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ictv virus taxonomy profile: dicistroviridae.dicistroviridae is a family of small non-enveloped viruses with monopartite, linear, positive-sense rna genomes of approximately 8-10 kb. viruses of all classified species infect arthropod hosts, with some having devastating economic consequences, such as acute bee paralysis virus in domesticated honeybees and taura syndrome virus in shrimp farming. conversely, the host specificity and other desirable traits exhibited by several members of this group make them potential natural enemies for inten ...201728366189
synthesis and biological evaluation of newer 1,3,4-oxadiazoles incorporated with benzothiazepine and benzodiazepine moieties.a series of thiazepines and diazepines having 1,3,4-oxadiazole moiety were synthesized, and they were analyzed for their in vitro antimicrobial activity against several bacteria (staphylococcus aureus, staphylococcus pyogenes, escherichia coli, and pseudomonas aeruginosa) and fungi (candida albicans, aspergillus niger, and aspergillus clavatus) and protozoa (entamoeba histolytica, giardia lamblia, trypanosoma cruzi and leishmania mexicana). few of the selected compounds were tested for their ant ...201728182579
antioxidant, antimicrobial, antiparasitic, and cytotoxic properties of various brazilian propolis extracts.propolis is known for its biological properties and its preparations have been continuously investigated in an attempt to solve the problem of their standardization, an issue that limits the use of propolis in food and pharmaceutical industries. the aim of this study was to evaluate in vitro antioxidant, antimicrobial, antiparasitic, and cytotoxic effects of extracts of red, green, and brown propolis from different regions of brazil, obtained by ethanolic and supercritical extraction methods. we ...201728358806
synthesis of novel quinoline-based 4,5-dihydro-1h-pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents.a new series of n-substituted 2-pyrazolines 9a-f, 10a-f, 11a-f, 12a-f and 13a-f were obtained from the cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones 8a-f with hydrazine hydrate and its derivatives. fourteen of the synthesized compounds including the starting chalcones were selected by us national cancer institute (nci) for testing their anticancer activity against 60 different human cancer cell lines, with the most important gi50 values ranging from 0.28 to 11.7 μm (0.13- ...201728329730
detection of a potential new bartonella species "candidatus bartonella rondoniensis" in human biting kissing bugs (reduviidae; triatominae).among the reduviidae family, triatomines are giant blood-sucking bugs. they are well known in central and south america where they transmit trypanosoma cruzi to mammals, including humans, through their feces. this parasitic protozoan is the causative agent of chagas disease, a major public health issue in endemic areas. because of the medical and economic impact of chagas disease, the presence of other arthropod-borne pathogens in triatomines was rarely investigated.201728095503
accuracy of chimeric proteins in the serological diagnosis of chronic chagas disease - a phase ii study.the performance of current serologic tests for diagnosing chronic chagas disease (cd) is highly variable. the search for new diagnostic markers has been a constant challenge for improving accuracy and reducing the number of inconclusive results.201728273127
δ9 desaturase from trypanosoma cruzi: key enzyme in the parasite metabolism. cloning and overexpression.desaturases, key enzymes in the metabolism of fatty acids, regulate the physical and biochemical properties of membranes. they adjust the composition of saturated and unsaturated fatty acids in response to changes in the environmental. we demonstrated the existence of δ9 desaturase activity in epimastigotes of the trypanosoma cruzi tulahuen strain. in the present study, showed that this enzyme has an approximate molecular mass of 50kda and a pi value of approximately 9. in order to characterize ...201727938860
performance of leishmania braziliensis enolase protein for the serodiagnosis of canine and human visceral leishmaniosis.in the present study, leishmania braziliensis enolase was cloned and the recombinant protein (renolase) was evaluated for the serodiagnosis of canine and human visceral leishmaniosis (vl). for the canine vl diagnosis, this study examined serum samples of leishmania infantum-infected dogs, from non-infected animals living in endemic or non-endemic areas of leishmaniosis, as well as those from leish-tec(®)-vaccinated dogs and trypanosoma cruzi or ehrlichia canis experimentally infected animals. fo ...201728385540
parasite infection, carcinogenesis and human malignancy.cancer may be induced by many environmental and physiological conditions. infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. here we review current concepts of carcinogenicity and its associations with parasitic infections. the helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan trypanosoma cruzi, the causing agent of chagas disease, has a dual role in the develo ...201727956028
glycosylated metal chelators as anti-parasitic agents with tunable selectivity.trypanosoma cruzi and leishmania amazonensis are the causative agents of chagas' disease and leishmaniasis, respectively. these conditions affect millions of people worldwide, especially in developing countries. as such, there is an urgent need for novel, efficient and cost-effective treatments for these diseases, given the growing resistance and side-effects of current therapies. this work details the synthesis and evaluation of the anti-parasitic activity of novel amino- and iminopyridyl metal ...201728382355
differences in the detection of brdu/edu incorporation assays alter the calculation for g1, s, and g2 phases of the cell cycle in trypanosomatids.trypanosomatids are the etiologic agents of various infectious diseases in humans. they diverged early during eukaryotic evolution and have attracted attention as peculiar models for evolutionary and comparative studies. here, we show a meticulous study comparing the incorporation and detection of the thymidine analogs brdu and edu in leishmania amazonensis, trypanosoma brucei, and trypanosoma cruzi to monitor their dna replication. we used brdu- and edu-incorporated parasites with the respectiv ...201728258618
design and synthesis of a new series of 3,5-disubstituted isoxazoles active against trypanosoma cruzi and leishmania amazonensis.chagas disease and leishmaniasis are neglected tropical diseases (ntds) endemic in developing countries. although there are drugs available for their treatment, efforts on finding new efficacious therapies are continuous. the natural lignans grandisin (1) and veraguensin (2) show activity against trypomastigote t. cruzi and their scaffold has been used as inspiration to design new derivatives with improved potency and chemical properties. we describe here the planning and microwave-irradiated sy ...201728152426
