| aromatic amino acid catabolism in trypanosomatids. | trypanosomatids cause important human diseases, like sleeping sickness, chagas disease, and the leishmaniases. unlike in the mammalian host, the metabolism of aromatic amino acids is a very simple pathway in these parasites. trypanosoma brucei and trypanosoma cruzi transaminate the three aromatic amino acids, the resulting 2-oxo acids being reduced to the corresponding lactate derivatives and excreted. in t. cruzi, two enzymes are involved in this process: a tyrosine aminotransferase (tat), whic ... | 2008 | 17433885 |
| comparative kinetics of cofactor association and dissociation for the human and trypanosomal s-adenosylhomocysteine hydrolases. 1. basic features of the association and dissociation processes. | the s-adenosyl-l-homocysteine (adohcy) hydrolases catalyze the reversible conversion of adohcy to adenosine and homocysteine, making use of a catalytic cycle in which a tightly bound nad+ oxidizes the 3-hydroxyl group of the substrate at the beginning of the cycle, activating the 4-ch bond for elimination of homocysteine, followed by michael addition of water to the resulting intermediate and a final reduction by the tightly bound nadh to give adenosine. the equilibrium and kinetic properties of ... | 2007 | 17447732 |
| a postgenomic view of the heat shock proteins in kinetoplastids. | the kinetoplastids leishmania major, trypanosoma brucei and trypanosoma cruzi are causative agents of a diverse spectrum of human diseases: leishmaniasis, sleeping sickness and chagas' disease, respectively. these protozoa possess digenetic life cycles that involve development in mammalian and insect hosts. it is generally accepted that temperature is a triggering factor of the developmental programme allowing the adaptation of the parasite to the mammalian conditions. the heat shock response is ... | 2007 | 17459115 |
| in vitro evaluation of the cytotoxic and trypanocidal activities of ampelozizyphus amazonicus (rhamnaceae). | ampelozizyphus amazonicus ducke is a tree commonly found in the amazon region and an extract of its stem bark is popularly used as an antimalarial and anti-inflammatory agent and as an antidote to snake venom. ursolic acid; five lupane type triterpenes: betulin, betulinic acid, lupenone, 3beta-hydroxylup-20(29)-ene-27,28-dioic acid, and 2alpha,3beta-dihydroxylup-20(29)-ene-27,28-dioic acid, and three phytosteroids: stigmasterol, sitosterol and campesterol, have been isolated from stem extracts o ... | 2007 | 17464428 |
| chagas' disease reactivation with skin symptoms in a patient with kidney transplant. | immunodepressed patients in the intermediate phase of chagas' disease may undergo reactivation of the disease together with atypical symptoms. the case of an immunodepressed kidney transplant patient with reactivation of chagas' disease with skin symptoms is reported. a 65-year-old man presented with infiltrated erythematous lesions on the anterior aspect of the right thigh of 2 weeks' duration. the lesions later extended to the abdomen, thorax, and lower limbs. in the histologic skin examinatio ... | 2007 | 17550560 |
| phytomonas serpens: immunological similarities with the human trypanosomatid pathogens. | the present review provides an overview of recent discoveries concerning the immunological similarities between phytomonas serpens, a tomato parasite, and human trypanosomatid pathogens, with special emphasis on peptidases. leishmania spp. and trypanosoma cruzi express peptidases that are well-known virulence factors, named leishmanolysin and cruzipain. p. serpens synthesizes two distinct classes of proteolytic enzymes, metallo- and cysteine-type peptidases, that share common epitopes with leish ... | 2007 | 17556002 |
| crystal structure of the parasite protease inhibitor chagasin in complex with a host target cysteine protease. | chagasin is a protein produced by trypanosoma cruzi, the parasite that causes chagas' disease. this small protein belongs to a recently defined family of cysteine protease inhibitors. although resembling well-known inhibitors like the cystatins in size (110 amino acid residues) and function (they all inhibit papain-like (c1 family) proteases), it has a unique amino acid sequence and structure. we have crystallized and solved the structure of chagasin in complex with the host cysteine protease, c ... | 2007 | 17561110 |
| histopathologic, immunohistochemical, and polymerase chain reaction assays in the study of cases with fatal sporadic myocarditis. | paraffin tissue blocks from 27 cases with sporadic myocarditis were collected during a 12-year period at a single medical examiner's office. blocks were studied by using histopathology; immunohistochemistry for viruses (adenovirus, enterovirus, influenza a and b, and human herpes types 4 and 5), bacteria (neisseria meningitidis, ehrlichia sp, spotted fever group rickettsia) and parasites (toxoplasma gondii and trypanosoma cruzi); and polymerase chain reaction (pcr)/rt-pcr for adenovirus and ente ... | 2007 | 17602724 |
| targeting the polyamine biosynthetic enzymes: a promising approach to therapy of african sleeping sickness, chagas' disease, and leishmaniasis. | trypanosomatids depend on spermidine for growth and survival. consequently, enzymes involved in spermidine synthesis and utilization, i.e. arginase, ornithine decarboxylase (odc), s-adenosylmethionine decarboxylase (adometdc), spermidine synthase, trypanothione synthetase (trys), and trypanothione reductase (tryr), are promising targets for drug development. the odc inhibitor alpha-difluoromethylornithine (dfmo) is about to become a first-line drug against human late-stage gambiense sleeping sic ... | 2007 | 17610127 |
| cross-priming of long lived protective cd8+ t cells against trypanosoma cruzi infection: importance of a tlr9 agonist and cd4+ t cells. | we recently described that vaccination of mice with a glutathione s transferase fusion protein representing amino acids 261-500 of the amastigote surface protein-2 efficiently cross-primed protective cd8+ t cells against a lethal challenge with the human protozoan parasite trypanosoma cruzi. in this study, we initially established that this protective immunity was long lived. subsequently, we studied the importance of tlr9 agonist cpg odn 1826, tlr4 and cd4+ t cells for the generation of these p ... | 2007 | 17629597 |
| human urine stimulates in vitro growth of trypanosoma cruzi and trypanosoma rangeli. | previous studies conducted in leishmania led us to test the hypothesis that addition of human urine (hu) to the liver infusion tryptose (lit) medium would stimulate the in vitro growth of trypanosoma cruzi and trypanosoma rangeli strains. herein, we show that the addition of 3% hu to lit medium (lit-hu3) significantly stimulated the growth of all the t. rangeli strains studied when compared with the parasite growth in conventional lit medium (p<0.05), and it was equivalent to the growth observed ... | 2007 | 17629735 |
| a cysteine protease inhibitor cures chagas' disease in an immunodeficient-mouse model of infection. | chagas' disease, caused by the parasite trypanosoma cruzi, remains the leading cause of cardiopathy in latin america with about 12 million people infected. classic clinical manifestations derive from infection of muscle cells leading to progressive cardiomyopathy, while some patients develop megacolon or megaesophagus. a very aggressive clinical course including fulminant meningoencephalitis has been reported in patients who contract chagas' disease in the background of immunodeficiency. this in ... | 2007 | 17698625 |
