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spermatogenesis in nesotriatoma bruneri (usinger 1944) (hemiptera, triatominae).the nesotriatoma genus consists of the species n. flavida n. bruneri and n. obscura, forming the flavida complex. variation in the size and morphological differences intraspecific of n. flavida led to the description of n. bruneri. two years later, the same author proposed the synonymization of n. bruneri with n. flavida. only in 1981 the specific status n. bruneri was recovered by means of morphological analysis of the genitalia. however, recently by genetic analysis, it was suggested that n. b ...201627706579
electrochemical magnetic microbeads-based biosensor for point-of-care serodiagnosis of infectious diseases.access to appropriate diagnostic tools is an essential component in the evaluation and improvement of global health. additionally, timely detection of infectious agents is critical in early diagnosis and treatment of infectious diseases. conventional pathogen detection methods such as culturing, enzyme linked immunosorbent assay (elisa) or polymerase chain reaction (pcr) require long assay times, and complex and expensive instruments making them not adaptable to point-of-care (poc) needs at reso ...201626802749
tolerance to trypanosomatids: a threat, or a key for disease elimination?so far, research on trypanosomatid infections has been driven by 'disease by disease' approaches, leading to different concepts and control strategies. it is, however, increasingly clear that they share common features such as the ability to generate long-lasting asymptomatic infections in their mammalian hosts. trypanotolerance, long integrated in animal african trypanosomiasis control, historically refers to the ability of cattle breeds to limit trypanosoma infection and pathology, but has onl ...201626643519
isolation and characterization of the corticotropin-releasing factor-related diuretic hormone receptor in rhodnius prolixus.rhodnius prolixus, the vector of human chagas disease, is a hemipteran insect that undergoes rapid post-feeding diuresis following ingestion of a blood meal that can be up to 10 times its initial body weight. corticotropin-releasing factor-related diuretic hormone (rhopr-crf/dh) and serotonin are neurohormones that are synergistic in increasing rates of fluid secretion by malpighian tubules during this rapid post-feeding diuresis. a rhopr-crf/dh receptor transcript has now been isolated and char ...201627237375
selective insecticide applications directed against triatoma infestans (hemiptera: reduviidae) affected a nontarget secondary vector of chagas disease, triatoma garciabesi.the control of nondomiciliated triatomine species adapted to peridomestic habitats represents a challenge because they are connected to sylvatic colonies, and pyrethroid insecticides have limited effects outdoors. the effects of residual insecticide spraying have rarely been assessed on secondary triatomines. triatoma garciabesi (carcavallo, martinez, cichero, prosen & ronderos, 1967) is a nontarget vector that inhabits the dry western chaco region, and a member of the triatoma sordida stål 1859 ...201626490000
zoonotic trypanosomes in south east asia: attempts to control trypanosoma lewisi using human and animal trypanocidal drugs.beside typical human trypanosomes responsible of sleeping sickness in africa and chagas disease in latin america, there is a growing number of reported atypical human infections due to trypanosoma evansi, a livestock parasite, or trypanosoma lewisi, a rat parasite, especially in asia. drugs available for the treatment of t. brucei ssp. in humans are obviously of choice for the control of t. evansi because it is derived from t. brucei. however, concerning t. lewisi, there is an urgent need to det ...201627491458
chagas heart disease: report on recent developments.chagas disease, caused by the parasite trypanosoma cruzi, is an important cause of cardiac disease in endemic areas of latin america. it is now being diagnosed in nonendemic areas because of immigration. typical cardiac manifestations of chagas disease include dilated cardiomyopathy, congestive heart failure, arrhythmias, cardioembolism, and stroke. clinical and laboratory-based research to define the pathology resulting from t. cruzi infection has shed light on many of the cellular and molecula ...201622293860
temporal variation of trypanosoma cruzi discrete typing units in asymptomatic chagas disease patients.chagas disease caused by trypanosoma cruzi is a public health problem in latin america. this parasite displays a high genetic diversity evidenced in six discrete typing units (dtus) namely tci-tcvi. the aim of this study was to observe the temporal variation of the dtus in asymptomatic patients at three different times (10 days interval). the results showed that intermittence is the rule in the bloodstream of chagas disease patients. the patients showed different detectable dtus with short time ...201623811021
the in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from salvia gilliesii.the search for new compounds with trypanocidal activity is crucial for the treatment of chagas' disease. previous in vitro studies have shown that the diterpene 5-epi-icetexone (ictx) is active against trypanosoma cruzi. the aim of this work was to evaluate the effect of ictx on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. swiss albino mice were infected with t. cruzi and treated daily with 10mg/kg/day ictx (i.p.). infected mice and mice in ...201626341064
heterogeneous infectiousness in guinea pigs experimentally infected with trypanosoma cruzi.guinea pigs are important reservoirs of trypanosoma cruzi, the causative parasite of chagas disease, and in the southern cone of south america, transmission is mediated mainly by the vector triatoma infestans. interestingly, colonies of triatoma infestans captured from guinea pig corrals sporadically have infection prevalence rates above 80%. such high values are not consistent with the relatively short 7-8 week parasitemic period that has been reported for guinea pigs in the literature. we expe ...201626432777
involvement of sulfates from cruzipain, a major antigen of trypanosoma cruzi, in the interaction with immunomodulatory molecule siglec-e.in order to investigate the involvement of sulfated groups in the trypanosoma cruzi host-parasite relationship, we studied the interaction between the major cysteine proteinase of t. cruzi, cruzipain (cz), a sulfate-containing sialylated molecule and the sialic acid-binding immunoglobulin like lectin-e (siglec-e). to this aim, elisa, indirect immunofluorescence assays and flow cytometry, using mouse siglec-e-fc fusion molecules and glycoproteins of parasites, were performed. competition assays v ...201626047932
analysis of cyclosporin a and a set of analogs as inhibitors of a t. cruzi cyclophilin by docking and molecular dynamics.cyclophilins (cyps) are enzymes involved in protein folding. in trypanosoma cruzi (t. cruzi), the most abundantly expressed cyp is the isoform tccyp19. it has been shown that tccyp19 is inhibited by the immunosuppressive drug cyclosporin a (csa) and analogs, which also proved to have potent trypanosomicidal activity in vitro. in this work, we continue and expand a previous study on the molecular interactions of csa, and a set of analogs modeled in complexes with tccyp19. the modeled complexes we ...201626046477
