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doxycycline and benznidazole reduce the profile of th1, th2, and th17 chemokines and chemokine receptors in cardiac tissue from chronic trypanosoma cruzi-infected dogs.chemokines (cks) and chemokine receptors (ckr) promote leukocyte recruitment into cardiac tissue infected by the trypanosoma cruzi. this study investigated the long-term treatment with subantimicrobial doses of doxycycline (dox) in association, or not, with benznidazole (bz) on the expression of ck and ckr in cardiac tissue. thirty mongrel dogs were infected, or not, with the berenice-78 strain of t. cruzi and grouped according their treatments: (i) two months after infection, dox (50 mg/kg) 2x/ ...201727688600
novel 2-arylazoimidazole derivatives as inhibitors of trypanosoma cruzi proliferation: synthesis and evaluation of their biological activity.in this work, the synthesis of a series of 2-arylazoimidazole derivatives 6-20 has been achieved through the reaction of imidazole with aryldiazonium salts, followed by ultrasound-assisted alkylation. this approach has important advantages including higher yield, shorter reaction times and milder reaction conditions. the structures of the compounds obtained were determined by ms, ir; and (1)h and (13)c nmr. the anti-trypanosoma cruzi activity of the 15 compounds obtained was evaluated. two compo ...201727688187
specific endocytosis blockade of trypanosoma cruzi exposed to a poly-lacnac binding lectin suggests that lectin-sugar interactions participate to receptor-mediated endocytosis.trypanosoma cruzi is a protozoan parasite transmitted by a triatomine insect, and causing human chagas disease in south america. this parasite undergoes a complex life cycle alternating between non-proliferative and dividing forms. owing to their high energy requirement, replicative epimastigotes of the insect midgut display high endocytic activity. this activity is mainly restricted to the cytostome, by which the cargo is taken up and sorted through the endosomal vesicular network to be deliver ...201727685262
dynamic flux of microvesicles modulate parasite-host cell interaction of trypanosoma cruzi in eukaryotic cells.extracellular vesicles released from pathogens may alter host cell functions. we previously demonstrated the involvement of host cell-derived microvesicles (mvs) during early interaction between trypanosoma cruzi metacyclic trypomastigote (meta) stage and thp-1 cells. here, we aim to understand the contribution of different parasite stages and their extracellular vesicles in the interaction with host cells. first, we observed that infective host cell-derived trypomastigote (tissue culture-derive ...201727665486
molecular mechanisms of cardiac electromechanical remodeling during chagas disease: role of tnf and tgf-β.chagas disease is caused by the trypanosomatid trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. chagas disease was initially restricted to latin america. however, due to migratory events, this disease may become a serious worldwide health problem. during chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti-arrhythmic therapy (e.g., amiodarone). here, we assimilate the cardiac form of chagas disease to an inflam ...201727622432
cysteine mutagenesis improves the production without abrogating antigenicity of a recombinant protein vaccine candidate for human chagas disease.a therapeutic vaccine for human chagas disease is under development by the sabin vaccine institute product development partnership. the aim of the vaccine is to significantly reduce the parasite burden of trypanosoma cruzi in humans, either as a standalone product or in combination with conventional chemotherapy. vaccination of mice with tc24 formulated with monophosphoryl-lipid a (mpla) adjuvant results in a th1 skewed immune response with elevated igg2a and ifnγ levels and a statistically sign ...201727737611
enhancing glycan isomer separations with metal ions and positive and negative polarity ion mobility spectrometry-mass spectrometry analyses.glycomics has become an increasingly important field of research since glycans play critical roles in biology processes ranging from molecular recognition and signaling to cellular communication. glycans often conjugate with other biomolecules, such as proteins and lipids, and alter their properties and functions, so glycan characterization is essential for understanding the effects they have on cellular systems. however, the analysis of glycans is extremely difficult due to their complexity and ...201727604268
in vitro activities of pfaffia glomerata root extract, its hydrolyzed fractions and pfaffic acid against trypanosoma cruzi trypomastigotes.this article reports on the in vitro activity of the hydroalcoholic extract of pfaffia glomerata roots, its hydrolyzed fractions, and pfaffic acid against trypanosoma cruzi. the hydroalcoholic extract obtained from dried, milled p. glomerata roots was submitted to acid hydrolysis followed by partition with chcl3 . the concentrated chcl3 fraction was suspended in meoh/h2 o and partitioned with hexane (f1), chcl3 (f2), and acoet (f3), in this sequence. the trypanocidal activity of the hydrolyzed e ...201727546206
behavioral fever response in rhodnius prolixus (reduviidae: triatominae) to intracoelomic inoculation of trypanosoma cruzi.behavioral fever is a response to infections with microorganisms observed in some poikilothermic animals. rhodnius prolixus is involved in the transmission of two parasites: trypanosoma cruzi (pathogenic for humans and transmitted in feces) and trypanosoma rangeli (non-pathogenic for humans, pathogenic for rhodnius and transmitted by the bite of an infected individual). only t. rangeli is found in the hemolymph of rhodnius as it travels to the salivary glands.201727598628
mif-driven activation of macrophages induces killing of intracellular trypanosoma cruzi dependent on endogenous production of tumor necrosis factor, nitric oxide and reactive oxygen species.the proinflammatory cytokine macrophage migration inhibitory factor (mif) is a key player in innate immunity. mif has been considered critical for controlling acute infection by the protozoan trypanosoma cruzi, but the underlying mechanisms are poorly understood. our study aimed to analyze whether mif could favor microbicidal activity of the macrophage, a site where t. cruzi grows and the initial effector cell against this parasite. using murine macrophages infected in vitro, we examined the eff ...201727591076
evaluation of the novel antichagasic activity of [1,2,3]triazolo[1,5-a]pyridine derivatives.trypanosoma cruzi is the causative agent of chagas disease. this parasite is vulnerable to the effects of ros as its main defense mechanism against exogenous agents trypanothione is also another weakness of the parasite that investigated related to the inhibition of enzymes belonging p450 system, mainly cyp51. in our group we have synthesized a series of triazoles known as [1,2,3]triazolo[1,5-a]pyridyl ketones, and pyridyl ketones. these families have shown interesting structural features due to ...201727558681
