Effects of a physical exercise or motor activity protocol on cognitive function, lipid profile, and BDNF levels in older adults with mild cognitive impairment.

This study analyzed the effects of a physical exercise program compared to the complexity of the motor task on the cognitive function, brain-derived neurotrophic factor (BDNF) levels, and lipid profile of older adults with mild cognitive impairment (MCI). Twenty-seven participants were randomized into three intervention groups: Physical Exercise (PE), Motor Task (MT), and Physical Exercise associated with Motor Task (PE + MT). Six months of intervention twice a week resulted in improvements in cognitive function, total cholesterol (TC), and LDL cholesterol (LDL-C) in the PE (p < 0.05). In the PE + MT, in addition to improved cognitive capacity, there was also a reduction in non-HDL cholesterol (NHDL-C) and LDL cholesterol (LDL-C) levels (p < 0.05), while in the MT, the values of TC, NHDL-C, and LDL-C decreased as a result of the intervention. BDNF levels were not affected by the interventions. In conclusion, PE alone or combined with MT is effective in promoting improvements in overall cognitive function and lipid profile in older adults with MCI; and BDNF seems not to be a sensitive marker for people with mild cognitive impairment.

A partial agonist of PPARγ prevents paclitaxel-induced peripheral neuropathy in mice, by inhibiting neuroinflammation.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of paclitaxel, affecting 30-50% of patients. Increased survival and concern with patients' quality of life have encouraged the search for new tools to prevent paclitaxel-induced neuropathy. This study presents the glitazone 4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-N-phenylbenzene-sulfonamide (TZD-A1) as a partial agonist of peroxisome proliferator-activated receptor γ (PPARγ), its toxicological profile and effects on paclitaxel-induced CIPN in mice. EXPERIMENTAL APPROACH: Interactions of TZD-A1 with PPARγ were analysed using in silico docking and in vitro reporter gene assays. Pharmacokinetics and toxicity were evaluated using in silico, in vitro and in vivo (C57Bl/6 mice) analyses. Effects of TZD-A1 on CIPN were investigated in paclitaxel-injected mice. Axonal and dorsal root ganglion damage, mitochondrial complex activity and cytokine levels, brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2 (Nrf2) and PPARγ, were also measured. KEY RESULTS: Docking analysis predicted TZD-A1 interactions with PPARγ compatible with partial agonism, which were corroborated by in vitro reporter gene assays. Good oral bioavailability and safety profile of TZD-A1 were shown in silico, in vitro and in vivo. Paclitaxel-injected mice, concomitantly treated with TZD-A1 by i.p. or oral administration, exhibited decreased mechanical and thermal hypersensitivity, effects apparently mediated by inhibition of neuroinflammation and mitochondrial damage, through increasing Nrf2 and PPARγ levels, and up-regulating BDNF. CONCLUSION AND IMPLICATIONS: TZD-A1, a partial agonist of PPARγ, provided neuroprotection and reduced hypersensitivity induced by paclitaxel. Allied to its safety profile and good bioavailability, TZD-A1 is a promising drug candidate to prevent and treat CIPN in cancer patients.

Probucol neuroprotection against manganese-induced damage in adult Wistar rat brain slices.

Manganese (Mn) is an abundant element used for commercial purposes and is essential for the proper function of biological systems. Chronic exposure to high Mn concentrations causes Manganism, a Parkinson's-like neurological disorder. The pathophysiological mechanism of Manganism remains unknown; however, it involves mitochondrial dysfunction and oxidative stress. This study assessed the neuroprotective effect of probucol, a hypolipidemic agent with anti-inflammatory and antioxidant properties, on cell viability and oxidative stress in slices of the cerebral cortex and striatum from adult male Wistar rats. Brain structure slices were kept separately and incubated with manganese chloride (MnCl2) and probucol to evaluate the cell viability and oxidative parameters. Probucol prevented Mn toxicity in the cerebral cortex and striatum, as evidenced by the preservation of cell viability observed with probucol (10 and 30 µM) pre-treatment, as well as the prevention of mitochondrial complex I inhibition in the striatum (30 µM). These findings support the protective antioxidant action of probucol, attributed to its ability to prevent cell death and mitigate Mn-induced mitochondrial dysfunction.