trypanosoma cruzi screening in texas blood donors, 2008-2012.chagas disease is an important emerging disease in texas that results in cardiomyopathy in about 30% of those infected with the parasite trypanosoma cruzi. between the years 2008 and 2012, about 1/6500 blood donors were t. cruzi antibody-confirmed positive. we found older persons and minority populations, particularly hispanic, at highest risk for screening positive for t. cruzi antibodies during routine blood donation. zip code analysis determined that t. cruzi is associated with poverty. chaga ...201625170765
importance of hybrids of meccus phyllosomus mazzottii, and m. p. pallidipennis, and m. p. phyllosomus to the transmission of trypanosoma cruzi in mexico.the time interval before beginning feeding, feeding time, and defecation delay for 3 triatominae subspecies, meccus phyllosomus mazzottii (ma), m. p. pallidipennis (pa), and m. p. phyllosomus (phy) and their laboratory hybrids were evaluated. the mean time interval for beginning feeding was between 0.1 and 10.1 min for all nymphal instars in each cohort, with significant (p < 0.05) differences among hybrids and parental cohorts. four (both mapa and maphy) hybrid cohorts had similar mean feeding ...201626255738
synthesis and pharmaceutical properties of n-acyloxymethyl prodrugs of allop with potential anti-trypanosomal activity.we report herein the synthesis, and the physicochemical and pharmacokinetic properties of n-acyloxymethyl prodrugs of allopurinol (allop) (2a-f). allop is a compound with activity against trypanosoma cruzi, a causative agent of chagas disease. its pathology leads to a huge number of infections and deaths per year, because in addition to many sufferers only having limited access to health services only an inefficient chemotherapy is available. relevant pharmaceutical properties (pka, stability, s ...201626181622
rhodnius prolixus supergene families of enzymes potentially associated with insecticide resistance.chagas disease or american trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, trypanosoma cruzi. once known as an endemic health problem of poor rural populations in latin american countries, it has now spread worldwide. the parasite is transmitted by triatomine bugs, of which rhodnius prolixus (hemiptera, reduviidae, triatominae) is one of the vectors and a model organism. this species occurs mainly in central and south american countries where the dise ...201626079630
the glycosomal-membrane associated phosphoglycerate kinase isoenzyme a plays a role in sustaining the glucose flux in trypanosoma cruzi epimastigotes.in trypanosoma cruzi three isoenzymes of phosphoglycerate kinase (pgk) are found which are simultaneously expressed: the cytosolic isoenzyme pgkb as well as two glycosomal enzymes, pgka and pgkc. in this paper, we show that pgka in t. cruzi epimastigotes is associated to the glycosomal membrane; it is responsible for about 23% of the glycosomal pgk activity, the fraction that remains in the pellet after osmotic shock treatment of purified organelles, in contrast to the 77% soluble activity that ...201625917939
resistance to normal human serum reveals trypanosoma lewisi as an underestimated human pathogen.human-infectious trypanosomes such as trypanosoma cruzi, t. brucei rhodesiense, and t. b. gambiense can be discriminated from those only infecting animals by their resistance to normal human serum (nhs). these parasites are naturally resistant to trypanolysis induced by the human-specific pore-forming serum protein apolipoprotein l1 (apol-1). t. lewisi, a worldwide distributed parasite, has been considered as rat-specific and non-pathogenic to the natural hosts. here we provide evidence that 19 ...201625858024
hydroxamic acid derivatives: a promising scaffold for rational compound optimization in chagas disease.this work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (had1) and p-ethoxy (had2) as substituent in the aromatic ring linked to the isoxazoline ring. had1 and had2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability. ultrastructural alterations af ...201626327246
infection rate by trypanosoma cruzi and biased vertebrate host selection in the triatoma dimidiata (hemiptera: reduvidae) species complex.chagas disease is a vector-borne disease, caused by the protozoan parasite trypanosoma cruzi and transmitted by hematophagous insects. triatoma dimidiata (hemiptera: reduvidae (latreille 1811)) is one of the main vectors, and recent molecular studies indicate that it is a species complex, with potentially different vectorial competences. we investigated the differences in natural t. cruzi infection rate within t. dimidiata complex in yucatan, mexico. its-2 hybrid bugs had a twofold higher infect ...201626474882
ten years (2004-2014) of chagas disease surveillance and vector control in ecuador: successes and challenges.to describe the current situation of chagas disease in ecuador and to evaluate the impact of vector control for the period 2004-2014.201626458237
molecular dynamics simulations of the free and inhibitor-bound cruzain systems in aqueous solvent: insights on the inhibition mechanism in acidic ph.the major cysteine protease of trypanosoma cruzi, cruzain (crz), has been described as a therapeutic target for chagas' disease, which affects millions of people worldwide. thus, a series of crz inhibitors has been studied, including a new competitive inhibitor, nequimed176 (neq176). nevertheless, the structural and dynamic basis for crz inhibition remains unclear. hoping to contribute to this ever-growing understanding of timescale dynamics in the crz inhibition mechanism, we have performed the ...201626414241
synthesis of galα(1,3)galβ(1,4)glcnacα-, galβ(1,4)glcnacα- and glcnac-containing neoglycoproteins and their immunological evaluation in the context of chagas disease.the protozoan parasite, trypanosoma cruzi, the etiologic agent of chagas disease (chd), has a cell surface covered by immunogenic glycoconjugates. one of the immunodominant glycotopes, the trisaccharide galα(1,3)galβ(1,4)glcnacα, is expressed on glycosylphosphatidylinositol-anchored mucins of the infective trypomastigote stage of t. cruzi and triggers high levels of protective anti-α-gal antibodies (abs) in infected individuals. here, we have efficiently synthesized the mercaptopropyl glycoside ...201626384953
risk factors associated with chagas disease in pregnant women in santander, a highly endemic colombian area.to determine the prevalence and risk factors associated with chagas disease in pregnant women in an endemic area of santander, colombia.201626578246
natural cysteine protease inhibitors in protozoa: fifteen years of the chagasin family.chagasin-type inhibitors comprise natural inhibitors of papain-like cysteine proteases that are distributed among protist, bacteria and archaea. chagasin was identified in the pathogenic protozoa trypanosoma cruzi as an approximately 11 kda protein that is a tight-binding and highly thermostable inhibitor of papain, cysteine cathepsins and endogenous parasite cysteine proteases. it displays an imunoglobulin-like fold with three exposed loops to one side of the molecule, where amino acid residues ...201626546840
