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autochthonous transmission of chagas disease in rio de janeiro state, brazil: a clinical and eco-epidemiological study.after the control of the main modes of chagas disease (cd) transmission in most endemic countries, it is important to identify the participation of native sylvatic vectors in cd transmission. although cd is not considered endemic in rio de janeiro state (rj), brazil, we identified patients with cd born in rj and investigated the possible autochthonous transmission in the state.201525566786
expression, purification, and biochemical characterization of recombinant dna polymerase beta of the trypanosoma cruzi tci lineage: requirement of additional factors and detection of phosphorylation of the native form.chagas disease, caused by the protozoan trypanosoma cruzi, is a major parasitic disease that affects millions of people in america. however, despite the high impact of this disease on human health, no effective and safe treatment has been found that eliminates the infecting parasite from human patients. among the possible chemotherapeutic targets that could be considered for study in t. cruzi are the dna polymerases, in particular dna polymerase beta (polß), which previous studies have shown to ...201525566774
nitric oxide-releasing indomethacin enhances susceptibility to trypanosoma cruzi infection acting in the cell invasion and oxidative stress associated with anemia.trypanosoma cruzi is the causative agent of chagas disease. approximately 8 million people are thought to be affected with this disease worldwide. t. cruzi infection causes an intense inflammatory response, which is critical for the control of parasite proliferation and disease development. nitric oxide-donating nonsteroidal anti-inflammatory drugs (no-nsaids) are an emergent class of pharmaceutical derivatives with promising utility as chemopreventive agents. in this study, we investigated the ...201525559858
treatment in vitro with pparα and pparγ ligands drives m1-to-m2 polarization of macrophages from t. cruzi-infected mice.trypanosoma cruzi, the etiological agent of chagas' disease, induces a persistent inflammatory response. macrophages are a first line cell phenotype involved in the clearance of infection. upon parasite uptake, these cells increase inflammatory mediators like no, tnf-α, il-1β and il-6, leading to parasite killing. although desired, inflammatory response perpetuation and exacerbation may lead to tissue damage. peroxisome proliferator-activated receptors (ppars) are ligand-dependent nuclear transc ...201525557389
trypanosoma cruzi infectivity assessment in "in vitro" culture systems by automated cell counting.chagas disease is an endemic, neglected tropical disease in latin america that is caused by the protozoan parasite trypanosoma cruzi. in vitro models constitute the first experimental approach to study the physiopathology of the disease and to assay potential new trypanocidal agents. here, we report and describe clearly the use of commercial software (matlab(®)) to quantify t. cruzi amastigotes and infected mammalian cells (bewo) and compared this analysis with the manual one. there was no stati ...201525553972
signal transducer and activator of transcription 1 (stat-1) plays a critical role in control of trypanosoma cruzi infection.the control of trypanosoma cruzi infection is related to interferon-γ (ifn-γ) activation leading to intracellular clearance of parasites. the transcription factor signal transducer and activator of transcription 1 (stat-1) is a key mediator of ifn-γ intracellular signalling and knockout of this protein leads to susceptibility to several intracellular microbes. to determine the role of stat-1 in host susceptibility to t. cruzi infection we compared the survival, parasite loads and balance of ifn- ...201525545325
reevaluating the trypanosoma cruzi proteomic map: the shotgun description of bloodstream trypomastigotes.chagas disease is a neglected disease, caused by the protozoan trypanosoma cruzi. this kinetoplastid presents a cycle involving different forms and hosts, being trypomastigotes the main infective form. despite various t. cruzi proteomic studies, the assessment of bloodstream trypomastigote profile remains unexplored. the aim of this work is t. cruzi bloodstream form proteomic description. employing shotgun approach, 17,394 peptides were identified, corresponding to 7514 proteins of which 5901 be ...201525534883
identification of a new amide-containing thiazole as a drug candidate for treatment of chagas' disease.although the parasitic infection chagas' disease was described over 100 years ago, even now there are not suitable drugs. the available drugs nifurtimox and benznidazole have limited efficacies and tolerances, with proven mutagenic effects. attempting to find appropriate drugs to deal with this problem, here we report on the development and pharmacological characterization of new amide-containing thiazoles. in the present study, we evaluated the in vitro and in vivo effects of new candidates aga ...201525512408
role of ip3 receptor signaling in cell functions and diseases.ip3 receptor (ip3r) was found to release ca(2+) from non-mitochondrial store but the exact localization and the mode of action of ip3 remained a mystery. ip3r was identified to be p400 protein, a protein, which was missing in the cerebellum of ataxic mutant mice lacking ca(2+) spikes in pukinje cells. ip3r was an ip3 binding protein and was a ca(2+) channel localized on the endoplasmic reticulum. full-length cdna of ip3r type 1 was initially cloned and later two other isoforms of ip3r (ip3r type ...201525497594
gene-deleted live-attenuated trypanosoma cruzi parasites as vaccines to protect against chagas disease.chagas disease is a neglected tropical disease caused by the protozoan parasite trypanosoma cruzi. this illness is now becoming global, mainly due to congenital transmission, and so far, there are no prophylactic or therapeutic vaccines available to either prevent or treat chagas disease. therefore, different approaches aimed at identifying new protective immunogens are urgently needed. live vaccines are likely to be more efficient in inducing protection, but safety issues linked with their use ...201525496192
match-making for posaconazole through systems thinking.currently available drugs for chagas' disease are limited by toxicity and low efficacy in the chronic stage. posaconazole, the most advanced new anti-chagasic drug candidate, did not fully confirm its initial potential in a phase ii clinical trial for chronic chagas' disease. given that posaconazole is highly active against trypanosoma cruzi in vitro, and was very well tolerated in clinical trials, it should not be abandoned. rather, a combination therapy may provide a highly promising outlook. ...201525486978
