological view of american trypanosomiasis or chagas disease has been formulated in recent decades. oral transmission of the etiological agent of chagas disease, trypanosoma cruzi, has been the most common form of transmission. the t. cruzi discrete typing units tci and tciv have been involved in tens outbreaks of acute cases of chagas disease in the brazilian amazon region. we investigated the intensity of infection in mice that were orally inoculated (or group) with four strains of ...201727876646
high hiv-trypanosoma cruzi coinfection levels in vulnerable populations in buenos aires, argentina. 201727875909
rhodnius prolixus: from physiology by wigglesworth to recent studies of immune system modulation by trypanosoma cruzi and trypanosoma rangeli.this review is dedicated to the memory of professor sir vincent b. wigglesworth (vw) in recognition of his many pioneering contributions to insect physiology which, even today, form the basis of modern-day research in this field. insects not only make vital contributions to our everyday lives by their roles in pollination, balancing eco-systems and provision of honey and silk products, but they are also outstanding models for studying the pathogenicity of microorganisms and the functioning of in ...201727866813
quantitative proteomic analysis of replicative and nonreplicative forms reveals important insights into chromatin biology of trypanosoma cruzi.chromatin associated proteins are key regulators of many important processes in the cell. trypanosoma cruzi, a protozoa flagellate that causes chagas disease, alternates between replicative and nonreplicative forms accompanied by a shift on global transcription levels and by changes in its chromatin architecture. here, we investigated the t. cruzi chromatin proteome using three different protocols and compared it between replicative (epimastigote) and nonreplicative (trypomastigote) forms by hig ...201727852749
prevalence of trypanosoma cruzi infection among bolivian immigrants in the city of são paulo, brazil.with the urbanisation of the population in developing countries and the process of globalisation, chagas has become an emerging disease in the urban areas of endemic and non-endemic countries. in 2006, it was estimated that the prevalence of chagas disease among the general bolivian population was 6.8%. the aim of the present study was to determine the prevalence of trypanosoma cruzi infection among bolivian immigrants living in são paulo, brazil. this study had a sample of 633 volunteers who we ...201727849221
the trypanosoma cruzi surface, a nanoscale patchwork quilt.the trypanosoma cruzi trypomastigote membrane provides a major protective role against mammalian host-derived defense mechanisms while allowing the parasite to interact with different cell types and trigger pathogenesis. this surface has been historically appreciated as a rather unstructured 'coat', mainly consisting of a continuous layer of glycolipids and heavily o-glycosylated mucins, occasionally intercalated with different developmentally regulated molecules displaying adhesive and/or enzym ...201727843019
exogenous calreticulin, incorporated onto non-infective trypanosoma cruzi epimastigotes, promotes their internalization into mammal host cells.chagas disease is an endemic pathology in latin america, now emerging in developed countries, caused by the intracellular protozoan trypanosoma cruzi, whose life cycle involves three stages: amastigotes, epimastigotes, and trypomastigotes. t. cruzi calreticulin (tccrt), an endoplasmic reticulum resident chaperone, translocates to the external cellular membrane, where it captures complement component c1, ficolins and mbl, thus inactivating the classical and lectin pathways. trypomastigote-bound c ...201727839837
trypanosoma cruzi infection in captive neotropical primates in the brazilian amazon.the aim of this study was to detect the infection by trypanosoma cruzi in captive neotropical primates in the brazilian amazon. from february 2013 to july 2014, 112 blood samples were collected from neotropical primates from the amazonas, amapá, and pará states, north of brazil. the subjects belonged to the families cebidae (n = 59), atelidae (n = 41), callitrichidae (n = 5), pitheciidae (n = 4), and aotidae (n = 3). blood smears also were examined for the presence of trypomastigotes by optical ...201727802362
rational design of nitrofuran derivatives: synthesis and valuation as inhibitors of trypanosoma cruzi trypanothione reductase.the rational design and synthesis of a series of 5-nitro-2-furoic acid analogues are presented. the trypanocidal activity against epimastigote forms of trypanosoma cruzi and the toxic effects on human hela cells were tested. between all synthetic compounds, three of thirteen had an ic50 value in the range of nfx, but compound 13 exhibited an improved effect with an ic50 of 1.0 ± 0.1 μm and a selective index of 70 in its toxicity against hela cells. we analyzed the activity of compounds 8, 12 and ...201727810595