Neuroprotective Effect of Vitamin D on Behavioral and Oxidative Parameters of Male and Female Adult Wistar Rats Exposed to Mancozeb (manganese/zinc ethylene bis-dithiocarbamate).

The constant exposure of rural workers to pesticides is a serious public health problem. Mancozeb (MZ) is a pesticide  linked to hormonal, behavioral, genetic, and neurodegenerative effects, mainly related to oxidative stress. Vitamin D is a promising molecule that acts as a protector against brain aging. This study aimed to evaluate the neuroprotective role of vitamin D in adult male and female Wistar rats exposed to MZ. Animals received 40 mg/kg of MZ i.p. and 12.5 µg/kg or 25 µg/kg vitamin D by gavage, twice a week, for 6 weeks. The concentration of manganese had a significant increase in the hippocampus of both sexes and in the striatum of females, unlike zinc, which did not show a significant increase. MZ poisoning led to mitochondrial changes in brain tissues and promoted anxiogenic effects, especially in females. Alterations in antioxidant enzymes, mainly in the catalase activity were observed in intoxicated rats. Taken together, our results showed that exposure to MZ leads to the accumulation of manganese in brain tissues, and the behavior and metabolic/oxidative impairment were different between the sexes. Furthermore, the administration of Vitamin D was effective in preventing the damage caused by the pesticide.

Protective Effects of Probucol on Different Brain Cells Exposed to Manganese.

Manganese (Mn) is an essential metal for many functions in the body. However, in excess, it can be neurotoxic and cause a Parkinson-like syndrome, known as manganism. Here, we aimed to identify a protective effect of probucol, a lipid-lowering agent with anti-inflammatory and antioxidant properties, against Mn-induced toxicity in human neuroblastoma (SH-SY5Y) and glioblastoma (C6) cell lines. The cells were incubated with increasing concentrations of Mn followed by probucol addition 1, 3, 6, and/or 24 h to assess the metal toxic doses and measure the protective effect of probucol against Mn-induced oxidative damage. Longer exposition to Mn showed decreased SH-SY5Y cellular viability in concentrations higher than 100 µM, and probucol was able to prevent this effect. The C6 cells were more sensitive to the Mn deleterious actions, decreasing the cell viability after 6 h of 500 µM Mn exposure. In addition, probucol prevents the complex I and II of the mitochondrial respiratory chain (MRC) inhibition caused by Mn and decreased the intracellular ROS production. Taken together, our results showed that Mn toxicity affects differently both cell lines and probucol has a protective effect against the oxidative imbalance in the central nervous system.

Salivary cytokines as biomarkers of oral cancer: a systematic review and meta-analysis.

BACKGROUND: Oral cancer (OC) is usually diagnosed at advanced clinical stages due to its asymptomatic nature and absence of pathognomonic signs in its early development phase. Delayed diagnosis is one of the major causes of OC treatment failure and poor prognosis. Development of alternative diagnostic approaches are imperative for improving early detection and therapeutic success rates. Salivary cytokines (SC) have been studied as potential diagnostic biomarkers for OC and may represent a potential tool for improvement of its early detection. METHODS: In this systematic review and meta-analysis we identified SC studied as OC biomarkers by systematically reviewing the PubMed and Cochrane Library databases using the terms: "oral cancer", "cytokine", and "saliva", and also combined with "interleukin" or "interferon". Only case-control studies that measured SC by ELISA from treatment naïve patients were included in the qualitative review. For the meta-analysis were included all comparable studies that provided enough data (sample size, mean and standard deviation or standard error of the mean) for SC levels in OC patients, non-cancer controls and patients with oral potentially malignant disorders (OPMD), including leukoplakia. Comparisons with patients with oral lichen planus (OLP) and gingivitis were included in the qualitative analysis. RESULTS: A total of 28 articles (from 2004 to 2018) were included in the systematic review, describing 10 different SC, being IL-8 and IL-6 the most studied ones. SC levels were consistently higher among OC patients when compared to healthy controls and to patients with OPMD, OLP and gingivitis. Meta-analysis including 23 eligible studies showed that IL-8, IL-6, TNF-α, IL-1ß and IL-10 salivary levels were significantly higher in OC patients compared to controls; and that IL-8, IL-6, TNF-α and IL-1ß salivary levels were also higher in OC patients compared to individuals with OPMD. When compared to healthy controls, OPMD patients showed significantly higher IL-6 and TNF-α salivary levels. CONCLUSIONS: Our analyses showed that the salivary levels of some cytokines are consistently different among OC, OPMD and healthy patients, indicating that these SC may represent potential diagnostic biomarkers for OC and OPMD. Despite of that, SC levels were highly variable among studies, suggesting that further technical improvement and standardization for SC measurement by ELISA is needed in order to successfully translate these biomarkers to the clinical practice.