| current situation of chagas disease in central america. | chagas disease in central america is known since 1913 when the first human case was reported in el salvador. the other central american countries reported their first cases between 1933 and 1967. on october 1997 was launched the central american initiative for chagas disease control (ipca). the objectives of this sub-regional initiative are: (1) the elimination of rhodnius prolixus in central america; (2) the reduction of the domiciliary infestation of triatoma dimidiata; and (3) the elimination ... | 2007 | 17713679 |
| chagas' disease: igg isotypes against cytoplasmic (cra) and flagellar (fra) recombinant repetitive antigens of trypanosoma cruzi in chronic chagasic patients. | the wide range of clinical chagas' disease manifestations, of which heart involvement is the most significant, because of its characteristics, frequency and consequences, and lack of treatment and cure, justify research in this area. specific immunoglobulin g (igg) antibody subclasses have been associated with human chagas' disease. thus, in this study, the profile of igg subclasses against cytoplasmic (cra) and flagellar (fra) recombinant repetitive t. cruzi-specific antigens was correlated wit ... | 2007 | 17847109 |
| [seroprevalence of american trypanosomiasis in adults in an area of the western brazilian amazon region]. | from january to march 2001 a seroepidemiological survey for american trypanosomiasis (chagas disease) was carried out among urban and rural human populations in areas of the upper purus basin, in the western brazilian amazon region, using serial testing with three different serological techniques. the sample was composed of 1,055 individuals: 844 from urban and 211 from rural areas. autochthonous infection was identified in nine individuals aged 16 to 72 years: five from urban and four from rura ... | 2007 | 17876467 |
| chagas disease in the amazon region. | the risk that chagas disease becomes established as a major endemic threat in amazonia (the world's largest tropical biome, today inhabited by over 30 million people) relates to a complex set of interacting biological and social determinants. these include intense immigration from endemic areas (possibly introducing parasites and vectors), extensive landscape transformation with uncontrolled deforestation, and the great diversity of wild trypanosoma cruzi reservoir hosts and vectors (25 species ... | 2007 | 17891274 |
| mucin-type o-glycosylation in mesocestoides vogae (syn. corti). | protein glycosylation is an important post-translational modification underlying host-parasite interactions, which may determine the outcome of infection. although mesocestoides vogae represents an important model for investigating the various aspects of cestode biology, virtually no information is available about the structure and synthesis of glycans in this parasite. in this work, focused on the initiation pathway of mucin-type o-glycosylation in m. vogae, we characterized o-glycoproteins bea ... | 2008 | 17892882 |
| members of a large retroposon family are determinants of post-transcriptional gene expression in leishmania. | trypanosomatids are unicellular protists that include the human pathogens leishmania spp. (leishmaniasis), trypanosoma brucei (sleeping sickness), and trypanosoma cruzi (chagas disease). analysis of their recently completed genomes confirmed the presence of non-long-terminal repeat retrotransposons, also called retroposons. using the 79-bp signature sequence common to all trypanosomatid retroposons as bait, we identified in the leishmania major genome two new large families of small elements--lm ... | 2007 | 17907803 |
| an exploration of the genetic robustness landscape of surface protein families in the human protozoan parasite trypanosoma cruzi. | the ability of genes to be robust to mutations at the codon level has been suggested as a key factor for understanding adaptation features. it has been proposed that genes relevant to host-parasite interactions will tend to exhibit high volatility or "antirobust" patterns, which may be related to the capacity of the parasite to evade the host immune system. we compared two superfamilies of surface proteins, trans-sialidase (ts)-like proteins and putative surface protein dispersed gene family-1 ( ... | 2007 | 17926780 |
| in vivo anti-chagas vinylthio-, vinylsulfinyl-, and vinylsulfonylbenzofuroxan derivatives. | new benzofuroxans were developed and studied as antiproliferative trypanosoma cruzi agents. compounds displayed remarkable in vitro activities against different strains, tulahuen 2, cl brener and y. its unspecific cytotoxicity was evaluated using human macrophages being not toxic at a concentration at least 8 times, and until 250 times, that of its t. cruzi ic50. some biochemical pathways were studied, namely parasite respiration, cysteinyl active site enzymes and reaction with glutathione, as t ... | 2007 | 17960923 |
| heteroallyl-containing 5-nitrofuranes as new anti-trypanosoma cruzi agents with a dual mechanism of action. | new heteroallyl-containing 5-nitrofuranes were synthesized as potential anti-trypanosoma cruzi agents with a dual mechanism of action, oxidative stress and inhibition of membrane sterol biosynthesis. some of the derivatives were found to have high and selective activity against the proliferative stages of the parasite, with ic(50) values against the clinically relevant intracellular amastigote forms in the low micromolar to sub-micromolar range. oxidative stress was verified measuring cyanide de ... | 2008 | 17981471 |
| perturbation of the dimer interface of triosephosphate isomerase and its effect on trypanosoma cruzi. | chagas disease affects around 18 million people in the american continent. unfortunately, there is no satisfactory treatment for the disease. the drugs currently used are not specific and exert serious toxic effects. thus, there is an urgent need for drugs that are effective. looking for molecules to eliminate the parasite, we have targeted a central enzyme of the glycolytic pathway: triosephosphate isomerase (tim). the homodimeric enzyme is catalytically active only as a dimer. because there ar ... | 2007 | 17989778 |
| the chagas' disease parasite trypanosoma cruzi exploits nerve growth factor receptor trka to infect mammalian hosts. | trypanosoma cruzi, the agent of chagas' disease, is an obligate intracellular parasite that invades various organs including several cell types in the nervous system that express the trk receptor tyrosine kinase. activation of trk is a major cell-survival and repair mechanism, and parasites could use trks to invade cells as a strategy to protect their habitat and prolong parasitism of vertebrate hosts. we show that t. cruzi binds to trka specifically and activates trka-dependent survival mechani ... | 2007 | 18005706 |
| cloning and expression of trypanothione reductase from a new world leishmania species. | trypanothione disulfide (t[s]2), an unusual form of glutathione found in parasitic protozoa, plays a crucial role in the regulation of the intracellular thiol redox balance and in the defense against oxidative stress. trypanothione reductase (tr) is central to the thiol metabolism in all trypanosomatids, including the human pathogens trypanosoma cruzi, trypanosoma brucei and leishmania. here we report the cloning, sequencing and expression of the tr encoding gene from l. (l.) amazonensis. multip ... | 2008 | 18060667 |
| fas/fas-l expression, apoptosis and low proliferative response are associated with heart failure in patients with chronic chagas' disease. | chagas' disease affects 16-18 million patients in south america and heart involvement is the major cause of morbidity and mortality. heart failure is the most severe clinical manifestation of the chronic phase of infection with trypanosoma cruzi. the intensity and nature of the immune response is associated with the clinical outcome of the disease. in murine models, a low proliferative response and t-cell apoptosis have been observed during acute infection. in the present study the immune respon ... | 2008 | 18078776 |