in vitro antiprotozoal activity of (s)-cis-verbenol against leishmania spp. and trypanosoma cruzi.(s)-cis-verbenol, a monoterpene frequently found as a component of essential oils, was assayed against leishmania amazonensis, leishmania infantum, leishmania brasiliensis and against two strains of trypanosoma cruzi. the cytotoxicity of the compound was also assayed against human fibroblast cells using a colorimetric method. benznidazole was used as reference drug against t. cruzi and amphotericin b was used against leishmania spp. the compound showed good activity against the trypanosomes, bei ...201728062234
use of recombinant antigens for sensitive serodiagnosis of american tegumentary leishmaniasis caused by different leishmania species.american tegumentary leishmaniasis (atl) (also known as cutaneous leishmaniasis [cl]) is caused by various species of protozoa of the genus leishmania the diagnosis is achieved on a clinical, epidemiological, and pathological basis, supported by positive parasitological exams and demonstration of leishmanin delayed-type hypersensitivity. serological assays are not routinely used in the diagnosis because many are considered to have low sensitivity and the particular leishmania species causing the ...201727927927
antiprotozoal and antioxidant alkaloids from alternanthera littoralis.five alkaloids, in addition to hydroxytyrosol and uridine, were isolated from aerial parts of alternanthera littoralis p. beauv. among the isolated compounds, alternamide a was an unusual tricyclic alkaloid with a bridged benzoazepine core. all isolated alkaloids have a catechol moiety, indicating a possible common biosynthetic route. their structures were established by 1d and 2d nmr spectroscopy in combination with extensive tandem ms experiments by collisional induced dissociation (cid). the ...201727889243
a proteomic road to acquire an accurate serological diagnosis for human tegumentary leishmaniasis.diagnostic tools are important for clinical management and epidemiological evaluation of tegumentary (tl) and visceral (vl) leishmaniasis. serology is not frequently used for the diagnosis of the tl form because low antibody titers and cross-reaction with vl. therefore, it is crucial to identify specific and immunogenic antigens from species associated with the tl form. here we employed a proteomic approach coupled to an in silico analysis and identified the most abundant and immunogenic protein ...201727262223
simple dialkyl pyrazole-3,5-dicarboxylates show in vitro and in vivo activity against disease-causing trypanosomatids.the synthesis and antiprotozoal activity of some simple dialkyl pyrazole-3,5-dicarboxylates (compounds 2-6) and their sodium salts (pyrazolates) (compounds 7-9) against trypanosoma cruzi, leishmania infantum and leishmania braziliensis are reported. in most cases the studied compounds showed, especially against the clinically significant amastigote forms, in vitro activities higher than those of the reference drugs (benznidazole for t. cruzi and glucantime for leishmania spp.); furthermore, the ...201728367781
evaluation of a hypothetical protein for serodiagnosis and as a potential marker for post-treatment serological evaluation of tegumentary leishmaniasis patients.the serodiagnosis for tegumentary leishmaniasis (tl) presents problems related to the sensitivity and/or specificity of the tests. in the present study, an enzyme-linked immunosorbent assay (elisa) technique was used to evaluate the performance from a leishmania braziliensis hypothetical protein, lbhym, in an attempt to compare its serological reactivity with a soluble leishmania antigenic preparation (sla) for the serodiagnosis of cutaneous (cl) and mucosal (ml) leishmaniasis. lbhym was predict ...201728150041
antiprotozoal glutathione derivatives with flagellar membrane binding activity against t. brucei rhodesiense.a new series of n-substituted s-(2,4-dinitrophenyl)glutathione dibutyl diesters were synthesized to improve in vitro anti-protozoal activity against the pathogenic parasites trypanosoma brucei rhodesiense, trypanosoma cruzi and leishmania donovani. the results obtained indicate that n-substituents enhance the inhibitory properties of glutathione diesters whilst showing reduced toxicity against kb cells as in the cases of compounds 5, 9, 10, 16, 18 and 19. we suggest that the interaction of n-sub ...201728131508
new primers for detection of leishmania infantum using polymerase chain reaction.leishmania infantum causes visceral leishmaniasis (vl) in the new world. the diagnosis of vl is confirmed by parasitological and serological tests, which are not always sensitive or specific. our aim was to design new primers to perform a polymerase chain reaction (pcr) for detecting l. infantum. sequences of the minicircle kinetoplast dna (kdna) were obtained from genbank, and the flc2/rlc2 primers were designed. samples of dna from l. infantum, leishmania amazonensis, leishmania braziliensis, ...201726603223
bmajpla2-ii, a basic lys49-phospholipase a2 homologue from bothrops marajoensis snake venom with parasiticidal potential.snake venoms contain various proteins, especially phospholipases a2 (pla2s), which present potential applications in diverse areas of health and medicine. in this study, a new basic pla2 from bothrops marajoensis with parasiticidal activity was purified and characterized biochemically and biologically. b. marajoensis venom was fractionated through cation exchange followed by reverse phase chromatographies. the isolated toxin, bmajpla2-ii, was structurally characterized with maldi-tof (matrix-ass ...201728390830
new alkenyl derivative from piper malacophyllum and analogues: antiparasitic activity against trypanosoma cruzi and leishmania infantum.alkylphenols isolated from piper malacophyllum (piperaceae), gibbilimbols a and b, showed interesting activity against the parasites trypanosoma cruzi and leishmania infantum. in continuation to our previous work, a new natural product from the essential oil of the leaves of p. malacophyllum was isolated, the 5-[(3e)-oct-3-en-1-il]-1,3-benzodioxole, and also a new set of five compounds was prepared. the antiparasitic activity of the natural product was evaluated in vitro against these parasites, ...201728371557
antiprotozoal activity of triazole derivatives of dehydroabietic acid and oleanolic acid.tropical parasitic diseases such as chagas disease and leishmaniasis are considered a major public health problem affecting hundreds of millions of people worldwide. as the drugs currently used to treat these diseases have several disadvantages and side effects, there is an urgent need for new drugs with better selectivity and less toxicity. structural modifications of naturally occurring and synthetic compounds using click chemistry have enabled access to derivatives with promising antiparasiti ...201728264505
methoxylated 2'-hydroxychalcones as antiparasitic hit compounds.chalcones display a broad spectrum of pharmacological activities. herein, a series of 2'-hydroxy methoxylated chalcones was synthesized and evaluated towards trypanosoma brucei, trypanosoma cruzi and leishmania infantum. among the synthesized library, compounds 1, 3, 4, 7 and 8 were the most potent and selective anti-t. brucei compounds (ec50 = 1.3-4.2 μm, selectivity index >10-fold). compound 4 showed the best early-tox and antiparasitic profile. the pharmacokinetic studies of compound 4 in bal ...201728064141