toxicity and loss of mitochondrial membrane potential induced by alkyl gallates in trypanosoma cruzi.american trypanosomiasis or chagas disease is a debilitating disease representing an important social problem that affects, approximately, 10 million people in the world. the main aggravating factor of this situation is the lack of an effective drug to treat the different stages of this disease. in this context, the search for trypanocidal substances isolated from plants, synthetic or semi synthetic molecules, is an important strategy. here, the trypanocidal potential of gallates was assayed in ...201527347554
deficiency in mannose-binding lectin-associated serine protease-2 does not increase susceptibility to trypanosoma cruzi infection.trypanosoma cruzi is the causative agent of chagas' disease, a chronic illness affecting 10 million people around the world. the complement system plays an important role in fighting microbial infections. the recognition molecules of the lectin pathway of complement activation, mannose-binding lectin (mbl), ficolins, and cl-11, bind to specific carbohydrates on pathogens, triggering complement activation through mbl-associated serine protease-2 (masp-2). previous in vitro work showed that human ...201525548381
the main sceneries of chagas disease transmission. the vectors, blood and oral transmissions--a comprehensive review.this review deals with transmission of trypanosoma cruzi by the most important domestic vectors, blood transfusion and oral intake. among the vectors, triatoma infestans, panstrongylus megistus, rhodnius prolixus, triatoma dimidiata, triatoma brasiliensis, triatoma pseudomaculata, triatoma sordida, triatoma maculata, panstrongylus geniculatus, rhodnius ecuadoriensis and rhodnius pallescens can be highlighted. transmission of chagas infection, which has been brought under control in some countrie ...201525466622
trypasonoma cruzi uses a specific subset of host cell lysosomes for cell invasion.trypanosoma cruzi is an intracellular parasite that depends on host cell lysosome recruitment and fusion for cell infection. recently, we have shown that host cells present two differentially regulated lysosome pools. treatment with methyl-beta cyclodextrin, a drug able to sequester cholesterol from plasma membrane, triggers the exocytosis of peripheral lysosomes, while treatment with latrunculin-a, an actin depolymerizing drug, recruits a more internal pool. in this work we aimed to study which ...201525463313
prospects of an alternative treatment against trypanosoma cruzi based on abietic acid derivatives show promising results in balb/c mouse model.chagas disease, caused by the protozoa parasite trypanosoma cruzi, is an example of extended parasitaemia with unmet medical needs. current treatments based on old-featured benznidazole (bz) and nifurtimox are expensive and do not fulfil the criteria of effectiveness, and a lack of toxicity devoid to modern drugs. in this work, a group of abietic acid derivatives that are chemically stable and well characterised were introduced as candidates for the treatment of chagas disease. in vitro and in v ...201525462275
comparative study of the biological properties of trypanosoma cruzi i genotypes in a murine experimental model.chagas disease is an endemic zoonosis in latin america and caused by the parasite trypanosoma cruzi. this kinetoplastid displays remarkable genetic variability, allowing its classification into six discrete typing units (dtus) from tci to tcvi. t. cruzi i presents the broadest geographical distribution in the continent and has been associated to severe forms of cardiomyopathies. recently, a particular genotype associated to human infections has been reported and named as tcidom (previously named ...201525461848
development of chagas cardiac manifestations among texas blood donors.chagas disease, infection with the parasite trypanosoma cruzi, has recently been identified as an important emerging parasitic disease in the united states. to describe the cardiac abnormalities in t. cruzi-positive blood donors in southeastern texas, a pilot study of donors who had screened positive from 2007 to 2012 was performed. this one-time assessment included (1) a questionnaire to evaluate the source of infection, cardiac symptoms, and health co-morbidities; (2) electrocardiography; (3) ...201525456877
experimental chagas disease in balb/c mice previously vaccinated with t. rangeli. ii. the innate immune response shows immunological memory: reality or fiction?trypanosoma cruzi is a real challenge to the host's immune system, because it requires strong humoral and cellular immune response to remove circulating trypomastigote forms, and to prevent the replication of amastigote forms in tissues, involving many regulator and effector components. this protozoan is responsible for chagas disease, a major public health problem in latinamerica. we have developed a model of vaccination with trypanosoma rangeli, a parasite closely related to t. cruzi, but nonp ...201525454810
molecular characterization of cyclophilin (tccyp19) in trypanosoma cruzi populations susceptible and resistant to benznidazole.cyclophilin (cyp), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biological functions that include roles in molecular chaperoning, stress response, immune modulation, and signal transduction. in this respect, cyp could serve as a potential drug target in disease-causing parasites. previous studies employing proteomics techniques have shown that the tccyp19 isoform was more abundant in a benznidazole (bz)-resistant trypanosoma cruzi population than in its susceptible count ...201525450774
metabolic control analysis of the trypanosoma cruzi peroxide detoxification pathway identifies tryparedoxin as a suitable drug target.the principal oxidative-stress defense in the human parasite trypanosoma cruzi is the tryparedoxin-dependent peroxide detoxification pathway, constituted by trypanothione reductase (tryr), tryparedoxin (txn), tryparedoxin peroxidase (txnpx) and tryparedoxin-dependent glutathione peroxidase a (gpxa). here, metabolic control analysis (mca) was applied to quantitatively prioritize drug target(s) within the pathway by identifying its flux-controlling enzymes.201525450181
rehabilitation practice patterns for patients with heart failure: the south american perspective.heart failure (hf) is an important public health issue in south america. economic impacts are substantial. chagas heart disease is a prevalent hf etiology; it is caused by the protozoan trypanosoma cruzi. cardiac rehabilitation (cr) is an integral component of hf care. the benefits of cr in hf patients need to be assessed. the effectiveness and safety of cr delivery, such as home-based interventions, should be explored. strategies to improve adherence in cr are imperative. we describe past and c ...201525432475
risk factors for chagas disease among pregnant women in el salvador.to determine the seroprevalence of chagas disease among pregnant women and estimate the risk factors for chagas disease during pregnancies.201525430666