| monocyte-derived dendritic cells from chagasic patients vs healthy donors secrete differential levels of il-10 and il-12 when stimulated with a protein fragment of trypanosoma cruzi heat-shock protein-70. | we analyzed the effect of the truncated heat-shock protein 70 from trypanosoma cruzi on maturation of human dendritic cells (dcs) derived from monocytes of peripheral blood mononuclear cells from healthy donors and chagasic patients. the results show that the t-hsp70 is capable of maturing human dcs inducing an increase in the expression level of the cd83, cd86 and human leukocyte antigen-dr surface markers, as well as in the secretion of interleukin (il)-12, tumor necrosis factor-alpha (tnf-alp ... | 2008 | 18180802 |
| behavioral plasticity of triatominae related to habitat selection in northeast brazil. | triatoma pseudomaculata corrêa and espínola, 1964 and triatoma juazeirensis costa and felix, 2007 ( = t. brasiliensis neiva, 1911 [part]), are sylvatic vectors of trypanosoma cruzi (chagas, 1909), the causative agent of chagas disease, in northeast brazil-especially in the caatinga region. in an area of caatinga in the state of bahia, we compared the wild and peridomestic habitats of these two species of triatominae to assess their behavioral plasticity in relation to habitat selection in differ ... | 2008 | 18283937 |
| melatonin enhances pro-inflammatory cytokine levels and protects against chagas disease. | pro-inflammatory and modulatory cytokines have an essential role in host defense against human and murine trypanosoma cruzi infection. control of t. cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. melatonin has been proposed to regulate the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several t helper (th)1 cytokines. the aims of this work were to ev ... | 2008 | 18284549 |
| comparative kinetics of cofactor association and dissociation for the human and trypanosomal s-adenosylhomocysteine hydrolases. 2. the role of helix 18 stability. | the s-adenosyl- l-homocysteine (adohcy) hydrolases (sahh) from homo sapiens (hs-sahh) and from the parasite trypanosoma cruzi (tc-sahh) are very similar in structure and catalytic properties but differ in the kinetics and thermodynamics of association and dissociation of the cofactor nad (+). the binding of nad (+) and nadh in sahh appears structurally to be mediated by helix 18, formed by seven residues near the c-terminus of the adjacent subunit. helix-propensity estimates indicate decreasing ... | 2008 | 18393535 |
| current concepts in immunoregulation and pathology of human chagas disease. | chagas disease is a complex ailment caused by infection with trypanosoma cruzi. it afflicts millions in latin america. years of studies have focused on the development of pathology in chagas disease and recent studies have helped us understand the cellular mechanisms behind differential clinical evolution of chagas disease. | 2008 | 18448974 |
| displacement of the occluding loop by the parasite protein, chagasin, results in efficient inhibition of human cathepsin b. | cathepsin b is a papain-like cysteine protease showing both endo- and exopeptidase activity, the latter due to a unique occluding loop that restricts access to the active site cleft. to clarify the mode by which natural protein inhibitors manage to overcome this obstacle, we have analyzed the structure and function of cathepsin b in complexes with the trypanosoma cruzi inhibitor, chagasin. kinetic analysis revealed that substitution of his-110e, which anchors the loop in occluding position, resu ... | 2008 | 18515357 |
| importance of species of triatominae (heteroptera: reduviidae) in risk of transmission of trypanosoma cruzi in western mexico. | the epidemiological risk of infection by trypanosoma cruzi chagas in human populations of western mexico is still under study. although most vectors in this region and their vector capability are already known, new studies estimating the risk and the importance of individual triatominae species (hemiptera: reduviidae) for t. cruzi transmission are necessary. for 1 yr, every month, > 400 human dwellings and their surroundings in eight communities of two western mexico states were searched for tri ... | 2008 | 18533443 |
| structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of trypanosoma cruzi dihydrofolate reductase function. | we have employed a structure-based three-dimensional quantitative structure-activity relationship (3d-qsar) approach to predict the biochemical activity for inhibitors of t. cruzi dihydrofolate reductase-thymidylate synthase (dhfr-ts). crystal structures of complexes of the enzyme with eight different inhibitors of the dhfr activity together with the structure in the substrate-free state (dhfr domain) were used to validate and refine docking poses of ligands that constitute likely active conform ... | 2008 | 18536013 |
| molecular typing of trypanosoma cruzi isolates, united states. | studies have characterized trypanosoma cruzi from parasite-endemic regions. with new human cases, increasing numbers of veterinary cases, and influx of potentially infected immigrants, understanding the ecology of this organism in the united states is imperative. we used a classic typing scheme to determine the lineage of 107 isolates from various hosts. | 2008 | 18598637 |
| different serological cross-reactivity of trypanosoma rangeli forms in trypanosoma cruzi-infected patients sera. | abstract: | 2008 | 18611261 |
| ecology, evolution, and the long-term surveillance of vector-borne chagas disease: a multi-scale appraisal of the tribe rhodniini (triatominae). | chagas disease incidence has sharply declined over the last decade. long-term disease control will, however, require extensive, longitudinal surveillance systems capable of detecting (and dealing with) reinvasion-reinfestation of insecticide-treated dwellings by non-domiciliated triatomines. sound surveillance design calls for reliable data on vector ecology, and these data must cover different spatial scales. we conducted a multi-scale assessment of ecological and evolutionary trends in members ... | 2009 | 18619938 |
| calcineurin b of the human protozoan parasite trypanosoma cruzi is involved in cell invasion. | during trypanosoma cruzi cell invasion, signal transduction pathways are triggered in parasite and host cells, leading to a rise in intracellular ca2+ concentration. we posed the question whether calcineurin (can), in particular the functional regulatory subunit canb, a ca2+-binding ef-hand protein, was expressed in t. cruzi and whether it played a role in cell invasion. here we report the cloning and characterization of cl strain canb gene, as well as the participation of canb in cell invasion. ... | 2008 | 18657458 |
| cyp51: a major drug target in the cytochrome p450 superfamily. | the cytochrome p540 (cyp) superfamily currently includes about 9000 proteins forming more than 800 families. the enzymes catalyze monooxygenation of a vast array of compounds and play essentially two roles. they provide biodefense (detoxification of xenobiotics, antibiotic production) and participate in biosynthesis of important endogenous molecules, particularly steroids. based on these two roles, sterol 14/*alpha*/-demethylases (cyp51) belong to the second group of p450s. the cyp51 family, how ... | 2008 | 18769951 |
