scholarly journals Chagas Disease Cardiomyopathy: Immunopathology and Genetics

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Edecio Cunha-Neto ◽  
Christophe Chevillard
Keyword(s):  
Chagas Disease ◽  
Genetic Factors ◽  
Disease Susceptibility ◽  
Familial Aggregation ◽  
Cardiomyocyte Hypertrophy ◽  
Case Control Studies ◽  
Antiparasitic Drugs ◽  
Heart Lesions ◽  
Chronic Chagas Disease ◽  
Shed Light

Chagas disease, caused by the protozoanTrypanosoma cruzi, is endemic in Latin America and affects ca. 10 million people worldwide. About 30% of Chagas disease patients develop chronic Chagas disease cardiomyopathy (CCC), a particularly lethal inflammatory cardiomyopathy that occurs decades after the initial infection, while most patients remain asymptomatic. Mortality rate is higher than that of noninflammatory cardiomyopathy. CCC heart lesions present a Th1 T-cell-rich myocarditis, with cardiomyocyte hypertrophy and prominent fibrosis. Data suggest that the myocarditis plays a major pathogenetic role in disease progression. Major unmet goals include the thorough understanding of disease pathogenesis and therapeutic targets and identification of prognostic genetic factors. Chagas disease thus remains a neglected disease, with no vaccines or antiparasitic drugs proven efficient in chronically infected adults, when most patients are diagnosed. Both familial aggregation of CCC cases and the fact that only 30% of infected patients develop CCC suggest there might be a genetic component to disease susceptibility. Moreover, previous case-control studies have identified some genes associated to human susceptibility to CCC. In this paper, we will review the immunopathogenesis and genetics of Chagas disease, highlighting studies that shed light on the differential progression of Chagas disease patients to CCC.

scholarly journals Inducibility of ventricular arrhythmias in Chronic Chagas disease predicted by clinical scores.

2021 ◽  
Author(s):  
Bruno Valdigem ◽  
rogerio andalaft ◽  
Dalmo Moreira ◽  
Luciana Armaganijan ◽  
felipe oliveira ◽  
...  
Keyword(s):  
High Risk ◽  
Chagas Disease ◽  
Low Voltage ◽  
Clinical Score ◽  
Electrophysiologic Study ◽  
Risk Of Death ◽  
Tertiary Center ◽  
Chronic Chagas Disease ◽  
Shed Light ◽  
Associated Variables

BACKGROUND Electrophysiologic Study (EPS) is a diagnostic tool that can further evaluate patients prone to arrhythmic death.OBJECTIVE To shed light on the causes of death in Chagas disease, specially on regards of importance of the VT induction and chances of death, as evaluated by Rassi clinical score. METHODS We evaluated data from 153 patients with Chagas disease from the electrophysiology laboratory from a tertiary center between January of 2011 and January 2013. All patients were evaluated with 1, 2, 3 or 4 ventricular extra-stimuli followed by runs of 10 beats fast ventricular stimulation. If VT or VF is inducible the patients are referred to ICD implant or VT ablation. RESULTS Of a total of 153 patients, 48% were male, mean age 58 ±12 years (24 - 84 years). As for risk of death according to the clinical score, 32% were evaluated as low risk, 35,4% intermediate, 32,6% high risk. NSVT on 24 hour Holter (p=0,009), stimulation on EPS (p<0,001), lower VEFE (p<0,01), cardiomegaly (p<0,001) and high risk on Rassi score (p<0,001) where the more associated variables to ventricular tachyarrithmias. CONCLUSIONS Clinical score is an interesting tool to further stratify patients in higher risk for VT induction during EPS, which is also a marker of higher risk of sudden cardiac death. Some characteristics as Non sustained VT, Pulmonary congestion, cardiomegaly and low voltage QRS were the most relevant determinants for inducible VT on EPS. The duration of NSVT is also important for VT induction in EPS.

scholarly journals Gut Reactions: How Far Are We from Understanding and Manipulating the Microbiota Complexity and the Interaction with Its Host? Lessons from Autism Spectrum Disorder Studies

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3492
Author(s):  
Martina Lombardi ◽  
Jacopo Troisi
Keyword(s):  
Social Communication ◽  
Genetic Factors ◽  
Familial Aggregation ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Beneficial Bacteria ◽  
Dietary Interventions ◽  
Case Control Studies ◽  
Autism Symptoms

Autism is a group of neurodevelopmental disorders, characterized by early onset difficulties in social communication and restricted, repetitive behaviors and interests. It is characterized by familial aggregation, suggesting that genetic factors play a role in disease development, in addition to developmentally early environmental factors. Here, we review the role of the gut microbiome in autism, as it has been characterized in case-control studies. We discuss how methodological differences may have led to inconclusive or contradictory results, even though a disproportion between harmful and beneficial bacteria is generally described in autism. Furthermore, we review the studies concerning the effects of gut microbial-based and dietary interventions on autism symptoms. Also, in this case, the results are not comparable due to the lack of standardized methods. Therefore, autism-specific microbiome signatures and, consequently, possible microbiome-oriented interventions are far from being recognized. We argue that a multi-omic longitudinal implementation may be useful to study metabolic changes connected to microbiome changes.