flavonoids and chagas' disease: the story so far!chagas disease is one of the major health problems in central and south america, which is caused by the parasitic protozoa, trypanosoma cruzi. it is commonly transmitted by members of blood-sucking subfamily triatominae. chagas disease is associated with cardiac and gastrointestinal manifestations. up to now, there are no effective vaccines for treatment of chagas disease and benznidazole and nifurtimox are the only effective anti-chagas drugs that cause different adverse and side effects. there ...201727558676
antiparasitic activity of diterpenoids against trypanosoma cruzi.twenty-seven diterpenes, including abietanes, labdanes, abeoabietanes, halimanes, and pimaranes, have been evaluated against epimastigote and intracellular amastigote forms of trypanosoma cruzi and also against lc5 and nctc cell lines. royleanones (3, 4, and 5) and a further abietane (12), obtained by purification of plectranthus spp. extracts, were the most active compounds on epimastigotes, showing ic50 values similar (1.73 µg/ml, 12) or even lower (0.39, 0.99, and 1.20 µg/ml, 3, 4, and 5 resp ...201727599261
decreased cruzipain and gp85/trans-sialidase family protein expression contributes to loss of trypanosoma cruzi trypomastigote virulence.two cell lines derived from a single trypanosoma cruzi clone by long-term passaging generated a highly virulent (c8c3hvir) and a low virulent (c8c3lvir) cell line. the c8c3hvir cell line was highly infective and lethal to balb/c mice, and the c8c3lvir cell line was three- to five-fold less infective to mouse cardiomyocytes than c8c3hvir. the highly virulent t. cruzi cell line abundantly expressed the major cysteine proteinase cruzipain (czp), complement regulatory protein (crp) and trans-sialida ...201727553285
the cytostome-cytopharynx complex of trypanosoma cruzi epimastigotes disassembles during cell division.the cytostome-cytopharynx complex is the main site for endocytosis in epimastigotes of trypanosoma cruzi it consists of an opening at the plasma membrane surface - the cytostome - followed by a membrane invagination - the cytopharynx. in g1/s cells, this structure is associated with two specific sets of microtubules, a quartet and a triplet. here, we used electron microscopy and electron tomography to build 3d models of the complex at different stages of the cell cycle. the cytostome-cytopharynx ...201727363990
tetradentate polyamines as efficient metallodrugs for chagas disease treatment in murine model.a series of tetraamine-based compounds was prepared, and their trypanocidal effects against trypanosoma cruzi and cytotoxicity were determined through the determination of ic50 values. in vivo assays were performed in mice, where parasitaemia levels were quantified by fresh blood examination and the assignment of a cure was determined by polymerase chain reaction and reactivation of blood parasitaemia levels after immunosuppression. the mechanisms of action were elucidated at metabolic and ultra ...201727251893
semisolid liver infusion tryptose supplemented with human urine allows growth and isolation of trypanosoma cruzi and trypanosoma rangeli clonal lineages.this work shows that 3% (v/v) human urine (hu) in semisolid liver infusion tryptose (ssl) medium favors the growth of trypanosoma cruzi and t. rangeli.201727384837
first report of rhodnius stali (hemiptera, reduviidae, triatominae) in the state of acre and in the brazilian amazon.this paper reports, for the first time, the presence of rhodnius stali in the state of acre and in the brazilian amazon.201727384836
triatomine physiology in the context of trypanosome infection.triatomines are hematophagous insects that feed on the blood of vertebrates from different taxa, but can occasionally also take fluids from invertebrate hosts, including other insects. during the blood ingestion process, these insects can acquire diverse parasites that can later be transmitted to susceptible vertebrates if they complete their development inside bugs. trypanosoma cruzi, the etiological agent of chagas disease, and trypanosoma rangeli are protozoan parasites transmitted by triatom ...201727401496
comprehensive glycoprofiling of the epimastigote and trypomastigote stages of trypanosoma cruzi.trypanosoma cruzi, the protozoan that causes chagas disease, has a complex life cycle involving insect and mammalian hosts and distinct developmental stages. during t. cruzi developmental stages, glycoproteins play important role in the host-parasite interaction, such as cellular recognition, host cell invasion and adhesion, and immune evasion. in this study, comprehensive glycoprofiling analysis was performed in the epimastigote and trypomastigote stages of t. cruzi using two glycopeptide enric ...201727318177
mitochondrial gene expression is responsive to starvation stress and developmental transition in trypanosoma cruzi.trypanosoma cruzi parasites causing chagas disease are passed between mammals by the triatomine bug vector. within the insect, t. cruzi epimastigote-stage cells replicate and progress through the increasingly nutrient-restricted digestive tract, differentiating into infectious, nonreplicative metacyclic trypomastigotes. thus, we evaluated how nutrient perturbations or metacyclogenesis affects mitochondrial gene expression in different insect life cycle stages. we compared mitochondrial rna abund ...201727303725
application of bioisosterism in design of the semicarbazone derivatives as cruzain inhibitors: a theoretical and experimental study.a series of semicarbazone, thiosemicarbazone, and aminoguanidine derivatives were synthesized and tested as antitrypanosomal agents. the theoretical nmr of the compounds was calculated using molecular modeling techniques (density functional theory (dft) calculations) and confirmed the formation of the compounds. the ability to inhibit cruzain and trypanosoma cruzi epimastigote replication was evaluated. cruzain inhibition ranged between 70 and 75% (100 μm), and ic50 values observed in epimastigo ...201727064715
a critical assessment of officially reported chagas disease surveillance data in mexico.chagas disease, a disease caused by trypanosoma cruzi, disproportionately affects poor people throughout latin america. in mexico, assessments of officially reported burden have not been previously reported. to evaluate discontinuity between surveillance data and data from other sources, we used data from the mexican ministry of health to describe the distribution of reported chagas disease over time in mexico and compare it with estimates from the literature.201726843671
