Evaluation of Galectin-3 as a Novel Biomarker for Chagas Cardiomyopathy

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-11-23T12:50:45Z No. of bitstreams: 1 Rabelo MMN Evaluation of galectin-3....pdf: 140623 bytes, checksum: 3f19bd9f18869f4e4c812b28c9829fdf (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-11-23T13:01:55Z (GMT) No. of bitstreams: 1 Rabelo MMN Evaluation of galectin-3....pdf: 140623 bytes, checksum: 3f19bd9f18869f4e4c812b28c9829fdf (MD5)Made available in DSpace on 2017-11-23T13:01:55Z (GMT). No. of bitstreams: 1 Rabelo MMN Evaluation of galectin-3....pdf: 140623 bytes, checksum: 3f19bd9f18869f4e4c812b28c9829fdf (MD5) Previous issue date: 2017FAPESBHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, BrasilHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilHospital São Rafael. Clinical Diagnostics Laboratory. Salvador, BA, BrasilHospital São Rafael. Clinical Diagnostics Laboratory. Salvador, BA, BrasilCenter for Biotechnology and Cell Therapy. Salvador, BA, BrasilHospital São Rafael. Department of Cardiology. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Center for Biotechnology and Cell Therapy. Salvador, BA, BrasilChagas cardiomyopathy has worse long-term outcomes than other cardiomyopathies. A biomarker strategy to refer subjects for noninvasive cardiac imaging may help in the early identification of cardiac damage in subjects with Chagas disease. Galectin-3 (Gal-3) is a mediator of cardiac fibrosis shown to be upregulated in animal models of decompensated heart failure. Here we assessed the correlation of Gal-3 with myocardial fibrosis in patients with Chagas disease. Methods: This study comprised 61 subjects with Chagas disease. All subjects underwent clinical assessments, Doppler echocardiography and magnetic resonance imaging. Plasmatic Gal-3 was determined by ELISA. Results: Delayed enhancement (DE) was identified in 37 of 61 subjects (64%). The total amount of myocardial fibrosis was 9.4% [interquartile interval (IQI): 2.4–18.4]. No differences were observed in Gal-3 concentration according to the presence or absence of myocardial fibrosis, with a median Gal-3 concentration of 11.7 ng/ml (IQI: 9.4–15) in subjects with DE versus 12.9 ng/ml (IQI: 9.2–14) in subjects without DE (p = 0.18). No correlation was found between myocardial fibrosis and Gal- 3 concentration (r = 0.098; p = 0.47). Conclusions: There is no correlation between the degree of myocardial fibrosis and the concentration of Gal-3 in subjects with Chagas diseas

Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-09-27T16:01:25Z No. of bitstreams: 1 Nonaka Vasques K.C Circulating.pdf: 2693091 bytes, checksum: ede286cd2f7ad2cf644ed62421a5a459 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-09-27T16:22:08Z (GMT) No. of bitstreams: 1 Nonaka Vasques K.C Circulating.pdf: 2693091 bytes, checksum: ede286cd2f7ad2cf644ed62421a5a459 (MD5)Made available in DSpace on 2019-09-27T16:22:09Z (GMT). No. of bitstreams: 1 Nonaka Vasques K.C Circulating.pdf: 2693091 bytes, checksum: ede286cd2f7ad2cf644ed62421a5a459 (MD5) Previous issue date: 2019-01-20Bahia State Foundation for Research (FAPESB) and Institutos Nacionais de Ciência e Tecnologia (INCT; 465656/2014-5). Milena B. P. Soares is a recipient of CNPq fellowship.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / São Rafael Hospital. Department of Cardiology. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Messejana Hospital. Fortaleza, CE, Brasil.Messejana Hospital. Fortaleza, CE, Brasil.São Rafael Hospital. Department of Cardiology. Salvador, BA, Brasil.University of Southern Denmark. Institute of Regional Health Research. Vejle Hospital. Department of Clinical Genetics. Vejle, Denmark.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil.Salvador, BA, Brasil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science and Technology for Regenerative Medicine. Rio de Janeiro, RJ, Brazil.Chagas disease (CD) affects approximately 6-7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC

Assessment of syndecan-4 expression in the hearts of Trypanosoma cruzi-infected mice and human subjects with chronic Chagas disease cardiomyopathy

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-01-25T17:30:27Z No. of bitstreams: 1 LAROCCA,T.F. Assessment of syndecan-4...2018.pdf: 10166331 bytes, checksum: 0c3c0d4a7677f38a2fd443a1fc5f6d95 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-01-25T17:58:58Z (GMT) No. of bitstreams: 1 LAROCCA,T.F. Assessment of syndecan-4...2018.pdf: 10166331 bytes, checksum: 0c3c0d4a7677f38a2fd443a1fc5f6d95 (MD5)Made available in DSpace on 2019-01-25T17:58:58Z (GMT). No. of bitstreams: 1 LAROCCA,T.F. Assessment of syndecan-4...2018.pdf: 10166331 bytes, checksum: 0c3c0d4a7677f38a2fd443a1fc5f6d95 (MD5) Previous issue date: 2018National Council for Research (CNPq), Research Foundation of Bahia State (FAPESB), and Funding Authority for Studies and Projects (FINEP).Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade federal da Bahia. Salvador, BA, Brasil.Messejana Hospital. Fortaleza, CE, Brasil.Messejana Hospital. Fortaleza, CE, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Chronic Chagas cardiomyopathy (CCC) is characterized by the presence of a multifocal inflammatory response and myocardial damage, leading to fibrosis, arrhythmias and ventricular dysfunction. The expression of syndecan-4, a transmembrane proteoglycan, was previously found to be increased in the hearts of mice chronically infected with Trypanosoma cruzi. The possible involvement of syndecan-4 in the disease pathogenesis, however, remains unknown. Here we evaluated the pattern of expression of syndecan-4 in the heart tissue of T. cruzi infected mice and subjects with Chagas cardiomyopathy, correlating with the degree of inflammation and fibrosis

Image-guided percutaneous intralesional administration of mesenchymal stromal cells in subjects with chronic complete spinal cord injury: a pilot study

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-16T13:31:50Z No. of bitstreams: 1 Larocca TF Image-guided....pdf: 387218 bytes, checksum: 3e5d59f868cf7e153f1aa904be8b2251 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-08-16T13:45:57Z (GMT) No. of bitstreams: 1 Larocca TF Image-guided....pdf: 387218 bytes, checksum: 3e5d59f868cf7e153f1aa904be8b2251 (MD5)Made available in DSpace on 2017-08-16T13:45:57Z (GMT). No. of bitstreams: 1 Larocca TF Image-guided....pdf: 387218 bytes, checksum: 3e5d59f868cf7e153f1aa904be8b2251 (MD5) Previous issue date: 2017Brazilian Development Bank (BNDES).Hospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / Hospital São Rafael. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / Hospital São Rafael. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / University of Bahia. Faculty of Pharmacy. Salvador, BA, BrazilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / Hospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, BrazilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, BrazilHospital São Rafael. Salvador, BA, BrasilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilHospital São Rafael. Center for Biotechnology and Cell Therapy. Salvador, BA, Brazil / National Institute of Science andTechnology for Regenerative Medicine. Rio de Janeiro, RJ, BrazilThe potential of cell therapies to improve neurological function in subjects with spinal cord injury (SCI) is currently under investigation. In this context, the choice of cell type, dose, route and administration regimen are key factors. Mesenchymal stromal cells (MSCs) can be easily obtained, expanded and are suitable for autologous transplantation. Here we conducted a pilot study that evaluated safety, feasibility and potential efficacy of intralesional MSCs transplantation performed through image-guided percutaneous injection, in subjects with chronic complete SCI. Methods. Five subjects with chronic traumatic SCI (>6 months), at thoracic level, classified as American Spinal Cord Injury Association impairment scale (AIS) grade A, complete injury, were included. Somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Autologous MSCs were injected directly into the lesion site through percutaneous injection guided by computerized tomography (CT). Results. Tomography-guided percutaneous cell transplantation was a safe procedure without adverse effects. All subjects displayed improvements in spinal cord independence measure (SCIM) scores and functional independence measure (FIM), mainly due to improvements in bowel movements and regularity. Three subjects showed improved sensitivity to tactile stimulation.Two subjects improved AIS grade to B, incomplete injury, although this was sustained in only one of them during the study follow-up. Conclusion. Autologous bone marrow MSC transplantation, performed through CT-guided percutaneous injection, was shown to be safe and feasible. Further studies are required to demonstrate efficacy of this therapeutic scheme