Glyphosate-based herbicide impairs energy metabolism and increases autophagy in C6 astroglioma cell line.

Several investigators demonstrated that glyphosate formulations produce neurotoxicity associated with oxidative stress, alterations in glutamatergic system, inhibition of acetylcholinesterase activity and mitochondrial dysfunction. However, the underlying molecular mechanisms following exposure to this herbicide on astrocytes are unclear. Thus, the aim of the present study was to determine the activity of enzymes related to energy metabolism, in addition to oxidative stress parameters, mitochondrial mass, nuclear area, and autophagy in astrocytes treated with a glyphosate-based herbicide. Our results showed that 24 h exposure to a glyphosate-based herbicide decreased (1) cell viability, (2) activities of mitochondrial respiratory chain enzymes and creatine kinase (CK), (3) mitochondrial mass, and (4) nuclear area in rat astroglioma cell line (C6 cells). However, non-protein thiol (NPSH) levels were increased but catalase activity was not changed in cells exposed to the herbicide at non-cytotoxic concentrations. Low glyphosate concentrations elevated content of cells positive to autophagy-related proteins. Nuclear factor erythroid 2-related factor (Nrf2), NAD(P)H dehydrogenase [quinone] 1 (NQO1) and PTEN-induced kinase 1 (PINK1) labeling were not markedly altered in cells exposed to glyphosate at the same concentrations that an increase in NPSH levels and positive cells to autophagy were found. It is conceivable that mitochondria and CK may be glyphosate-based herbicides targets. Further, autophagy induction and NPSH increase may be mechanisms initiated to avoid oxidative stress and cell death. However, more studies are needed to clarify the role of autophagy in astrocytes exposed to the herbicide and which components of the formulation might be triggering the effects observed here.

The influence of different types of fasting on lipid profile of volunteers from a city of Rio Grande do Sul, Brazil / A influência de diferentes tipos de jejum no perfil lipídico em voluntários de um município do Rio Grande do Sul, Brasil

ABSTRACT Introduction: Determination of lipid profile includes triglycerides (TG), total cholesterol and fractions as high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c). These parameters are valuable in the risk assessment of developing cardiovascular disease. However, some pre-analytical factors, such as the fasting state, may interfere with the results of these tests. Objective: The aim of this study was to evaluate differences on lipid profile measurements in blood samples collected at different fasting periods in men and women with or without a diagnosis of hypercholesterolemia. Methods: Fifty volunteers of both sexes, aged between 22 and 86 years, were evaluated. Sociodemographic data and two blood samples were collected, one after 12 hours fast and another during postprandial period, with subsequent measurement of total cholesterol, HDL-c, LDL-c and TG. Results: Comparing the values of the lipid profile obtained in the two collections, it was observed that the total cholesterol and HDL-c did not present significant differences among the evaluated subjects. On the other hand, LDL-c and TG showed significant higher values on postprandial samples, preferably in male group. Conclusion: These data suggest that TG and LDL-c levels are the fractions with greater susceptibility to variations when they are collected without prior fasting.

RESUMEN Introducción: La determinación del perfil lipídico incluye los triglicéridos (TG), colesterol total y fracciones del colesterol de la lipoproteína de alta densidad (HDL-c) y colesterol de la lipoproteína de baja densidad (LDL-c). Eses parámetros son muy valiosos en la evaluación del riesgo cardiovascular. Sin embargo, algunos factores preanalíticos, como el estado de ayuno, pueden interferir en los resultados de esos exámenes. Objetivo: Evaluar si hay diferencias significativas en la determinación del perfil lipídico en muestras de sangre recolectadas de hombres y mujeres con o sin diagnóstico de hipercolesterolemia. Método: Se evaluaron 50 voluntarios de ambos sexos, con edades comprendidas entre 22 y 86 años. Se recolectaron informaciones sociodemográficas y dos muestras de sangre, una con ayuno previo de 12 horas y otra posprandial, con determinación posterior de colesterol total, HDL-c, LDL-c, y TG. Resultados: Comparándose los valores obtenidos del perfil lipídico en las dos coletas, se observó que el colesterol total y el HDL-c no presentaron diferencias significativas en los sujetos evaluados. Al mismo tiempo, LDL-c y TG mostraron valores significativamente más elevados en la recolecta posprandial, preferencialmente en el grupo masculino. Conclusión: El conjunto de datos obtenidos sugiere que los niveles de TG y LDL-c son las fracciones con mayor susceptibilidad a variaciones cuando son recolectadas sin ayuno previo.