| complement c2 receptor inhibitor trispanning confers an increased ability to resist complement-mediated lysis in trypanosoma cruzi. | the ability to resist complement differs between the y and colombiana trypanosoma cruzi strains. we found that the y strain of t. cruzi was more able to resist the classical and lectin pathways of complement activation than the colombiana strain. the complement c2 receptor inhibitor trispanning gene (crit) is highly conserved in both strains. at the protein level, crit is expressed only in stationary-phase epimastigotes of the y but not the colombiana strain and is expressed in infectious metacy ... | 2008 | 18781865 |
| an agent-based model for predicting the prevalence of trypanosoma cruzi i and ii in their host and vector populations. | trypanosoma cruzi is the causative agent of chagas disease, an endemic human parasitosis in latin america. this protozoan is transmitted to human and other mammals by blood-feeding bugs belonging to the triatominae subfamily. there are two strains (t. cruzi i and t. cruzi ii) presenting different biological and ecological characteristics. an original agent-based model (abm) was designed for predicting the prevalence (i.e., proportion of infected individuals in the total population at a given tim ... | 2008 | 18805428 |
| trypanosoma cruzi transmission cycle among wild and domestic mammals in three areas of orally transmitted chagas disease outbreaks. | we report trypanosoma cruzi infection in wild and domestic mammals from three orally acquired chagas disease outbreak areas in brazil. cachoeiro do arari (pará) displayed a panzootic scenery (positive mammals in all ecologic strata), and human cases were probably the consequence of their exposure within the sylvatic t. cruzi transmission cycle. in navegantes (santa catarina), didelphis spp. was the main reservoir host, given that 93% were infected. in redenção (ceará), monodelphis domestica and ... | 2008 | 18981516 |
| trypanosoma cruzi in brazilian amazonia: lineages tci and tciia in wild primates, rhodnius spp. and in humans with chagas disease associated with oral transmission. | in this study, we provide phylogenetic and biogeographic evidence that the trypanosoma cruzi lineages t. cruzi i (tci) and t. cruzi iia (tciia) circulate amongst non-human primates in brazilian amazonia, and are transmitted by rhodnius species in overlapping arboreal transmission cycles, sporadically infecting humans. tci presented higher prevalence rates, and no lineages other than tci and tciia were found in this study in wild monkeys and rhodnius from the amazonian region. we characterised tc ... | 2009 | 19041313 |
| biological activity of 1,2,3,4-tetrahydro-beta-carboline-3-carboxamides against trypanosoma cruzi. | several beta-carboline compounds were evaluated for in vitro trypanocidal activity against trypanosoma cruzi and their potential toxic effects was also assessed. beta-carboline derivative 4 showed good activity against epimastigote, trypomastigote, and amastigote forms of t. cruzi, with a dose-dependent inhibitory effect. it showed an ic(50) of 14.9 microm against the epimastigote form and an ec(50) of 45 microm and 33 microm against trypomastigote and amastigote forms, respectively. additionall ... | 2009 | 19063858 |
| oxidosqualene cyclase from saccharomyces cerevisiae, trypanosoma cruzi, pneumocystis carinii and arabidopsis thaliana expressed in yeast: a model for the development of novel antiparasitic agents. | a series of 25 compounds, some of which previously were described as inhibitors of human liver microsomal oxidosqualene cyclase (osc), were tested as inhibitors of saccharomyces cerevisiae, trypanosoma cruzi, pneumocystis carinii and arabidopsis thaliana oscs expressed in an osc-defective strain of s. cerevisiae. the screening identified three derivatives particularly promising for the development of novel anti-trypanosoma agents and eight derivatives for the development of novel anti-pneumocyst ... | 2009 | 19119009 |
| congenital chagas disease involves trypanosoma cruzi sub-lineage iid in the northwestern province of salta, argentina. | trypanosoma cruzi is genetically classified into six discrete phylogenetic lineages on the basis of different genetic markers. identifying lineages circulating among humans in different areas is essential to understand the molecular epidemiology of chagas disease. in the present study, 18 t. cruzi isolates from congenitally infected newborns in the northwestern province of salta-argentina were studied by multilocus enzyme electrophoresis (mlee) and random amplified polymorphic dna (rapd). all is ... | 2009 | 19162237 |
| trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates leishmania infection. | innate immunity is the first line of defense against invading microorganisms. trypanosome lytic factor (tlf) is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of african trypanosomes, which belong to the kinetoplastida order. herein, we demonstrate the broader protective effects of human tlf, which inhibits intracellular infection by leishmania, a kinetoplastid that replicates in phagolysosomes o ... | 2009 | 19165337 |
| [chagas disease]. | chagas disease (human american trypanosomiasis) is a zoonose caused by the protozoan trypanosoma cruzi. vectors are triatoma spp. insects. t. cruzi can also be transmitted by blood transfusion, organ transplantation, and transplacentally. infection is generally acquired during infancy. the acute infection is rarely symptomatic and is followed by a chronic phase. chronic infected people are asymptomatic (indeterminate stage) and may remain at this stage for the rest of their lives. about a third ... | 2009 | 19201068 |
| rational modification of a candidate cancer drug for use against chagas disease. | chagas disease is one of the major neglected diseases of the world. existing drug therapies are limited, ineffective, and highly toxic. we describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. the protein farnesyltransferase (pft) inhibitor tipifarnib, now in phase iii anticancer clinical trials, was previously found to kill trypanosoma cruzi by blocking sterol 14 alpha-demethylase (14dm). w ... | 2009 | 19239254 |
| immunodominance: a new hypothesis to explain parasite escape and host/parasite equilibrium leading to the chronic phase of chagas' disease? | intense immune responses are observed during human or experimental infection with the digenetic protozoan parasite trypanosoma cruzi. the reasons why such immune responses are unable to completely eliminate the parasites are unknown. the survival of the parasite leads to a parasite-host equilibrium found during the chronic phase of chagasic infection in most individuals. parasite persistence is recognized as the most likely cause of the chagasic chronic pathologies. therefore, a key question in ... | 2009 | 19287899 |
| increased myeloperoxidase activity and protein nitration are indicators of inflammation in patients with chagas' disease. | in this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with chagas' disease. we used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and stat-pak immunochromatography) to screen human serum samples (n = 1,481) originating from chiapas, mexico, for trypanosoma cruzi-specific antibodies. we identified 121 subjects who were seropositive for t. cruzi-specific antibodies, a finding indicative of an 8.5% seroprevalenc ... | 2009 | 19297613 |
| its-rflp- and rapd-based genetic variability of trypanosoma cruzi i, human and vector strains in santander, colombia. | chagas disease is a severe public health problem in latin-american countries. in colombia, the predominance of trypanosoma cruzi i has been described in the literature, with a broad heterogeneity between strains. however, most of the studies carried out centered on isoenzyme analysis, with a smaller number that focus on other molecular methods. in this report, we discuss the results of a molecular analysis of t. cruzi i strains, isolated from the domestic cycle, from the department of santander, ... | 2009 | 19347363 |