use of venoarterial extracorporeal membrane oxygenation in fulminant chagasic myocarditis as a bridge to heart transplant.a 17-year-old brazilian male presented with progressive dyspnea for 15 days, worsening in the last 24 hours, and was admitted in respiratory failure and cardiogenic shock, with multiple organ dysfunctions. echocardiography showed a left ventricle ejection fraction of 11%, severe diffuse hypokinesia, and a systolic pulmonary artery pressure of 50mmhg, resulting in the need for hemodynamic support with dobutamine (20mcg/kg/min) and noradrenaline (1.7mcg/kg/min). after 48 hours with no clinical or ...201726761479
aspirin prevents atrophy of esophageal nitrergic myenteric neurons in a mouse model of chronic chagas disease.the consequences of using aspirin (asa) for the pathogenesis of chagas disease are unclear. this study evaluated the effects of treatment of chagas disease with asa on the esophageal nitrergic myenteric neuron population and esophageal wall in mice. we observed that treatment of chagasic infection with asa protects the esophageal myenteric neurons from the atrophy caused by the trypanosoma cruzi infection. the mice were infected with 1300 trypomastigotes of y strain t. cruzi intraperitoneally. p ...201726725535
membranous nephropathy pla2r+ associated with chagas disease.chagas disease (cd) - a tropical parasitic disease caused by the protozoan trypanosoma cruzi - is a major health problem in latin america. the immune response against the parasite is responsible for chronic cd lesions. currently, there are no reports of an association between cd and membranous nephropathy (mn). the detection of the phospholipase a2 receptor (pla2r) as a target antigen in idiopathic mn can improve the differential diagnosis of primary and secondary forms of mn. the authors report ...201726558244
first report of acute chagas disease by vector transmission in rio de janeiro state, brazil.chagas disease (cd) is an endemic anthropozoonosis from latin america of which the main means of transmission is the contact of skin lesions or mucosa with the feces of triatomine bugs infected by trypanosoma cruzi. in this article, we describe the first acute cd case acquired by vector transmission in the rio de janeiro state and confirmed by parasitological, serological and pcr tests. the patient presented acute cardiomyopathy and pericardial effusion without cardiac tamponade. together with f ...201726422165
a family cluster of chagas disease detected through selective screening of blood donors: a case report and brief review.chagas disease (cd) is a protozoan infection caused by trypanosoma cruzi, which is transmitted by triatomine insect vectors in parts of latin america. in a nonendemic country, such as canada, spread can still occur via vertical transmission, and infected blood or organ donations. the canadian blood services and héma-québec have both implemented selective screening of blood donors for cd based on risk factors. in 2011, héma-québec identified two seropositive 'at-risk' chilean siblings who had don ...201726236358
effects of vitamin c supplementation on the chronic phase of chagas disease.in order to examine the effectiveness of vitamin c (ascorbic acid) in combating the oxidative insult caused by trypanosoma cruzi during the development of the chronic phase of chagas disease, swiss mice were infected intraperitoneally with 5.0 × 104 trypomastigotes of t. cruzi qm1strain.201726200966
comparison of biological fitness in crosses between subspecies of meccus phyllosomus (hemiptera: reduviidae: triatominae) in southern mexico.understanding the biological parameters of some triatomine subspecies of meccus phyllosomus (burmeister) is a crucial first step in estimating the epidemiologic importance of this group. biological parameters related to hatching, lifetime, number of blood meals to molt, percentage of females at the end of the cycle, number of laid eggs, and mortality for each instar of 3 m. phyllosomus subspecies [m. p. mazzottii (usinger), m. p. pallidipennis (stål), and m. p. phyllosomus] and their laboratory ...201726118997
prevalence of chagas disease in the bolivian population of majorca (spain).to establish the prevalence of trypanosoma cruzi infection in bolivian (spain) participants.201726026727
[western blot technique standardization for specific diagnosis of chagas disease using excretory-secretory antigens of trypanosoma cruzi epimastigotes].evaluate the effectiveness of western blot for the specific diagnosis of chagas disease using excretory-secretory antigens of trypanosoma cruzi epimastigotes.201725597713
evidence of polymorphism on the antitrypanosomal naphthoquinone (4e)-2-(1h-pyrazol-3-ylamino)-4-(1h-pyrazol-3-ylimino)naphthalen-1(4h)-one.the aim of this study was to characterize the solid state properties of (4e)-2-(1h-pyrazol-3-ylamino)-4-(1h-pyrazol-3-ylimino)naphthalen-1(4h)-one (bipnq), a compound with a significant inhibitory activity against trypanosoma cruzi, the etiological agent of chagas disease (american trypanosomiasis). methods used included differential scanning calorimetry (dsc), thermogravimetry (tg), fourier transform infrared spectroscopy (ftir), powder x-ray diffraction (pxrd), hot stage, and confocal microsco ...201724106678
jaburetox affects gene expression and enzyme activities in rhodnius prolixus, a chagas' disease vector.jaburetox, a recombinant peptide of ∼11kda derived from one of the canavalia ensiformis (jack bean) urease isoforms, is toxic and lethal to insects belonging to different orders when administered orally or via injection. previous findings indicated that jaburetox acts on insects in a complex fashion, inhibiting diuresis and the transmembrane potential of malpighian tubules, interfering with muscle contractility and affecting the immune system. in vitro, jaburetox forms ionic channels and alters ...201728108369
wing polymorphism and trypanosoma cruzi infection in wild, peridomestic, and domestic collections of mepraia spinolai (hemiptera: reduviidae) from chile.mepraia spinolai (porter) is a vector of trypanosoma cruzi that causes chagas disease. females are always wingless, but males may be winged or wingless. we determined by pcr the infection percentage with t. cruzi of m. spinolai adults and nymphs in domestic, peridomestic, and wild collections, in different regions of chile. in all regions, winged males were more abundant than females and wingless males. winged males collected inside houses were less parasitized than were those from peridomestic ...201728399301
chronic chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the benznidazole evaluation for interrupting trypanosomiasis (benefit) trial.chagas cardiomyopathy is the most frequent and most severe manifestation of chronic chagas disease, and is one of the leading causes of morbidity and death in latin america. although the pathogenesis of chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. in the past three decades, a ...201728225900
chronic chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the benznidazole evaluation for interrupting trypanosomiasis (benefit) trial.chagas cardiomyopathy is the most frequent and most severe manifestation of chronic chagas disease, and is one of the leading causes of morbidity and death in latin america. although the pathogenesis of chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. in the past three decades, a ...201728225894