RESUMO Introdução: A determinação do perfil lipídico inclui dosagens de triglicerídeos (TG), colesterol total e frações do colesterol da lipoproteína de alta densidade (HDL-c) e do colesterol da lipoproteína de baixa densidade (LDL-c). Esses parâmetros são muito valiosos na avaliação do risco do desenvolvimento de doenças cardiovasculares. Porém, alguns fatores pré-analíticos, como o estado de jejum, podem interferir nos resultados desses exames. Objetivo: Avaliar se existem diferenças significativas nas dosagens do perfil lipídico em amostras de sangue coletadas em diferentes períodos de jejum em homens e mulheres com ou sem diagnóstico de hipercolesterolemia. Método: Foram avaliados 50 voluntários de ambos os sexos, com faixa etária entre 22 e 86 anos. Foram coletadas informações sociodemográficas e duas amostras de sangue, uma com jejum prévio de 12 horas e outra pós-prandial, com posterior dosagem de colesterol total, HDL-c, LDL-c e TG. Resultados: Ao comparar os valores obtidos do perfil lipídico nas duas coletas, observou-se que o colesterol total e o HDL-c não apresentaram diferenças significativas nos sujeitos avaliados. Por outro lado, o LDL-c e o TG expressaram valores significativamente mais elevados na coleta realizada de forma pós-prandial, preferencialmente no grupo masculino. Conclusão: O conjunto dos dados obtidos sugere que os níveis de TG e LDL-c são as frações com maior suscetibilidade a variações quando são coletadas sem jejum prévio.

Effects of photobiomodulation on mitochondria of brain, muscle, and C6 astroglioma cells.

The purpose of this study was to investigate the effect of different doses of photobiomodulation (PBM) on mitochondrial respiratory complexes and oxidative cellular energy metabolic enzymes in the mitochondria of brain, muscle, and C6 glioma cells after different time intervals. C6 cells were irradiated with an AlGaInP laser at 10, 30, and 60 J/cm2 for 20, 60, and 120 s, respectively. After irradiation, the cells were maintained in serum-free Dulbecco's Modified Eagle's medium for 24 h, and biochemical measurements were made subsequently. Mitochondrial suspensions from adult rat skeletal muscles/brains were irradiated with an AlGaInP laser at the abovementioned doses. In one group, the reaction was stopped 5 min after irradiation and in the other 60 min after irradiation. Both the C6 cells that received the doses of 10 and 30 J/cm² showed increased complex I activity; the cells that were irradiated at 30 J/cm2 showed increased hexokinase activity. Five minutes after the introduction of PBM of the muscle mitochondria (at 30 and 60 J/cm2), the activity of complex I increased, while the activity of complex IV increased only at 60 J/cm2. One hour after the laser session, complex II activity increased in the cells treated with 10 and 60 J/cm²; however, complex IV activity showed an increase in all PBM groups. In brain mitochondria, 5 min after irradiation only the activity of complex IV increased in all PBM groups. One hour after the laser session, complex II activity increased at 60 J/cm2, and complex IV activity increased for all PBM groups when compared to controls. PBM could increase the activity of respiratory chain complexes in an apparently dose- and time-dependent manner.

Sex differences in subacute manganese intoxication: Oxidative parameters and metal deposition in peripheral organs of adult Wistar rats.