leishmania infantum mimotopes and a phage-elisa assay as tools for a sensitive and specific serodiagnosis of human visceral leishmaniasis.serological methods used to diagnose visceral leishmaniasis (vl) are considered minimally invasive, but they present problems related with their sensitivity and/or specificity. in this study, a subtractive selection using the phage display technology against antibodies from healthy subjects living in endemic and non-endemic areas of disease, as well as from chagas disease patients and those developing active vl, was developed. the aim of this study was to select bacteriophage-fused epitopes to b ...201727939286
antiprotozoal activity of major constituents from the bioactive fraction of verbesina encelioides.the bioactive petroleum ether fraction of verbesina encelioides, previously studied by the authors, was chosen for the isolation of antiprotozoal metabolites. pseudotaraxasterol-3β-acetate (1), benzyl 2,6-dimethoxy benzoate (2), 16β-hydroxy-pseudotaraxasterol-3β-palmitate (3) and pseudotaraxasterol (4), in addition to β-sitosterol glucoside (5) and β-sitosterol galactoside (6) were isolated and identified based on one-dimensional and two-dimensional spectral analysis. this is the first report de ...201727154232
antiparasitic lead discovery: toward optimization of a chemotype with activity against multiple protozoan parasites.human african trypanosomiasis (hat), chagas disease, and leishmaniasis present a significant burden across the developing world. existing therapeutics for these protozoal neglected tropical diseases suffer from severe side effects and toxicity. previously, neu-1045 (3) was identified as a promising lead with cross-pathogen activity, though it possessed poor physicochemical properties. we have designed a library of analogues with improved calculated physicochemical properties built on the quinoli ...201728337329
the effectiveness of natural diarylheptanoids against trypanosoma cruzi: cytotoxicity, ultrastructural alterations and molecular modeling studies.curcumin (cur) is the major constituent of the rhizomes of curcuma longa and has been widely investigated for its chemotherapeutic properties. the well-known activity of cur against leishmania sp., trypanosoma brucei and plasmodium falciparum led us to investigate its activity against trypanosoma cruzi. in this work, we tested the cytotoxic effects of cur and other natural curcuminoids on different forms of t. cruzi, as well as the ultrastructural changes induced in epimastigote form of the para ...201727658305
dissecting biochemical peculiarities of the atpase activity of tcsub2, a component of the mrna export pathway in trypanosoma cruzi.the rna helicase dead-box protein sub2 (yeast)/uap56 (mammals) is conserved across eukaryotes and is essential for mrna export in trypanosomes. despite the high conservation of sub2 in lower eukaryotes such as trypanosoma cruzi, the low conservation of other mrna export factors raises questions regarding whether the mode of action of tcsub2 is similar to that of orthologs from other eukaryotes. mutation of the conserved k87 residue of tcsub2 abolishes atpase activity, showing that its atpase dom ...201728212935
rapid chagas disease drug target discovery using directed evolution in drug-sensitive yeast.recent advances in cell-based, high-throughput phenotypic screening have identified new chemical compounds that are active against eukaryotic pathogens. a challenge to their future development lies in identifying these compounds' molecular targets and binding modes. in particular, subsequent structure-based chemical optimization and target-based screening require a detailed understanding of the binding event. here, we use directed evolution and whole-genome sequencing of a drug-sensitive s. cere ...201727977118
ex vivo infection of human placental chorionic villi explants with trypanosoma cruzi and toxoplasma gondii induces different toll-like receptor expression and cytokine/chemokine profiles.trypanosoma cruzi and toxoplasma gondii present, respectively, low and high congenital transmission rates. the placenta as an immune regulatory organ expresses tlrs, leading to the secretion of cytokines. both parasites are recognized by tlr-2, tlr-4, and tlr-9. here, we studied if the parasites induce differences in tlr protein expression, cytokine profiles, and whether receptor inhibition is related to parasite infection.201728328108
antiparasitic activity of sulfur- and fluorine-containing bisphosphonates against trypanosomatids and apicomplexan parasites.based on crystallographic data of the complexes 2-alkyl(amino)ethyl-1,1-bisphosphonates-trypanosoma cruzi farnesyl diphosphate synthase, some linear 1,1-bisphosphonic acids and other closely related derivatives were designed, synthesized and biologically evaluated against t. cruzi, the responsible agent of chagas disease and against toxoplasma gondii, the etiologic agent of toxoplasmosis and also towards the target enzymes farnesyl pyrophosphate synthase of t. cruzi (tcfpps) and t gondii (tgfpps ...201728054995
host-parasite relationships and life histories of trypanosomes in australia.trypanosomes constitute a group of flagellate protozoan parasites responsible for a number of important, yet neglected, diseases in both humans and livestock. the most significantly studied include the causative agents of african sleeping sickness (trypanosoma brucei) and chagas disease (trypanosoma cruzi) in humans. much of our knowledge about trypanosome host-parasite relationships and life histories has come from these two human pathogens. recent investigations into the diversity and life his ...201728325373
adipose tissue: a safe haven for parasites?adipose tissue (at) is no longer regarded as an inert lipid storage, but as an important central regulator in energy homeostasis and immunity. three parasite species are uniquely associated with at during part of their life cycle: trypanosoma cruzi, the causative agent of chagas disease; trypanosoma brucei, the causative agent of african sleeping sickness; and plasmodium spp., the causative agents of malaria. in at, t. cruzi resides inside adipocytes, t. brucei is found in the interstitial space ...201728007406
the effect of specific proline residues on the kinetic stability of the triosephosphate isomerases of two trypanosomes.the effect of specific residues on the kinetic stability of two closely related triosephosphate isomerases (from trypanosoma cruzi, tctim and trypanosoma brucei, tbtim) has been studied. based on a comparison of their β-turn occurrence, we engineered two chimerical enzymes where their super secondary β-loop-α motifs 2 ((βα)2 ) were swapped. differential scanning calorimetry (dsc) experiments showed that the (βα)2 motif of tctim inserted into tbtim (2tc) increases the kinetic stability. on the ot ...201728002620
trypanocidal activity of flavokawin b, a component of polygonum ferrugineum wedd.the trypanocidal potential of the natural chalcone flavokawin b, which was isolated from the hexanic extract of polygonum ferrugineum wedd., is reported here. although flavokawin b is widespread, this is the first report about its trypanocidal properties on both trypanosoma cruzi (ic50 = 9.5 µm, ic50 = 34.7 µm benznidazol, y strain) epimastigotes and trypanosoma brucei (ic50 = 4.8 µm, ic50 = 6.4 µm pentamidine, 29-13 strain) procyclic forms, which was also corroborated on t. brucei strain 427 (i ...201727442262
