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- ItemSomente MetadadadosAssociations of blood pressure with functional and cognitive changes in patients with alzheimer's disease(Consel Brasil Oftalmologia, 2016) de Oliveira, Fabricio Ferreira [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Smith, Marilia Cardoso [UNIFESP]; Ferreira Bertolucci, Paulo Henrique [UNIFESP]Background: Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy. Methods: Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and APOE haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report. Results: Variations in systolic BP (-11.76 +/- 17.1 mm Hg), diastolic BP (-4.92 +/- 10.3 mm Hg) and pulse pressure (-6.84 +/- 12.6 mm Hg) were significant after 1 year (n = 191;. < 0.01). For APOE4+ carriers, rises in systolic or diastolic BP improved Clinical Dementia Rating Scale Sum of Boxes scores (rho < 0.04), with marginally significant improvements in MiniMental State Examination scores resulting from risen systolic (rho = 0.069) or diastolic BP (. = 0.079), and in basic independence only regarding risen diastolic BP (rho = 0.055). APOE4-carriers resisted any functional or cognitive effects of BP variations. No differences were found regarding any antihypertensive class for variations in BP or any test scores, regardless of APOE haplotypes. Conclusions: Targeting mild BP elevations brings better functional and cognitive results for APOE4+ carriers with AD. (C) 2016 S. Karger AG, Basel
- ItemSomente MetadadadosBlocking fgf2 with a new specific monoclonal antibody impairs angiogenesis and experimental metastatic melanoma, suggesting a potential role in adjuvant settings(Elsevier ireland ltd, 2016) de Aguiar, Rodrigo Barbosa [UNIFESP]; Parise, Carolina Bellini [UNIFESP]; Teixeira Souza, Carolina Rosal; Braggion, Camila [UNIFESP]; Quintilio, Wagner; Moro, Ana Maria; Navarro Marques, Fabio Luiz; Buchpiguel, Carlos Alberto; Chammas, Roger; de Moraes, Jane Zveiter [UNIFESP]Compelling evidence suggests that fibroblast growth factor 2 (FGF2), overexpressed in melanomas, plays an important role in tumor growth, angiogenesis and metastasis. In this study, we evaluated the therapeutic use of a new anti-FGF2 monoclonal antibody (mAb), 3F12E7, using for that the B16-F10 melanoma model. The FGF2 neutralizing effect of this antibody was certified by in vitro assays, which allowed the further track of its possible in vivo application. 3F12E7 mAb could be retained in B16-F10 tumors, as shown by antibody low-pH elution and nuclear medicine studies, and also led to reduction in number and size of metastatic foci in lungs, when treatment starts one day after intravenous injection of B16-F10 cells. Such data were accompanied by decreased CD34(+) tumor vascular density and impaired subcutaneous tumor outgrowth. Treatments starting one week after melanoma cell intravenous injection did not reduce tumor burden, remaining the therapeutic effectiveness restricted to early-adopted regimens. Altogether, the presented anti-FGF2 3F12E7 mAb stands as a promising agent to treat metastatic melanoma tumors in adjuvant settings. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
- ItemAcesso aberto (Open Access)Can breast tumors affect the oxidative status of the surrounding environment? A comparative analysis among cancerous breast, mammary adjacent tissue, and plasma(Hindawi ltd, 2016) Panis, C.; Victorino, V. J.; Herrera, A. C. S. A.; Cecchini, A. L.; Simao, A. N. C.; Tomita, L. Y. [UNIFESP]; Cecchini, R.In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-alpha and nitric oxide.
- ItemSomente MetadadadosImpaired glucose metabolism moderates the course of illness in bipolar disorder(Elsevier Science Bv, 2016) Mansur, Rodrigo Barbachan [UNIFESP]; Rizzo, Lucas Bortolotto [UNIFESP]; Santos, Camila Mauricio [UNIFESP]; Asevedo, Elson [UNIFESP]; Cunha, Graccielle Rodrigues da [UNIFESP]; Noto, Mariane Nunes [UNIFESP]; Pedrini, Mariana [UNIFESP]; Zeni, Maiara [UNIFESP]; Cordeiro, Quirino [UNIFESP]; McIntyre, Roger S.; Brietzke, Elisa [UNIFESP]Background: The longitudinal course of bipolar disorder (BD) is highly heterogeneous, and is moderated by the presence of general medical comorbidities. This study aimed to investigate the moderating effects of impaired glucose metabolism (IGM) on variables of illness course and severity in a BD population. Methods: Fifty-five patients with BD were evaluated. All subjects were evaluated with respect to current and past psychiatric and medical disorders, as well as lifetime use of any medication. Body mass index (BMI) and metabolic parameters were obtained. IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Results: Thirty (54.5%) individuals had IGM. After adjustment for age, gender, ethnicity, alcohol use, smoking, BMI and past and current exposure to psychotropic medications, individuals with IGM, when compared to euglycemic participants, had an earlier age of onset (RR: 0.835, p=0.024), longer illness duration (RR: 1.754, p=0.007), a higher number of previous manic/hypomanic episodes (RR: 1.483, p=0.002) and a higher ratio