INTRODUCTION: Manganese (Mn) is an essential element required for several biological systems. However, it is toxic in excessive accumulation. The toxic effects following Mn overexposure is well known in the CNS but other studies evaluating other target tissues remain scarce. OBJECTIVE: This study aimed to investigate sex-related differences in oxidative stress, metabolic parameters and Mn deposition in peripheral organs of Wistar rats exposed to subacute model of intoxication. METHODS: Male and female adult Wistar rats received 6 or 15 mg/kg of MnCl2, intraperitoneally, 5 days a week, for 4 consecutive weeks to mimic subacute intoxication. Control group received sterile saline 0,9% following the same protocol. After this period, the metal accumulation, oxidative stress, mitochondrial activity and histological parameters in cardiac muscle, kidney, lungs and liver were analysed. RESULTS: Increased Mn concentrations were found in all organs, especially kidneys. The cardiac muscle analysis revealed increased lipid peroxidation and decreasing of GSH levels in both doses of Mn in male and female rats. The increase of lipid peroxidation in liver was more evident in the male group, and there was a significant decrease of antioxidant capacity in males' kidney. Nevertheless, there was an increase of mitochondrial complex I activity in kidney of females and increase of mitochondrial complex II activity in male group. Histological analysis revealed morphological changes in hepatic and pulmonary tissue. CONCLUSION: Taken together, our results showed that subacute Mn exposure lead to significant metabolic, biochemical alterations especially in kidney and liver. Nevertheless, despite Mn deposition was virtually the same in the peripheral organs of male and female rats, it promotes different toxic effects between sexes.

Impact of homocysteine on vasculogenic factors and bone formation in chicken embryos.

Developmental endochondral ossification requires constant blood supply, which is provided by the embryonic vascular network. High levels of homocysteine (Hcy) have vasculotoxic properties, but it remains unclear how Hcy disrupts blood vessel formation in endochondral ossification. Thus, we investigated the toxicity of Hcy on contents of vasculogenic factors (VEGF, VCAM-1, NOS3) and osteocalcin, using developing limbs as model. Chicken embryos were submitted to treatment with 20 µmol D-L Hcy at 12H&H and the analyses occur at 29H&H and 36H&H. We did not identify differences in the area of limb ossification in Hcy-treated (7.5 × 105 µm2 ± 3.9 × 104) and untreated embryos (7.6 × 105 µm2 ± 3.3 × 104) at 36H&H. In Hcy-treated embryos, we observed a significantly decrease of 46.8% at 29H&H and 26.0% at 36H&H in the number of VEGF-reactive cells. Also, treated embryos showed decrease of 98.7% in VCAM-1-reactive cells at 29H&H and 34.6% at 36H&H. The number of NOS3-reactive cells was reduced 54.0% at 29H&H and 91.5% at 36H&H, in the limbs of Hcy-treated embryos. Finally, in Hcy-treated embryos at 36H&H, we observed a reduction of 58.86% in the number of osteocalcin-reactive cells. Here, we demonstrated for the first time that the toxicity of Hcy is associated with a reduction in the contents of proteins involved in blood vessel formation and bone mineralization, which interferes with endochondral ossification of the limb during embryonic development. Graphical abstract.

Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation.

Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromised cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in rats. The mechanisms appear to be linked to reduced active DNA demethylation and diminished expression of the neuroprotective transcription factor REST. The impact of the relationship between adiposity and DNA hypermethylation on REST expression was also demonstrated in peripheral blood mononuclear cells in obese children with reduced levels of blood ascorbate. The reversible nature of epigenetic modifications and the cognitive impairment reported in obese children, adolescents, and adults suggest that the correction of the anthropometry and the peripheral metabolic alterations would protect brain homeostasis and reduce the risk of developing neurodegenerative diseases.

Low-concentration exposure to glyphosate-based herbicide modulates the complexes of the mitochondrial respiratory chain and induces mitochondrial hyperpolarization in the Danio rerio brain.

