JOSE MARCELO FARFEL
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Ortopediae Traumatologia, Faculdade de Medicina - Docente
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
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- Association between adiposity and systemic atherosclerosis: a protocol of a cross-sectional autopsy study(2016) NISHIZAWA, Aline; SUEMOTO, Claudia Kimie; FARIAS, Daniela Souza; CAMPOS, Fernanda Marinho; SILVA, Karen Cristina Souza da; CUELHO, Anderson; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; GRINBERG, Lea Tenenholz; FARFEL, Jose Marcelo; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos AugustoIntroduction: Adiposity has been associated with atherosclerosis in clinical studies. However, few autopsy studies have investigated this association, and they had only examined the coronary artery disease. Moreover, most studies had small sample sizes and were limited to middle-aged or young adults. Our aim is to investigate the association between adiposity and systemic atherosclerosis in an autopsy study. Methods and analysis: A sample of 240 deceased with 30 years or more will be evaluated. The sample size was calculated using the lowest correlation coefficient found in previous studies (r=0.109), assuming a power of 90% and alpha=0.05. We will collect information about sociodemographics, frequency of previous contact of the deceased's next of kin and cardiovascular risk factors. We will measure neck, waist and hip circumferences, weight, height and abdominal subcutaneous tissue thickness, and then we will calculate the body mass index, waist-to-hip ratio, waist-to-height ratio and body shape index. We will also weigh the pericardial and abdominal visceral fat, the heart, and we will measure the left ventricular wall thickness. We will evaluate the presence of myocardial infarction, the degree of atherosclerosis in the aorta, carotid, coronary and cerebral arteries and plaque composition in carotid, coronary and cerebral arteries. For each individual, we will fix arterial and adipose tissue samples in 10% formalin and freeze another adipose tissue sample at -80 degrees C for future studies. Ethics and dissemination: Ethical approval was granted by the Ethics Committee of University of Sao Paulo Medical School, Brazil. Results will be submitted for publication in a peer-reviewed journal.
- The human cerebral cortex is neither one nor many: neuronal distribution reveals two quantitatively different zones in the gray matter, three in the white matter, and explains local variations in cortical folding(2013) RIBEIRO, Pedro F. M.; VENTURA-ANTUNES, Lissa; GABI, Mariana; MOTA, Bruno; GRINBERG, Lea T.; FARFEL, Jose M.; FERRETTI-REBUSTINI, Renata E. L.; LEITE, Renata E. P.; FILHO, Wilson J.; HERCULANO-HOUZEL, SuzanaThe human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas.
- DNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKM zeta(2023) PRAMIO, Dimitrius Tansini; VIECELI, Felipe Monteleone; VARELLA-BRANCO, Elisa; GOES, Carolina Purcell; KOBAYASHI, Gerson Shigeru; PELEGRINA, Diogo Vieira da Silva; MORAES, Beatriz Caroline de; ALLAM, Aicha El; KUMAR, Bony De; JARA, Gabriel; FARFEL, Jose Marcelo; BENNETT, David Alan; KUNDU, Somanath; VIAPIANO, Mariano S.; REIS, Eduardo Moraes; OLIVEIRA, Paulo Sergio Lopes de; PASSOS-BUENO, Maria Rita dos Santos; ROTHLIN, Carla V.; GHOSH, Sourav; SCHECHTMAN, DeborahProtein kinase M zeta, PKM?, is a brain enriched kinase with a well characterized role in Long-Term Potentiation (LTP), the activity-dependent strengthening of synapses involved in long-term memory formation. However, little is known about the molecular mechanisms that maintain the tissue specificity of this kinase. Here, we characterized the epigenetic factors, mainly DNA methylation, regulating PKM?expression in the human brain. The PRKCZ gene has an upstream promoter regulating Protein kinase C ? (PKC?), and an internal promoter driving PKM?expression. A demethylated region, including a canonical CREB binding site, situated at the in-ternal promoter was only observed in human CNS tissues. The induction of site-specific hypermethylation of this region resulted in decreased CREB1 binding and downregulation of PKM?expression. Noteworthy, CREB binding sites were absent in the upstream promoter of PRKCZ locus, suggesting a specific mechanism for regulating PKM? expression. These observations were validated using a system of human neuronal differentiation from induced pluripotent stem cells (iPSCs). CREB1 binding at the internal promoter was detected only in differentiated neurons, where PKM?is expressed. The same epigenetic mechanism in the context of CREB binding site was identified in other genes involved in neuronal differentiation and LTP. Additionally, aberrant DNA hyper-methylation at the internal promoter was observed in cases of Alzheimer's disease, correlating with decreased expression of PKM?in patient brains. Altogether, we present a conserved epigenetic mechanism regulating PKM? expression and other genes enhanced in the CNS with possible implications in neuronal differentiation and Alzheimer's disease.
- Factors associated with morphometric brain changes in cognitively normal aging(2015) FERRETTI-REBUSTINI, Renata Eloah de Lucena; JACOB-FILHO, Wilson; SUEMOTO, Claudia Kimie; FARFEL, José Marcelo; LEITE, Renata Elaine Paraiso; GRINBERG, Lea Tenenholz; PASQUALUCCI, Carlos Augusto; NITRINI, RicardoOBJECTIVE: Cognitive impairment is associated with reductions in brain weight and volume. The factors related to morphometric brain changes in cognitively normal aging remain unknown. We aimed to identify which clinical factors are associated with morphometric brain changes in cognitively normal aging. METHODS: A cross-sectional study of 414 subjects, ≥50 years old submitted to clinical assessment and brain autopsy, after informed consent, was carried out at the São Paulo Autopsy Service, Brazil. Data on cognitive and functional evaluations were collected through structured interview applied to the next-of-kin. Brain weight (g) and volume (mL) measurements were obtained and adjusted for head circumference (cm). Associations between brain weight/volume and related factors were obtained through univariate and multivariate analysis. RESULTS: Participants were predominantly male (60.4%), Caucasian (69%), with mean age of 67.1 ± 10.9 years. Mean brain weight was 1219.2 ± 140.9 g, and mean brain volume was 1217.1 ± 152.3 mL. Head circumference was independently associated with low brain weight (p<0.001) and volume (p<0.001). Total and adjusted brain weight and volume decreased in some conditions. Female gender (p<0.001), hypertension (p<0.009), coronary artery disease (p<0.013) and walking assistance (p<0.011) were associated with lower adjusted brain weight while schooling was associated with higher adjusted brain weight (p<0.003). Female gender (p<0.001), age (p<0.001) and hypertension (p<0.011) were associated with low adjusted brain volume. CONCLUSION: Morphometric brain changes occur despite the absence of cognitive impairment and were predominantly associated with age, female gender, mobility impairment and cardiovascular conditions. Schooling may be a protective factor.