development and evaluation of a nanoemulsion containing ursolic acid: a promising trypanocidal agent : nanoemulsion with ursolic acid against t. cruzi.over a hundred years after the discovery of chagas disease, this ailment continues to affect thousands of people. for more than 40 years, only two drugs have been available to treat it. ursolic acid is a naturally occurring terpene that has shown a good trypanocidal action. however, the hydrophobicity of this compound presents a challenge for the development of proper delivery systems. nanostructured systems are a prominent in delivering lipophilic drugs. thus, a nanoemulsion containing ursolic ...201728224391
radiological findings in megaesophagus secondary to chagas disease: chest x-ray and esophagogram.to identify and classify the radiographic patterns of megaesophagus in chagas disease, as seen on esophagograms and chest x-rays.201728100930
dobutamine stress echocardiography safety in chagas disease patients.a few decades ago, patients with chagas disease were predominantly rural workers, with a low risk profile for obstructive coronary artery disease (cad). as urbanization has increased, they became exposed to the same risk factors for cad of uninfected individuals. dobutamine stress echocardiography (dse) has proven to be an important tool in cad diagnosis. despite being a potentially arrhythmogenic method, it is safe for coronary patients without chagas disease. for chagas disease patients, howev ...201728099588
plasma concentrations of ccl3 and ccl4 in the cardiac and digestive clinical forms of chronic chagas disease.the aim of this study was to investigate the plasma levels of the ccl3 and ccl4 chemokines in patients with the cardiac and digestive clinical forms of chronic chagas disease and in cardiac patients with and without left ventricular systolic dysfunction (lvsd). plasma samples from 75 patients were evaluated by enzyme-linked immunosorbent assay (elisa) to confirm infection by t. cruzi. plasma levels of the ccl3 and ccl4 chemokines were measured using milliplex® map assay (millipore). there were n ...201728002786
postfundoplication dysphagia causes similar water ingestion dynamics as achalasia.- after surgical treatment of gastroesophageal reflux disease dysphagia is a symptom in the majority of patients, with decrease in intensity over time. however, some patients may have persistent dysphagia.201727305416
early and late assessment of esophagocardioplasty in the surgical treatment of advanced recurrent megaesophagus.since chagas disease has esophageal manifestations with different degrees of involvement, the best surgical option is controversial, especially for patients with advanced chagasic megaesophagus and recurrent symptoms after previous treatment.201727706452
chronotropic incompetence in chagas disease: usefulness of dual sensor pacemaker based on volume minute and accelerometer. 201726313733
cardiac resynchronization therapy in patients with chronic chagas cardiomyopathy: long-term follow up.chagas disease is a major cause of cardiomyopathy and sudden death in our country. it has a high mortality when their patients develop new york heart association (nyha) class iv.201724896160
bioinformatics insights on targets receptors of amiodarone in human and acanthamoeba castellanii.amiodarone is prescribed for certain cardiac arrhythmias in medical practice. the drug targets and inhibits voltage dependent sodium (na+v), calcium (ca+2v), potassium (k+v) channels, and enzymes like cytochrome p450 and oxidosqualene cyclase. past studies have shown that amiodarone exerts anti-amoebic effects against trypanosoma cruzi and acanthamoeba castellanii.201728637420
analytical sensitivity and specificity of a loop-mediated isothermal amplification (lamp) kit prototype for detection of trypanosoma cruzi dna in human blood samples.this study aimed to assess analytical parameters of a prototype lamp kit that was designed for detection of trypanosoma cruzi dna in human blood. the prototype is based on the amplification of the highly repetitive satellite sequence of t.cruzi in microtubes containing dried reagents on the inside of the caps. the reaction is carried out at 65°c during 40 minutes. calcein allows direct detection of amplified products with the naked eye. inclusivity and selectivity were tested in purified dna fro ...201728727723
infectious diseases causing autonomic dysfunction.to review infectious diseases that may cause autonomic dysfunction.201728730326
trypanosoma infection favors brucella elimination via il-12/ifnγ-dependent pathways.this study develops an original co-infection model in mice using brucella melitensis, the most frequent cause of human brucellosis, and trypanosoma brucei, the agent of african trypanosomiasis. although the immunosuppressive effects of t. brucei in natural hosts and mice models are well established, we observed that the injection of t. brucei in mice chronically infected with b. melitensis induces a drastic reduction in the number of b. melitensis in the spleen, the main reservoir of the infecti ...201728824630
a voucher system to speed review could promote a new generation of insecticides to fight vector-borne diseases.many in the scientific community are concerned about the potential increase in prevalence of insect-borne diseases such as chagas disease, chikungunya, dengue fever, malaria, and zika in the united states and around the world. beyond vaccines and drugs to prevent and treat these diseases, a comprehensive approach to fighting these diseases should include control of disease-carrying vectors, such as mosquitoes. vector-control methods, such as using insecticides to treat bed nets and spray the wal ...201728784739
[knowledge of vector-borne diseases (dengue, rickettsiosis and chagas disease) in physicians].the ecological conditions of yucatan made it a suitable region for the acquisition of vector-borne diseases such as dengue, rickettsiosis, and chagas disease. as the epidemiological burden of these diseases shows an alarming increase of severe cases, the early establishment of diagnosis and therapeutics by first-contact physicians is a critical step that is not being fulfilled due to several reasons, including poor knowledge.201728763070
developing a casper survey to assess the prevalence of risk factors for neglected tropical diseases in texas.while more than a billion people live at risk of neglected tropical diseases in areas of asia, sub-saharan africa, and latin america, the degree to which such diseases burden countries like the united states is currently unclear. even though many neglected tropical diseases such as dengue, leishmaniasis, and chagas disease are not endemic to the united states, the possibility of their emergence is noteworthy, especially in states like texas, which has high levels of poverty, a large immigrant po ...201728636445