Lack of association between serum syndecan-4, myocardial fibrosis and ventricular dysfunction in subjects with chronic Chagas disease

<div><p>Background</p><p>Syndecan-4 is a transmembrane glycoprotein associated with inflammation and fibrosis. Increased syndecan-4 levels were previously detected after acute myocardial infarction and in subjects with heart failure. However, the levels of syndecan-4 in subjects with Chagas disease have not so far been investigated. The aim of this study was to investigate the potential role of serum sydencan-4 as a novel biomarker for myocardial fibrosis and cardiac dysfunction in subjects with Chagas disease.</p><p>Methods</p><p>This study comprised subjects with Chagas disease (n = 56), being 14 (25%) with the indeterminate form, 16 (29%) with the cardiac form without ventricular dysfunction, and 26 (46%) with the cardiac form with ventricular dysfunction.</p><p>Results</p><p>Syndecan-4 serum concentrations did not correlate with presence or absence of myocardial fibrosis (P = 0.386) nor disease severity in subjects with Chagas disease (P = 0.918). Additionally, no correlation was found either between the degree of myocardial fibrosis and serum syndecan-4 [r = 0.08; P = 0.567] or between left ventricular ejection fraction and syndecan-4 [r = 0.02; P = 0.864]. In contrast, NT-proBNP levels correlated with ejection fraction and myocardial fibrosis.</p><p>Conclusions</p><p>Our results demonstrate the lack of correlations between serum syndecan-4, myocardial fibrosis and cardiac dysfunction in subjects with Chagas disease. Further studies are required to show if syndecan-4 concentrations can be marker for prognosis assessment or disease progression.</p></div

Correlation between percentage of myocardial fibrosis assessed by cardiovascular MRI and concentration of syndecan-4 and NT-ProBNP.

<p>A: Pearson’s correlation, r = 0.08, P = 0.567. B: Pearson’s correlation, r = 0.469, P<0.001.</p

Clinical and demographic characteristics of subjects with Chagas disease.

<p>Clinical and demographic characteristics of subjects with Chagas disease.</p

Clinical Trials Using Mesenchymal Stem Cells for Spinal Cord Injury: Challenges in Generating Evidence

Spinal cord injury (SCI) remains an important public health problem which often causes permanent loss of muscle strength, sensation, and function below the site of the injury, generating physical, psychological, and social impacts throughout the lives of the affected individuals, since there are no effective treatments available. The use of stem cells has been investigated as a therapeutic approach for the treatment of SCI. Although a significant number of studies have been conducted in pre-clinical and clinical settings, so far there is no established cell therapy for the treatment of SCI. One aspect that makes it difficult to evaluate the efficacy is the heterogeneity of experimental designs in the clinical trials that have been published. Cell transplantation methods vary widely among the trials, and there are still no standardized protocols or recommendations for the therapeutic use of stem cells in SCI. Among the different cell types, mesenchymal stem/stromal cells (MSCs) are the most frequently tested in clinical trials for SCI treatment. This study reviews the clinical applications of MSCs for SCI, focusing on the critical analysis of 17 clinical trials published thus far, with emphasis on their design and quality. Moreover, it highlights the need for more evidence-based studies designed as randomized controlled trials and potential challenges to be addressed in context of stem cell therapies for SCI

Echocardiographic and CMR findings in subjects with Chagas disease.

<p>Echocardiographic and CMR findings in subjects with Chagas disease.</p