trypanosoma cruzi invasion is associated with trogocytosis.trogocytosis was originally thought to be restricted to the interaction of cells of the immune system with cancer cells. such membrane exchanges are probably a general process in cell biology, and membrane exchange has been demonstrated to occur between non-immune cells within an organism. herein, we report that membrane and protein exchange, consistent with trogocytosis, between trypanosoma cruzi (both the brazil and tulahuen strains) and the mammalian cells it infects. transfer of labeled memb ...201525448052
microcavia australis (caviidae, rodentia), a new highly competent host of trypanosoma cruzi i in rural communities of northwestern argentina.rodents are well-known hosts of trypanosoma cruzi but little is known on the role of some caviomorph rodents. we assessed the occurrence and prevalence of t. cruzi infection in microcavia australis ("southern mountain, desert or small cavy") and its infectiousness to the vector triatoma infestans in four rural communities of tafí del valle department, northwestern argentina. parasite detection was performed by xenodiagnosis and polymerase chain reaction amplification of the hyper-variable region ...201525447830
trypanosoma cruzi antigens induce inflammatory angiogenesis in a mouse subcutaneous sponge model.acute inflammation and angiogenesis are persistent features of several pathological conditions induced by biological agents leading to the resolution of local and systemic events. glycoproteins derived from the protozoan trypanosoma cruzi are suggested to mediate angiogenesis induced by inflammatory cells with still undescribed mechanisms. in this study, we investigated the effects of total antigen from trypomastigote forms of t. cruzi (y strain), inoculated in sponges 24h after implantation in ...201525446369
trypanosoma cruzi diversity in the gran chaco: mixed infections and differential host distribution of tcv and tcvi.the transmission cycles of trypanosoma cruzi in the gran chaco are complex networks involving domestic and wild components, whose interrelationships are not well understood. knowing the circuit of transmission of the different discrete typing units (dtus) of t. cruzi in the complex environment of the chaco region is relevant to understanding how the different components (reservoirs, vectors, ecotopes) interact. in the present study we identified the dtus infecting humans and dogs in two rural ar ...201525445658
colchicine treatment reversibly blocks cytokinesis but not mitosis in trypanosoma cruzi epimastigotes.this work analyzes the effect of the alkaloid colchicine on the growth of trypanosoma cruzi epimastigotes, using immunofluorescence microscopy and flow cytometry techniques. we found that colchicine reversibly inhibited cytokinesis but not synthesis or segregation of nuclear and kinetoplastid dna, in a concentration-dependent manner. we showed that, once colchicine was removed from the growth medium, cytokinesis was restored but abnormal segregation of kinetoplasts and nuclei generated zoids and ...201525407128
bed bugs (cimex lectularius) as vectors of trypanosoma cruzi.populations of the common bed bug, cimex lectularius, have recently undergone explosive growth. bed bugs share many important traits with triatomine insects, but it remains unclear whether these similarities include the ability to transmit trypanosoma cruzi, the etiologic agent of chagas disease. here, we show efficient and bidirectional transmission of t. cruzi between hosts and bed bugs in a laboratory environment. most bed bugs that fed on experimentally infected mice acquired the parasite. a ...201525404068
blockade of ctla-4 promotes the development of effector cd8+ t lymphocytes and the therapeutic effect of vaccination with an attenuated protozoan expressing ny-eso-1.the development of cancer immunotherapy has long been a challenge. here, we report that prophylactic vaccination with a highly attenuated trypanosoma cruzi strain expressing ny-eso-1 (cl-14-ny-eso-1) induces both effector memory and effector cd8(+) t lymphocytes that efficiently prevent tumor development. however, the therapeutic effect of such a vaccine is limited. we also demonstrate that blockade of cytotoxic t lymphocyte antigen 4 (ctla-4) during vaccination enhances the frequency of ny-eso- ...201525403749
molecular genotyping of trypanosoma cruzi for lineage assignment and population genetics.trypanosoma cruzi, the etiological agent of chagas disease, remains a major public health problem in latin america. infection with t. cruzi is lifelong and can lead to a spectrum of pathological sequelae ranging from subclinical to lethal cardiac and/or gastrointestinal complications. isolates of t. cruzi can be assigned to six genetic lineages or discrete typing units (dtus), which are broadly associated with disparate ecologies, transmission cycles, and geographical distributions. this extensi ...201525388123
abundance, natural infection with trypanosomes, and food source of an endemic species of triatomine, panstrongylus howardi (neiva 1911), on the ecuadorian central coast.the elimination of domestic triatomines is the foundation of chagas disease control. regional initiatives are eliminating introduced triatomine species. in this scenario, endemic triatomines can occupy the ecological niches left open and become a threat to long-term chagas disease control efforts. this study determined the abundance, colonization, and trypanosoma cruzi infection rate of the endemic panstrongylus howardi in 10 rural communities located in ecuador's manabí province. in total, 518 ...201525385867
circulating serum markers and qrs scar score in chagas cardiomyopathy.approximately 8 million people have trypanosoma cruzi infection, and nearly 30% will manifest chagas cardiomyopathy (cc). identification of reliable early indicators of cc risk would enable prioritization of treatment to those with the highest probability of future disease. serum markers and electrocardiogram (ekg) changes were measured in 68 t. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without t. cruzi infection or cardiac disease. t. cruzi-infected indi ...201525385865
arthritis and benznidazole: more closely related than we thought.chagas disease is a parasitic infection that leads to a significant public health problem in countries where the disease is endemic and where it is nonendemic. benznidazole is the most commonly used drug for the etiological treatment of chagas disease. patients treated with benznidazole suffer frequent adverse drug reactions. although arthralgia is common, arthritis has been reported as a very rare side effect. the objective of this study was to describe arthritis in a cohort of trypanosoma cruz ...201525385100