spectrum and burden of neglected tropical diseases observed in an infectious and tropical diseases unit in florence, italy (2000-2015).neglected tropical diseases (ntds) are a diverse group of acute and chronic conditions with distinct characteristics that thrive mainly among the poorest populations, almost exclusively in tropical countries. to evaluate the relevance and impact of ntds in a temperate area, the number and features of patients diagnosed with ntds at the infectious and tropical diseases unit (itdu), azienda ospedaliero-universitaria careggi, florence, italy between 2000 and 2015 were retrospectively reviewed. over ...201728054225
identifying gaps in research prioritization: the global burden of neglected tropical diseases as reflected in the cochrane database of systematic reviews.neglected tropical diseases (ntds) impact disadvantaged populations in resource-scarce settings. availability of synthesized evidence is paramount to end this disparity. the aim of the study was to determine whether ntd systematic reviews or protocols in the cochrane database of systematic reviews (cdsr) reflect disease burden.201726985407
diterpenes as lead molecules against neglected tropical diseases.nowadays, neglected tropical diseases (ntds) are reported to be present everywhere. poor and developing areas in the world have received great attention to ntds. drug resistance, safety profile, and various challenges stimulate the search for alternative medications. plant-based drugs are viewed with great interest, as they are believed to be devoid of side effects. diterpenes, a family of essential oils, have showed attractive biological effects. a systematic review of the literature was carrie ...201727896890
a survey of zoonotic pathogens carried by house mouse and black rat populations in yucatan, mexico.the house mouse (mus musculus) and the black rat (rattus rattus) are reservoir hosts for zoonotic pathogens, several of which cause neglected tropical diseases (ntds). studies of the prevalence of these ntd-causing zoonotic pathogens, in house mice and black rats from tropical residential areas are scarce. three hundred and two house mice and 161 black rats were trapped in 2013 from two urban neighbourhoods and a rural village in yucatan, mexico, and subsequently tested for trypanosoma cruzi, hy ...201728689507
synthesis and in vitro evaluation of ca(2+) channel blockers 1,4-dihydropyridines analogues against trypanosoma cruzi and leishmania amazonensis: sar analysis.drugs containing the1,4-dihydropyridine (dhp) core have recently attracted attention concerning their antiparasitic effect against various species of leishmania and trypanosoma. this approach named drugs repositioning led to interesting results, which have prompted us to prepare 21 dhp's analogues. the 1,4-dhp scaffold was decorated with different function groups at tree points including the nitrogen atom (nh and n-phenyl), the aryl group attached to c-4 (various substituted aryl residues) and t ...201728801098
efficacy of a binuclear cyclopalladated compound therapy for cutaneous leishmaniasis in the murine model of infection with leishmania amazonensis and its inhibitory effect on topoisomerase 1b.leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the leishmania genus. despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. the high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. we report here the evaluation of a binuclear cyclopalladated complex containing pd(ii) and ...201728507113
a new l-amino acid oxidase from bothrops jararacussu snake venom: isolation, partial characterization, and assessment of pro-apoptotic and antiprotozoal activities.a new l-amino acid oxidase (laao) from bothrops jararacussu venom (bjussulaao-ii) was isolated by using a three-step chromatographic procedure based on molecular exclusion, hydrophobicity, and affinity. bjussulaao-ii is an acidic enzyme with pi=3.9 and molecular mass=60.36kda that represents 0.3% of the venom proteins and exhibits high enzymatic activity (4884.53u/mg/mim). we determined part of the primary sequence of bjussulaao-ii by identifying 96 amino acids, from which 34 compose the n-termi ...201728495622
voacamine alters leishmania ultrastructure and kills parasite by poisoning unusual bi-subunit topoisomerase ib.indole alkaloids possess a large spectrum of biological activities including anti-protozoal action. here we report for the first time that voacamine, isolated from the plant tabernaemontana coronaria, is an antiprotozoal agent effective against a large array of trypanosomatid parasites including indian strain of leishmania donovani and brazilian strains of leishmania amazonensis and trypanosoma cruzi. it inhibits the relaxation activity of topoisomerase ib of l. donovani (ldtop1b) and stabilizes ...201728483460
the use of herbs against neglected diseases: evaluation of in vitro leishmanicidal and trypanocidal activity of stryphnodendron rotundifolium mart.the evaluation of the leishmanicidal and trypanocidal activity of the hydroalcoholic extract of the bark of stryphnodendron rotundifolium mart. (ehcsr) was carried out to find an alternative treatment for parasitic diseases. ehcsr was prepared and used at four different concentrations (1000, 500, 250, 125 μg/ml) in in vitro assays for activity against leishmania promastigotes using the species leishmania brasiliensis and leishmania infantum and for trypanocidal activity using the epimastigotes o ...201728855804
in vitro antileishmanial activity and iron superoxide dismutase inhibition of arylamine mannich base derivatives.leishmaniasis is one of the world's most neglected diseases, and it has a worldwide prevalence of 12 million. there are no effective human vaccines for its prevention, and treatment is hampered by outdated drugs. therefore, research aiming at the development of new therapeutic tools to fight leishmaniasis remains a crucial goal today. with this purpose in mind, we present 20 arylaminoketone derivatives with a very interesting in vitro and in vivo efficacy against trypanosoma cruzi that have now ...201728789716
rapid detection of trypanosoma cruzi by colorimetric loop-mediated isothermal amplification (lamp): a potential novel tool for the detection of congenital chagas infection.early diagnosis of congenital trypanosomacruzi transmission in newborns is essential because babies show high indices of cure. conventional diagnosis is based on microscopic examination and serology. molecular diagnosis is a promising alternative to replace conventional diagnosis, although it is not well suited for adoption in laboratories with limited resources. isothermal dna amplification methods have the advantage of not requiring expensive equipment. the aim of this work was to apply loop-m ...201728684052