determination of the ribosome structure to a resolution of 2.5 å by single-particle cryo-em.with the advance of new instruments and algorithms, and the accumulation of experience over decades, single-particle cryo-em has become a pivotal part of structural biology. recently, we determined the structure of a eukaryotic ribosome at 2.5 å for the large subunit. the ribosome was derived from trypanosoma cruzi, the protozoan pathogen of chagas disease. the high-resolution density map allowed us to discern a large number of unprecedented details including rrna modifications, water molecules, ...201727750394
participation of tlr2 and tlr4 in cytokines production by patients with symptomatic and asymptomatic chronic chagas disease.chagas disease (cd), caused by the protozoan trypanosoma cruzi, is a serious public health issue. its evolution involves an acute stage, characterized by no specific symptoms, and the chronic stage during most individuals are asymptomatic, but about 30-40% of them become symptomatic presenting the cardiac or digestive disease. host immune response mechanisms involved in symptomatic or asymptomatic chronic disease are not fully understood. the pro-inflammatory cytokines are crucial in host resist ...201727783847
dantrolene improves in vitro structural changes induced by serum from trypanosoma cruzi-infected mice.dystrophin, an important protein of the dystrophin-glycoprotein complex, has been implicated in the pathogenesis of experimental chagas disease. it is important for the maintenance of cell shape and contraction force transmission. dystrophin loss has been related to end-stage cardiac myopathies and proposed as a common route for myocardial dysfunction and progression to advanced heart failure. evidence suggests that calpains, calcium-dependent proteases, digest dystrophin when the calcium concen ...201727730362
evaluation of parameters impacting drug susceptibility in intracellular trypanosoma cruzi assay protocols.in order to understand the key parameters influencing drug susceptibility, different trypanosoma cruzi assay protocols were evaluated using a comparative assay design. the assays compared in this study were an image-based intracellular t. cruzi assay quantified through an image-mining algorithm and an intracellular assay utilizing a β-galactosidase-expressing t. cruzi strain. thirty-one reference compounds known to exhibit activities against intracellular t. cruzi were used as benchmarks. initia ...201727729503
ultrastructural and physiological changes induced by different stress conditions on the human parasite trypanosoma cruzi.trypanosoma cruzi is the etiological agent of chagas disease. the life cycle of this protozoan parasite is digenetic because it alternates its different developmental forms through two hosts, a vector insect and a vertebrate host. as a result, the parasites are exposed to sudden and drastic environmental changes causing cellular stress. the stress response to some types of stress has been studied in t. cruzi, mainly at the molecular level; however, data about ultrastructure and physiological sta ...201727714535
epitope capsid-incorporation: new effective approach for vaccine development for chagas disease.previously we reported that a hexon-modified adenovirus (ad) vector containing the invasive neutralizing epitope of trypanosoma cruzi (t. cruzi) trypomastigote gp83 (ad5-gp83) provided immunoprotection against t. cruzi infection. the purpose of this work was to design an improved vaccine for t. cruzi using a novel epitope capsid incorporation strategy. thus, we evaluated the immunoprotection raised by co-immunization with ad5-gp83 and an ad vector containing an epitope (asp-m) of the t. cruzi am ...201727709126
murine models susceptibility to distinct trypanosoma cruzi i genotypes infection.chagas disease is a complex zoonosis that affects around 8 million people worldwide. this pathology is caused by trypanosoma cruzi, a kinetoplastid parasite that shows tremendous genetic diversity evinced in six distinct discrete typing units (tci-tcvi) including a recent genotype named as tcbat and associated with anthropogenic bats. tci presents a broad geographical distribution and has been associated with chronic cardiomyopathy. recent phylogenetic studies suggest the existence of two genoty ...201727829476
relationships between altitude, triatomine (triatoma dimidiata) immune response and virulence of trypanosoma cruzi, the causal agent of chagas' disease.little is known about how the virulence of a human pathogen varies in the environment it shares with its vector. this study focused on whether the virulence of trypanosoma cruzi (trypanosomatida: trypanosomatidae), the causal agent of chagas' disease, is related to altitude. accordingly, triatoma dimidiata (hemiptera: reduviidae) specimens were collected at three different altitudes (300, 700 and 1400 m a.s.l.) in chiapas, mexico. the parasite was then isolated to infect uninfected t. dimidiata ...201727753118
Refresh
firstprev
12345678910...
nextlast
Displaying items 101 - 200 of 17982