Aim for the Readers! Bromodomains As New Targets Against Chagas’ Disease

2019 ◽  
Vol 26 (36) ◽  
pp. 6544-6563
Author(s):  
Victoria Lucia Alonso ◽  
Luis Emilio Tavernelli ◽  
Alejandro Pezza ◽  
Pamela Cribb ◽  
Carla Ritagliati ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Chagas Disease ◽  
Causative Agent ◽  
Current Knowledge ◽  
Sequence Similarity ◽  
Lysine Acetylation ◽  
Specific Manner ◽  
Lysine Residues ◽  
Antiparasitic Drugs

Bromodomains recognize and bind acetyl-lysine residues present in histone and non-histone proteins in a specific manner. In the last decade they have raised as attractive targets for drug discovery because the miss-regulation of human bromodomains was discovered to be involved in the development of a large spectrum of diseases. However, targeting eukaryotic pathogens bromodomains continues to be almost unexplored. We and others have reported the essentiality of diverse bromodomain- containing proteins in protozoa, offering a new opportunity for the development of antiparasitic drugs, especially for Trypansoma cruzi, the causative agent of Chagas’ disease. Mammalian bromodomains were classified in eight groups based on sequence similarity but parasitic bromodomains are very divergent proteins and are hard to assign them to any of these groups, suggesting that selective inhibitors can be obtained. In this review, we describe the importance of lysine acetylation and bromodomains in T. cruzi as well as the current knowledge on mammalian bromodomains. Also, we summarize the myriad of small-molecules under study to treat different pathologies and which of them have been tested in trypanosomatids and other protozoa. All the information available led us to propose that T. cruzi bromodomains should be considered as important potential targets and the search for smallmolecules to inhibit them should be empowered.

Effects of repetitive stress during the acute phase ofTrypanosoma cruziinfection on chronic Chagas' disease in rats

Stress ◽  
2009 ◽  
Vol 12 (2) ◽  
pp. 144-151 ◽  
Author(s):  
Leony Cristina Caetano ◽  
Vânia Brazão ◽  
Marina Del Vecchio Filipin ◽  
Fabricia Helena Santello ◽  
Luana Naiara Caetano ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Acute Phase ◽  
Repetitive Stress ◽  
Chronic Chagas Disease

Ficolin‐3 in chronic Chagas disease: Low serum levels associated with the risk of cardiac insufficiency

2021 ◽  
Author(s):  
Kárita Cláudia Freitas Lidani ◽  
Fabiana Antunes Andrade ◽  
Marcia Holsbach Beltrame ◽  
Indira Chakravarti ◽  
Maria Regina Tizzot ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Serum Levels ◽  
Cardiac Insufficiency ◽  
Chronic Chagas Disease ◽  
Low Serum

scholarly journals Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1041
Author(s):  
Mohammad Tarek ◽  
Hana Abdelzaher ◽  
Firas Kobeissy ◽  
Hassan A. N. El-Fawal ◽  
Mohammed M. Salama ◽  
...  
Keyword(s):  
Immune Response ◽  
Genetic Factors ◽  
Bioinformatics Analysis ◽  
Expression Patterns ◽  
Spike Protein ◽  
Target Cells ◽  
Health Crisis ◽  
Expression Levels ◽  
Different Populations ◽  
Shed Light

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2’s receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN’s potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

scholarly journals The molecular genetics of intrahepatic cholestasis of pregnancy

2008 ◽  
Vol 1 (2) ◽  
pp. 65-71 ◽  
Author(s):  
P H Dixon ◽  
C Williamson
Keyword(s):  
Molecular Genetics ◽  
Intrahepatic Cholestasis ◽  
Genetic Factors ◽  
Preterm Labour ◽  
Intrauterine Death ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Liver Impairment ◽  
Cholestasis Of Pregnancy ◽  
Shed Light

Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, causes maternal pruritus and liver impairment, and may be complicated by spontaneous preterm labour, fetal asphyxial events and intrauterine death. Our understanding of the aetiology of this disease has expanded significantly in the last decade due to a better understanding of the role played by genetic factors. In particular, advances in our knowledge of bile homeostasis has led to the identification of genes that play a considerable role in susceptibility to ICP. In this review we consider these advances and discuss the disease in the context of bile synthesis and metabolism, focusing on the genetic discoveries that have shed light on the molecular aetiology and pathophysiology of the condition.

scholarly journals Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?

2016 ◽  
Vol 54 (6) ◽  
pp. 1566-1572 ◽  
Author(s):  
Alba Abras ◽  
Montserrat Gállego ◽  
Teresa Llovet ◽  
Silvia Tebar ◽  
Mercedes Herrero ◽  
...  
Keyword(s):  
Chagas Disease ◽  
False Positive ◽  
Disease Diagnosis ◽  
Cross Reactivity ◽  
Human Migration ◽  
Serological Diagnosis ◽  
Content Type ◽  
New Generation ◽  
Single Technique ◽  
Chronic Chagas Disease

Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity withLeishmaniaspp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity withLeishmaniaspecies. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease.

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