in vitro drug susceptibility of two strains of the wildlife trypanosome, trypanosoma copemani: a comparison with trypanosoma cruzi.trypanosomes are blood protozoan parasites that are capable of producing illness in the vertebrate host. within australia, several native trypanosoma species have been described infecting wildlife. however, only trypanosoma copemani has been associated with pathological lesions in wildlife hosts and more recently has been associated with the drastic decline of the critically endangered woylie (bettongia penicillata). the impact that some trypanosomes have on the health of the vertebrate host has ...201728040568
[chagas disease affecting the central nervous system in a patient with aids demonstrated by quantitative molecular methods].although infrequent, trypanosoma cruzi reactivation is possible among patients with hiv/aids infection that develop a tumor-like or granulomatous lesion in the cns. we report the case of a 60 years old male patient with hiv/aids and low cd4 lymphocytes count with cerebellar symptoms and mild paresis, associated to supra and infratentorial hypodense lesions and positive serology tests both to t. gondii and trypanosoma cruzi. empirical therapy against toxoplasmosis was prescribed together with ant ...201728394985
[chagas disease in the central nervous system in patient infected with hiv: diagnostic and therapeutic difficulties].chagas disease (chd), caused by the protozoan trypanosoma cruzi, is an endemic anthropozoonosis in latin america, linked to deficients socio-economic and cultural aspects and is considered one of the neglected tropical diseases. we report a fatal case of chagas disease reactivation with central nervous system involvement in a patient with hiv infection, whose diagnosis was confirmed by positive pcr (polymerase chain reaction) test of blood, with treatment response efficiency with benznidazol and ...201728394983
unraveling chagas disease transmission through the oral route: gateways to trypanosoma cruzi infection and target tissues.oral transmission of trypanosoma cruzi, the causative agent of chagas disease, is the most important route of infection in brazilian amazon and venezuela. other south american countries have also reported outbreaks associated with food consumption. a recent study showed the importance of parasite contact with oral cavity to induce a highly severe acute disease in mice. however, it remains uncertain the primary site of parasite entry and multiplication due to an oral infection. here, we evaluated ...201728379959
potential role of carvedilol in the cardiac immune response induced by experimental infection with trypanosoma cruzi.trypanosoma cruzi causes a cardiac infection characterized by an inflammatory imbalance that could become the inciting factor of the illness. to this end, we evaluated the role of carvedilol, a beta-blocker with potential immunomodulatory properties, on the immune response in c57bl/6 mice infected with vl-10 strain of t. cruzi in the acute phase. animals (n = 40) were grouped: (i) not infected, (ii) infected, (iii) infected + carvedilol, and (iv) not infected + carvedilol. we analyzed parameters ...201728377930
deciphering the effects of nelfinavir and lopinavir on epimastigote forms of trypanosoma cruzi. 201728377050
melatonin: antioxidant and modulatory properties in age-related changes during trypanosoma cruzi infection.the purpose of this study was to investigate the effects of melatonin on selected biomarkers of innate and humoral immune response as well as the antioxidant/oxidant status (superoxide dismutase- sod and reduced glutathione levels (gsh) to understand whether age-related changes would influence the development of acute trypanossoma cruzi (t. cruzi) infection. young (5 weeks) and middle-aged (18 months) wistar rats were orally treated with melatonin (gavage) (05 mg/kg/day). 9 days after infection. ...201728370218
towards improving early diagnosis of congenital chagas disease in an endemic setting.congenital trypanosoma cruzi transmission is now estimated to account for 22% of new infections, representing a significant public health problem across latin america and internationally. treatment during infancy is highly efficacious and well tolerated, but current assays for early detection fail to detect >50% of infected neonates and 9 month follow-up is low.201728369287
rapid diagnostic tests duo as alternative to conventional serological assays for conclusive chagas disease diagnosis.chagas disease is caused by the parasite trypanosoma cruzi. it affects several million people, mainly in latin america, and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients. disease acute stage is mostly asymptomatic and infection goes undiagnosed. in the chronic phase direct parasite detection is hampered due to its concealed presence and diagnosis is achieved by serological methods, like elisa or indirect hemagglutination assays. agreement in at ...201728369081
prevalence of trypanosoma cruzi antibodies in blood donors from the sao paulo state, brazil, between 2012 and 2014.american tripanosomiasis (chagas disease), the second most neglected disease in the world, is caused by the protozoan parasite trypanosoma cruzi. though natural transmission by insect vectors has been controlled, there is significant risk of t. cruzi transmission by blood transfusion in non-endemic regions, generally due to immigration processes from endemic areas.201728368863
an in vitro and in vivo evaluation of new potential trans-sialidase inhibitors of trypanosoma cruzi predicted by a computational drug repositioning method.chagas disease is one of the most important neglected parasitic diseases afflicting developed and undeveloped countries. there are currently limited options for inexpensive and secure pharmacological treatment. in this study, we employed a structure-based virtual screening protocol for 3180 fda-approved drugs for repositioning of them as potential trans-sialidase inhibitors. in vitro and in vivo evaluations were performed for the selected drugs against trypomastigotes from the inc-5 and ninoa st ...201728364659
heme modulates trypanosoma cruzi bioenergetics inducing mitochondrial ros production.trypanosoma cruzi is the causative agent of chagas disease and has a single mitochondrion, an organelle responsible for atp production and the main site for the formation of reactive oxygen species (ros). t. cruzi is an obligate intracellular parasite with a complex life cycle that alternates between vertebrate and invertebrate hosts, therefore the development of survival strategies and morphogenetic adaptations to deal with the various environments is mandatory. over the years our group has bee ...201728363600
aryl- or heteroaryl-based hydrazinylphthalazine derivatives as new potential antitrypanosomal agents.a series of twenty phthalazinyl-hydrazones were synthesized and tested as potential anti-trypanosoma cruzi agents. the phthalazines containing 5-nitroheteroaryl moiety 3l and 3m displayed an excellent in vitro antitrypanosomal profile, exhibiting low micromolar ec50 values against proliferative epimastigote of t. cruzi and minimal toxicity toward vero cells. these derivatives were more potent than the reference drug benznidazole against the epimastigote stage of the parasite. structure-property ...201728359970
