MARCELO ALVES FERREIRA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina
7 resultados
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- Titanium dioxide induced inflammation in the small intestine(2012) NOGUEIRA, Carolina Maciel; AZEVEDO, Walter Mendes de; DAGLI, Maria Lucia Zaidan; TOMA, Sergio Hiroshi; LEITE, Andre Zonetti de Arruda; LORDELLO, Maria Laura; NISHITOKUKADO, Ieda; ORTIZ-AGOSTINHO, Carmen Lucia; DUARTE, Maria Irma Seixas; FERREIRA, Marcelo Alves; SIPAHI, Aytan MirandaAIM: To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO2) and microparticles (MPTiO2) on the inflammatory response in the small intestine of mice. METHODS: BI 57/6 male mice received distilled water suspensions containing TiO2 (100 mg/kg body weight) as NPTiO2 (66 nm), or MPTiO2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-alpha (TNF-alpha), intracellular interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4(+) and CD8(+) T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immunohistochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4(+) cells (cells/mm(2)) in duodenum: NP 1240 +/- 139.4, MP 1070 +/- 154.7 vs 458 +/- 50.39 (P < 0.01); jejunum: NP 908.4 +/- 130.3, MP 813.8 +/- 103.8 vs 526.6 +/- 61.43 (P < 0.05); and ileum: NP 818.60 +/- 123.0, MP 640.1 +/- 32.75 vs 466.9 +/- 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-alpha, IFN-gamma and TGF-beta. The cytokine production was more pronounced in the ileum (mean SE): IL-12: NP 33.98 +/- 11.76, MP 74.11 +/- 25.65 vs 19.06 +/- 3.92 (P < 0.05); IL-4: NP 17.36 +/- 9.96, MP 22.94 +/- 7.47 vs 2.19 +/- 0.65 (P < 0.05); IL-23: NP 157.20 +/- 75.80, MP 134.50 +/- 38.31 vs 22.34 +/- 5.81 (P < 0.05); TNF alpha: NP 3.71 +/- 1.33, MP 5.44 +/- 1.67 vs 0.99 +/- 019 (P < 0.05); IFN gamma: NP 15.85 +/- 9.99, MP 34.08 +/- 11.44 vs 2.81 +/- 0.69 (P < 0.05); and TGF-alpha: NP 780.70 +/- 318.50, MP 1409.00 +/- 502.20 vs 205.50 +/- 63.93 (P < 0.05). CONCLUSION: Our findings indicate that TiO2 particles induce a Th1-mediated inflammatory response in the small bowel in mice.
- Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape(2023) OLIVEIRA, Jamille Ramos; RUIZ, Cesar Manuel Remuzgo; MACHADO, Rafael Rahal Guaragna; MAGAWA, Jhosiene Yukari; DAHER, Isabela Pazotti; URBANSKI, Alysson Henrique; SCHMITZ, Gabriela Justamante Haendel; ARCURI, Helen Andrade; FERREIRA, Marcelo Alves; SASAHARA, Greyce Luri; MEDEIROS, Giuliana Xavier de; JR, Roberto Carlos Vieira Silva; DURIGON, Edison Luiz; BOSCARDIN, Silvia Beatriz; ROSA, Daniela Santoro; SCHECHTMAN, Deborah; NAKAYA, Helder. I. I.; CUNHA-NETO, Edecio; GADERMAIER, Gabriele; KALIL, Jorge; COELHO, Veronica; SANTOS, Keity SouzaIntroductionConsidering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information. MethodsWe used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. ResultsWe found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity. DiscussionThis peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.
- Analysis of genetic polymorphisms associated with the presence of freckles for phenotypic prediction(2022) FRIDMAN, Cintia; FERREIRA, Marcelo Alves; MARANO, Leonardo Arduino; FORLENZA, Bettina StingelinThe prediction of externally visible characteristics (EVCs) is a commonly used practice by the forensic sciences as an important resource in the investigation of criminal cases in which the identity of perpetrators or victims is unknown or even to recognize decomposed cadavers. With this purpose, genetic markers associated with pigmentation traits have been widely studied by forensic scientists and, nowadays, it is possible to predict phenotypic characteristics such as hair, eyes and skin colour, as well as the presence of skin freckles by analysing single nucleotide polymorphisms (SNPs). In this study, we analysed the association of six SNPs located in pigmentation genes to the presence of freckles in individuals from the Brazilian population for forensic DNA phenotyping. The study was based within the context of a larger project on a population sample of 534 adult Brazilians of both sexes and different skin colours. DNA was extracted from peripheral blood and genotyped using the TaqMan & REG; OpenArray & REG; Real-Time PCR System (ThermoFischer Scientific) technique. Statistical analyses were carried out with the R software (version 4.0.2). As for the results obtained, three SNPs were shown to be statistically associated to the freckling, rs12203592, rs1800404 and rs222847, with CT, AG and AA genotypes being the main contributors, respectively. Variables such as sex of the individuals and skin colour were found to also contribute to the manifestation of this pigmentation trait. Further statistical analyses will be carried out to evaluate the possibility of using the SNPs in this study for phenotyping prediction of the Brazilian population, improving existing DNA phenotyping models in forensic sciences.
