Sirtuins Modulators Counteract Mitochondrial Dysfunction in Cellular Models of Hypoxia: Relevance to Schizophrenia.

Schizophrenia (SZ) is a neurodevelopmental-associated disorder strongly related to environmental factors, such as hypoxia. Because there is no cure for SZ or any pharmacological approach that could revert hypoxia-induced cellular damages, we evaluated whether modulators of sirtuins could abrogate hypoxia-induced mitochondrial deregulation as a neuroprotective strategy. Firstly, astrocytes from control (Wistar) and Spontaneously Hypertensive Rats (SHR), a model of both SZ and neonatal hypoxia, were submitted to chemical hypoxia. Then, cells were exposed to different concentrations of Nicotinamide (NAM), Resveratrol (Resv), and Sirtinol (Sir) for 48hrs. Our data indicate that sirtuins modulation reduces cell death increasing the acetylation of histone 3. This outcome is related to the rescue of loss of mitochondrial membrane potential, changes in mitochondrial calcium buffering capacity, decreased O2-rad levels and increased expression of metabolic regulators (Nrf-1 and Nfe2l2) and mitochondrial content. Such findings are relevant not only for hypoxia-associated conditions, named pre-eclampsia but also for SZ since prenatal hypoxia is a relevant environmental factor related to this burdensome neuropsychiatric disorder.

Impact of Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography on the Therapeutic Decision of Prostate Carcinoma Primary Staging: A Retrospective Analysis at the Brazilian National Public Health System.

BACKGROUND: Prostate cancer (PCa) is the most common malignant tumor in males and conventional imaging does not provide accurate primary staging. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) presents superior performance and strongly affects therapeutic choice. OBJECTIVE: The aim of this study was to evaluate the impact of PSMA PET, compared with conventional imaging methods, on the therapeutic approach in primary staging scenarios in patients with PCa treated at the Brazilian National Public Health System. METHODS: Overall, 35 patients diagnosed with PCa were evaluated using PSMA after conventional staging imaging with multiparametric magnetic resonance (MMR) and/or total abdominal computed tomography (CT) scan and bone scintigraphy (BS). The PCa extension identified by PET was compared with conventional imaging; staging changes and the management impact were then determined. PET comparison with conventional imaging, staging, and decision-making changes was analyzed using descriptive statistics. RESULTS: PET revealed local disease (LD) in 15 (42.9%) patients, seminal vesicle invasion (SVI) in 5 (14.3%) patients, pelvic nodal impairment (PNI) in 7 (20%) patients, pelvic and distant nodes in 3 (8.6%) patients, pelvic nodes and bone metastasis in 4 (11.4%) patients, and pelvic and distant nodes and bone metastasis in 1 (2.8%) patient. Staging changes were observed in 60% of patients, with downstaging predominance (76.2%). Volume increase was identified in 11 (31.4%) patients (only 4 related to upstaging, 36.4%). The board changed management decisions for 60% of the patients. The main limitations of this study were the sample size and its retrospective nature. CONCLUSIONS: PSMA findings changed the management decisions in more than half of the patients, which made the majority eligible for locoregional treatment and avoided unnecessary procedures in the systemic disease scenario.