characterisation of the fumarate hydratase repertoire in trypanosoma cruzi.nifurtimox and benznidazole represent the only treatments options available targeting chagas disease, the most important parasitic infection in the americas. however, use of these is problematic as they are toxic and ineffective against the more severe stages of the disease. in this work, we used a multidisciplinary approach to characterise the fumarases from trypanosoma cruzi, the causative agent of chagas disease. we showed this trypanosome expresses cytosolic and mitochondrial fumarases that ...201728359888
batf2 inhibits immunopathological th17 responses by suppressing il23a expression during trypanosoma cruzi infection.inappropriate il-17 responses are implicated in chronic tissue inflammation. il-23 contributes to trypanosoma cruzi-specific il-17 production, but the molecular mechanisms underlying regulation of the il-23-il-17 axis during t. cruzi infection are poorly understood. here, we demonstrate a novel function of batf2 as a negative regulator of il23a in innate immune cells. il-17, but not ifn-γ, was more highly produced by cd4(+) t cells from spleens and livers of t. cruzi-infected batf2(-/-) mice tha ...201728356392
metabolomics profiling reveals a finely tuned, starvation-induced metabolic switch in trypanosoma cruzi epimastigotes.trypanosoma cruzi, the etiological agent of chagas disease, is a protozoan parasite with a complex lifecycle involving a triatomine insect and mammals. throughout its lifecycle, the t. cruzi parasite faces several alternating events of cell division and cell differentiation in which exponential and stationary growth phases play key biological roles. it is well accepted that arrest of the cell division in the epimastigote stage, both in the midgut of the triatomine insect and in vitro, is require ...201728356355
biodegradable polymeric nanocapsules prevent cardiotoxicity of anti-trypanosomal lychnopholide.chagas disease is a neglected parasitic disease caused by the protozoan trypanosoma cruzi. new antitrypanosomal options are desirable to prevent complications, including a high rate of cardiomyopathy. recently, a natural substance, lychnopholide, has shown therapeutic potential, especially when encapsulated in biodegradable polymeric nanocapsules. however, little is known regarding possible adverse effects of lychnopholide. here we show that repeated-dose intravenous administration of free lychn ...201728349937
performance of tci/tcvi/tcii chagas-flow ate-igg2a for universal and genotype-specific serodiagnosis of trypanosoma cruzi infection.distinct trypanosoma cruzi genotypes have been considered relevant for patient management and therapeutic response of chagas disease. however, typing strategies for genotype-specific serodiagnosis of chagas disease are still unavailable and requires standardization for practical application. in this study, an innovative tci/tcvi/tcii chagas flow ate-igg2a technique was developed with applicability for universal and genotype-specific diagnosis of t. cruzi infection. for this purpose, the reactivi ...201728333926
interdisciplinary approach at the primary healthcare level for bolivian immigrants with chagas disease in the city of são paulo.in a pioneering cross-sectional study among bolivian immigrants in the city of são paulo, brazil, the epidemiological profile, clinical manifestations and morbidity of chagas disease were described. the feasibility of the management of chagas disease at primary healthcare clinics using a biomedical and psychosocial interdisciplinary approach was also tested. previously, a trypanosoma cruzi (t. cruzi) infection rate of 4.4% among 633 immigrants was reported. the samples were screened using two co ...201728333923
analysis of the seroprevalence of and factors associated with chagas disease in an endemic area in northeastern brazil.chagas disease (cd) is currently considered a neglected disease; hence, identifying the factors associated with its high prevalence is essential. this study aimed to identify the seroprevalence of and the possible factors associated with cd in inhabitants of the city of limoeiro do norte, northeastern brazil.201728327801
trypanosoma cruzi i genotype among isolates from patients with chronic chagas disease followed at the evandro chagas national institute of infectious diseases (fiocruz, brazil).trypanosoma cruzi is the etiologic agent of chagas disease in humans, mainly in latin america. trypanosome stocks were isolated by hemoculture from patients followed at evandro chagas national institute of infectious diseases (fiocruz) and studied using different approaches.201728327800
differential cytokine profiling in chagasic patients according to their arrhythmogenic-status.chagas disease is caused by the protozoan trypanosoma cruzi and is characterized by heart failure and sudden death. identifying which factors are involved in evolution and treatment response is actually challenging. thus, the aim of this work was to determine the th1/th17 (il-6, il-2, tnf, il-17 and ifn-γ) and th2 (il-4 and il-10) serum profile in venezuelan chagasic patients stratified according amiodarone treatment, hypertension and arrhythmias.201728327099
chagas disease diagnostic applications: present knowledge and future steps.chagas disease, caused by the protozoan trypanosoma cruzi, is a lifelong and debilitating illness of major significance throughout latin america and an emergent threat to global public health. being a neglected disease, the vast majority of chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into r&d for drug and vaccine development. in this context, identification of novel biomarkers able to transcend the current limits of diagnostic ...201728325368
minicircle classes heterogeneity within the tciii and tciv discrete typing units of trypanosoma cruzi.the taxon trypanosoma cruzi, causative agent of chagas disease, is composed of several discrete typing units (dtus) named tci-tcvi, and tcbat. the history of the taxon t. cruzi is known, even though several controversial aspects remain as the relationships between tciii and tciv. we analyzed cloned t. cruzi stocks pertaining to the seven dtus by filter hybridization tests of pcr amplicons from minicircle variable regions and kinetoplast dna probes. minicircle dna blots from the cloned stocks and ...201728323069
mechanistic insights into the anti-angiogenic activity of trypanosoma cruzi protein 21 and its potential impact on the onset of chagasic cardiomyopathy.chronic chagasic cardiomyopathy (ccc) is arguably the most important form of the chagas disease, caused by the intracellular protozoan trypanosoma cruzi; it is estimated that 10-30% of chronic patients develop this clinical manifestation. the most common and severe form of ccc can be related to ventricular abnormalities, such as heart failure, arrhythmias, heart blocks, thromboembolic events and sudden death. therefore, in this study, we proposed to evaluate the anti-angiogenic activity of a rec ...201728322302