| quantitative structure-activity relationships for a series of inhibitors of cruzain from trypanosoma cruzi: molecular modeling, comfa and comsia studies. | human parasitic diseases are the foremost threat to human health and welfare around the world. trypanosomiasis is a very serious infectious disease against which the currently available drugs are limited and not effective. therefore, there is an urgent need for new chemotherapeutic agents. one attractive drug target is the major cysteine protease from trypanosoma cruzi, cruzain. in the present work, comparative molecular field analysis (comfa) and comparative molecular similarity indices analysi ... | 2009 | 19376735 |
| characterization of a gene encoding alcohol dehydrogenase in benznidazole-susceptible and -resistant populations of trypanosoma cruzi. | alcohol dehydrogenases (adh) are a class of oxidoreductases that catalyse the reversible oxidation of ethanol to acetaldehyde. in the human parasite trypanosoma cruzi the tcadh gene was identified through microarray analysis as having reduced transcription in an in vitro induced benznidazole (bz)-resistant population. in the present study, we have extended these results by characterizing the tcadh gene from 11 strains of t. cruzi that were either susceptible or naturally resistant to benznidazol ... | 2009 | 19426664 |
| major cysteine protease (cruzipain) in z3 sylvatic isolates of trypanosoma cruzi from rio de janeiro, brazil. | trypanosoma cruzi, the etiologic agent of chagas' disease, is represented by a set of parasites which circulate between man, vectors, domestic and wild animals. recently, our group isolated from triatoma vitticeps strains of t. cruzi that were characterized as belonging to the z3 phylogenetic lineage. since very little is known about the biological and/or biochemical markers of sylvatic z3 isolates, we have studied the protein and protease profiles of distinct z3 isolates designated as smm10, sm ... | 2009 | 19437041 |
| heterozygosity for the s180l variant of mal/tirap, a gene expressing an adaptor protein in the toll-like receptor pathway, is associated with lower risk of developing chronic chagas cardiomyopathy. | chagas disease is caused by the protozoan parasite trypanosoma cruzi. among t. cruzi-infected individuals, only a subgroup develops severe chronic chagas cardiomyopathy (ccc); the majority remain asymptomatic. t. cruzi displays numerous ligands for the toll-like receptors (tlrs), which are an important component of innate immunity that lead to the transcription of proinflammatory cytokines by nuclear factor-kappab. because proinflammatory cytokines play an important role in ccc, we hypothesized ... | 2009 | 19456234 |
| trypanosoma cruzi shsp16: characterization of an alpha-crystallin small heat shock protein. | this report describes the characterization of a member of the alpha-crystallin small heat shock protein family in a trypanosomatid, which was isolated from the human pathogen trypanosoma cruzi. one alpha-crystallin small heat shock protein gene was identified in a database search. the coding region is located in an open reading frame of 429bp encoding a protein of 142 amino acids. the amino acid sequence was deduced from the isolated gene. the protein has an alpha-crystallin domain characteristi ... | 2009 | 19595996 |
| cd8+ t cells in trypanosoma cruzi infection. | cd8(+) t cells have emerged as crucial players in the control of a number of protozoan pathogens, including trypanosoma cruzi, the agent of human chagas disease. the recent identification of the dominant targets of t. cruzi-specific t cells has allowed investigators to follow the generation of and document the functionality of t cell responses in both mice and humans. although slow to develop in the early stages of the infection, t. cruzi-specific cd8(+) t cells reach prodigious levels and remai ... | 2009 | 19646853 |
| perforin and gamma interferon expression are required for cd4+ and cd8+ t-cell-dependent protective immunity against a human parasite, trypanosoma cruzi, elicited by heterologous plasmid dna prime-recombinant adenovirus 5 boost vaccination. | a heterologous prime-boost strategy using plasmid dna, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit cd4(+) and cd8(+) t-cell-mediated protective immunity against intracellular pathogens. we confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited cd4(+) and cd8(+) t-cell-mediated protective immunity (reduction of ... | 2009 | 19651871 |
| the steady-state transcriptome of the four major life-cycle stages of trypanosoma cruzi. | chronic chagasic cardiomyopathy is a debilitating and frequently fatal outcome of human infection with the protozoan parasite, trypanosoma cruzi. microarray analysis of gene expression during the t. cruzi life-cycle could be a valuable means of identifying drug and vaccine targets based on their appropriate expression patterns, but results from previous microarray studies in t. cruzi and related kinetoplastid parasites have suggested that the transcript abundances of most genes in these organism ... | 2009 | 19664227 |
| trypanosoma cruzi iic: phylogenetic and phylogeographic insights from sequence and microsatellite analysis and potential impact on emergent chagas disease. | trypanosoma cruzi, the etiological agent of chagas disease, is highly genetically diverse. numerous lines of evidence point to the existence of six stable genetic lineages or dtus: tci, tciia, tciib, tciic, tciid, and tciie. molecular dating suggests that t. cruzi is likely to have been an endemic infection of neotropical mammalian fauna for many millions of years. here we have applied a panel of 49 polymorphic microsatellite markers developed from the online t. cruzi genome to document genetic ... | 2009 | 19721699 |
| a century of research: what have we learned about the interaction of trypanosoma cruzi with host cells? | since the discovery of trypanosoma cruzi and the brilliant description of the then-referred to 'new tripanosomiasis' by carlos chagas 100 years ago, a great deal of scientific effort and curiosity has been devoted to understanding how this parasite invades and colonises mammalian host cells. this is a key step in the survival of the parasite within the vertebrate host, and although much has been learned over this century, differences in strains or isolates used by different laboratories may have ... | 2009 | 19753462 |
| cellular and genetic mechanisms involved in the generation of protective and pathogenic immune responses in human chagas disease. | perhaps one of the most intriguing aspects of human chagas disease is the complex network of events that underlie the generation of protective versus pathogenic immune responses during the chronic phase of the disease. while most individuals do not develop patent disease, a large percentage may develop severe forms that eventually lead to death. although many efforts have been devoted to deciphering these mechanisms, there is still much to be learned before we can fully understand the pathogenes ... | 2009 | 19753476 |
| searching for new clues about the molecular cause of endomyocardial fibrosis by way of in silico proteomics and analytical chemistry. | endomyocardial fibrosis (emf) -is a chronic inflammatory disease of the heart with related pathology to that of late stage chaga's disease. indeed, both diseases are thought to result from auto-immune responses against myocardial tissue. as is the case that molecular mimicry between the acidic termini of trypanosoma cruzi ribosomal p0, p1 and p2beta (or simply tcp0, tcp1, and tcp2beta) proteins and myocardial tissue causes chaga's disease, excessive exposure to certain infections, toxins includi ... | 2009 | 19823676 |
