ALEXANDRE TELES GARCEZ
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
17 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 17
- The contributions of dipeptidyl peptidase IV to inflammation in heart failure(2016) SALLES, Thiago de Almeida; ZOGBI, Camila; LIMA, Thais Martins de; CARNEIRO, Camila de Godoi; GARCEZ, Alexandre Teles; BARBEIRO, Hermes Vieira; ANTONIO, Ednei Luiz; SANTOS, Leonardo dos; PEREIRA, Alexandre da Costa; TUCCI, Paulo Jose Ferreira; FARIA, Daniele de Paula; SORIANO, Francisco Garcia; GIRARDI, Adriana Castello CostaCirculating dipeptidyl peptidase IV (DPPIV) activity correlates with cardiac dysfunction in humans and experimental heart failure (HF) models. Similarly, inflammatory markers are associated with poorer outcomes in HF patients. However, the contributions of DPPIV to inflammation in HF remain elusive. Therefore, this study aimed to investigate whether the cardioprotective effects of DPPIV inhibition after myocardial injury are accompanied by reduced cardiac inflammation, whether circulating DPPIV activity correlates with the levels of systemic inflammatory markers in HF patients, and whether leukocytes and/or splenocytes may be one of the sources of circulating DPPIV in HF. Experimental HF was induced in male Wistar rats by left ventricular myocardial injury after radiofrequency catheter ablation. The rats were divided into three groups: sham, HF, and HF + DPPIV inhibitor (sitagliptin). Six weeks after surgery, cardiac function, perfusion and inflammatory status were evaluated. Sitagliptin treatment improved cardiac function and perfusion, reduced macrophage infiltration, and diminished the levels of inflammatory biomarkers including TNF-alpha, IL-1 beta, and CCL2. In HF patients, serum DPPIV activity correlated with CCL2, suggesting that leukocytes may be the source of circulating DPPIV in HF. Unexpectedly, DPPIV release was higher in splenocytes from HF rats and similar in HF circulating mononuclear cells compared with those from sham, suggesting an organ-specific modulation of DPPIV in HF. Collectively, our data provide new evidence that the cardioprotective effects of DPPIV inhibition in HF may be due to suppression of inflammatory cytokines. Moreover, they suggest that a vicious circle between DPPIV and inflammation may contribute to HF development and progression.
- Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters (vol 45, pg 616, 2020)(2020) COUTINHO, Artur Martins; BUSATTO, Geraldo F.; PORTO, Fabio Henrique de Gobbi; FARIA, Daniele de Paula; ONO, Carla Rachel; GARCEZ, Alexandre Teles; SQUARZONI, Paula; DURAN, Fabio Luiz de Souza; OLIVEIRA, Maira Okada de; TRES, Eduardo Sturzeneker; BRUCKI, Sonia Maria Dozzi; FORLENZA, Orestes Vicente; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto
- Evaluation of GX1 and RGD-GX1 peptides as new radiotracers for angiogenesis evaluation in experimental glioma models(2016) OLIVEIRA, Erica Aparecida de; FAINTUCH, Bluma Linkowski; TARGINO, Roselaine Campos; MORO, Ana Maria; MARTINEZ, Raquel Chacon Ruiz; PAGANO, Rosana Lima; FONOFF, Erich Talamoni; CARNEIRO, Camila de Godoi; GARCEZ, Alexandre Teles; FARIA, Daniele de Paula; BUCHPIGUEL, Carlos AlbertoGliomas are the most common type among all central nervous system tumors. The aggressiveness of gliomas is correlated with the level of angiogenesis and is often associated with prognosis. The aim of this study is to evaluate the novel GX1 peptide and the heterodimer RGD-GX1 radiolabeled with technetium-99m, for angiogenesis detection in glioma models. Radiolabeling and radiochemical controls were assessed for both radioconjugates. In vitro binding studies in glioma tumor cells were performed, as well as biodistribution in SCID mice bearing tumor cells, in order to evaluate the biological behavior and tumor uptake of the radiocomplexes. Blocking and imaging studies were also conducted. MicroSPECT/CT images were acquired in animals with experimentally implanted intracranial tumor. Open field activity was performed to evaluate behavior, as well as perfusion and histology analysis. The radiochemical purity of both radiotracers was greater than 96 %. In vitro binding studies revealed rather similar binding profi le for each molecule. The highest binding was for RGD-GX1 peptide at 120 min in U87MG cells (1.14 +/- A 0.35 %). Tumor uptake was also favorable for RGD-GX1 peptide in U87MG cells, reaching 2.96 +/- A 0.70 % at 1 h p.i. with 47 % of blocking. Imaging studies also indicated better visualization for RGD-GX1 peptide in U87MG cells. Behavior evaluation pointed brain damage and histology studies confirmed actual tumor in the uptake site. The results with the angiogenesis seeking molecule Tc-99m-HYNIC-E-[c(RGDfk)-c(GX1)] were successful, and better than with Tc-99m-HYNIC-PEG(4)-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended.