association of cardiac galectin-3 expression, myocarditis, and fibrosis in chronic chagas disease cardiomyopathy.chronic chagas disease cardiomyopathy, caused by trypanosoma cruzi infection, is a major cause of heart failure in latin america. galectin-3 (gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. herein, we investigated the involvement of gal-3 in the disease pathogenesis and its role as a target for disease intervention. gal-3 expression in mouse hearts was evaluated during t. cruzi infection by confocal microscopy and flow cytometry analysis, ...201728322201
early polymerase chain reaction detection of chagas disease reactivation in heart transplant patients.heart transplantation is a valuable therapeutic option for chagas disease patients with severe cardiomyopathy. during patient follow-up, the differential diagnosis between cardiac transplant rejection and chagas disease infection reactivation remains a challenging task, which hinders rapid implementation of the appropriate treatment. herein we investigate whether polymerase chain reaction (pcr) strategies could facilitate early detection of trypanosoma cruzi (t cruzi) in transplanted endomyocard ...201728320630
mutagenic and cytotoxicity lqb 123 profile: safety and tripanocidal effect of a phenyl-t-butylnitrone derivative.the therapeutic options for chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. therefore, new therapeutical options are mandatory. in the present work, we evaluated the effect of a phenyl-tert-butylnitrone (pbn) derivate, lqb 123, against trypanosoma cruzi forms. lqb 123 presented a trypanocidal effect against bloodstream trypomastigotes (ic50 = 259.4 ± 6.1 μm) a ...201728316976
trypanocidal effect of isotretinoin through the inhibition of polyamine and amino acid transporters in trypanosoma cruzi.polyamines are essential compounds to all living organisms and in the specific case of trypanosoma cruzi, the causative agent of chagas disease, they are exclusively obtained through transport processes since this parasite is auxotrophic for polyamines. previous works reported that retinol acetate inhibits leishmania growth and decreases its intracellular polyamine concentration. the present work describes a combined strategy of drug repositioning by virtual screening followed by in vitro assays ...201728306713
trypanothione reductase: a target for the development of anti-trypanosoma cruzi drugs.chagas disease or american trypanosomiasis is a major parasitic disease in latin america with treatment available via two drugs: nifurtimox and benznidazole. these two treatments are ineffective in the chronic phase of the disease. therefore, there is a need for the development of new, efficient and safe drugs for the treatment of these diseases. with this goal, one of the promising targets proposed is the trypanothione reductase (tr), a key enzyme important in the metabolism of trypanosoma cruz ...201728302040
computer-aided quantification of microvascular networks: application to alterations due to pathological angiogenesis in the hamster.angiogenesis is both a physiological and a pathological process of great complexity, which is difficult to measure objectively and automatically. the hamster cheek pouch (hcp) prepared for intravital-microscopy (ivm) has been used to characterize microvascular functions in many studies and was chosen to investigate microvascular characteristics observed in normal non-infected hamsters as compared to those hcps parasitized by trypanosoma cruzi. images of hcps captured at ivm were subjected to com ...201728300547
frequency of trypanosoma cruzi parasitemia among infected blood donors with a potential association between parasite lineage and transfusion transmission.trypanosoma cruzi is endemic to the americas where it demonstrates multiple lineages over a vast geographic range (i.e., united states to argentina). these lineages possess divergent geographic and biologic characteristics, including variations in disease manifestations. herein, we report the frequency of parasitemia among seropositive us blood donors and the potential association between parasite lineage and transfusion transmission.201728295355
immune complexes in chronic chagas disease patients are formed by exovesicles from trypanosoma cruzi carrying the conserved masp n-terminal region.the exovesicles (evs) are involved in pathologic host-parasite immune associations and have been recently used as biomarkers for diagnosis of infectious diseases. the release of evs by trypanosoma cruzi, the causative agent of chagas disease, has recently been described, with different protein cargoes including the masp multigene family of proteins masps are specific to this parasite and characterized by a conserved c-terminal (c-term) region and an n-terminal codifying for a signal peptide (sp) ...201728294160
challenges in the chemotherapy of chagas disease: looking for possibilities related to the differences and similarities between the parasite and host.almost 110 years after the first studies by dr. carlos chagas describing an infectious disease that was named for him, chagas disease remains a neglected illness and a death sentence for infected people in poor countries. this short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. the primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its ...201728289519
cord blood sample screening for evidence of maternal chagas disease. 201728287373
transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition in trypanosoma cruzi.american trypanosomiasis is a chronic and endemic disease which affects millions of people. trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. this requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. in this work we conducted an rnaseq analysis of the three major life cycle stages of t. cruzi: amastigotes, epimastigotes a ...201728286708
differential effects of two widely used solvents, dmso and ethanol, on the growth and recovery of trypanosoma cruzi epimastigotes in culture.trypanosoma cruzi is the etiological agent of chagas disease. epimastigote forms of t. cruzi can be readily cultured in axenic conditions. ethanol and dimethyl sulfoxide (dmso) are commonly used solvents employed as vehicles for hydrophobic compounds. in order to produce a reference plot of solvent dependent growth inhibition for t. cruzi research, the growth of epimastigotes was analyzed in the presence of different concentrations of ethanol (0.1-4.0%) and dmso (0.5-7.5%). the ability of the pa ...201728285511
purinergic ecto-enzymes participate in the thromboregulation in acute in mice infection by trypanosoma cruzi.coagulation disorders have been described in chagas disease with thrombocytopenia as an important event. several mechanisms may be related to this pathogenesis, such as enzymes of the purinergic system, purine, and receptors involved in the regulation and modulation of physiological events related to hemostasis. therefore, the aim of this study was to evaluate the activities of e-ntpdase, e-5'nucleotidase, and ecto-adenosine deaminase (e-ada) in platelets of mice experimentally infected by trypa ...201728285362
