Circulating miR-146a as a possible candidate biomarker in the indeterminate phase of Chagas disease.

BACKGROUND: Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. MicroRNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-ß signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction. RESULTS: Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated. CONCLUSIONS: The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.

Evaluation of biomarkers of joint damage in patients subjected to arthroscopy.

AIMS: Recently, the determination of biochemical markers has been intensely explored to better understand the mechanisms underlying knee OA. In this study, we aimed to explore the expression pattern of five biochemical markers in patients with knee OA. METHODS: After IRB approval and signed informed consent, 26 patients were enrolled. Serum and synovial samples were collected prior to knee arthroscopy. Pre-operative assessment included diagnosis, Lysholm, Tegner Activity Scale, IKDC score, and radiographic Kellgren and Lawrence classification. ELISA of CTX-I, CTX-II, NTX-I, MMP3, and MMP13 were measured in serum and synovial fluid samples. RESULTS: Twenty-six patients were included, with a mean age of 42 ± 15 years old. Mean results and standard deviation of the biomarkers in serum were as follows: CTX-I 5.8 ± 5.5 ng/mL, CTX-II 3.8 ± 1.7 ng/mL, NTX-I 52 ± 71 (nM BCE), MMP3 1.18 ± 0.6 ng/mL, and MMP13 1243.6 ± 1422 pg/mL; synovial fluid results were as follows: CTX-I 0.74 ± 0.5 ng/mL, CTX-II 5.1 ± 2.5 ng/mL, NTX-I 254 ± 85 (nM BCE), MMP3 0.4 ± 0.4 ng/mL, and MMP13 797 ± 1391 pg/mL. We observed a differential pattern of expression in serum NTX-I in patients with chronic meniscus injuries when compared with ACL injuries or cartilage lesions. CONCLUSIONS: In conclusion, the clinical criteria of early OA are useful to categorize patients with knee conditions. The biochemical markers explored did not yield a differential pattern that can be associated with this classification. Serum NTX-I could be a useful marker of chronic meniscal lesion in future longitudinal studies, after adjusting for age and sex.

Circulating miR-146a as a possible candidate biomarker in the indeterminate phase of Chagas disease

BACKGROUND: Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. Micro-RNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-ß signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction. RESULTS: Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated. CONCLUSIONS: The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.

[Electro-histological comparison in a case of Chagasic chronic cardiomyopathy]. / Cotejo electro-histológico en un caso de miocardiopatía chagásica crónica.

The case of a 50 years old man, coming from an endemic Chagas' disease zone, is reported. This patient came with a dilated cardiomyopathy, likely of Chagasic etiology, and heart failure. He died in our Institute, were it was possible to register an ECG, and perform the necropsy, on the same day of his death. The ECG showed signs of heart chambers dilatation, inactive myocardium in subendocardial anterolateral regions of the left ventricle, and extensive subepicardial injury. The anatomical study demonstrated the four heart chambers dilatation, and a subendocardial fibrosis essentially located in anterolateral portions of the left ventricle. The histological examination proved that the distribution of injured zones corresponded to location of the inflammatory foci. Furthermore, Trypanosoma cruzi inoculation in mice produced inflammatory foci, predominantly located in the ventricular epicardial and subepicardial regions.

Cotejo electro-histológico en un caso de miocardiopatía chagásica crónica / Electro-histological comparison in a case of Chagasic chronic cardiomyopathy

The case of a 50 years old man, coming from an endemic Chagas' disease zone, is reported. This patient came with a dilated cardiomyopathy, likely of Chagasic etiology, and heart failure. He died in our Institute, were it was possible to register an ECG, and perform the necropsy, on the same day of his death. The ECG showed signs of heart chambers dilatation, inactive myocardium in subendocardial anterolateral regions of the left ventricle, and extensive subepicardial injury. The anatomical study demonstrated the four heart chambers dilatation, and a subendocardial fibrosis essentially located in anterolateral portions of the left ventricle. The histological examination proved that the distribution of injured zones corresponded to location of the inflammatory foci. Furthermore, Trypanosoma cruzi inoculation in mice produced inflammatory foci, predominantly located in the ventricular epicardial and subepicardial regions.