- Heparin Therapy Improving Hypoxia in COVID-19 Patients - A Case Series(2020) NEGRI, Elnara Marcia; PILOTO, Bruna Mamprim; MORINAGA, Luciana Kato; JARDIM, Carlos Viana Poyares; LAMY, Shari Anne El-Dash; FERREIRA, Marcelo Alves; D'AMICO, Elbio Antonio; DEHEINZELIN, DanielIntroduction Elevated D-dimer is a predictor of severity and mortality in COVID-19 patients, and heparin use during in-hospital stay has been associated with decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting that hypercoagulability is a prominent feature of organ failure in these patients. Interestingly, in COVID-19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure. Methods We describe a series of 27 consecutive COVID-19 patients admitted to Sirio-Libanes Hospital in Sao Paulo-Brazil and treated with heparin in therapeutic doses tailored to clinical severity. Results PaO2/FiO2 ratio increased significantly over the 72 h following the start of anticoagulation, from 254(+/- 90) to 325(+/- 80), p = 0.013, and 92% of the patients were discharged home within a median time of 11 days. There were no bleeding complications or fatal events. Discussion Even though this uncontrolled case series does not offer absolute proof that micro thrombosis in the pulmonary circulation is the underlying mechanism of respiratory failure in COVID-19, patient's positive response to heparinization contributes to the understanding of the pathophysiological mechanism of the disease and provides valuable information for the treatment of these patients while we await the results of further prospective controlled studies.
- Development, validation and application of a questionnaire to qualify the indoor environmental exposure of patients with respiratory allergy(2023) SOUZA, Barbara de; FERREIRA, Marcelo Alves; KALIL, Jorge; GIAVINA-BIANCHI, Pedro; AGONDI, Rosana CamaraObjective Environmental control includes measures to prevent exposure to common aeroallergens in an individual's home. Questionnaires are part of the clinical practice of health assessment, and are also widely used in research. Our aim was to develop and validate a questionnaire to identify possible sources of aeroallergens present in the indoor environment. Methods This study describes the development, validation and application of a questionnaire. For content validation the Content Validation Index and Ordinal Cronbach's Alpha Index have been used; Polychoric Correlations for the agreement between judges; and an Exploratory Factor Analysis for the structure of the questionnaire, while for reliability assessment, Intraclass Correlation Coefficient has been applied. Results Twenty-one doctors participated as judges to validate the questionnaire, which 204 patients answered. The Content Validity Index for all the questions on the ""Clarity"" aspect was 0.846 +/- 0.152 and on the ""Relevance"" aspect, 0.954 +/- 0.080. Cronbach's alpha coefficient for the ""Clarity"" aspect was 0.88 with a 95% confidence intervals (CI) and the ""Relevance"" aspect, 0.94 with a 95% CI. The average Intraclass Correlation Coefficient was 0.94 and all the F tests were highly significant. Conclusions The questionnaire developed by our group was considered valid and reliable, and is capable of portraying the home environment without the need for a personal visit to the patient's home. This questionnaire would be a good tool to use in research or during patient consultations to assess the patient's home environment, as this latter assessment is essential for the management of patients with respiratory allergies.
- Neutrophils LL-37 migrate to the nucleus during overwhelming infection(2013) SILVA, Fabiano Pinheiro da; MEDEIROS, Maria Cristina Rodrigues; SANTOS, Angela Batista Gomes dos; FERREIRA, Marcelo Alves; GARIPPO, Ana Lucia; CHAMMAS, Roger; CALDINI, Elia; VELASCO, Irineu Tadeu; SOUZA, Heraldo Possolo de; MACHADO, Marcel Cerqueira CesarLL-37 is the only cathelicidin produced by human cells. It is secreted by a variety of cell types, including monocyte/macrophages, neutrophils, mast cells, keratinocytes and epithelial cells, acting on the extracellular milieu by directly killing bacteria or boosting innate immunity. Here, we show that LL-37 translocates to the nucleus following overwhelming infection, putting in evidence that its role may be even broader, with new potential important implications to cell biology. Future studies are necessary to address if LL-37 is able to induce or affect transcription, since it can lead to a novel cell signaling pathway that probably will contribute to the understanding of complex diseases.
- Comparative long-term study between two dermal regeneration templates for the reconstruction of burn scar contractures in humans: Clinical and histological results(2020) VANA, Luiz Philipe Molina; BATTLEHNER, Claudia Naves; FERREIRA, Marcelo Alves; CALDINI, Elia Garcia; GEMPERLI, Rolf; ALONSO, NivaldoThe advent of dermal regeneration templates has fostered major advances in the treatment of acute bums and their sequelae, in the last three decades. Both data on morphological aspects of the newly-formed tissue, and clinical trials comparing different templates, are few. The goal of this study was to prospectively analyze the outcome of randomized patients treated with two of the existing templates, followed by thin skin autograft. They are both 2mm-thick bovine collagen templates (Matriderm (R) and Integra (R)), the latter includes a superficial silicone layer. Surgery was performed on patients with impaired mobility resulting from bum sequelae (n =12 per template) in a two-step procedure. Negative pressure therapy was applied after surgery; patients were monitored for 12 months. No infra or postoperative complications were observed. Data on scar skin quality (Vancouver scar scale), rate of mobility recovery, and graft contraction were recorded; as well as morphological analyses at light microscopical level. Improvement in mobility and skin quality were demonstrated along with graft contraction, in all patients. The double layer template showed the best performance in retraction rate, skin quality and mobility recovery. The subepidermal newly-formed connective tissue showed no histoarchitectural differences between the templates. The double layer template was not absorbed up to 12 months after placement.