of manic/hypomanic to depressive episodes (RR: 1.753, p=0.028). Moreover, we observed a moderating effect of IGM on the association between number of mood episodes and other variables of illness course, with the correlation between lifetime mood episodes and frequency of episodes being significantly greater in the IGM subgroup (RR: 1.027, p=0.029). All associations observed herein remained significant after adjusting for relevant confounding factors (e.g. age, alcohol and tobacco use, exposure to psychotropic agents, BMI). Limitations: Cross-sectional design, small sample size. Conclusions: Comorbid IGM may be a key moderator of illness progression in BD. (C) 2016 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosLeukocyte telomere length variation in different stages of schizophrenia(Pergamon-Elsevier Science Ltd, 2018) Maurya, Pawan Kumar [UNIFESP]; Rizzo, Lucas Bortolotto [UNIFESP]; Xavier, Gabriela [UNIFESP]; Tempaku, Priscila Farias [UNIFESP]; Ota, Vanessa Kiyomi [UNIFESP]; Santoro, Marcos L. [UNIFESP]; Spindola, Leticia M. [UNIFESP]; Moretti, Patricia S. [UNIFESP]; Mazzotti, Diego R.; Gadelha, Ary [UNIFESP]; Gouvea, Eduardo S.; Noto, Cristiano [UNIFESP]; Maes, Michael; Cordeiro, Quirino; Bressan, Rodrigo A. [UNIFESP]; Brietzke, Elisa [UNIFESP]; Belangero, Sintia Iole [UNIFESP]Recent research has demonstrated that telomere maintenance might be a key integrating point for the cumulative effect of genetic and environmental factors in patients with first-episode psychosis (FEP) and schizophrenia (SCZ). Eighty-one participants with antipsychotic-naive FEP, 173 with SCZ and 438 HC were enrolled in this study. Psychiatric diagnosis was assessed using the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I). The Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS) and Calgary Depression Scale for Schizophrenia (CDSS) were used to measure symptoms severity. Telomere length (TL) was determined using a multiplex qPCR assay. After adjustment for age, years of education, and smoking status, we found that patients with SCZ had longer TL (relative ratio (RR) = 1.08) than the HC group (RR = 1.00, Wald chi(2) = 12.48, p = 0.002). Further, non-remitted SCZ patients presented longer TL (RR = 1.00) compared to remitted SCZ (RR = 0.88, Wald chi(2) = 7.20, p = 0.007). TL in patients also correlated to psychopathology assessment in terms of total (p = 0.003) and positive PANSS scores (p = 0.001). No correlation with negative PANSS, YMRS, and CDSS or effects of medication was found on TL. Although the exact pathways underlying longer TL in SCZ patients remain unclear, these findings raise more questions than answers and suggest that TL may be of immense value on SCZ progression. Further studies are required to investigate the association of TL in FEP and SCZ.
- ItemSomente MetadadadosNecrosis is a consistent factor to recurrence of meningiomas: should it be a stand-alone grading criterion for grade II meningioma?(Springer, 2018) Goes, Pedro [UNIFESP]; Santos, Bruno Fernandes Oliveira de [UNIFESP]; Suzuki, Fernando Seiji [UNIFESP]; Salles, Debora [UNIFESP]; Stavale, Joao Noberto [UNIFESP]; Cavalheiro, Sergio [UNIFESP]; Paiva Neto, Manoel Antonio de [UNIFESP]The purpose of this study was to evaluate spontaneous necrosis as a possible isolated factor for progression and recurrence in grade I meningiomas classified according to the current World Health Organization (WHO) classification. Meningiomas are the most frequently reported primary intracranial tumours, accounting for more than 35%. The 2016 WHO classification of central nervous system tumors stratifies meningiomas in grades I (benign), II (atypical), and III (malignant), according to histopathological aspects and the risk of progression or recurrence. Among 110 patients with intracranial meningiomas, 70 were WHO grade I meningiomas with no findings of atypia (G1WON), 15 were WHO grade I with necrosis (G1WN), 21 were WHO grade II (G2), and 4 were WHO grade III (G3). The mean follow-up was 5.9 +/- 0.2 years. High performance scale (KPS >= 80) was different (p < 0.001) between WHO grade I meningiomas without (81.4%) and with (60%) necrosis. The 5-year mortality rate was 1.4, 6.7 and 5.9% for G1WON, G1WN and G2, respectively, with significant difference (p = 0.011) related to the presence of necrosis. The risk of recurrence was 3.7 times higher in G1WN than in G1WON (p = 0.017), and 4.2 times in G2 (p = 0.010). Progression-free survival (PFS) was clearly higher in patients with G1WON compared to G1WN and G2 (p = 0.002 and p < 0.001, respectively). There was no significant difference in PFS between G1WN and G2 (p = 0.692). Retreatment was also superior in meningioma with necrosis. Our findings provide clear statistical data to consider that patients with benign meningiomas and histologic findings of spontaneous necrosis are at increased risk of progression and recurrence compared to those with benign lesion without atypical features. Statistical analysis curves also suggest that these lesions behave more similarly to those currently classified as WHO grade II meningioma.