- Topography of C-11-Pittsburgh compound B uptake in Alzheimer's disease: a voxel-based investigation of cortical and white matter regions(2019) FARIA, Daniele de P.; DURAN, Fabio L.; SQUARZONI, Paula; COUTINHO, Artur M.; GARCEZ, Alexandre T.; SANTOS, Pedro P.; BRUCKI, Sonia M.; OLIVEIRA, Maira O. de; TRES, Eduardo S.; FORLENZA, Orestes V.; NITRINI, Ricardo; BUCHPIGUEL, Carlos A.; BUSATTO FILHO, GeraldoObjective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (C-11-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer's disease (AD), and explore possible group differences in C-11-PIB binding to white matter. Methods: C-11-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher C-11-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased C-11-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise C-11-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased C-11-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.
conferenceObject 7-Ketocholesterol loaded-phosphatidylserine liposome induces cell death, autophagy, and growth inhibition of melanoma and breast adenocarcinoma.(2018) FAVERO, Giovani Marino; TORTELLI JR., Tharcisio Citrangulo; FERNANDES, Daniel; PRESTES, Ana Paula; KMETIUK, Louise N. B.; OTAKE, Andreia Hanada; ANDRADE, Luciana N. S.; FARIA, Daniele de Paula; CARNEIRO, Camila de Godoi; GARCEZ, Alexandre Teles; MARQUES, Fabio L. N.; CHAMMAS, Roger- [C-11]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis(2019) CARVALHO, Robert H. F.; REAL, Caroline C.; CININI, Simone; GARCEZ, Alexandre T.; DURAN, Fabio L. S.; MARQUES, Fabio L. N.; MELLO, Luiz Eugenio; BUSATTO FILHO, Geraldo; VRIES, Erik F. J. de; BRITTO, Luiz R. G. de; BUCHPIGUEL, Carlos A.; FARIA, Daniele de PaulaBackground: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [C-11]PIB is widely used for detection of beta-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [C-11]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS. Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of re-combinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [C-11]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis. Results: All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [C-11]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [C-11]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [C-11]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r(2) = 0.32, P < 0.0001) and the rhMOG/CFA group (r(2) = 0.46, P < 0.0001). Conclusion: [C-11]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS.
conferenceObject Is the early phase (CPIB)-C-11 PET imaging similar to (18)FFDG PET imaging in normal elderly and Alzheimer's disease(2018) CARNEIRO, Camila; COUTINHO, Artur; DURAN, Fabio; ONO, Carla; GARCEZ, Alexandre; PICOLO, Douglas; BUSATTO, Geraldo; FARIA, Daniele; BUCHPIGUEL, Carlos- The Brazilian Zika virus strain causes birth defects in experimental models(2016) CUGOLA, Fernanda R.; FERNANDES, Isabella R.; RUSSO, Fabiele B.; FREITAS, Beatriz C.; DIAS, Joao L. M.; GUIMARAES, Katia P.; BENAZZATO, Cecilia; ALMEIDA, Nathalia; PIGNATARI, Graciela C.; ROMERO, Sarah; POLONIO, Carolina M.; CUNHA, Isabela; FREITAS, Carla L.; BRANDAO, Wesley N.; ROSSATO, Cristiano; ANDRADE, David G.; FARIA, Daniele de P.; GARCEZ, Alexandre T.; BUCHPIGEL, Carlos A.; BRACONI, Carla T.; MENDES, Erica; SALL, Amadou A.; ZANOTTO, Paolo M. de A.; PERON, Jean Pierre S.; MUOTRI, Alysson R.; BELTRAO-BRAGA, Patricia C. B.Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel rhesus monkeys(1). Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on Yap Island in Micronesia(2). Patients experienced fever, skin rash, arthralgia and conjunctivitis(2). From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America3. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barre syndrome(4,5). Despite clinical evidence, direct experimental evidence showing that the Brazilian ZIKV (ZIKVBR) strain causes birth defects remains absent(6). Here we demonstrate that ZIKVBR infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells in vitro, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKVBR crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKVBR outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKVBR in human neurodevelopment.