the use of kdna minicircle subclass relative abundance to differentiate between leishmania (l.) infantum and leishmania (l.) amazonensis.leishmaniasis is a neglected disease caused by many leishmania species, belonging to subgenera leishmania (leishmania) and leishmania (viannia). several qpcr-based molecular diagnostic approaches have been reported for detection and quantification of leishmania species. many of these approaches use the kinetoplast dna (kdna) minicircles as the target sequence. these assays had potential cross-species amplification, due to sequence similarity between leishmania species. previous works demonstrate ...201728511704
multi-anti-parasitic activity of arylidene ketones and thiazolidene hydrazines against trypanosoma cruzi and leishmania spp.a series of fifty arylideneketones and thiazolidenehydrazines was evaluated against leishmania infantum and leishmania braziliensis. furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against trypanosoma cruzi. the cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their anti-parasitic effects. seven thiazolidenehydrazine derivatives and ten arylideneketones had good activity against th ...201728481276
alkaloid constituents of the amaryllidaceae plant amaryllis belladonna l.the plant family amaryllidaceae is well-known for its unique alkaloid constituents, which exhibit a wide range of biological activities. its representative, amaryllis belladonna, has a geographical distribution covering mainly southern africa, where it has significant usage in the traditional medicine of the native people. in this study, a. belladonna samples collected in brazil were examined for alkaloid content. alkaloid profiles of a. belladonna bulbs were generated by a combination of chroma ...201728858260
lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles.a library of 89 synthetic benzenesulfonyl derivatives of heterocycles with drug-like properties was assayed for in vitro antiparasitic activity and the results were added to our previously reported derivatives for a comprehensive sar evaluation. four compounds showed an ic50 between 0.25 and 3μm against leishmania donovani and low cytotoxicity. compound g{16} (1-(2,3,5,6-tetramethylphenylsulfonyl)-2-methylindoline), was particularly interesting with an ic50 similar to the reference drug miltefos ...201728789893
homology modeling of leishmania donovani enolase and its molecular interaction with novel inhibitors.the treatment of indian tropical disease such as kala-azar is likely to be troublesome to the clinicians as ampb- and miltefosine-resistant leishmania donovani has been reported. the rationale behind designed a novel inhibitors of model of l. donovani enolase and performing a binding study with its inhibitors to gain details of the interaction between protein residues and ligand molecules.201728717332
alkamides from anacyclus pyrethrum l. and their in vitro antiprotozoal activity.in our ongoing study to evaluate the antiprotozoal activity of alkamides from asteraceae, a dichloromethane extract from the roots of anacycluspyrethrum l. showed a moderate in vitro activity against the nf54 strain of plasmodium falciparum and against leishmaniadonovani (amastigotes, mhom/et/67/l82 strain). seven pure alkamides and a mixture of two further alkamides were isolated by column chromatography followed by preparative high performance liquid chromatography. the alkamides were identifi ...201728498323
antiparasitic sesquiterpenes from the cameroonian spice scleria striatinux and preliminary in vitro and in silico dmpk assessment.the antiparasitic activity and preliminary in vitro and in silico drug metabolism and pharmacokinetic (dmpk) assessment of six isomeric sesquiterpenes (1-6), isolated from the cameroonian spice scleria striatinux de wild (cyperaceae) is reported. the study was prompted by the observation that two of the compounds (1 and 2) exhibited varying levels of antiparasitic activity on plasmodium falciparum, trypanosoma brucei rhodesiense, trypanosoma cruzi and leishmania donovani. the in silico method em ...201728421410
anti-trypanosomatid elemanolide sesquiterpene lactones from vernonia lasiopus o. hoffm.sleeping sickness or human african trypanosomiasis (hat) is a neglected tropical disease (ntd) threatening millions of peoples' lives with thousands infected. the disease is endemic in poorly developed regions of sub-saharan africa and is caused by the kinetoplastid "protozoan" parasite trypanosoma brucei. the parasites are transmitted to humans through bites of infected tsetse flies of the genus glossina. the few available drugs for treatment of this disease are highly toxic, difficult to admin ...201728397756
structural characterization of acidic m17 leucine aminopeptidases from the tritryps and evaluation of their role in nutrient starvation in trypanosoma brucei.leucine aminopeptidase (lap) is found in all kingdoms of life and catalyzes the metal-dependent hydrolysis of the n-terminal amino acid residue of peptide or amino acyl substrates. laps have been shown to participate in the n-terminal processing of certain proteins in mammalian cells and in homologous recombination and transcription regulation in bacteria, while in parasites, they are involved in host cell invasion and provision of essential amino acids for growth. the enzyme is essential for su ...201728815215
the superfamily keeps growing: identification in trypanosomatids of ribj, the first riboflavin transporter family in protists.trypanosomatid parasites represent a major health issue affecting hundreds of million people worldwide, with clinical treatments that are partially effective and/or very toxic. they are responsible for serious human and plant diseases including trypanosoma cruzi (chagas disease), trypanosoma brucei (sleeping sickness), leishmania spp. (leishmaniasis), and phytomonas spp. (phytoparasites). both, animals and trypanosomatids lack the biosynthetic riboflavin (vitamin b2) pathway, the vital precursor ...201728406895
a strong and fortuitous case of dyspnea.a 48 year-old man with no past medical history was sent to our emergency department (ed); from a primary care clinic for hypertensive urgency of 200/130. the man reported an intermittent non-productive cough of approximately one year's duration and worsening dyspnea on exertion and orthopnea over the last month with lower extremity swelling. of note, he emigrated from honduras twenty years ago. blood pressure normalized with administration of lasix in the ed. physical exam revealed rales in lung ...201728414672
6-nitro-2,3-dihydroimidazo[2,1-b][1,3]thiazoles: facile synthesis and comparative appraisal against tuberculosis and neglected tropical diseases.as part of a quest for backups to the antitubercular drug pretomanid (pa-824), we investigated the unexplored 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]-thiazoles and related -oxazoles. the nitroimidazothiazoles were prepared in high yield from 2-bromo-4-nitroimidazole via heating with substituted thiiranes and diisopropylethylamine. equivalent examples of these two structural classes provided broadly comparable mics, with 2-methyl substitution and extended aryloxymethyl side chains preferred; albei ...201728462832