heart transplantation for chagas cardiomyopathy.chagas cardiomyopathy (cc) is one of the chronic manifestations of trypanosoma cruzi (t. cruzi) infection and is a major public health disease in latin america. since it is a chronic systemic infection, chagas disease was long considered a potential contraindication for transplantation because of the risk of recurrence with immunosuppression. however, early south american experience in the 1980's established the feasibility of heart transplantation (ht) in patients with chagas disease. indeed, t ...201728284779
comparison and validation of two computational models of chagas disease: a thirty year perspective from venezuela.mathematical models can help aid public health responses to chagas disease. models are typically developed to fulfill a particular need, and comparing outputs from different models addressing the same question can help identify the strengths and weaknesses of the models in answering particular questions, such as those for achieving the 2020 goals for chagas disease.201728279459
the role of interleukin 17-mediated immune response in chagas disease: high level is correlated with better left ventricular function.interleukin 17a (il-17a) has been associated with protective rather than pathogenic response in chagas disease (chd). however, it is not established whether or not il-17a-mediated immune response is correlated with patient's left ventricular (lv) function in chd. to address this question we have gathered cardiac functional parameters from chd patients and analysed the possible relationship between their plasma il-17a levels and lv function. plasma il-17a levels were measured by bd cytometric bea ...201728278264
transcriptome and functional genomics reveal the participation of adenine phosphoribosyltransferase in trypanosoma cruzi resistance to benznidazole.currently, the only available treatments for trypanosoma cruzi are benznidazole (bz) and nifurtimox (nfx). the mechanisms of action and resistance to these drugs in this parasite are not complete known. in order to identify differentially expressed transcripts between sensitive and resistant parasites, a massive pyrosequencing of the t. cruzi transcriptome was carried out. additionally, the 2d gel electrophoresis profile of sensitive and resistant parasites was analyzed and the data were support ...201728276600
different genotypes of trypanosoma cruzi produce distinctive placental environment genetic response in chronic experimental infection.congenital infection of trypanosoma cruzi allows transmission of this parasite through generations. despite the problematic that this entails, little is known about the placenta environment genetic response produced against infection. we performed functional genomics by microarray analysis in c57bl/6j mice comparing placentas from uninfected animals and from animals infected with two different t. cruzi strains: k98, a clone of the non-lethal myotropic ca-i strain (tci), and vd (tcvi), isolated f ...201728273076
s. mansoni-t. cruzi co-infection modulates arginase-1/inos expression, liver and heart disease in mice.although schistosoma species and trypanosoma cruzi share common endemic areas, co-infections by these parasites remains overlooked. by using a murine model of s. mansoni and t. cruzi co-infection, we investigated if and to what extent these infections might interact to change the pathological outcomes typically observed when the host is infected by a single parasite species. swiss mice were randomized into four groups: uninfected (ni) and those infected by s. mansoni (sm), t. cruzi (tc) or co-in ...201728268114
antiparasitic treatment induces an improved cd8(+) t cell response in chronic chagasic patients.chagas disease is a chronic infection caused by trypanosoma cruzi, an intracellular protozoan parasite. chronic chagasic patients (ccps) have dysfunctional cd8(+) t cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. most patients diagnosed in the chronic phase of chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease. antiparasitic treatment is con ...201728258194
correction to in vitro and in vivo anti-trypanosoma cruzi activity of new arylamine mannich base-type derivatives. 201728257207
cost-effectiveness of chagas disease screening in latin american migrants at primary health-care centres in europe: a markov model analysis.chagas disease is currently prevalent in european countries hosting large communities from latin america. whether asymptomatic individuals at risk of chagas disease living in europe should be screened and treated accordingly is unclear. we performed an economic evaluation of systematic chagas disease screening of the latin american population attending primary care centres in europe.201728256340
a novel stage-specific glycosomal nucleoside diphosphate kinase from trypanosoma cruzi.nucleoside diphosphate kinases (ndpk) are key enzymes involved in the intracellular nucleotide maintenance in all living organisms, especially in trypanosomatids which are unable to synthesise purines de novo. four putative ndpk isoforms were identified in the trypanosoma cruzi chagas, 1909 genome but only two of them were characterised so far. in this work, we studied a novel isoform from t. cruzi called tcndpk3. this enzyme presents an atypical n-terminal extension similar to the dm10 domains. ...201728246372
evaluation of the antichagasic activity of batroxicidin, a cathelicidin-related antimicrobial peptide found in bothrops atrox venom gland.antimicrobial peptides (amps) are potential alternatives to conventional antibiotics, as they have a fast mode of action, a low likelihood of resistance development and can act in conjunction with existing drug regimens. we report in this study the effects of batroxicidin (batxc), a cathelicidin-related amp from bothrops atrox venom gland, over trypanosoma cruzi, a protozoan that causes chagas' disease. batxc inhibited all t. cruzi (y strain: benznidazole-resistant) developmental forms, with sel ...201728246023
endocrine immunology of chagas disease.the concept of immunoendocrine interactions, existing in normal and pathological conditions, is relatively recent. accordingly, cells from the immune system and from endocrine glands share common receptors for cytokines and hormones, allowing systemic and local regulatory mechanisms. in this context, lymphoid organs are under physiological hormonal control. disturbances in these systems, as those caused by pathogens changes the physiological profile of these interactions, with the release of pro ...201728245460
nuclear compartmentalization contributes to stage-specific gene expression control in trypanosoma cruzi.in the protozoan parasite trypanosoma cruzi, as in other trypanosomatids, transcription of protein coding genes occurs in a constitutive fashion, producing large polycistronic transcription units. these units are composed of non-functionally related genes which are pervasively processed to yield each mrna. therefore, post-transcriptional processes are crucial to regulate gene expression. considering that nuclear compartmentalization could contribute to gene expression regulation, we comparativel ...201728243589