- ItemAcesso aberto (Open Access)Prevalência e fatores associados à progressão da doença renal crônica em idosos(Universidade Federal de São Paulo (UNIFESP), 2018-09-27) Totoli, Claudia [UNIFESP]; Canziani, Maria Eugenia Fernandes [UNIFESP]; Carvalho, Aluízio B. de [UNIFESP]; http://lattes.cnpq.br/7909431111187945; http://lattes.cnpq.br/8616590420890318; http://lattes.cnpq.br/9083418436399395Introdução: A doença renal crônica (DRC) é um problema de saúde pública mundial. Sua prevalência está crescendo principalmente na população idosa, em consequência do envelhecimento populacional, impulsionado pela melhora das condições socioeconômicas e pelo aumento da expectativa de vida. Existem poucos estudos sobre a perda de função renal em pacientes idosos. Assim, o objetivo desse estudo foi avaliar os fatores associados à progressão da DRC nessa população. Métodos: Este estudo retrospectivo observacional incluiu 340 pacientes com 65 anos ou mais, com DRC estágios 3a5ND (não diálise), incidentes no ambulatório de uremia e que foram acompanhados pelo período médio de 2,1 anos. A progressão da DRC foi avaliada pela variação da taxa de filtração glomerular estimada (TFGe), obtida pelas fórmulas CKDEPI e BIS1, ao longo do tempo. Os pacientes foram divididos em progressores e não progressores (variação da TFGe < 0 ou ≥ 0 mL/min/ano, respectivamente). Resultados: Houve declínio da função renal em 193 (57%) pacientes. Neste grupo a taxa de progressão foi de 2,83 (5,1/ 1,1) mL/min/ano. Comparado aos não progressores, os progressores eram mais jovens [72 (6978) vs. 76 (6980) anos; p=0,02]; apresentavam, na admissão, fósforo sérico mais elevado [3,8 (3,34,1) vs. 3,5 (3,94,1) mg/dL; p=0,04] e maior proteinúria [0,10 (00,9 vs. 0 (00,3) g/L; p=0,007)]. Na análise de regressão logística ajustada para gênero e TFGe inicial, a presença de proteinúria, mas não idade e fósforo, esteve independentemente associada à progressão da DRC [Odds Ratio 2,07; 95% IC (1,383,17) ; p < 0,001]. Conclusão: A progressão da DRC foi observada na maioria dos idosos, sendo a proteinúria, o mais importante fator associado ao declínio da função renal nesta população.
- ItemAcesso aberto (Open Access)Statins for aortic valve stenosis(Inst Oceanografico, Univ Sao Paulo, 2016) Thiago, Luciana; Tsuji, Selma Rumiko; Nyong, Jonathan; Puga, Maria Eduarda dos Santos [UNIFESP]; Gois, Aecio Flavio Teixeira de [UNIFESP]; Macedo, Cristiane Rufino de [UNIFESP]; Valente, Orsine [UNIFESP]; Atallah, Álvaro Nagib [UNIFESP]Background Aortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis. Objectives To evaluate the effectiveness and safety of statins in aortic valve stenosis. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS ‐ IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions. Selection criteria Randomised controlled clinical trials (RCTs) comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care. Data collection and analysis Primary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity), freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalisation for any reason, overall mortality, adverse events and patient quality of life. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO) was used to import data from Review Manager 5.3 to create a 'Summary of findings' table. Main results We included four RCTs with 2360 participants comparing statins (1185 participants) with placebo (1175 participants). We found low‐quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD) ‐0.54, 95% confidence interval (CI) ‐1.88 to 0.80; participants = 1935; studies = 2), valve area (MD ‐0.07, 95% CI ‐0.28 to 0.14; participants = 127; studies = 2), and aortic jet velocity (MD ‐0.06, 95% CI ‐0.26 to 0.14; participants = 155; study = 1). Moderate‐quality evidence showed no effect on freedom from valve replacement with statins (risk ratio (RR) 0.93, 95% CI 0.81 to 1.06; participants = 2360; studies = 4), and no effect on muscle pain as an adverse event (RR 0.91, 95% CI 0.75 to 1.09; participants = 2204; studies = 3; moderate‐quality evidence). Low‐ and very low‐quality evidence showed uncertainty around the effect of statins on death from cardiovascular cause (RR 0.80, 95% CI 0.56 to 1.15; participants = 2297; studies = 3; low‐quality evidence) and hospitalisation for any reason (RR 0.84, 95% CI 0.39 to 1.84; participants = 155; study = 1; very low‐quality evidence). None of the four included studies reported on overall mortality and patient quality of life. Authors' conclusions Result findings showed uncertainty surrounding the effect of statins for aortic valve stenosis.The quality of evidence from the reported outcomes ranged from moderate to very low. These results give support to European and USA guidelines (2012 and 2014, respectively) that so far there is no clinical treatment option for aortic valve stenosis.