the exocyst is required for trypanosome invasion and the repair of mechanical plasma membrane wounds.the process of host cell invasion by trypanosoma cruzi shares mechanistic elements with plasma membrane injury and repair. both processes require ca(2+)-triggered exocytosis of lysosomes, exocytosis of acid sphingomyelinase and formation of ceramide-enriched endocytic compartments. t. cruzi invades at peripheral sites, suggesting a need for spatial regulation of membrane traffic. here, we show that exo70 and sec8 (also known as exoc7 and exoc4, respectively), components of the exocyst complex, a ...201525380822
a new class of quinazoline-sulfonamides acting as efficient inhibitors against the α-carbonic anhydrase from trypanosoma cruzi.the protozoan parasite trypanosoma cruzi is the agent responsible for trypanosomiasis (chagas disease) in humans and other animals. it has been recently reported that this pathogen encodes for an α-class carbonic anhydrase (ca, ec 4.2.1.1), denominated tcca, which was shown to be crucial for its life cycle. inhibition studies of a class of 4-oxoquinazoline containing a benzensulfonamide moiety and their 4-thioxo bioisosteres against the protozoan enzyme tcca are described here. most of 4-oxoquin ...201525373503
house-level risk factors for triatoma dimidiata infestation in colombia.in colombia, the main vectors of trypanosoma cruzi, the causative agent of chagas disease, are rhodnius prolixus and triatoma dimidiata. t. dimidiata is present in the east region of colombia as domestic, peridomestic, and sylvatic populations, resulting in difficulties for its control. a cost-effective way to prioritize houses for treatment is to stratify houses based on risk factors. in this study, risk factors were evaluated for potential associations with domicile infestation of t. dimidiata ...201525349372
unveiling the effects of berenil, a dna-binding drug, on trypanosoma cruzi: implications for kdna ultrastructure and replication.trypanosoma cruzi, the etiological agent of chagas disease, exhibits a single mitochondrion with an enlarged portion termed kinetoplast. this unique structure harbors the mitochondrial dna (kdna), composed of interlocked molecules: minicircles and maxicircles. kdna is a hallmark of kinetoplastids and for this reason constitutes a valuable target in chemotherapeutic and cell biology studies. in the present work, we analyzed the effects of berenil, a minor-groove-binding agent that acts preferenti ...201525349143
prokineticin receptor identified by phage display is an entry receptor for trypanosoma cruzi into mammalian cells.trypanosoma cruzi trypomastigotes invade a great variety of mammalian cells, with several molecules being implicated in this complex event. herein, the sequence ggialag present in prokineticin-2 receptor (pkr2), selected by phage display technology, is described as a new t. cruzi receptor for the tc85 group of glycoproteins belonging to the gp85/ts superfamily and involved in cellular invasion of mammalian hosts. this finding is confirmed by the inhibitory activity of mcf10-a (human mammary) cel ...201525324134
recent clinical trials for the etiological treatment of chronic chagas disease: advances, challenges and perspectives.chagas disease, a chronic systemic parasitosis caused by the kinetoplastid protozoon trypanosoma cruzi, is the first cause of cardiac morbidity and mortality in poor rural and suburban areas of latin america and the largest parasitic disease burden in the continent, now spreading worldwide due to international migrations. a recent change in the scientific paradigm on the pathogenesis of chronic chagas disease has led to a consensus that all t. cruzi-seropositive patients should receive etiologic ...201525284065
lead identification to clinical candidate selection: drugs for chagas disease.chagas disease affects 8 million people worldwide and remains a main cause of death due to heart failure in latin america. the number of cases in the united states is now estimated to be 300,000, but there are currently no food and drug administration (fda)-approved drugs available for patients with chagas disease. to fill this gap, we have established a public-private partnership between the university of california, san francisco and the genomics institute of the novartis research foundation ( ...201525281737
from genome screening to creation of vaccine against trypanosoma cruzi by use of immunoinformatics.chagas disease is caused by the protozoan parasite trypanosoma cruzi, and activation of cd8(+) t cells is crucial for a protective immune response. therefore, the identification of antigens with major histocompatibility complex class i epitopes is a crucial step for vaccine development against t. cruzi. our aim was to identify novel antigens and epitopes by immunoinformatics analysis of the parasite proteome (12 969 proteins) and to validate their immunotherapeutic potential in infected mice. we ...201525070943
evidence of autochthonous chagas disease in southeastern texas.autochthonous transmission of trypanosoma cruzi in the united states is rarely reported. here, we describe five newly identified patients with autochthonously acquired infections from a small pilot study of positive blood donors in southeast texas. case-patients 1-4 were possibly infected near their residences, which were all in the same region ∼100 miles west of houston. case-patient 5 was a young male with considerable exposure from routine outdoor and camping activities associated with a yout ...201525371187
prevalence of trypanosoma cruzi antibodies in blood donors from veracruz state, mexico.trypanosoma cruzi is the causal agent of chagas disease. of the mexican states, veracruz is among the most affected by this sickness. however, the actual epidemiologic situation of this disease is not well understood. this study sought to determine the prevalence and risk factors for chagas disease among veracruzan blood donors.201525208459
identification of n-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole.chagas disease is an endemic infection in latin america with a high health impact. caused by the parasite trypanosoma cruzi, it has expanded to non-endemic regions such as north america and european countries via immigration of infected people. this infectious disease has been rising in the ranking of international health priorities due to the growing migration flows from endemic to non-endemic areas. benznidazole (bzn), a nitroheterocyclic drug, is one of the two trypanocidal drugs currently in ...201524711214
[diagnostic performance of surface electrocardiogram in early detection of chagasic cardiomyopathy].contrast-enhanced cardiac magnetic resonance imaging (cmr) allows early detection of myocardial involvement by trypanosoma cruzi infection. the aim of our study was to assess the diagnostic performance of the surface electrocardiogram (ecg) in the early detection of chagas' cardiomyopathy (ccm) compared with cmr.201524629695