peroxisome proliferator-activated receptor-γ-mediated polarization of macrophages in neospora caninum infection.neospora caninum is an apicomplexan parasite closely related toxoplasma gondii, which causes neurological disease and abortion in multiple animal species. macrophage polarization plays an important role in host immune responses to parasites infection, such as toxoplasma gondii, leishmania, trypanosoma cruzi. however, the dynamics of macrophage polarization, as well as the possible mechanism that regulate macrophage polarization, during n. caninum infection remains unclear.201728527905
in vitro and in silico antidiabetic and antimicrobial evaluation of constituents from kickxia ramosissima (nanorrhinum ramosissimum).background and aims:kickxia ramosissima (wall.) janch (or nanorrhinum ramosissimum (wall.) betsche is a well-known medicinal plant in pakistan that is traditionally used in diabetic and inflammatory conditions. because little information is available on its phytochemical composition, a range of constituents were isolated and evaluated in vitro in assays related to the traditional use. methods: dried whole plant material was extracted and chromatographically fractionated. isolated constituents we ...201728507520
rna-binding proteins and their role in the regulation of gene expression in trypanosoma cruzi and saccharomyces cerevisiae.rna-binding proteins (rbps) have important functions in the regulation of gene expression. rbps play key roles in post-transcriptional processes in all eukaryotes, such as splicing regulation, mrna transport and modulation of mrna translation and decay. rbps assemble into different mrna-protein complexes, which form messenger ribonucleoprotein complexes (mrnps). gene expression regulation in trypanosomatids occurs mainly at the post-transcriptional level and rbps play a key role in all processes ...201728463381
within-host temporal fluctuations of trypanosoma cruzi discrete typing units: the case of the wild reservoir rodent octodon degus.chagas disease caused by trypanosoma cruzi is considered a major public health problem in america. after an acute phase the disease changes to a chronic phase with very low parasitemia. the parasite presents high genetic variability with seven discrete typing units (dtus): tci-tcvi and tc bat. the aim of this work is to evaluate fluctuation of parasitemia and t. cruzi dtus in naturally infected octodon degus.201728784152
survey of pediatric infectious diseases society members about congenital chagas disease.participants in a survey about congenital chagas disease, distributed electronically to pediatric infectious diseases society members, perceived having limited knowledge about congenital trypanosoma cruzi infection. most rarely or never consider the diagnosis in infants born to parents from latin america. improved awareness of congenital chagas disease and assessment of at-risk infants is needed.201728777208
chagas disease: importance of rats as reservoir hosts of trypanosoma cruzi (chagas, 1909) in western mexico.in mexico, the role of most species of mammals involved in the transmission cycle of trypanosoma cruzi chagas, 1909 is poorly known. it was carried out a study to investigate the importance of rats as reservoir of t. cruzi in western mexico, an area with important risk of transmission of t. cruzi to human. thirty-eight human dwellings were searched on two representative towns of western mexico along twelve months for collection of rats and triatomines. study rats (rattus norvegicus) berkenhout, ...201728774654
galectin-3 knockdown impairs survival, migration, and immunomodulatory actions of mesenchymal stromal cells in a mouse model of chagas disease cardiomyopathy.therapies based on transplantation of mesenchymal stromal cells (msc) hold promise for the management of inflammatory disorders. in chronic chagas disease cardiomyopathy (ccc), caused by chronic infection with trypanosoma cruzi, the exacerbated immune response plays a critical pathophysiological role and can be modulated by msc. here, we investigated the role of galectin-3 (gal-3), a beta-galactoside-binding lectin with several actions on immune responses and repair process, on the immunomodulat ...201728769980
maldi-tof ms protein profiling for the rapid identification of chagas disease triatomine vectors and application to the triatomine fauna of french guiana.triatomines are haematophagous insects involved in the transmission of trypanosoma cruzi, the aetiological agent of chagas disease. the vector competence of these arthropods can be highly variable, depending on the species. a precise identification is therefore crucial for the epidemiological surveillance of t. cruzi and the determination of at-risk human populations. to circumvent the difficulties of morphological identification and the lack of comprehensiveness of the genbank database, we here ...201728768559
description of an oral chagas disease outbreak in venezuela, including a vertically transmitted case.we describe the eleventh major outbreak of foodborne trypanosoma cruzi transmission in urban venezuela, including evidence for vertical transmission from the index case to her fetus. after confirming fetal death at 24 weeks of gestation, pregnancy interruption was performed. on direct examination of the amniotic fluid, trypomastigotes were detected. t. cruzi specific-polymerase chain reaction (pcr) also proved positive when examining autopsied fetal organs. finally, microscopic fetal heart exami ...201728767982
bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease.chagas disease is a public health problem caused by infection with the protozoan trypanosoma cruzi. there is currently no effective therapy for chagas disease. although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare.201728767980
inhibition of protein-protein interactions: new options for developing drugs against neglected tropical diseases.wake up! sleeping sickness and chagas disease are neglected tropical diseases caused by trypanosome infections. small molecules that disrupt a crucial protein-protein interaction in the parasites offer a new approach to drug development for these diseases.201728766862
chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. this enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. thus, the aim of this study was to investigate whether trypanosoma cruzi infection can alter the acti ...201728766165
in silico molecular docking studies of new potential 4-phthalazinyl-hydrazones on selected trypanosoma cruzi and leishmania enzyme targets.recently, a series of 4-phthalazinyl-hydrazones under its e-configuration have exhibited excellent in vitro antichagasic and antileishmanial profiles. preliminary assays on both parasites suggested that the most active derivatives act through oxidative and nitrosative stress mechanisms; however, their exact mode of actions as anti-trypanosomal and anti-leishmanial agents have not been completely elucidated. this motivated to perform a molecular docking study on essential trypanosomatid enzymes s ...201728763686