multilocus analysis indicates that trypanosoma cruzi i genetic substructure associated with sylvatic and domestic cycles is not an attribute conserved throughout colombia.trypanosoma cruzi, the causative agent of chagas disease, has been classified into six discrete typing units (dtus) named tci to tcvi. furthermore, subcontinental scale studies based on analysis of the splice leader intergenic region (sl-ir) of the mini-exon gene have subdivided tci in five genetic groups (ia-ie) related to the domestic and non-domestic cycles. however, a current review of this marker among all the sequences deposited in the genbank demonstrates no correlation between the geneti ...201626631812
lysosome biogenesis/scattering increases host cell susceptibility to invasion by trypanosoma cruzi metacyclic forms and resistance to tissue culture trypomastigotes.a fundamental question to be clarified concerning the host cell invasion by trypanosoma cruzi is whether the insect-borne and mammalian-stage parasites use similar mechanisms for invasion. to address that question, we analysed the cell invasion capacity of metacyclic trypomastigotes (mt) and tissue culture trypomastigotes (tct) under diverse conditions. incubation of parasites for 1 h with hela cells in nutrient-deprived medium, a condition that triggered lysosome biogenesis and scattering, incr ...201626572924
trypanosoma cruzi mitochondrial tryparedoxin peroxidase is located throughout the cell and its pull down provides one step towards the understanding of its mechanism of action.trypanosoma cruzi depends on the effectiveness of redox metabolism to survive and ensure infection in the host. homeostasis of redox metabolism in t. cruzi is achieved by the actions of several proteins that differ in many aspects from host proteins. although extensive research has been performed examining hydroperoxide cytosolic antioxidant defense centered on trypanothione, the mechanisms of mitochondrial antioxidant defense are not yet known. the aim of this study was to elucidate the partner ...201626527457
trypanosoma cruzi infection induces the expression of cd40 in murine cardiomyocytes favoring cd40 ligation-dependent production of cardiopathogenic il-6.the inflammatory response in the myocardium is an important aspect of the pathogenesis of chagas' heart disease raised by trypanosoma cruzi. cd40, a transmembrane type i receptor belonging to the tumor necrosis factor receptor (tnfr) family, is expressed in a broad spectrum of cell types and is crucial in several inflammatory and autoimmune diseases. activation of cd40 through ligation to cd40l (cd154) induces multiple effects, including the secretion of proinflammatory molecules. in the present ...201626526953
trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers.trypanosoma cruzi, the protozoan parasite that causes chagas' disease, has anticancer effects mediated, at least in part, by parasite-derived products which inhibit growth of tumor cells. we investigated whether immunity to t. cruzi antigens could induce antitumor activity, using two rat models which reproduce human carcinogenesis: colon cancer induced by 1,2-dimethylhydrazine (dmh), and mammary cancer induced by n-nitroso-n-methylurea (nmu). we found that vaccination with t. cruzi epimastigote ...201626519949
glycosomal bromodomain factor 1 from trypanosoma cruzi enhances trypomastigote cell infection and intracellular amastigote growth.acetylation is a ubiquitous protein modification present in prokaryotic and eukaryotic cells that participates in the regulation of many cellular processes. the bromodomain is the only domain known to bind acetylated lysine residues. in the last few years, many bromodomain inhibitors have been developed in order to treat diseases caused by aberrant acetylation of lysine residues and have been tested as anti-parasitic drugs. in the present paper, we report the first characterization of trypanosom ...201626500280
biochemical characterization of branched chain amino acids uptake in trypanosoma cruzi.trypanosoma cruzi is the etiological agent of chagas disease. during its life cycle, it alternates among vertebrate and invertebrate hosts. metabolic flexibility is a main biochemical characteristic of this parasite, which is able to obtain energy by oxidizing a variety of nutrients that can be transported from the extracellular medium. moreover, several of these metabolites, more specifically amino acids, have a variety of functions beyond being sources of energy. branched chain amino acids (bc ...201626496801
potent and selective inhibitors of trypanosoma cruzi triosephosphate isomerase with concomitant inhibition of cruzipain: inhibition of parasite growth through multitarget activity.triosephosphate isomerase (tim) is an essential trypanosoma cruzi enzyme and one of the few validated drug targets for chagas disease. the known inhibitors of this enzyme behave poorly or have low activity in the parasite. in this work, we used symmetrical diarylideneketones derived from structures with trypanosomicidal activity. we obtained an enzymatic inhibitor with an ic50 value of 86 nm without inhibition effects on the mammalian enzyme. these molecules also affected cruzipain, another esse ...201626492824
sexual transmission of trypanosoma cruzi in murine model.trypanosoma cruzi is mainly transmitted by blood-sucking triatomines, but other routes also have epidemiological importance, such as blood transfusion and congenital transmission. although the possibility of sexual transmission of t. cruzi has been suggested since its discovery, few studies have been published on this subject. we investigated acquisition of t. cruzi by sexual intercourse in an experimental murine model. male and female mice in the chronic phase of chagas disease were mated with ...201626724377
interactions between trypanosoma cruzi the chagas disease parasite and naturally infected wild mepraia vectors of chile.chagas disease, which ranks among the world's most neglected diseases, is a chronic, systemic, parasitic infection caused by the protozoan trypanosoma cruzi. mepraia species are the wild vectors of this parasite in chile. host-parasite interactions can occur at several levels, such as co-speciation and ecological host fitting, among others. thus, we are exploring the interactions between t. cruzi circulating in naturally infected mepraia species in all areas endemic of chile. we evaluated t. cru ...201626771702
early regulation of profibrotic genes in primary human cardiac myocytes by trypanosoma cruzi.the molecular mechanisms of trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. primary human cardiomyoctes (phcm) exposed to invasive t. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). the identification of early molecular host responses to t. cruzi infection can be exploited to delineate important molecular signatures that can be ...201626771187
characterization of tccyc6 from trypanosoma cruzi, a gene with homology to mitotic cyclins.trypanosoma cruzi, the etiologic agent of chagas disease, is a protozoan parasite with a life cycle that alternates between replicative and non-replicative forms, but the components and mechanisms that regulate its cell cycle are poorly described. in higher eukaryotes, cyclins are proteins that activate cyclin-dependent kinases (cdks), by associating with them along the different stages of the cell cycle. these cyclin-cdk complexes exert their role as major modulators of the cell cycle by phosph ...201626709077