- SUV Normalized by Skeletal Volume on F-18-Fluoride PET/CT Studies(2016) CARVALHO, Giovanna; MARIN, Jose Flavio Gomes; GARCEZ, Alexandre Teles; DUARTE, Paulo Schiavom; SAPIENZA, Marcelo Tatit; BUCHPIGUEL, Carlos AlbertoObjective: To propose a technique for SUV normalization on F-18-fluoride PET/CT (F-18-NaF) studies based on skeletal volume and to compare the SUVs normalized by this technique with the ones normalized by body weight. Methods: SUVs were obtained in volumes of interest (VOIs) in proximal diaphyseal regions of the right humerus (HD) and right femur (FD) in 12 selected F-18-NaF studies. The 12 studies presented both regions considered normal by visual examination on PET and CT and were performed in patients presenting body weight below 50 kg (B50) or above 90 kg (A90) (6 patients in each group). The maximum SUVs were calculated in these 2 bone regions in both groups of patients using body weight (SUV BW) and skeletal volume (SUV SV) methodologies. The total skeletal volume for each patient was estimated based on whole skeletal VOIs automatically defined on the CT component of the PET/CT study. The maximum SUVs calculated using the 2 methodologies were compared. Results: The maximum SUVs BW were statistically higher in the group A90 in both regions, with a P < 0.001 and P < 0.008 for FD and HD, respectively. The maximum SUVs SV in the 2 regions were not statistically different between the groups B50 and A90, P values of 0.27 and 0.87 for FD and HD, respectively. Conclusions: The SUVs normalized by skeletal volume present similar results in groups of patients with extremes of body weight. Therefore, this methodology could be more adequate than the one normalized by body weight to semiquantitatively analyze F-18-NaF studies.
- In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment(2020) BUSATTO, Geraldo F.; PORTO, Fabio Henrique de Gobbi; FARIA, Daniele de Paula; SQUARZONI, Paula; COUTINHO, Artur Martins; GARCEZ, Alexandre Teles; ROSA, Pedro Gomes Penteado; COSTA, Naomi Antunes da; CARVALHO, Cleudiana Lima; TORRALBO, Leticia; HERNANDES, Jullie Rosana de Almeida; ONO, Carla Rachel; BRUCKI, Sonia Maria Dozzi; NITRINI, Ricardo; BUCHPIGUEL, Carlos Alberto; DURAN, Fabio Luis Souza; FORLENZA, Orestes VicenteINTRODUCTION: Reduced cognitive reserve (CR) due to very low educational (VLE) levels may influence high dementia rates in low-middle income environments, leading to decreased cognitive resilience (RES) to Alzheimers disease (AD) pathology. However, in vivo findings in VLE groups confirming this prediction are lacking. METHODS: Cognitively impaired patients (with clinically defined AD dementia or amnestic mild cognitive impairment) and cognitively unimpaired older adults (n = 126) were recruited for a positron emission tomography (PET) and magnetic resonance imaging (MRI) investigation in Brazil, including 37 VLE individuals (<= 5 years of education). A CR score was generated combining educational attainment and vocabulary knowledge. RES indices to AD pathology were calculated using standardized residuals from linear regression models relating current cognitive performance (episodic memory or overall cognition) to amyloid beta (A beta) burden Pittsburgh compound-B ([11C]PiB-PET). RESULTS: A beta burden was lower in VLE relative to highly-educated subjects (controlling for age, sex, and Mini-Mental Status Exam [MMSE] scores) in the overall cognitively impaired sample, and in dementia subjects when the three clinically defined groups were evaluated separately. In bivariate regression analyses for the overall sample, the RES index based on a composite cognitive score was predicted by CR, socioeconomic status, and hippocampal volume (but not white matter hyperintensities or intracranial volume [ICV]); in the multivariate model, only CR retained significance (and similar results were obtained in the A beta-positive subsample). In the multivariate model for the overall sample using the RES index based on memory performance, CR, hippocampal volume, and ICV were significant predictors, whereas only CR retained significance in A beta-positive subjects. DISCUSSION: Lower CR consistently predicted less resilience to AD pathology in older adults from a low-middle income environment.