A Genome-Wide Association Study Identifies Novel Susceptibility loci in Chronic Chagas Cardiomyopathy.

Background: Chagas disease is an infectious disease caused by the parasite Trypanosoma cruzi and is endemic from Latin American countries. The goal of our study was to identify novel genetic loci associated with chronic Chagas cardiomyopathy development in Chagas disease patients from different Latin American populations.

Methods: We performed a cross-sectional, nested case-control study including 3 sample collections from Colombia, Argentina, and Bolivia.

[Goniometry of flexion-extension ankle movement: comparative analysis between bone reference method and neutral 0 method].

Introduction: Two different methods are used in goniometry of the ankle: the neutral zero method (N0M) and the bone reference method (BRM). In addition, the N0M has a subtype (N0I), with a different technique.

Purpose: To determine the average of the amplitude of flexion-extension of the ankle, measured in different body positions, using N0M, N0I and BRM, in young adults of both sexes, with the objective of providing evidence so that the ankle goniometry is more reliable.

SCN5A gene variants as potential markers of the progression of chronic chagasic cardiac alterations.

Host genetic factors have been proposed as determinants of the variable progression of Chagas disease (ChD). Two polymorphisms, H558R and A572D, of the voltage-gated sodium channel α-subunit SCN5A gene were studied in chagasic patients in order to determine their contribution to the susceptibility to the development and/or to the progression of the cardiovascular disease. A total of 104 patients were classified as seronegative or seropositive for Trypanosoma cruzi antibodies.

Lack of Association of IL6 polymorphism with the susceptibility to Chagas disease in Latin American populations.

The aim of the present study was to analyze IL6 rs1800795 genetic variant in the susceptibility to Trypanosoma cruzi infection and in the development of chronic Chagas cardiomyopathy (CCC), in five independent Latin American cohorts. A total of 3,087 individuals from Latin American countries (Argentina, Bolivia, Peru, and two cohorts from Colombia) were studied. In all cohorts, patients were classified as seropositive for T.

Genetic polymorphisms of IL17A associated with Chagas disease: results from a meta-analysis in Latin American populations.

Genetic factors and the immunologic response have been suggested to determine the susceptibility against the infection and the outcome of Chagas disease. In the present study, we analysed three IL17A genetic variants (rs4711998, rs8193036 and rs2275913) regarding the predisposition to Trypanosoma cruzi infection and the development of chronic Chagas cardiomyopathy (CCC) in different Latin American populations. A total of 2,967 individuals from Colombia, Argentina, Bolivia and Brazil, were included in this study.

Analysis of mitochondrial enzymatic activity in blood lymphomonocyte fractions during infection with different Trypanosoma cruzi strains.

Proinflammatory and inflammatory mediators induced by Trypanosoma cruzi infection increase the oxidative stress, generating toxicity for cells targeting mitochondria of different tissues. We studied the activity of citrate synthase and complexes I-IV of respiratory chain in mitochondria of blood lymphomonocyte fraction, from albino Swiss mice infected with different isolates of T. cruzi , during Chagas disease evolution.

Association of IL18 genetic polymorphisms with Chagas disease in Latin American populations.

Host genetic factors have been suggested to play an important role in the susceptibility to Chagas disease. Given the influence of interleukin 18 (IL-18) in the development of the disease, in the present study, we analyzed three IL18 genetic variants (rs2043055, rs1946518, rs360719) regarding the predisposition to Trypanosoma cruzi infection and the development of chronic Chagas cardiomyopathy (CCC), in different Latin America populations. Genetic data of 3,608 patients from Colombia, Bolivia, Argentina, and Brazil were meta-analyzed to validate previous findings with increased statistical power.

In vitro and in vivo drug combination for the treatment of Trypanosoma cruzi infection: A multivariate approach.

Combination therapies based on the available drugs have been proposed as promising therapeutic alternatives for many diseases. Clomipramine (CLO) has been found to modify the evolution of the experimental infection. The objective of this study was to evaluate the combined effect of benznidazole (BZ) and clomipramine (CLO) against different life-stages of Trypanosoma cruzi in vitro and their efficacy in a murine model.

Quantitative PCR and unconventional serological methods to evaluate clomipramine treatment effectiveness in experimental Trypanosoma cruzi infection.

Clomipramine (CLO), a tricyclic antidepressant drug, has been used for the treatment of mice infected with Trypanosoma cruzi. In this work we evaluated the effectiveness of CLO treatment upon T. cruzi-infected mice in the chronic phase of the experimental infection using Quantitative polymerase chain reaction (qPCR) and recombinant ELISA.