a comparative study of trypanosoma cruzi infection in sylvatic mammals from a protected and a disturbed area in the argentine chaco.understanding the complex epidemiology of trypanosoma cruzi transmission cycles requires comparative studies in widely different environments. we assessed the occurrence of t. cruzi infection in sylvatic mammals, their infectiousness to the vector, and parasite genotypes in a protected area of the argentine chaco, and compared them with information obtained similarly in a nearby disturbed area. a total of 278 mammals from >23 species in the protected area were diagnosed for t. cruzi infection us ...201626708994
morpholino antisense oligo inhibits trans-splicing of pre-inositol 1,4,5-trisphosphate receptor mrna of trypanosoma cruzi and suppresses parasite growth and infectivity.morpholino antisense oligos (maos) are used to investigate physiological gene function by inhibiting gene translation or construction of specific alternative splicing variants by blocking cis-splicing. maos are attractive drug candidates for viral- and bacterial-infectious disease therapy because of properties such as in vivo stability and specificity to target genes. recently, we showed that phosphorothioate antisense oligos against trypanosoma cruzi inositol 1,4,5-trisphosphate receptor (tcip( ...201626680159
quantitative enzymatic production of sialylated galactooligosaccharides with an engineered sialidase from trypanosoma rangeli.sialylated galactooligosaccharides (gos) represent a potential infant formula ingredient, which is believed to contribute with a combination of the beneficial properties of the prebiotic gos as well as of sialylated human milk oligosaccharides. sialylated gos do not exist in natural milk, but can be produced from κ(kappa)-casein glycomacropeptide (cgmp), a sialylated side stream component from cheese-making, by sialidase-catalyzed transsialylation. using a rationally designed mutant of the siali ...201626672447
insights into the regulation of mrna processing of polycistronic transcripts mediated by drbd4/ptb2, a trypanosome homolog of the polypyrimidine tract-binding protein.trypanosomes regulate gene expression mostly by posttranscriptional mechanisms, including control of mrna turnover and translation efficiency. this regulation is carried out via certain elements located at the 3'-untranslated regions of mrnas, which are recognized by rna-binding proteins. in trypanosomes, trans-splicing is of central importance to control mrna maturation. we have previously shown that tcdrbd4/ptb2, a trypanosome homolog of the human polypyrimidine tract-binding protein splicing ...201626663092
synthesis of glycosylphosphatidylinositol (gpi)-anchor glycolipids bearing unsaturated lipids.2-naphthyl-methyl ethers as permanent protecting groups are readily removed under acidic conditions and are key to the synthesis of complex glycosylphosphatidylinositol anchors containing unsaturated lipids. the total synthesis of the gpi pseudo-disaccharide core found on the surface of the trypanosoma cruzi parasite serves to illustrate the power of the strategy.201626660677
multi-epitope proteins for improved serological detection of trypanosoma cruzi infection and chagas disease.we previously reported that tandem repeat (tr) proteins from trypanosoma cruzi could serve as targets of the antibody response and be useful as diagnostic indicators. to optimize reagents for detecting t. cruzi infection we evaluated individual tr proteins and identified several that were recognized by the majority of chagas patient's sera collected from individuals form brazil. we then produced novel, recombinant fusion proteins to combine the reactive tr proteins into a single diagnostic produ ...201626658314
clinical candidate vt-1161's antiparasitic effect in vitro, activity in a murine model of chagas disease, and structural characterization in complex with the target enzyme cyp51 from trypanosoma cruzi.a novel antifungal drug candidate, the 1-tetrazole-based agent vt-1161 [(r)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1h-tetrazol-1-yl)-1-{5-[4-(2,2,2-trifluoroethoxy)phenyl]pyridin-2-yl}propan-2-ol], which is currently in two phase 2b antifungal clinical trials, was found to be a tight-binding ligand (apparent dissociation constant [kd], 24 nm) and a potent inhibitor of cytochrome p450 sterol 14α-demethylase (cyp51) from the protozoan pathogen trypanosoma cruzi. moreover, vt-1161 revealed a high l ...201626643331
trypanosoma cruzi: single cell live imaging inside infected tissues.although imaging the live trypanosoma cruzi parasite is a routine technique in most laboratories, identification of the parasite in infected tissues and organs has been hindered by their intrinsic opaque nature. we describe a simple method for in vivo observation of live single-cell trypanosoma cruzi parasites inside mammalian host tissues. balb/c or c57bl/6 mice infected with dsred-cl or gfp-g trypomastigotes had their organs removed and sectioned with surgical blades. ex vivo organ sections we ...201626639617
identification and characterization of the trypanosoma cruzi b-cell superantigen tc24.trypanosoma cruzi causes life-long disease after infection and leads to cardiac disease in 30% of infected individuals. after infection, the parasites are readily detectable in the blood during the first few days before disseminating to infect numerous cell types. preliminary data suggested that the tc24 protein that localizes to the t. cruzi membrane during all life stages possesses b-cell superantigenic properties. these antigens facilitate immune escape by interfering with antibody-mediated r ...201626598565
human polymorphisms in placentally expressed genes and their association with susceptibility to congenital trypanosoma cruzi infection.it is currently unclear why only a proportion of children born to trypanosoma cruzi-infected mothers acquire the infection. we have examined the association of 11 single-nucleotide polymorphisms (snps) located in genes coding for placental expression enzymes as genetic markers of susceptibility to congenital t. cruzi infection (hereafter, "congenital infection"): rs2014683 and rs1048988 in alpp; rs11244787 and rs1871054 in adam12; rs243866, rs243865, rs17859821, rs243864, and rs2285053 in mmp2; ...201626597259
dibenzylideneacetones are potent trypanocidal compounds that affect the trypanosoma cruzi redox system.despite ongoing efforts, the available treatments for chagas' disease are still unsatisfactory, especially in the chronic phase of the disease. our previous study reported the strong trypanocidal activity of the dibenzylideneacetones a3k2a1 and a3k2a3 against trypanosoma cruzi (z. ud din, t. p. fill, f. f. de assis, d. lazarin-bidóia, v. kaplum, f. p. garcia, c. v. nakamura, k. t. de oliveira, and e. rodrigues-filho, bioorg med chem 22:1121-1127, 2014, http://dx.doi.org/10.1016/j.bmc.2013.12.020 ...201626596953
new scheme of intermittent benznidazole administration in patients chronically infected with trypanosoma cruzi: a pilot short-term follow-up study with adult patients.there is a clinical need to test new schemes of benznidazole administration that are expected to be at least as effective as the current therapeutic scheme but safer. this study assessed a new scheme of benznidazole administration in chronic chagas disease patients. a pilot study with intermittent doses of benznidazole at 5 mg/kg/day in two daily doses every 5 days for a total of 60 days was designed. the main criterion of response was the comparison of quantitative pcr (qpcr) findings prior to ...201626596935