| synthesis, inhibition potency, binding mode, and antiprotozoal activities of fluorescent inhibitors of trypanothione reductase based on mepacrine-conjugated diaryl sulfide scaffolds. | trypanothione reductase (tr) is a flavoenzyme unique to trypanosomatid parasites and a target for lead discovery programs. various inhibitor scaffolds have emerged in the past, exhibiting moderate affinity for the parasite enzyme. herein we show that the combination of two structural motifs of known tr inhibitors - diaryl sulfides and mepacrine - enables the simultaneous addressing of two hydrophobic patches in the active site. the binding efficacy of these conjugates is enhanced over that of th ... | 2009 | 19847846 |
| identification and optimization of inhibitors of trypanosomal cysteine proteases: cruzain, rhodesain, and tbcatb. | trypanosoma cruzi and trypanosoma brucei are parasites that cause chagas' disease and african sleeping sickness, respectively. both parasites rely on essential cysteine proteases for survival: cruzain for t. cruzi and tbcatb/rhodesain for t. brucei. a recent quantitative high-throughput screen of cruzain identified triazine nitriles, which are known inhibitors of other cysteine proteases, as reversible inhibitors of the enzyme. structural modifications detailed herein, including core scaffold mo ... | 2010 | 19908842 |
| neurodegeneration and increased production of nitrotyrosine, nitric oxide synthase, ifn-gamma and s100beta protein in the spinal cord of il-12p40-deficient mice infected with trypanosoma cruzi. | chagas' disease is caused by trypanosoma cruzi and occurs in most latin american countries. the protozoan may colonize the central nervous system (cns) of immune-compromised human hosts, thus causing neuronal disorders. systemic control of the intracellular forms of the parasite greatly depends on the establishment of a th1 response and subsequent nitric oxide (no) release. at the cns, it is known that low concentrations of no promote neuronal survival and growth, while high concentrations exert ... | 2010 | 19923851 |
| cytotoxic and anti-infective sesquiterpenes present in plagiochila disticha (plagiochilaceae) and ambrosia peruviana (asteraceae). | a pharmacological screening of the ethanol extract and fractions of two peruvian medicinal plants, plagiochila disticha and ambrosia peruviana, led to the isolation and characterization of three ent-2,3-secoaromadendrane-type sesquiterpenoids, named plagiochiline a ( 1), i ( 2), and r ( 3), as well as of two pseudoguaianolids, damsin ( 4) and confertin ( 5), which exhibited significant cytotoxic activity against a panel of human tumor cell lines. compounds 1, 4, and 5 were also investigated for ... | 2010 | 19960415 |
| in vitro cytotoxic, antiprotozoal and antimicrobial activities of medicinal plants from vanuatu. | sixty-three extracts obtained from 18 plants traditionally used in the south pacific archipelago vanuatu for the treatment of infectious diseases were screened for antimicrobial and antiprotozoal activities. in addition, the extracts were subjected to a detailed analysis on cytotoxic effects toward a panel of human cancer cell lines, designed as a smaller version of the nci60 screen. intriguingly, 15 plant extracts exhibited strong cytotoxic effects specific for only one cancer cell line. extrac ... | 2010 | 20014163 |
| early endosome localization and activity of rasgef1b, a toll-like receptor-inducible ras guanine-nucleotide exchange factor. | guanine-nucleotide exchange factors (gefs) stimulate the intrinsic gdp/gtp exchange activity of ras and promote the formation of active ras-gtp, which in turn controls diverse signalling networks important for the regulation of cell proliferation, survival, differentiation, vesicular trafficking, and gene expression. rasgef1b is a gef, whose expression is induced in macrophages on stimulation with toll-like receptor (tlr) agonists. here, we showed that in vitro rasgef1b expression by macrophages ... | 2010 | 20090772 |
| role of endothelin receptors in the control of central nervous system parasitism in trypanosoma cruzi infection in rats. | endothelin has been implicated in the pathogenesis of experimental and human chagas disease. in the present study, we investigated whether the treatment with bosentan, an antagonist of both et(a)/et(b) endothelin receptors, modified parasite load and inflammation in the central nervous system (cns) of trypanosomacruzi-infected rats. the cerebellum was the most affected region in the cns with marked parasitism and inflammation. treatment with bosentan enhanced parasitemia and cns parasitism, but ... | 2010 | 20116865 |
| nitric oxide donor trans-[rucl([15]anen)no] as a possible therapeutic approach for chagas' disease. | benznidazole (bz) is the therapy currently available for clinical treatment of chagas' disease. however, many strains of trypanosoma cruzi parasites are naturally resistant. nitric oxide (no) produced by activated macrophages is crucial to the intracellular killing of parasites. here, we investigate the in vitro and in vivo activities against t. cruzi, of the no donor, trans-[rucl([15]anen(4))no](2+). | 2010 | 20128813 |
| [chagas carlos justiniano ribeiro (1879-1934)]. | the story of the life of carlos chagas is closely associated with the discovery of american human trypanosomiasis, caused by trypanosoma cruzi. indeed, he worked on this for almost all of his life. nowadays he is considered as a national hero, but, when he was alive, he was criticised more severely in his own country than elsewhere, often unjustly and motivated by jealousy, but sometimes with good reason. cases of chagas disease in non-endemic countries became such a concern that public health m ... | 2009 | 20131419 |
| crystal structures of trypanosomal histidyl-trna synthetase illuminate differences between eukaryotic and prokaryotic homologs. | crystal structures of histidyl-trna synthetase (hisrs) from the eukaryotic parasites trypanosoma brucei and trypanosoma cruzi provide a first structural view of a eukaryotic form of this enzyme and reveal differences from bacterial homologs. hisrss in general contain an extra domain inserted between conserved motifs 2 and 3 of the class ii aminoacyl-trna synthetase catalytic core. the current structures show that the three-dimensional topology of this domain is very different in bacterial and ar ... | 2010 | 20132829 |
| gap junction reduction in cardiomyocytes following transforming growth factor-beta treatment and trypanosoma cruzi infection. | gap junction connexin-43 (cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-beta (tgf-beta). this cytokine increases during trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. we studied cx43 expression in cardiomyocytes exposed or not to tgf-beta t. cruzi, or sb-431542, an inhibitor of tgf-beta receptor type i (alk-5). cx43 expression was also examined in hearts with dilated cardiopathy from ch ... | 2009 | 20140368 |
| inheritance of dna transferred from american trypanosomes to human hosts. | interspecies dna transfer is a major biological process leading to the accumulation of mutations inherited by sexual reproduction among eukaryotes. lateral dna transfer events and their inheritance has been challenging to document. in this study we modified a thermal asymmetric interlaced pcr by using additional targeted primers, along with southern blots, fluorescence techniques, and bioinformatics, to identify lateral dna transfer events from parasite to host. instances of naturally occurring ... | 2010 | 20169193 |