triatominae biochemistry goes to school: evaluation of a novel tool for teaching basic biochemical concepts of chagas disease vectors.we evaluate a new approach to teaching the basic biochemistry mechanisms that regulate the biology of triatominae, major vectors of trypanosoma cruzi, the causative agent of chagas disease. we have designed and used a comic book, "carlos chagas: 100 years after a hero's discovery" containing scientific information obtained by seven distinguished contemporary brazilian researchers working with triatominaes. students (22) in the seventh grade of a public elementary school received the comic book. ...201524687369
uneventful benznidazole treatment of acute chagas disease during pregnancy: a case report.this report describes the case of a patient with acute chagas disease in tocantins, brazil, who was unaware of her pregnancy during benznidazole treatment. she presented with impaired cardiac function during the acute phase (pericarditis and incomplete right bundle-branch block) that resolved favorably after benznidazole therapy. serological results also became negative, as determined by hemagglutination assays, enzyme-linked immunosorbent assays, and immunofluorescence assays. the child was bor ...201525075496
reactivation of chagas disease: implications for global health.reactivation of chagas disease (cd) is a global public health issue. reactivation of disease can affect the management of cd and its clinical outcome, adding pressure to global health systems because it exacerbates symptoms, leading to misdiagnosis and delays in the administration of correct treatments. concurrent infections complicate the issue of reactivation, because there are various parasites and disease treatment regimens that are able to influence or suppress the immune system of the host ...201526458782
comparative effect of human and trypanosoma cruzi calreticulin in wound healing.in orthopaedics, the use of factors that enhance granulation tissue formation and prevent or delay new bone regeneration is sometimes desirable. calreticulin (crt), a unique endoplasmic reticulum luminal ca(2+) -binding chaperone widely distributed in eukaryotic cells, is involved in many cellular functions. among them, crt has an important influence in cutaneous wound healing and diverse processes associated with cutaneous repair, inhibition of angiogenesis, promotion of cell adhesion and antit ...201523109509
trypanosomal trans-sialidases: valuable synthetic tools and targets for medicinal chemistry.in contrast to the general hydrolases, trans-sialidase from trypanosoma cruzi (tcts) shows excellent regio- and stereoselectivity as well as high yields in transfer reactions. discussed are the occurrence of trans-sialidases and studies on the transfer mechanism. in detail, the preparative use by chemoenzymatic syntheses with tcts are outlined with emphasis on the design of modified donor and acceptor substrates. another section focuses on attempts to develop inhibitors for tcts, and these endea ...201522648866
effect of the urease-derived peptide jaburetox on the central nervous system of triatoma infestans (insecta: heteroptera).triatoma infestans is the main vector of chagas'disease in southern cone countries. in triatomines, symptoms suggesting neurotoxicity were observed after treatment with jaburetox (jbtx), the entomotoxic peptide obtained from jackbean urease. here, we study its effect in the central nervous system (cns) of this species.201525445710
prevalence of chagas disease in latin-american migrants living in europe: a systematic review and meta-analysis.few studies have assessed the burden of chagas disease in non-endemic countries and most of them are based on prevalence estimates from latin american (la) countries that likely differ from the prevalence in migrants living in europe. the aim of this study was to systematically review the existing data informing current understanding of the prevalence of chagas disease in la migrants living in european countries.201525680190
cardiac contractility structure-activity relationship and ligand-receptor interactions; the discovery of unique and novel molecular switches in myosuppressin signaling.peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. myosuppressin (ms), a decapeptide, diminishes cardiac contractility and gut motility. myosuppressin binds to g protein-coupled receptor (gpcr) proteins. two drosophila melanogaster myosuppressin receptors (drmms-rs) exist; however, no mechanism underlying ms-r activation is reported. we predicted dr ...201525793503
trypanosoma cruzi infection induces myocardial nitric oxide synthase.chagas' disease caused by trypanosoma cruzi, is an important cause of myocarditis and cardiomyopathy. acute and chronic infection is associated with myocardial dysfunction, including dysrhythmias, conduction disturbances, and congestive heart failure. nitric oxide (no) has been implicated in the myocardial dysfunction associated with diseases of the myocardium. the inducible form of nitric oxide synthase (inos) mediates the synthesis of no and l-citrulline from l-arginine. an abundance of inos m ...201525850327
chagas' disease: microvascular and interstitial matrix abnormalities characteristic of congestive cardiomyopathy of diverse etiology.chagas' disease, due to a chronic and persistent infection with the parasite trypanosoma cruzi, is the cause of one of the most prevalent forms of congestive cardiomyopathy in south and central america. in common with other congestive cardiomyopathies due to acquired and hereditary etiologies seen worldwide, chagasic cardiomyopathy is characterized by cardiomegaly, ventricular chamber remodeling, myocellular necrosis, and multifocal areas of interstitial and replacement fibrosis. the microscopic ...201525851575
beneficial effects of gangliosides on the natural history of acute chagasic myocarditis in rats.this study was designed to investigate the effects of ganglioside treatment on acutely trypanosoma cruzi-infected rats with emphasis on the heart. newly weaned wistar rats were infected with t. cruzi (colombian strain, 50,000 parasites/kg body weight injected intraperitoneally). two groups of 25 infected rats received daily injections of saline or ganglioside (10 mg/kg body weight) intraperitoneally between the 14th and 30th days after infection. two groups of 10 noninfected rats were similarly ...201525851009
absence of trypanosoma cruzi myocardial infection reactivation in chagas' heart transplant.the risk of trypanosoma cruzi myocardial infection reactivation after immunosuppressive therapy has led to precluding heart transplantation as a therapeutic procedure for patients with end-stage chagas' heart disease. we report a case of an orthotopic heart transplantation in a 43-year-old critically ill chagasic patient with an uneventful postoperative period. he was treated with azathioprine and cyclosporine to control graft rejection and showed no reactivation of the chagasic infection. one y ...201525991019