desing and synthesis of potent anti-trypanosoma cruzi agents new thiazoles derivatives which induce apoptotic parasite death.chagas disease, caused by the kinetoplastid protozoan parasite trypanosoma cruzi, remains a relevant cause of illness and premature death and it is estimated that 6 million to 7 million people are infected worldwide. although chemotherapy options are limited presenting serious problems, such as low efficacy and high toxicity. t. cruzi is susceptible to thiazoles, making this class of compounds appealing for drug development. previously, thiazoles resulted in an increase in anti-t. cruzi activity ...201728242550
recently differentiated epimastigotes from trypanosoma cruzi are infective to the mammalian host.trypanosoma cruzi, the etiologic agent of chagas disease, has a complex life cycle in which four distinct developmental forms alternate between the insect vector and the mammalian host. it is assumed that replicating epimastigotes present in the insect gut are not infective to mammalian host, a paradigm corroborated by the widely acknowledged fact that only this stage is susceptible to the complement system. in the present work, we establish a t. cruzi in vitro and in vivo epimastigogenesis mode ...201728240790
rhenium(i) tricarbonyl compounds of bioactive thiosemicarbazones: synthesis, characterization and activity against trypanosoma cruzi.american trypanosomiasis is a chronic infection discovered and described in 1909 by the brazilian scientist carlos chagas. it is caused by the protozoan parasite trypanosoma cruzi. although it affects about 10million people in latin america, the current chemotherapy is still inadequate. the discovery of new drugs is urgently needed. our group is focused on the development of prospective metal-based drugs mainly based on bioactive ligands and pharmacologically interesting metal ions. in this work ...201728237731
immunization with tc52 or its amino terminal domain adjuvanted with c-di-amp induces th17+th1 specific immune responses and confers protection against trypanosoma cruzi.the development of new adjuvants enables fine modulation of the elicited immune responses. ideally, the use of one or more adjuvants should result in the induction of a protective immune response against the specific pathogen. we have evaluated the immune response and protection against trypanosoma cruzi infection in mice vaccinated with recombinant tc52 or its n- and c-terminal domains (ntc52 and ctc52) adjuvanted either with the sting (stimulator of interferon genes) agonist cyclic di-amp (c-d ...201728234897
induction of cellular proliferation in a human astrocytoma cell line by a trypanosoma cruzi-derived antigen: a mechanism of pathogenesis?trypanosoma cruzi can compromise the human central nervous system (cns) during acute infection or reactivation in immune-suppressed hosts. astrocytes have been identified as targets of t. cruzi's cns infection in humans. despite a high degree of parasitism and cellular lysis by t. cruzi in vitro the number of astrocytoma cells did not change when compared to uninfected cultures. this work evaluated cellular proliferation, changes in major histocompatibility complex (mhc) expression as a reflecti ...201728234621
inhibition of autolysosome formation in host autophagy by trypanosoma cruzi infection.autophagy has emerged as an essential component of the defense system against intracellular pathogens. we demonstrated that trypanosoma cruzi, an intracellular protozoan parasite, was not eliminated by the host's autophagic machinery despite exposure to the host cell cytoplasm. puncta of microtubule-associated protein 1 light chain 3 (lc3), an autophagy marker, and lc3-ii, a lipidated form of lc3, were significantly increased after infection with t. cruzi, indicating that the parasite activated ...201728232068
benznidazole and posaconazole in eliminating parasites in asymptomatic t. cruzi carriers: the stop-chagas trial.benznidazole is recommended for treatment of chagas infection. effects of combination therapy with benznidazole and posaconazole have not been tested in trypanosoma cruzi carriers.201728231946
cynomolgus macaques naturally infected with trypanosoma cruzi-i exhibit an overall mixed pro-inflammatory/modulated cytokine signature characteristic of human chagas disease.non-human primates have been shown to be useful models for chagas disease. we previously reported that natural t. cruzi infection of cynomolgus macaques triggers clinical features and immunophenotypic changes of peripheral blood leukocytes resembling those observed in human chagas disease. in the present study, we further characterize the cytokine-mediated microenvironment to provide supportive evidence of the utility of cynomolgus macaques as a model for drug development for human chagas diseas ...201728225764
parasite control and skeletal myositis in trypanosoma cruzi-infected and exercised rats.non-pharmacological strategies have been rarely described in the treatment of infectious diseases. although exercise training has been recently incorporated in the clinical management of chagas disease, the rationale basis that supports this indication is poorly understood. thus, we investigated the effect of an aerobic exercise on the parasitism, inflammation and oxidative tissue damage in a murine model of trypanosoma cruzi-induced skeletal myositis. wistar rats were randomized into four group ...201728223068
towards a new strategy for the diagnosis of congenital trypanosoma cruzi infection.the immigration of latin american women of childbearing age has spread the congenital transmission of chagas disease to non-endemic areas, and the disease is now a worldwide problem. some european health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy, common for all laboratories. our aims were (i) to analyze the trend of passive igg antibodies in the newborn by means of five ...201728202792
treatment of infected women of childbearing age prevents congenital trypanosoma cruzi infection by eliminating the parasitemia detected by pcr. 201728201741
comparative and functional triatomine genomics reveals reductions and expansions in insecticide resistance-related gene families.triatomine insects are vectors of trypanosoma cruzi, a protozoan parasite that is the causative agent of chagas' disease. this is a neglected disease affecting approximately 8 million people in latin america. the existence of diverse pyrethroid resistant populations of at least two species demonstrates the potential of triatomines to develop high levels of insecticide resistance. therefore, the incorporation of strategies for resistance management is a main concern for vector control programs. t ...201728199333
engineering oral and parenteral amorphous amphotericin b formulations against experimental trypanosoma cruzi infections.chagas disease (cd) is a parasitic zoonosis endemic in most mainland countries of central and south america affecting nearly 10 million people, with 100 million people at high risk of contracting the disease. treatment is only effective if received at the early stages of the disease. only two drugs (benznidazole and nifurtimox) have so far been marketed, and both share various limitations such as variable efficacy, many side effects, and long duration of treatment, thus reducing compliance. the ...201728198632
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