| the challenge of chagas' disease: has the human pathogen, trypanosoma cruzi, learned how to modulate signaling events to subvert host cells? | chagas' disease, caused by trypanosoma cruzi, is an urgent and highly prevalent danger that is endemic to latin america, and which the research community continues to ignore. each year, chagas' disease kills more people in latin america compared to any other parasite-borne disease, including malaria. in addition, between 15 and 18 million people worldwide are afflicted with this potentially lethal disease. despite these devastating numbers, less than 0.5% of worldwide research and development fo ... | 2010 | 20172059 |
| dhea and testosterone therapies in trypanosoma cruzi-infected rats are associated with thymic changes. | the ability of the gonadal hormones to influence diverse immunological functions during the course of several infections has been extensively studied in the latest decades. testosterone has a suppressive effect on immune response of vertebrates and increases susceptibility toward numerous parasitic diseases. dehydroepiandrosterone is an abundant steroid hormone secreted by the human adrenal cortex and it is considered potent immune-activator. in this paper, it was examined the effects of dhea an ... | 2010 | 20202657 |
| genetic analyses of trypanosoma cruzi isolates from naturally infected triatomines and humans in northeastern brazil. | trypanosoma cruzi genetic diversity was investigated in 25 isolates (vectors and humans) from the semiarid zone of the state of rio grande do norte, brazil. molecular markers (3' region of the 24salpha rrna; mitochondrial cytochrome oxidase subunit 2 (coii) gene; spliced leader intergenic region (sl-ir) gene; allelic size microsatellite polymorphism) identified 56% tciii (100% panstrongyluslutzi; 50% triatomabrasiliensis); 40% tcii (91.7% humans; 50% t. brasiliensis) and 4% tci (human). microsat ... | 2010 | 20303924 |
| lack of association between il-6-174g/c gene polymorphism and chagas disease. | the aim of this study was to investigate the role of the il-6-174g/c gene polymorphism in susceptibility/resistance to trypanosoma cruzi infection in two independent cohorts from colombia and peru. we determined the il-6-174g/c genotypes in a sample of 399 seronegative individuals and 317 serologically positive patients from colombia and peru. all individuals are from regions where t. cruzi infection is endemic. no statistically significant differences in the frequency of il-6-174g/c gene polymo ... | 2010 | 20331841 |
| chagas disease: 100 years after its discovery. a systemic review. | although chagas disease was only discovered in 1909, it began millions of years ago as an enzootic disease among wild animals. its transmission to man began accidentally as an anthropozoonosis when mankind invaded wild ecotopes. endemic chagas disease became established as a zoonosis over the last 200-300 years through deforestation for agriculture and livestock rearing and adaptation of triatomines to dwellings and to humans and domestic animals as food sources. when t. cruzi is transmitted to ... | 2010 | 20382097 |
| sudden death caused by chronic chagas disease in a non-endemic country: autopsy report. | chagas disease is a tropical disease that is prevalent in latin america. described herein is an autopsy case of the sudden death of a 48-year-old brazilian man who had stayed in japan for 7 years. the man, who had a history of chagas disease, collapsed unexpectedly at work. because the cause of death was unknown, forensic autopsy examination was performed. as gross findings, the heart was dilated and rounded with an increase in size and weight. the esophagus and large intestine were dilated mode ... | 2010 | 20403051 |
| role of ccl3/mip-1alpha and ccl5/rantes during acute trypanosoma cruzi infection in rats. | chagas' disease is caused by trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. chemokines are produced during infection and drive tissue inflammation. in rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. we investigated the role of ccl3 and ccl5 during infection by using dna vaccination encoding for each chemokine separately or simultaneously. metrantes treatment was u ... | 2010 | 20452453 |
| gene network analysis during early infection of human coronary artery smooth muscle cells by trypanosoma cruzi and its gp83 ligand. | trypanosoma cruzi, the causative agent of chagas' disease, infects heart and muscle cells leading to cardiac arrest, followed by death. the genetic architectures in the early t. cruzi infection process of human cells are unknown. to understand the genetic architectures of the early invasion process of t. cruzi, we conducted gene transcription microarray analysis, followed by gene network construction of the host cell response in primary human coronary artery smooth muscle (hcasm) cells infected ... | 2010 | 20491065 |
| rapid detection of trypanosoma cruzi in human serum by use of an immunochromatographic dipstick test. | we evaluated a commercially available immunochromatographic dipstick test to detect trypanosoma cruzi infection in 366 human serum samples with known serological results from argentina, ecuador, mexico, and venezuela. one hundred forty-nine of 366 (40.7%) and 171/366 (46.7%) samples tested positive by dipstick and serology, respectively. dipstick sensitivity was calculated to be 84.8% (range between countries, 77.5 to 95%), and specificity was 97.9% (95.9 to 100%). | 2010 | 20534801 |
| trypanosoma cruzi induces tissue disorganization and destruction of chorionic villi in an ex vivo infection model of human placenta. | congenital chagas' disease, endemic in latin america and also present with lower frequency in other countries, is associated with premature labor, miscarriage, and placentitis. the mechanism of tissue invasion and infection of human placenta by the parasite trypanosoma cruzi (t. cruzi) remains unclear. in order to explore some morphological aspects of this infection in the placenta, we incubated chorionic villous explants from normal human placentae ex vivo with the parasite and studied the resu ... | 2010 | 20541804 |
| targeting isoprenoid biosynthesis for drug discovery: bench to bedside. | the isoprenoid biosynthesis pathways produce the largest class of small molecules in nature: isoprenoids (also called terpenoids). not surprisingly then, isoprenoid biosynthesis is a target for drug discovery, and many drugs--such as lipitor (used to lower cholesterol), fosamax (used to treat osteoporosis), and many anti-infectives--target isoprenoid biosynthesis. however, drug resistance in malaria, tuberculosis, and staph infections is rising, cheap and effective drugs for the neglected tropic ... | 2010 | 20560544 |
| 16-bromoepiandrosterone, an activator of the mammalian immune system, inhibits glucose 6-phosphate dehydrogenase from trypanosoma cruzi and is toxic to these parasites grown in culture. | glucose 6-phosphate dehydrogenase (g6pdh) catalyzes the first step of the pentose-phosphate pathway which supplies cells with ribose 5-phosphate (r5p) and nadph. r5p is the precursor for the biosynthesis of nucleotides while nadph is the cofactor of several dehydrogenases acting in a broad range of biosynthetic processes and in the maintenance of the cellular redox state. rna interference-mediated reduction of g6pdh levels in bloodstream-form trypanosoma brucei validated this enzyme as a drug ta ... | 2010 | 20570159 |