Mitochondrial dysfunction in skeletal muscle during experimental Chagas disease.

Trypanosoma cruzi invasion and replication in cardiomyocytes and other tissues induce cellular injuries and cytotoxic reactions, with the production of inflammatory cytokines and nitric oxide, both sources of reactive oxygen species. The myocyte response to oxidative stress involves the progression of cellular changes primarily targeting mitochondria. Similar alterations could be taking place in mitochondria from the skeletal muscle; if that is the case, a simple skeletal muscle biopsy would give information about the cardiac energetic production that could be used as a predictor of the chagasic cardiopathy evolution.

Functional and structural alterations of cardiac and skeletal muscle mitochondria in heart failure patients.

Background And Aims: The fundamental mechanisms involved in the genesis and progression of heart failure are not clearly understood. The present study was conducted to analyze the cardiac mitochondrial involvement in heart failure, the possible parallelism between cardiac and skeletal muscle and if there is a link between clinical symptoms and mitochondrial damage.

Methods: Left ventricle and pectoral biopsies were obtained from patients with heart failure (n: 21) and patients with inter-auricular communication as the unique diagnosis for surgery (n: 6).

Chronic indeterminate phase of Chagas' disease: mitochondrial involvement in infection with two strains.

Chagasic cardiopathy has become one of the most frequent causes of heart failure and sudden death, as well as one of the most common causes of cardio-embolic stroke in Latin America. The myocyte response to oxidative stress involves the progression of cellular changes, primarily targeting the mitochondria and modifying therefore the energy supply. In this paper we analysed the effect of the infection of mice with 2 different strains of Trypanosoma cruzi (Tulahuen and SGO Z12) in the chronic indeterminate stage (75 days post-infection), upon the structure and function of cardiac mitochondria.

Mitochondrial involvement in chronic chagasic cardiomyopathy.

The pathogenesis of chronic chagasic cardiopathy is still under discussion; there is considerable evidence that inflammatory infiltrates and their mediators have a direct effect on cardiac cells. Here we studied the structure and function of cardiac mitochondria in chronic chagasic myocardiopathy. Cardiac mitochondrial structure and enzyme activity of citrate synthase and complexes I to IV of the respiratory chain were studied in albino Swiss mice infected with Trypanosoma cruzi (Tulahuen strain or SGO Z12 isolate) on 365 days post-infection (dpi).

[Importance of host sex in the development of trypanosoma cruzi infection].

Multiple factors, both dependent on the host and the parasite are involved in determining resistance or susceptibility to infection with T. cruzi, but the influence of the sex of the host is a factor that has not been clearly established. In this paper we analyzed the influence of this factor upon the infected individuals.

Association of clomipramine and allopurinol for the treatment of the experimental infection with Trypanosoma cruzi.

We have previously shown that clomipramine and allopurinol used separately are effective in preventing chronic chagasic cardiomyopathy. The aim of the present study was to evaluate the effect of the association of clomipramine (Clo--5 mg/kg/day/90 days) and allopurinol (Allo--5, 10, or 15 mg/kg/day/90 days) for the treatment of experimental Chagas disease in the acute stage. Treatment effectiveness was evaluated through parasitemia, survival, electrocardiography, serology, and cardiac histopathology.

Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease.

Aim: To evaluate the role of genetic factors in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), we investigated the single nucleotide polymorphisms (SNPs) of NOD2/CARD15 (R702W, G908R and L1007finsC), and Toll-like receptor 4 (TLR4) genes (D299G and T399I) in a selected inflammatory bowel disease (IBD) population coming from Southern Italy.

Methods: Allele and genotype frequencies of NOD2/CARD15 (R702W, G908R and L1007finsC) and TLR4 (D299G and T399I) SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed.

Chemotherapy of chronic indeterminate Chagas disease: a novel approach to treatment.

Treatment of Chagas disease is a controversial issue because the available drugs are highly toxic. Clomipramine is a tricyclic antidepressant drug that inhibits Trypanosoma cruzi's trypanothione reductase, provoking the death of the parasite and preventing the cardiac damage when used for the treatment of acutely infected mice. Here, we studied the effectiveness of clomipramine (5 mg/kg/day for one month) as chemotherapy for T.

Allopurinol is effective to modify the evolution of Trypanosoma cruzi infection in mice.