Blood transfusion and iatrogenic risks in Mexico City. Anti-Trypanosoma cruzi seroprevalence in 43,048 blood donors, evaluation of parasitemia, and electrocardiogram findings in seropositive.

Iatrogenous transmission of Trypanosoma cruzi by blood transfusion was suggested as a potential risk by Pellegrino (1949). Seropositive blood donors in Mexico were first reported in 1978, however, limited information is available due to small sampling, the use of heterogeneous serologic assays, and geographically limited studies. A wide survey carried out in 18 out of the 32 states of Mexico, showed a national mean of 1.6% seropositive among 64,969 donors, ranging from 0.2 to 2.8%. In the present study, we have screened 43,048 voluntary blood donors in a period of five years at the Instituto Nacional de Cardiología I. Chávez, a concentration hospital located in Mexico city which serves mainly the metropolitan area and accepts from all over the country. Standardized ELISA and IIF were used to identify seropositive individuals in addition to hemoculture, PCR and standard 12 lead ECG tests that were applied to a group of seropositive patients (29/161). The result showed a seropositivity of 0.37% (161/43,048). From the group of seropositive individuals 40% (12/29) were potential carriers of T. cruzi at the donation time and 5/29 had subclinical ECG abnormalities. Parasitological tests performed in 70 erythrocyte and platelet fractions from seropositive units (70/161) showed negative results. Our findings strongly support T. cruzi screening in the transfusion medicine practice and identify subclinical heart disease among seropositive blood donors.

Blood transfusion and iatrogenic risks in Mexico city: anti-Trypanosoma cruzi seroprevalence in 43,048 blood donors, evaluation of parasitemia, and electrocardiogram findings in seropositive

Iatrogenous transmission of Trypanosoma cruziby blood transfusion was suggested as a potential risk by Pellegrino (1949). Seropositive blood donors in Mexico were first reported in 1978, however, limited information is available due to small sampling, the use of heterogeneous serologic assays, and geographically limited studies. A wide survey carried out in 18 out of the 32 states of Mexico, showed a national mean of 1.6 percent seropositive among 64,969 donors, ranging from 0.2 to 2.8 percent. In the present study, we have screened 43,048 voluntary blood donors in a period of five years at the Instituto Nacional de Cardiología I. Chávez, a concentration hospital located in Mexico city which serves mainly the metropolitan area and accepts from all over the country. Standardized ELISA and IIF were used to identify seropositive individuals in addition to hemoculture, PCR and standard 12 lead ECG tests that were applied to a group of seropositive patients (29/161). The result showed a seropositivity of 0.37 percent (161/43,048). From the group of seropositive individuals 40 percent (12/29) were potential carriers of T. cruzi at the donation time and 5/29 had subclinical ECG abnormalities. Parasitological tests performed in 70 erythrocyte and platelet fractions from seropositive units (70/161) showed negative results. Our findings strongly support T. cruzi screening in the transfusion medicine practice and identify subclinical heart disease among seropositive blood donors.

Seroprevalence of human Trypanosoma cruzi infection in diferent geografic zones of Chiapas, Mexico

Foi feito um estudo sorológico em quatro zonas geográficas do estado de Chiapas México. Foram colhidas 1333 amostras dos habitantes das 13 comunidades situadas na costa, na região central montanhosa, na floresta lacandona e na região chamada mesochiapas. Cento cinqüenta e uma pessoas (11,3 por cento) foram identificadas como soropositivas. A infecção pelo Trypanosoma cruzi teve a influência da geografia local. Na floresta lacandona nas montanhas centrais, foi encontrada uma prevalência de 32,1 e 13,8 por cento respectivamente, mais que na costa 1,2 por cento. Na zona de mesochiapas não foi encontrada nenhuma pessoa com sorologia positiva entre 137 estudadas. Como encontramos sorologia positiva em crianças menores de 10 anos, pensamos que exista uma transmissão ativa contínua. Na costa foi reconhecido o vetor Triatoma dimidiata e na floresta Lacandona o Rhodnius prolixus