| prevalence of trypanosoma cruzi in dogs (canis familiaris) and triatomines during 2008 in a sanitary region of the state of mexico, mexico. | american trypanosomiasis is a public health problem in latin america and southern parts of the united states. infection in triatomines (vector) and domestic dogs (reservoir host) is a good indicator of trypanosoma cruzi circulation and human risk of infection. the state of mexico, mexico, has been considered free of t. cruzi, and no detailed epidemiologic study has been conducted to assess the intricacies of the transmission cycle of the parasite in the region. such studies would enhance our und ... | 2011 | 20575648 |
| trypanosoma cruzi tciii / z3 genotype as agent of an outbreak of chagas disease in the brazilian western amazonia. | summary chagas' disease is an emerging and neglected disease in the brazilian amazon region, where t. cruzi i predominates among the acute cases of the disease; and t. cruzi iii/z3, a population cluster from sylvatic areas of the amazon basin, is rarely associated with human infections. on 23rd april 2007, the foundation for health surveillance of the state of amazonas, brazil reported an outbreak of acute chagas disease in the municipality of coari on the solimões river banks. fresh blood exami ... | 2010 | 20579319 |
| the pre-mrna splicing machinery of trypanosomes: complex or simplified? | trypanosomatids are early-diverged, protistan parasites of which trypanosoma brucei, trypanosoma cruzi, and several species of leishmania cause severe, often lethal diseases in humans. to better combat these parasites, their molecular biology has been a research focus for more than 3 decades, and the discovery of spliced leader (sl) trans splicing in t. brucei established a key difference between parasites and hosts. in sl trans splicing, the capped 5'-terminal region of the small nuclear sl rna ... | 2010 | 20581293 |
| investigation of plant extracts in traditional medicine of the brazilian cerrado against protozoans and yeasts. | to investigate the activities of the 217 plant extracts in traditional medicine of the brazilian cerrado against protozoans and yeasts. | 2010 | 20600775 |
| on an acute case of chagas disease in a region under vector control in the state of são paulo, brazil. | no vector transmitted cases of chagas disease had been notified in the state of são paulo since the 1970s. however, in march, 2006, the death of a six-year-old boy from the municipality of itaporanga was notified to the center for epidemiological survey of the são paulo state health secretariat: an autochthonous case of acute chagas disease. the postmortem histopathological examination performed in the hospital das clínicas of the botucatu school of medicine confirmed the diagnosis. reference to ... | 2010 | 20602025 |
| trypanosoma cruzi-induced activation of functionally distinct αβ and γδ cd4- cd8- t cells in individuals with polar forms of chagas' disease. | cd4(-) cd8(-) (double-negative [dn]) t cells have recently been shown to display important immunological functions in human diseases. they express γδ or αβ t-cell receptors that recognize lipid/glycolipid antigens presented via the nonclassical major histocompatibility complex molecules of the cd1 family. we recently demonstrated that while αβ dn t cells serve primarily to express inflammatory cytokines, γδ dn t cells express mainly interleukin-10 (il-10) in patients with cutaneous leishmaniasis ... | 2010 | 20696836 |
| inflammatory and prothrombotic activation with conserved endothelial function in patients with chronic, asymptomatic chagas disease. | previously, our group showed a prothrombotic state in asymptomatic patients with chronic chagas disease. the current paper studies the inflammatory status and endothelial function in these patients. methods: in 40 patients and 40 healthy volunteers, we evaluated prothrombotic state, blood parasitemia (molecular biology: polymerized chain reaction [pcr]-amplification), tissue factor pathway inhibitor antibodies (atfpi), interleukin 6 (il-6), and vascular cell adhesion molecule-1 (vcam-1). endothe ... | 2010 | 20699256 |
| targeting trypanothione metabolism in trypanosomatid human parasites. | the diseases caused by the trypanosomatid parasites trypanosoma brucei, trypanosoma cruzi and leishmania are widely distributed throughout the world. because of the toxic side-effects and the economically unviable cost of the currently used pharmaceutical treatments, the search for new drug targets continues. since the antioxidant metabolism in these parasites relies on trypanothione [t(sh)(2)], a functional analog of glutathione, most of the pathway enzymes involved in its synthesis, utilizatio ... | 2010 | 20735352 |
| favorably orienting recombinant proteins to develop amperometric biosensors to diagnose chagas' disease. | clinical immunoassays often display suitable sensitivity but some lack of specificity or vice versa. as a trade-off between specificity improvement and sensitivity loss, biosensors were designed to perform indirect immunoassays with amperometric detection using tailor-made chimeric receptors to react with the analyte, specific anti-trypanosoma cruzi immunoglobulin g (igg). recombinant chimeras were designed to favor their oriented covalent attachment. this allows the chimeras to properly expose ... | 2011 | 20828530 |
| the transcriptome of the human pathogen trypanosoma brucei at single-nucleotide resolution. | the genome of trypanosoma brucei, the causative agent of african trypanosomiasis, was published five years ago, yet identification of all genes and their transcripts remains to be accomplished. annotation is challenged by the organization of genes transcribed by rna polymerase ii (pol ii) into long unidirectional gene clusters with no knowledge of how transcription is initiated. here we report a single-nucleotide resolution genomic map of the t. brucei transcriptome, adding 1,114 new transcripts ... | 2010 | 20838601 |
| differentiation of trypanosoma cruzi and trypanosoma rangeli of colombia using minicircle hybridization tests. | although trypanosoma rangeli is harmless for humans, it is a serious problem since it may be confused with diagnosis of trypanosoma cruzi, the etiologic agent of chagas disease. both parasites overlap geographically, share antigenic protein, and are able to infect the same triatominae vector and vertebrate host, including human. our objective was to differentiate t. cruzi and t. rangeli isolates from colombia based on polymerase chain reaction (pcr) amplification of the minicircles followed by a ... | 2010 | 20850248 |
| massive screening yields novel and selective trypanosoma cruzi triosephosphate isomerase dimer-interface-irreversible inhibitors with anti-trypanosomal activity. | triosephosphate isomerase from trypanosoma cruzi (tctim), an enzyme in the glycolytic pathway that exhibits high catalytic rates of glyceraldehyde-3-phosphate- and dihydroxyacetone-phosphate-isomerization only in its dimeric form, was screened against an in-house chemical library containing nearly 230 compounds belonging to different chemotypes. after secondary screening, twenty-six compounds from eight different chemotypes were identified as screening positives. four compounds displayed selecti ... | 2010 | 20889239 |
| structural modelling and comparative analysis of homologous, analogous and specific proteins from trypanosoma cruzi versus homo sapiens: putative drug targets for chagas' disease treatment. | trypanosoma cruzi is the etiological agent of chagas' disease, an endemic infection that causes thousands of deaths every year in latin america. therapeutic options remain inefficient, demanding the search for new drugs and/or new molecular targets. such efforts can focus on proteins that are specific to the parasite, but analogous enzymes and enzymes with a three-dimensional (3d) structure sufficiently different from the corresponding host proteins may represent equally interesting targets. in ... | 2010 | 21034488 |