systems biology approach to model the life cycle of trypanosoma cruzi.due to recent advances in reprogramming cell phenotypes, many efforts have been dedicated to developing reverse engineering procedures for the identification of gene regulatory networks that emulate dynamical properties associated with the cell fates of a given biological system. in this work, we propose a systems biology approach for the reconstruction of the gene regulatory network underlying the dynamics of the trypanosoma cruzi's life cycle. by means of an optimisation procedure, we embedded ...201626752404
the trypanosoma cruzi protein tchte is critical for heme uptake.trypanosoma cruzi, the etiological agent of chagas' disease, presents nutritional requirements for several metabolites. it requires heme for the biosynthesis of several heme-proteins involved in essential metabolic pathways like mitochondrial cytochromes and respiratory complexes, as well as enzymes involved in the biosynthesis of sterols and unsaturated fatty acids. however, this parasite lacks a complete route for its synthesis. in view of these facts, t. cruzi has to incorporate heme from the ...201626752206
trypanosoma cruzi proline transport presents a cell density-dependent regulation.trypanosoma cruzi, the etiological agent of chagas disease, uses proline as its main carbon source, essential for parasite growth and stage differentiation in epimastigotes and amastigotes. since proline is mainly obtained from extracellular medium by transport proteins, in this work we studied the regulation of the t. cruzi proline transporter tcaaap069. proline uptake and intracellular concentration presented oscillations during epimastigote growth phases, increasing during the early exponenti ...201626750517
synthesis and biological evaluation of quinoxaline di-n-oxide derivatives with in vitro trypanocidal activity.we report the synthesis and in vitro activity against trypanosoma cruzi epimastigotes of 15 novel quinoxaline derivatives. ten of the derivatives presented ic50 values lower than the reference drugs nfx and bzn; four of them standed out with ic50 values lower than 1.5 μm. moreover, unspecific cytotoxicity and genotoxicity studies are also reported. compound 14 showed a si higher than 24, whereas compound 10 was the only one that was negative in the genotoxicity screening.201626750255
current drug therapy and pharmaceutical challenges for chagas disease.one of the most significant health problems in the american continent in terms of human health, and socioeconomic impact is chagas disease, caused by the protozoan parasite trypanosoma cruzi. infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. likewise, chaga ...201626747009
trypanosoma cruzi experimental infection impacts on the thymic regulatory t cell compartment.the dynamics of regulatory t cells in the course of trypanosoma cruzi infection is still debated. we previously demonstrated that acute murine t. cruzi infection results in an impaired peripheral cd4+foxp3+ t cell differentiation due to the acquisition of an abnormal th1-like phenotype and altered functional features, negatively impacting on the course of infection. moreover, t. cruzi infection induces an intense thymic atrophy. as known, the thymus is the primary lymphoid organ in which thymic- ...201626745276
genetically determined mbl deficiency is associated with protection against chronic cardiomyopathy in chagas disease.chagas disease (cd) is caused by trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (mbl), a soluble pattern-recognition molecule that activates the lectin pathway of complement. mbl levels and protein activity are affected by polymorphisms in the mbl2 gene. we sequenced the mbl2 promoter and exon 1 in 196 chronic cd patients and 202 controls. the mbl2*c allele, which causes mbl deficiency, was associated with protection against cd (p = 0.007, or = 0.32). compared wi ...201626745156
use of noninvasive parameters to evaluate swiss webster mice during trypanosoma cruzi experimental acute infection.until now, there has been neither an agreed-upon experimental model nor descriptors of the clinical symptoms that occur over the course of acute murine infection. the aim of this work is to use noninvasive methods to evaluate clinical signs in swiss webster mice that were experimentally infected with the y strain of trypanosoma cruzi during acute phase (inf group). infected mice showed evident clinical changes beginning in the second week of infection (wpi) when compared to the noninfected group ...201626741817
facing chagas' disease: trypanocidal properties of new coumarin-chalcone scaffolds.with the aim of finding new chemical entities based on coumarin and chalcone scaffolds, new hybrid compounds 2-5 were designed and synthesized. the trypanocidal activity of these compounds was tested against the epimastigote, trypomastigote and amastigote stages of the trypanosoma cruzi parasite. cytotoxicity assays were also performed in raw 264.7 and vero cells. compound 5 presented the highest trypanocidal activity of the series, with trypanocidal values higher than nifurtimox for the trypoma ...201626740208
applicability of a novel immunoassay based on surface plasmon resonance for the diagnosis of chagas disease.we defined the methodological criteria for the interpretation of the results provided by a novel immunoassay based on surface plasmon resonance (spr) to detect antibodies anti-trypanosoma cruzi in human sera (sprcruzi). then, we evaluated its applicability as a diagnostic tool for chagas disease.201626731593
human trypanosomiasis in the eastern plains of colombia: new transmission scenario.characteristics of trypanosoma cruzi infection were studied in a rural area of the eastern plains of colombia. using enzyme-linked immunosorbent assay and indirect fluorescent-antibody tests, the infection was determined in 11.6% of the inhabitants of 142 dwellings. during 6 months of community surveillance, in 42.3% dwellings, 609 triatomines were collected (597 rhodnius prolixus and seven, three, one, and one of panstrongylus geniculatus, psammolestes arturi, eratyrus mucronatus, and triatoma ...201626728765
detection of trypanosoma cruzi by polymerase chain reaction.american trypanosomiasis (chagas disease) is an infectious disease caused by the hemoflagellate parasite trypanosoma cruzi which is transmitted by reduviid bugs. t. cruzi infection occurs in a broad spectrum of reservoir animals throughout north, central, and south america and usually evolves into an asymptomatic chronic clinical stage of the disease in which diagnosis is often challenging. this chapter describes the application of polymerase chain reaction (pcr) for the detection of trypanosoma ...201626843052
genotyping of trypanosoma cruzi dtus and trypanosoma rangeli genetic groups in experimentally infected rhodnius prolixus by pcr-rflp.the specific detection and genetic typing of trypanosomes that infect humans, mammalian reservoirs, and vectors is crucial for diagnosis and epidemiology. we utilized a pcr-rflp assay that targeted subunit ii of cytochrome oxidase and 24sα-rdna to simultaneously detect and discriminate six trypanosoma cruzi discrete typing units (dtus) and two genetic groups of trypanosoma rangeli (kp1+/kp1-) in intestinal contents of experimentally infected rhodnius prolixus. the pcr assays showed that in 23 of ...201626792202