correlation between trypanosoma cruzi parasitism and myocardial inflammatory infiltrate in human chronic chagasic myocarditis: light microscopy and immunohistochemical findings.trypanosoma cruzi parasites are only rarely identified in conventional histological sections of hearts from chronic chagasic patients. this finding suggests that t. cruzi plays no important direct role in the chronic myocarditis that accordingly has been considered mainly an autoimmune process. we reinvestigated this issue using a polyclonal anti-t. cruzi antibody serum to map immunohistochemically the t. cruzi antigen(s) in 9 different regions of 8 necropsy hearts and 24 septal fragments from 2 ...201525990604
development of a community-based intervention for the control of chagas disease based on peridomestic animal management: an eco-bio-social perspective.integrated vector management strategies depend on local eco-bio-social conditions, community participation, political will and inter-sectorial partnership. previously identified risk factors for persistent triatoma dimidiata infestation include the presence of rodents and chickens, tiled roofs, dirt floors, partial wall plastering and dog density.201525604767
genomic and functional characterization of a methoprene-tolerant gene in the kissing-bug rhodnius prolixus.metamorphosis, which depends upon a fine balance between two groups of lipid-soluble hormones such as juvenile hormones (jhs) and ecdysteroids, is an important feature in insect evolution. while it is clear that the onset of metamorphosis depends on the decrease of jh levels, the way in which these hormones exert their activities is not fully understood in triatominae species. the discovery of a drosophila melanogaster mutant resistant to the treatment with the jh analog methoprene, led finally ...201525963043
functional characterization and expression analysis of the myoinhibiting peptide receptor in the chagas disease vector, rhodnius prolixus.myoinhibiting peptides (mips), which are also known as b-type allatostatins, are a family of neuropeptides found in protostomes. their primary structure is characterized by an amidated carboxyl-terminal motif consisting of a conserved pair of tryptophan residues normally separated by six non-conserved amino acids (w(x6)wamide). in the fruit fly drosophila melanogaster, mips are likely the ancestral ligands of the sex peptide receptor, which plays an important role in courtship and reproduction. ...201525218475
evidence of selection on phenotypic plasticity and cost of plasticity in response to host-feeding sources in the major chagas disease vector triatoma infestans.phenotypic plasticity is the ability of a genotype to display alternative phenotypes in different environments. understanding how plasticity evolves and the factors that favor and constrain its evolution have attracted great interest. we investigated whether selection on phenotypic plasticity and costs of plasticity affect head and wing morphology in response to host-feeding sources in the major chagas disease vector triatoma infestans. full-sib families were assigned to blood-feeding on either ...201526433077
host-feeding sources and habitats jointly affect wing developmental stability depending on sex in the major chagas disease vector triatoma infestans.fluctuating asymmetry (fa), a slight and random departure from bilateral symmetry that is normally distributed around a 0 mean, has been widely used to infer developmental instability. we investigated whether habitats (ecotopes) and host-feeding sources influenced wing fa of the hematophagous bug triatoma infestans. because bug populations occupying distinct habitats differed substantially and consistently in various aspects such as feeding rates, engorgement status and the proportion of gravid ...201526318543
chagasic meningoencephalitis in an hiv infected patient with moderate immunosuppression: prolonged survival and challenges in the haart era.the reactivation of chagas disease in hiv infected patients presents high mortality and morbidity. we present the case of a female patient with confirmed chagasic meningoencephalitis as aids-defining illness. interestingly, her tcd4+ lymphocyte cell count was 318 cells/mm3. after two months of induction therapy, one year of maintenance with benznidazol, and early introduction of highly active antiretroviral therapy (haart), the patient had good clinical, parasitological and radiological evolutio ...201527049711
genetic susceptibility to cardiac and digestive clinical forms of chronic chagas disease: involvement of the ccr5 59029 a/g polymorphism.the clinical manifestations of chronic chagas disease include the cardiac form of the disease and the digestive form. not all the factors that act in the variable clinical course of this disease are known. this study investigated whether the ccr5δ32 (rs333) and ccr5 59029 a/g (promoter region--rs1799987) polymorphisms of the ccr5 gene are associated with different clinical forms of chronic chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic chag ...201526599761
genetically attenuated trypanosoma cruzi parasites as a potential vaccination tool.chagas disease is the clinical manifestation of the infection produced by the parasite trypanosoma cruzi. currently there is no vaccine to prevent this disease and the protection attained with vaccines containing non-replicating parasites is limited. genetically attenuated trypanosomatid parasites can be obtained by deletion of selected genes. gene deletion takes advantage of the fact that this parasite can undergo homologous recombination between endogenous and foreign dna sequences artificiall ...201522705838
right ventricular doppler echocardiographic study of indeterminate form of chagas disease.patients with indeterminate form of chagas disease/cardiac normality (icd/cn) exhibited normal electrocardiograms and chest x-rays; however, more sophisticated tests detected some degree of morphological and functional changes in the heart.201525517391
entoepidemiology of chagas disease in the western region of the state of são paulo from 2004 to 2008, and cytogenetic analysis in rhodnius neglectus (hemiptera, triatominae).to complement the epidemiological data and assist in the prophylaxis of chagas disease in the state of são paulo, we examined entomological lifting conducted in 40 municipalities of the western region of the state from 2004 to 2008, highlighted the main vector species in this region, and reanalyzed the cytogenetic characteristics of rhodnius neglectus from 3 different brazilian states (formoso/go, frutal/mg, guaíra/sp, and pitangueiras/sp). the municipalities of castilho and santo antônio do aca ...201526125776