knockout of the gamma subunit of the ap-1 adaptor complex in the human parasite trypanosoma cruzi impairs infectivity and differentiation and prevents the maturation and targeting of the major protease cruzipain.the ap-1 adaptor complex assists clathrin-coated vesicle assembly in the trans-golgi network (tgn) of eukaryotic cells. however, the role of ap-1 in the protozoan trypanosoma cruzi-the chagas disease parasite-has not been addressed. here, we studied the function and localization of ap-1 in different t. cruzi life cycle forms, by generating a gene knockout of the large ap-1 subunit gamma adaptin (tcap1-γ), and raising a monoclonal antibody against tcap1-γ. co-localization with a golgi marker and ...201728759609
from lemongrass to ivermectin: ethnomedical management of chagas disease in tropical bolivia.chagas disease is a neglected tropical disease; the only viable drugs are outdated and produce frequent side effects, and the overwhelming majority of cases are undiagnosed and untreated. globally, people encounter numerous impediments to accessing biomedical treatment for chagas disease. however, little is known about how people with chagas disease manage their health outside the biomedical system. in this article, i discuss knowledge of ethnomedical treatments among marginalized patients in an ...201728759265
endogenous c-terminal tagging by crispr/cas9 in trypanosoma cruzi.to achieve the c-terminal tagging of endogenous proteins in t. cruzi we use the cas9/ptrex-n vector (lander et al., 2015) to insert a specific tag sequence (3xha or 3xc-myc) at the 3' end of a specific gene of interest (goi). chimeric sgrna targeting the 3' end of the goi is pcr-amplified and cloned into cas9/ptrex-n vector. then a dna donor molecule to induce dna repair by homologous recombination is amplified. this donor sequence contains the tag sequence and a marker for antibiotic resistance ...201728758140
dynamized ethyl alcohol improves immune response and behavior in murine infection with trypanosoma cruzi.to evaluate the effects of dynamized ethyl alcohol (ethylicum)6ch and 30ch in mice infected with t. cruzi.201728757362
phosphorus protects cardiac tissue by modifying the immune response in rats infected by trypanosoma cruzi.this study evaluates and correlates the number of myocarditis focuses and production of cytokines in rattus norvegicus (wistar lineage), experimentally infected with t. cruzi and treated with phosphorus.201728757361
a community-based screening program for chagas disease in the usa.chagas disease (cd) affects over 300 000 people in the usa, many with limited access to healthcare. although early detection and treatment prevents life-threatening complications, <1% of people with cd receive diagnosis, and routine screening is virtually nonexistent in the usa. we describe a program that led to an increase in cd screening in the latin american-born population of los angeles.201728756912
identification of structure-stabilizing interactions in enzymes: a novel mechanism to impact enzyme activity.cruzain, a cysteine protease in the cathepsin family, is pivotal to the life-cycle of trypanosoma cruzi, the etiological agent in chagas disease. current inhibitors of cruzain suffer from drawbacks involving gastrointestinal and neurological side effects and as a result have spurred the search for alternative anti-trypanocidals. through sequence alignment studies and intra-residue interaction analysis of the pro-protein of cruzain (pro-cruzain), we have identified a host of non-active site resid ...201728756483
heteroleptic oxidovanadium(iv) complexes of 2-hydroxynaphtylaldimine and polypyridyl ligands against trypanosoma cruzi and prostate cancer cells.in latin america chagas disease is an endemic illness caused by the parasite trypanosoma cruzi (t. cruzi), killing more people than any other parasitic disease. current chemotherapies are old and inadequate, thus the development of efficient ones is urgently needed. vanadium-based complexes have been shown to be a promising approach both against parasitic diseases and cancer and this study aims to achieve significant advances in the pursue of effective compounds. heteroleptic vanadium complexes ...201728755573
in silico, in vitro, x-ray crystallography, and integrated strategies for discovering spermidine synthase inhibitors for chagas disease.chagas disease results from infection by trypanosoma cruzi and is a neglected tropical disease (ntd). although some treatment drugs are available, their use is associated with severe problems, including adverse effects and limited effectiveness during the chronic disease phase. to develop a novel anti-chagas drug, we virtually screened 4.8 million small molecules against spermidine synthase (spdsyn) as the target protein using our super computer "tsubame2.5" and conducted in vitro enzyme assays ...201728751689
development, validation and application of a gc-ms method for the simultaneous detection and quantification of neutral lipid species in trypanosoma cruzi.the development and validation of an analytical method for the simultaneous analysis of five neutral lipids in trypanosoma cruzi epimastigotes by gc-ms is presented in this study. the validated method meets all validation parameters for all components and the chromatographic conditions have been optimized during its development. this analytical method has demonstrated good selectivity, accuracy, within-day precision, recovery and linearity in each of the established ranges. in addition, detectio ...201728750236
case report: successful lung transplantation from a donor seropositive for trypanosoma cruzi infection (chagas disease) to a seronegative recipient.the increasing shortage of organs for transplantation has prompted transplant programs to investigate the use of extended criteria donors, such as those with transmissible infectious diseases. successful cases of organ transplantation (mostly kidney and liver) from trypanosoma cruzi seropositive donors to seronegative recipients have been reported. we present a case of lung transplantation from a donor serologically positive for chagas disease to a seronegative recipient, and provide a review of ...201728749767
potential triazole-based molecules for the treatment of neglected diseases.neglected diseases (nds) affect million of people, especially the poorest population around the world. several efforts to an effective treatment have proved insufficient at the moment. in this context, triazole derivatives have shown great relevance in medicinal chemistry due to a wide range of biological activities. this review aims to describe some of the most relevant and recent research focused on 1,2,3- and 1,2,4-triazole-based molecules targeting four expressive nds: chagas disease, malari ...201728748757
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