reproductive biology of triatoma brasiliensis (hemiptera, triatominae) during the imaginal molt.the triatomines are vectors of the protozoan trypanosoma cruzi, etiologic agent of chagas disease. these insects are sexually active after the imaginal molt. some aspects have been studied in triatoma brasiliensis during the imaginal molt, such as autogeny in virgin females and the relationship between blood ingestion by fifth instar nymph and the realization of the imaginal molt. thus, to aid in the understanding of reproductive biology and developmental physiology of these vectors, this articl ...201626787143
sialic acid glycobiology unveils trypanosoma cruzi trypomastigote membrane physiology.trypanosoma cruzi, the flagellate protozoan agent of chagas disease or american trypanosomiasis, is unable to synthesize sialic acids de novo. mucins and trans-sialidase (ts) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for t. cruzi life cycle. the acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. a major drawback to studying the sialyla ...201627058585
chagas' disease in aboriginal and creole communities from the gran chaco region of argentina: seroprevalence and molecular parasitological characterization.most indigenous ethnias from northern argentina live in rural areas of "the gran chaco" region, where trypanosoma cruzi is endemic. serological and parasitological features have been poorly characterized in aboriginal populations and scarce information exist regarding relevant t. cruzi discrete typing units (dtu) and parasitic loads. this study was focused to characterize t. cruzi infection in qom, mocoit, pit'laxá and wichi ethnias (n=604) and creole communities (n=257) inhabiting rural village ...201627057620
the trypanosoma cruzi diamine transporter is essential for robust infection of mammalian cells.trypanosoma cruzi is incapable of synthesizing putrescine or cadaverine de novo, and, therefore, salvage of polyamines from the host milieu is an obligatory nutritional function for the parasite. a high-affinity diamine transporter (tcpot1) from t. cruzi has been identified previously that recognizes both putrescine and cadaverine as ligands. in order to assess the functional role of tcpot1 in intact parasites, a δtcpot1 null mutant was constructed by targeted gene replacement and characterized. ...201627050410
role of monokine induced by interferon gamma in discrimination and prognosis of patients with chagas' disease and idiopathic dilated cardiomyopathy.monokine induced by interferon gamma (mig) is a chemokine that has been found to increase in the myocardium of mice infected with trypanosoma cruzi. it is not known whether mig is regulated in patients with chagas' disease (cd) and idiopathic dilated cardiomyopathy (dcm). therefore, we aimed to investigate the possible diagnostic and/or prognostic value of mig in these patients.201626828323
a high throughput analysis of cytokines and chemokines expression during the course of trypanosoma cruzi experimental oral infection.trypanosoma cruzi has high biological and biochemical diversity and variable tissue tropism. here we aimed to verify the kinetics of cytokine and chemokine in situ secretion in animals infected with two distinct t. cruzi strains after oral inoculation. also, we investigated parasite migration, residence and pathological damage in stomach, heart and spleen. our results showed that host immune response against t. cruzi infection is an intricate phenomenon that depends on the parasite strain, on th ...201626827742
[update chagas disease].the constant migration flows have favored the presence of people with chagas disease in regions traditionally regarded as non-endemic, such as north america, europe, asia and oceania. this has forced both health authorities and professionals to be updated in order to respond to such a demand for assistance. recent years have led to significant progress in the field of diagnosis and treatment of chagas disease, one of the most neglected tropical diseases. recent clinical trials are providing new ...201626827133
aspirin treatment exacerbates oral infections by trypanosoma cruzi.oral transmission of the protozoan parasite trypanosoma cruzi, the etiological agent of chagas disease, has been documented in latin american countries. the reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. there have been few studies on the physiopathology of the disease in oral transmission cases. gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infectio ...201626826555
gibbilimbol analogues as antiparasitic agents--synthesis and biological activity against trypanosoma cruzi and leishmania (l.) infantum.the essential oils from leaves of piper malacophyllum (piperaceae) showed to be mainly composed by two alkenylphenol derivatives: gibbilimbols a and b. after isolation and structural characterization by nmr and ms data analysis, both compounds were evaluated against promastigote/amastigote forms of leishmania (l.) infantum as well as trypomastigote/amastigote forms of trypanosoma cruzi. the obtained results indicated that gibbilimbol b displayed potential against the tested parasites and low tox ...201626821820
synthesis and evaluation of oxyguanidine analogues of the cysteine protease inhibitor wrr-483 against cruzain.a series of oxyguanidine analogues of the cysteine protease inhibitor wrr-483 were synthesized and evaluated against cruzain, the major cysteine protease of the protozoan parasite trypanosoma cruzi. kinetic analyses of these analogues indicated that they have comparable potency to previously prepared vinyl sulfone cruzain inhibitors. co-crystal structures of the oxyguanidine analogues wrr-666 (4) and wrr-669 (7) bound to cruzain demonstrated different binding interactions with the cysteine prote ...201626819670
colonization of rhodnius prolixus gut by trypanosoma cruzi involves an extensive parasite killing.trypanosoma cruzi, the etiological agent of chagas disease, is ingested by triatomines during their bloodmeal on an infected mammal. aiming to investigate the development and differentiation of t. cruzi inside the intestinal tract of rhodnius prolixus at the beginning of infection we fed insects with cultured epimastigotes and blood trypomastigotes from infected mice to determine the amount of recovered parasites after ingestion. approximately 20% of the ingested parasites was found in the insec ...201626818093
the dynamics of brazilian protozoology over the past century.brazilian scientists have been contributing to the protozoology field for more than 100 years with important discoveries of new species such as trypanosoma cruzi and leishmania spp. in this work, we used a brazilian thesis database (coordination for the improvement of higher education personnel) covering the period from 1987-2011 to identify researchers who contributed substantially to protozoology. we selected 248 advisors by filtering to obtain researchers who supervised at least 10 theses. ba ...201626814646
vector-borne transmission of trypanosoma cruzi among captive neotropical primates in a brazilian zoo.neotropical primates are important sylvatic hosts of trypanosoma cruzi, the etiological agent of chagas disease. infection is often subclinical, but severe disease has been described in both free-ranging and captive primates. panstrongylus megistus, a major t. cruzi vector, was found infesting a small-primate unit at brasília zoo (zoob), brazil. zoob lies close to a gallery-forest patch where t. cruzi circulates naturally. here, we combine parasitological and molecular methods to investigate a f ...201626813657