There is a real need for new and less toxic drugs for the treatment of Chagas disease, as nifurtimox and benznidazole are effective but toxic and provoke unpleasant side effects, especially in adult patients. Allopurinol, commonly used to treat the hiperuricemia, is also used by the Trypanosoma cruzi's hypoxantine guanine fosforyltransferase as an alternative substrate incorporating it into the parasite's ribonucleic acid, provoking the death of the parasite. However, the results of using allopurinol as chemotherapy for Chagas disease are not clear.

Comprehensive gas chromatography coupled to mass spectrometry for the separation of pesticides in a very complex matrix.

The present research is focused on the development of a comprehensive two-dimensional gas chromatography-rapid scanning quadrupole mass spectrometric (GC x GC-qMS) methodology for the analysis of trace-amount pesticides contained in a complex real-world sample. Reliable peak assignment was carried out by using a recently developed, dedicated pesticide MS library (for comprehensive GC analysis), characterized by a twin-filter search procedure, the first based on a minimum degree of spectral similarity and the second on the interactive use of linear retention indices (LRI). The library was constructed by subjecting mixtures of commonly used pesticides to GC x GC-qMS analysis and then deriving their pure mass spectra and LRI values.

Reinfections and Trypanosoma cruzi strains can determine the prognosis of the chronic chagasic cardiopathy in mice.

Chronic Chagas' disease represents the result of the interaction between the host and the parasite, producing different clinical features: from a mild disease to a severe heart failure. In the present investigation, we analyzed whether Trypanosoma cruzi strain and/or reinfections in the acute stage, determine changes in the chronic phase (135 days postinfection, d.p.

Evaluation of leaf-derived extracts as an environmentally sustainable source of essential oils by using gas chromatography-mass spectrometry and enantioselective gas chromatography-olfactometry.

In consideration of the world's present environmental situation and the threat of species extinction, investigations concerning alternative sustainable sources of natural substances represent an extremely important issue. In this respect, the present research is focused on the analytical evaluation of Brazilian rosewood (Aniba rosaeodora Ducke) leaves, as an alternative source (with respect to wood) of rosewood essential oil and, as such, of natural linalool, which is extensively used in perfumery. Enantioselective-gas chromatography-olfactometry (Es-GC-O) was used as a tool for the simultaneous stereodifferentiation and olfactive evaluation of the volatile optically active components present in the analyzed samples.

Intestinal permeability and genetic determinants in patients, first-degree relatives, and controls in a high-incidence area of Crohn's disease in Southern Italy.

Objective: A defect of gastrointestinal barrier function is considered to represent an important step in the pathogenesis of Crohn's disease (CD) but the mechanisms leading to an increased intestinal permeability (IP) are poorly understood. Since IP is influenced by pro-inflammatory mediators, it seems likely that a genetically determined abnormal immune response may lead to a loss of barrier function.

Methods: In a geographic area in Southern Italy with high incidence of CD we investigated IP (lactulose/mannitol testing) together with the three main mutations of the NOD2/CARD15 and the D299G polymorphism of the toll-like receptor (TLR)-4 gene in 23 families of CD patients (patients and first-degree relatives).

High-throughput analysis of bergamot essential oil by fast solid-phase microextraction-capillary gas chromatography-flame ionization detection.

The advantages of using a narrow-bore column in headspace solid-phase microextraction-gas chromatographic (HS-SPME-GC) analysis are investigated. An automated rapid HS-SPME-GC method for the determination of volatile compounds in a complex sample (bergamot essential oil) was developed. A low-capacity (7 microm) SPME fibre was employed, enabling a short equilibration time (15 min).

Determination of flavonoids in citrus juices by micro-HPLC-ESI/MS.

Flavonoids are a large class of naturally occurring aromatic secondary plant metabolites. They constitute one of the most characteristic classes found in nature and more than 4000 flavonoids have been identified and divided into several subclasses. Flavonoids have several effects on human health, mainly related to their antioxidant activity.

Reliable characterization of coffee bean aroma profiles by automated headspace solid phase microextraction-gas chromatography-mass spectrometry with the support of a dual-filter mass spectra library.

This investigation is based on the automated solid phase microextraction GC-MS analysis of the volatile fraction of a variety of coffee bean matrices. Volatile analytes were extracted by headspace (HS)-SPME which was achieved with the support of automated instrumentation. The research was directed towards various important aspects relating to coffee aroma analysis: monitoring of the volatile fraction formation during roasting; chromatographic differentiation of the two main coffee species (Arabica and Robusta) and of a single species from different geographical origins; evaluation of the influence of specific industrial treatments prior to roasting.