neglected diseases prioritized in brazil under the perspective of metabolomics: a review.this review article compiles in a critical manner literature publications regarding seven neglected diseases (nd) prioritized in brazil (chagas disease, dengue, leishmaniasis, leprosy, malaria, schistosomiasis, and tuberculosis) under the perspective of metabolomics. both strategies, targeted and untargeted metabolomics, were considered in the compilation. the majority of studies focused on biomarker discovery for diagnostic purposes, and on the search of novel or alternative therapies against t ...201526095472
antitrypanosomal acetylene fatty acid derivatives from the seeds of porcelia macrocarpa (annonaceae).chagas' disease is caused by a parasitic protozoan and affects the poorest population in the world, causing high mortality and morbidity. as a result of the toxicity and long duration of current treatments, the discovery of novel and more efficacious drugs is crucial. in this work, the hexane extract from seeds of porcelia macrocarpa r.e. fries (annonaceae) displayed in vitro antitrypanosomal activity against trypomastigote forms of t. cruzi by the colorimetric mtt assay (ic50 of 65.44 μg/ml). u ...201525961159
drug design for neglected disease in brazil.neglected tropical diseases (ntd) are a group of 17 diseases transmitted by virus, protozoa, helminthes and bacteria. these illnesses are responsible for millions of deaths per year, affecting mainly the poorest populations in the world. the therapeutic drugs available are obsolete, toxic, have questionable efficacy and there are reports of resistance. therefore, the discovery of new, safe, effective and affordable active molecules is urgently needed. considering that, the main purpose of this m ...201525769971
sudden cardiac death in brazil: a community-based autopsy series (2006-2010).sudden cardiac death (scd) is a sudden unexpected event, from a cardiac cause, that occurs in less than one hour after the symptoms onset, in a person without any previous condition that would seem fatal or who was seen without any symptoms 24 hours before found dead. although it is a relatively frequent event, there are only few reliable data in underdeveloped countries.201525424162
neurologic manifestations of the neglected tropical diseases.the world health organization has identified 17 neglected tropical diseases (ntds) that disproportionately affect the world's poorest populations. the neurologic aspects of many of these ntds have received relatively little attention.201525623803
innovative community-based ecosystem management for dengue and chagas disease prevention in low and middle income countries in latin america and the caribbean.in 2009, the who special programme for research and training in tropical diseases (tdr) and the international development research centre (idrc) launched a call for innovative community-based ecosystem management research projects for dengue and chagas disease prevention in low and middle income countries in latin america and the caribbean. eight research institutions were selected. the outputs of these projects led to a better understanding of the interaction between ecological, biological, soc ...201525604758
innovative community-based vector control interventions for improved dengue and chagas disease prevention in latin america: introduction to the special issue. 201525604757
chagas disease: morbidity profile in an endemic area of northeastern brazil.this study evaluated the clinical forms and manifestation severities of chagas disease among serologically reactive individuals from western rio grande do norte (northeastern brazil).201526676495
giant fecaloma causing small bowel obstruction: case report and review of the literature.fecaloma is a mass of hardened feces being impacted mostly in rectum and sigmoid. the most common sites of the fecaloma is the sigmoid colon and the rectum. there are several causes of fecaloma and have been described in association with hirschsprung's disease, psychiatric patients, chagas disease, both inflammatory and neoplastic, and in patients suffering with chronic constipation. up to now several cases of giant fecaloma has been reported in the literature most of them presenting with megaco ...201527162906
mitral subvalvular aneurysm in a patient with chagas disease and recurrent episodes of ventricular tachycardia.subvalvular left ventricular aneurysm is a rare disease of obscure origin suggesting unique causes such as congenital, traumatic, and inflammatory or infectious diseases. its mortality is closely related to heart failure, mitral insufficiency, thromboembolic phenomena, and cardiac arrhythmias. although association with coronary artery disease is not described, the compression of epicardial vessels by the aneurysm may lead to ischemic manifestations. we report here a case of mitral subvalvular le ...201526634158
hit and lead criteria in drug discovery for infectious diseases of the developing world.reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. the quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. with this in mind, the japanese global health innovative technology (ghit) fund convened with experts from the medicines for mala ...201526435527
controlled but not cured: structural processes and explanatory models of chagas disease in tropical bolivia.dressler (2001:456) characterizes medical anthropology as divided between two poles: the constructivist, which focuses on the "meaning and significance that events have for people," and the structuralist, which emphasizes socioeconomic processes and relationships. this study synthesizes structuralist and constructivist perspectives by investigating how structural processes impact explanatory models of chagas disease in a highly endemic area. the research took place from march-june 2013 through t ...201526432176
clinical predictors of inducible sustained ventricular tachycardia during electrophysiologic study in patients with chronic chagas' heart disease.clinical independent predictors of inducible sustained ventricular tachycardia (vt) during electrophysiologic study (eps) are not known in patients with chronic chagas' heart disease. the purpose of this investigation was to fill this gap.201528785714
oral outbreak of chagas disease in santa catarina, brazil: experimental evaluation of a patient's strain.chagas disease is a worldwide public health problem. although the vectorial transmission of chagas disease has been controlled in brazil there are other ways of transmission, such as the ingestion of t. cruzi contaminated food, which ensures the continuation of this zoonosis. here, we demonstrate the influence of the inoculation route on the establishment and development of the sc2005 t. cruzi strain infection in mice. groups of swiss mice were infected intragastrically (ig) or intraperitoneally ...201526469517