increased mortality attributed to chagas disease: a systematic review and meta-analysis.the clinical outcomes associated with chagas disease remain poorly understood. in addition to the burden of morbidity, the burden of mortality due to trypanosoma cruzi infection can be substantial, yet its quantification has eluded rigorous scrutiny. this is partly due to considerable heterogeneity between studies, which can influence the resulting estimates. there is a pressing need for accurate estimates of mortality due to chagas disease that can be used to improve mathematical modelling, bur ...201626813568
semisynthesis of new aphidicolin derivatives with high activity against trypanosoma cruzi.chagas disease continues to be a difficult disease to eradicate, largely because of the widespread populations it affects as well as the highly toxic effects of current therapies. thus, the exploration of innovative scaffolds, ideally with distinct mechanisms of action, is urgently needed. the natural product aphidicolin and its effects on cell cycle division have been widely studied; it is a potent inhibitor of parasitic cells. in the present study, we report for the first time the semisynthesi ...201626810263
phenotypic features of circulating leukocytes from non-human primates naturally infected with trypanosoma cruzi resemble the major immunological findings observed in human chagas disease.cynomolgus macaques (macaca fascicularis) represent a feasible model for research on chagas disease since natural t. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. however, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. we have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus ...201626808481
molecular diversity of trypanosoma cruzi detected in the vector triatoma protracta from california, usa.trypanosoma cruzi, causative agent of chagas disease in humans and dogs, is a vector-borne zoonotic protozoan parasite that can cause fatal cardiac disease. while recognized as the most economically important parasitic infection in latin america, the incidence of chagas disease in the united states of america (us) may be underreported and even increasing. the extensive genetic diversity of t. cruzi in latin america is well-documented and likely influences disease progression, severity and treatm ...201626797311
histopathological correlates of global and segmental left ventricular systolic dysfunction in experimental chronic chagas cardiomyopathy.chronic chagas cardiomyopathy in humans is characterized by segmental left ventricular wall motion abnormalities (wma), mainly in the early stages of disease. this study aimed at investigating the detection of wma and its correlation with the underlying histopathological changes in a chronic chagas cardiomyopathy model in hamsters.201626796255
ruthenium(ii) complexes of 1,3-thiazolidine-2-thione: cytotoxicity against tumor cells and anti-trypanosoma cruzi activity enhanced upon combination with benznidazole.three new mixed and mononuclear ru(ii) complexes containing 1,3-thiazolidine-2-thione (tzdth) were synthesized and characterized by spectroscopic analysis, molar conductivity, cyclic voltammetry, high-resolution electrospray ionization mass spectra and x-ray diffraction. the complexes presented unique stereochemistry and the proposed formulae are: [ru(tzdt)(bipy)(dppb)]pf6 (1), cis-[ru(tzdt)2(pph3)2] (2) and trans-[ru(tzdt)(pph3)2(bipy)]pf6 (3), where dppb=1,4-bis(diphenylphosphino)butane and bi ...201626795676
new 1,3-thiazole derivatives and their biological and ultrastructural effects on trypanosoma cruzi.in previous studies, the compound 3-(bromopropiophenone) thiosemicarbazone was described as a potent anti-trypanosoma cruzi and cruzain inhibitor. in view to optimize this activity, 1,3-thiazole core was used as building-block strategy to access new lead generation of anti t. cruzi agents. in this way a series of thiazole derivatives were synthesized and most of these derivatives exhibited antiparasitic activity similar to benznidazole (bzd). among them, compounds (1c) and (1g) presented better ...201627295485
wc-9 a lead drug with great prospects for american trypanosomiasis and toxoplasmosis.trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien- 3β-ol brings forth an inhibition of proliferation on trypanosoma cruzi, the etiologic agent of american trypanosomiasis or chagas disease. these metabolites are crucial; consequently, ...201627290911
trypanosoma cruzi modulates gene expression of plasma membrane repair-related proteins.plasma membrane injury and repair is particularly prevalent in muscle cells. here, we aimed to verify dysferlin, acid sphingomyelinase and transcriptional factor eb gene expression during trypanosoma cruzi infection in vitro and in vivo. our results showed that the parasite modulates gene expression of these proteins in a way dependent on the number of plasma membrane interacting parasites and in a rapamycin-sensitive manner.201627288707
expression and the peculiar enzymatic behavior of the trypanosoma cruzi nth1 dna glycosylase.trypanosoma cruzi, the etiological agent of chagas' disease, presents three cellular forms (trypomastigotes, epimastigotes and amastigotes), all of which are submitted to oxidative species in its hosts. however, t. cruzi is able to resist oxidative stress suggesting a high efficiency of its dna repair machinery.the base excision repair (ber) pathway is one of the main dna repair mechanisms in other eukaryotes and in t. cruzi as well. dna glycosylases are enzymes involved in the recognition of ox ...201627284968
a versatile qpcr assay to quantify trypanosomatidic infections of host cells and tissues.the majority of pcr-based detection systems for leishmania spp. and trypanosoma cruzi aim at high sensitivity and specificity, rather than an accurate parasite load quantification required for experimental infections in basic research and drug development. here, we describe the use of a dual-labelled probe qpcr to detect and quantify intracellular old world leishmania spp. and t. cruzi amastigotes after in vitro and in vivo infection experiments. we show that quantification of parasite actin gen ...201627283847
trypanosoma cruzi invasion into host cells: a complex molecular targets interplay.chagas' disease is still a worldwide threat, with estimated from 6 to 7 million infected people, mainly in latin america. despite all efforts, especially from international consortia (dndi, nmtrypi), to develop an innovative therapeutic strategy against this disease, no candidate has achieved full requirements for clinical use yet. in this review, we point out the general molecular and cellular mechanisms involved in t. cruzi cell invasion and elucidate the roles of specific parasite and host ta ...201627281167
the c-terminal region of trypanosoma cruzi masps is antigenic and secreted via exovesicles.trypanosoma cruzi is the etiological agent of chagas disease, a neglected and emerging tropical disease, endemic to south america and present in non-endemic regions due to human migration. the masp multigene family is specific to t. cruzi, accounting for 6% of the parasite's genome and plays a key role in immune evasion. a common feature of masps is the presence of two conserved regions: an n-terminal region codifying for signal peptide and a c-terminal (c-term) region, which potentially acts as ...201627270330