adenosine deaminase activity and serum c-reactive protein as prognostic markers of chagas disease severity.chagas disease is a public health problem worldwide. the availability of diagnostic tools to predict the development of chronic chagas cardiomyopathy is crucial to reduce morbidity and mortality. here we analyze the prognostic value of adenosine deaminase serum activity (ada) and c-reactive protein serum levels (crp) in chagasic individuals. one hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase i (n = 35), ii (n = 29), and iii (n ...201526603224
developments in the management of chagas cardiomyopathy.over 100 years have elapsed since the discovery of chagas disease and there is still much to learn regarding pathogenesis and treatment. although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. a recently released negative clinical trial with benznidazole in patients with chronic chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. new drugs and new delivery systems, including those based o ...201526496376
importation and transmission of parasitic and other infectious diseases associated with international adoptees and refugees immigrating into the united states of america.each year, hundreds of millions of people travel across international borders or even oceans, and up to 230 million may remain for long periods. among these, 3-5 million settle permanently in their new homes, with about 1 million migrating permanently to the united states of america. this may result in transport of parasites and other pathogens, which might become established, infecting individuals in the new location. beyond concern of disease spread, the health of migrants is of concern since ...201526583130
revisiting the posttherapeutic cure criterion in chagas disease: time for new methods, more questions, doubts, and polemics or time to change old concepts?one of the most relevant issues beyond the effectiveness of etiological treatment of chagas disease is the lack of consensual/feasible tools to identify and certify the definitive parasitological cure. several methods of distinct natures (parasitological, serological, and molecular) have been continuously proposed and novel perspectives are currently under investigation. although the simultaneous use of distinct tests may offer better contributions and advances, it also leads to controversies of ...201526583124
determination of nifurtimox in dog plasma by stable-isotope dilution lc-ms/ms.nifurtimox is a 5-nitrofuran derived antiprotozoal drug used to treat diseases caused by trypanosomes including chagas' disease and sleeping sickness (african trypanosomiasis). available methods for the determination of nifurtimox in plasma are tedious and of low sensitivity. for the first time, an isotope dilution hplc/ms/ms method for the sensitive quantitation of nifurtimox down to 10.0 μg/l in plasma is described.201526564573
chagas' disease. 201526535524
chagas' disease. 201526535523
chagas' disease. 201526535522
should trypanocidal therapy be used to treat patients in the chronic phase of chagas disease?antiparasitic treatment of patients with chagas’ disease in chronic stage could prevent the complications related to the disease. searching in epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including eight randomized trials and 11 observational studies. we combined the evidence using meta-analysis and generated a summary of findings table following the grade approach. we concluded it is not clear whether antiparasitic treatment improv ...201526523987
long-term follow-up of a patient since the acute phase of chagas disease (south american trypanosomiasis): further treatment and cure of the infection.a woman had been followed since 1957 for acute phase chagas disease. parasitological and serological tests were positive, and treatment included benznidazole in 1974. following treatment, parasitological test results were negative and conventional serology remained positive until 1994, with subsequent discordant results (1995-1997). the results became consistently negative since 1999. she had an indeterminate chronic form until 1974. only two minor and transitory nonspecific alterations on elect ...201526516979
chagas disease: are we there yet? 201526513768
clinical and epidemiological profile of elderly patients with chagas disease followed between 2005-2013 by pharmaceutical care service in ceará state, northeastern brazil.by controlling the transmission of chagas disease, the challenge of providing assistance to millions of infected patients that reach old age arises. in this study, the socioeconomic, demographic and comorbidity records of all elderly chagasic patients followed at the pharmaceutical care service of the chagas disease research laboratory were assessed. the information related to the clinical form of the disease was obtained from medical records provided by the walter cantídio university hospital. ...201525923894
is pentraxin 3 a cardiovascular marker in patients with chronic chagas disease? 201525920034
economic evaluation of chagas disease screening in spain.although spain is the european country with the highest chagas disease burden, the country does not have a national control program of the disease. the purpose of this study is to evaluate the efficiency of several strategies for chagas disease screening among latin american residents living in spain. the following screening strategies were evaluated: (1) non-screening; (2) screening of the latin american pregnant women and their newborns; (3) screening also the relatives of the positive pregnan ...201525917718
deltamethrin toxicological profile of peridomestic triatoma sordida in the north of minas gerais, brazil.in general, there was a large reduction in the occurrence of cases of chagas disease in the last decades in brazil. however, despite all of these efforts, there have been various reports of persistent reinfestations of t. sordida in a large part of the state of minas gerais, for reasons still little investigated. thus, this purpose of this study was to characterize the deltamethrin susceptibility profile of peridomestic t. sordida populations from north of minas gerais-brazil.201525952153
where do these bugs come from? phenotypic structure of triatoma infestans populations after control interventions in the argentine chaco.house re-invasion by native triatomines after insecticide-based control campaigns represents a major threat for chagas disease vector control. we conducted a longitudinal intervention study in a rural section (area iii, 407 houses) of pampa del indio, northeastern argentina, and used wing geometric morphometry to compare pre-spray and post-spray (re-infestant bugs) triatoma infestans populations. the community-wide spraying with pyrethroids reduced the prevalence of house infestation by t. infes ...201525946158
effect of pacemaker site on b-type natriuretic peptide levels and left ventricular function in a population with high prevalence of chagas disease. 201525935619
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