the nuclear elongation factor-1α gene: a promising marker for phylogenetic studies of triatominae (hemiptera: reduviidae).molecular systematics is a remarkable approach for understanding the taxonomic traits and allows the exploration of the inter-population dynamics of several species in the triatominae subfamily that are involved in trypanosoma cruzi transmission. compared to other relevant species that transmit vector-borne diseases, such as some species of the diptera, there are relatively few nuclear genetic markers available for systematic studies in the triatominae subfamily. molecular systematic studies per ...201627268149
trypanosoma cruzi: time for international recognition as a foodborne parasite. 201627253136
domestic pig (sus scrofa) as an animal model for experimental trypanosoma cruzi infection.pigs were infected with a bolivian strain of trypanosoma cruzi (genotype i) and evaluated up to 150 days postinoculation (dpi) to determine the use of pigs as an animal model of chagas disease. parasitemia was observed in the infected pigs during the acute phase (15-40 dpi). anti-t. cruzi immunoglobulin m was detected during 15-75 dpi; high levels of anti-t. cruzi immunoglobulin g were detected in all infected pigs from 75 to 150 dpi. parasitic dna was observed by western blot (58%, 28/48) and p ...201626928841
effects of aspirin-triggered resolvin d1 on peripheral blood mononuclear cells from patients with chagas' heart disease.chagas disease is caused by trypanosoma cruzi (t. cruzi). in some patients with chagas disease, symptoms progress to chronic chagasic cardiomyopathy. endogenously, inflammation is resolved in the presence of lipid mediators such as aspirin-triggered rvd1 (at-rvd1) which has anti-inflammatory and pro-resolution effects. here, we demonstrated, for the first time, the effects of at-rvd1 on t. cruzi antigen-stimulated peripheral blood mononuclear cells (pbmcs) from patients with chagas heart disease ...201626927755
here, there, and everywhere: the ubiquitous distribution of the immunosignaling molecule lysophosphatidylcholine and its role on chagas disease.chagas disease is a severe illness, which can lead to death if the patients are not promptly treated. the disease is caused by the protozoan parasite trypanosoma cruzi, which is mostly transmitted by a triatomine insect vector. there are 8-10 million people infected with t. cruzi in the world, but the transmission of such disease by bugs occurs only in the americas, especially latin america. chronically infected patients will develop cardiac diseases (30%) and up digestive, neurological, or mixe ...201626925065
norfloxacin and n-donor mixed-ligand copper(ii) complexes: synthesis, albumin interaction, and anti-trypanosoma cruzi activity.copper(ii) complexes with the first-generation quinolone antibacterial agent norfloxacin containing a nitrogen donor heterocyclic ligand 2,2'-bipyridine (bipy) or 1,10-phenanthroline (phen) were prepared and characterized by ir, epr spectra, molar conductivity, and elemental analyses. the experimental data suggest that norfloxacin was coordinated to copper(ii) through the carboxylato and ketone oxygen atoms. the interaction of the copper(ii) complexes with bovine serum albumin (bsa) and human se ...201626924953
in vitro screening of 2-(1h-imidazol-1-yl)-1-phenylethanol derivatives as antiprotozoal agents and docking studies on trypanosoma cruzi cyp51.sterol 14α-demethylase (cyp51) is a key enzyme involved in the survival and virulence of many parasite protozoa, such as trypanosoma and leishmania species, thus representing a valuable drug target for the treatment of kinetoplastid diseases. a set of azole-based compounds selected from an in-house compound library was in vitro screened against different human protozoan parasites. several compounds showed selective activity against trypanosoma cruzi, with compound 7 being the most active (ic50 = ...201626922226
antennal phenotype of mexican haplogroups of the triatoma dimidiata complex, vectors of chagas disease.triatoma dimidiata (latreille) is a species complex that spans north, central, and south america and which is a key vector of all known discrete typing units (dtu) of trypanosoma cruzi, the etiologic agent of chagas disease. morphological and genetic studies indicate that t. dimidiata is a species complex with three principal haplogroups (hg) in mexico. different markers and traits are still inconclusive regarding if other morphological differentiation may indicate probable behavioral and vector ...201626921798
chronic trypanosoma cruzi infection potentiates adipose tissue macrophage polarization toward an anti-inflammatory m2 phenotype and contributes to diabetes progression in a diet-induced obesity model.chronic obesity and chagas disease (caused by the protozoan trypanosoma cruzi) represent serious public health concerns. the interrelation between parasite infection, adipose tissue, immune system and metabolism in an obesogenic context, has not been entirely explored. a novel diet-induced obesity model (dio) was developed in c57bl/6 wild type mice to examine the effect of chronic infection (dio+i) on metabolic parameters and on obesity-related disorders. dyslipidemia, hyperleptinemia, and cardi ...201626921251
changes in proteome profile of peripheral blood mononuclear cells in chronic chagas disease.trypanosoma cruzi (tc) infection causes chagasic cardiomyopathy; however, why 30-40% of the patients develop clinical disease is not known. to discover the pathomechanisms in disease progression, we obtained the proteome signature of peripheral blood mononuclear cells (pbmcs) of normal healthy controls (n/h, n = 30) and subjects that were seropositive for tc-specific antibodies, but were clinically asymptomatic (c/a, n = 25) or clinically symptomatic (c/s, n = 28) with cardiac involvement and le ...201626919708
host and parasite genetics shape a link between trypanosoma cruzi infection dynamics and chronic cardiomyopathy.host and parasite diversity are suspected to be key factors in chagas disease pathogenesis. experimental investigation of underlying mechanisms is hampered by a lack of tools to detect scarce, pleiotropic infection foci. we developed sensitive imaging models to track trypanosoma cruzi infection dynamics and quantify tissue-specific parasite loads, with minimal sampling bias. we used this technology to investigate cardiomyopathy caused by highly divergent parasite strains in balb/c, c3h/hen and c ...201626918803
inhibition of carbonic anhydrase from trypanosoma cruzi for the management of chagas disease: an underexplored therapeutic opportunity.an α-carbonic anhydrases (cas, ec 4.2.1.1) was recently discovered, cloned and characterized in the genome of the protozoan parasite trypanosoma cruzi, the causative agent of chagas disease, a neglected but widespread tropical disease. inhibition of this α-cas (tcca) with anions, sulfonamides, sulfamates, thiols and hydroxamates has been investigated in detail, with several low nanomolar in vitro inhibitors. although the sulfonamides were the best in vitro inhibitors, they showed no ex vivo anti ...201626898220
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