Glyphosate (N-phosphonomethyl-glycine) (GLY) is the active ingredient of the most used herbicides in the world. GLY is applied in formulated products known as glyphosate-based herbicides (GBH), which could induce effects that are not predicted by toxicity assays with pure GLY. This herbicide is classified as organophosphorus compound, which is known to induce neurotoxic effects. Although this compound is classified as non-neurotoxic by regulatory agencies, acute exposure to GBH causes neurological symptoms in humans. However, there is no consensus in relation to neurotoxic effects of GBH. Thus, the aim of this study was to investigate the neurotoxic effects of the GBH in the zebrafish Danio rerio, focusing on acute toxicity, the activity and transcript levels of mitochondrial respiratory chain complexes, mitochondrial membrane potential, reactive species (RS) formation, and behavioral repertoire. Adult zebrafish were exposed in vivo to three concentrations of GBH Scout®, which contained GLY in formulation (fGLY) (0.065, 1.0 and 10.0 mg L-1 fGLY) for 7 d, and an in vitro assay was performed using also pure GLY. Our results show that GBH induced in zebrafish brain a decrease in cell viability, inhibited mitochondrial complex enzymatic activity, modulated gene expression related to mitochondrial complexes, induced an increase in RS production, promoted hyperpolarization of mitochondrial membrane, and induced behavioral impairments. Together, our data contributes to the knowledge of the neurotoxic effects of GBH. Mitochondrial dysfunction has been recognized as a relevant cellular response that should not be disregarded. Moreover, this study pointed to the mitochondria as an important target of GBH.

Suicídio assistido e eutanásia na perspectiva de profissionais e acadêmicos de um hospital universitário / Assisted suicide and euthanasia from the perspective of professionals and academics in a university hospital / Suicidio asistido y eutanasia en la perspectiva de profesionales y estudiantes de un hospital universitario

Resumo Objetivou-se identificar a atitude de profissionais e acadêmicos de enfermagem, fisioterapia, medicina e psicologia de um hospital universitário perante suicídio assistido e eutanásia. O estudo foi desenvolvido por meio de questionário de autopreenchimento e contou com 354 participantes, entre os quais, 68,1% concordaram com a legalização do suicídio assistido e 73,2% com a legalização da eutanásia para pacientes com doenças terminais. A concordância com a legalização do suicídio assistido ou da eutanásia foi de 46,9% em casos de pacientes com doenças neurodegenerativas progressivas e de 30,8% em casos de tetraplegia. Em casos de doenças terminais, se legalizados, 45% dos participantes cometeriam suicídio assistido, 57% solicitariam eutanásia, 36,5% auxiliariam suicídio assistido e 39,9% auxiliariam eutanásia. Conclui-se que a ampla aceitação da legalização da eutanásia e do suicídio assistido entre os participantes enfatiza a necessidade de se ampliar a discussão sobre o tema entre a população.

Abstract The objective of this study was to identify the attitude of professionals and academics in a university hospital regarding assisted suicide and euthanasia. The study was conducted using a questionnaire and included 354 participants. In cases of patients with terminal illnesses, 68.1% of participants supported the legalization of assisted suicide and 73.2% supported the legalization of euthanasia. The support for legalization of assisted suicide or euthanasia was 46.9% in cases of patients with progressive neurodegenerative diseases and 30.8% in cases of tetraplegia. In cases of terminal illnesses, if those were legalized, 45% of participants would commit assisted suicide, 57% would request euthanasia, 36.5% would aid in assisted suicide and 39.9% would aid in euthanasia. In conclusion, the great support for legalization of euthanasia and assisted suicide among the participants emphasizes the need to broaden the discussion on the subject in the population.

Resumen Se tuvo como objetivo identificar la actitud de profesionales y estudiantes de enfermería, fisioterapia, medicina y psicología de un hospital universitario ante el suicidio asistido y la eutanasia. El estudio fue desarrollado por medio de un cuestionario de auto-llenado y contó con 354 participantes, entre los cuales el 68,1% concordó con la legalización del suicidio asistido y el 73,2% con la legalización de la eutanasia para pacientes con enfermedades terminales. La concordancia con la legalización del suicidio asistido o de la eutanasia fue del 46,9% en casos de pacientes con enfermedades neurodegenerativas progresivas y del 30,8% en casos de tetraplejia. En los casos de enfermedades terminales, si se legalizara, el 45% de los participantes practicaría suicidio asistido, el 57% solicitaría eutanasia, el 36,5% colaboraría en el suicidio asistido y el 39,9% colaboraría en la eutanasia. Se concluye que la amplia aceptación de la legalización de la eutanasia y del suicidio asistido entre los participantes enfatiza la necesidad de ampliar la discusión sobre el tema entre la población.

Oxidative stress and mitochondrial adaptive shift during pituitary tumoral growth.

The cellular transformation of normal functional cells to neoplastic ones implies alterations in the cellular metabolism and mitochondrial function in order to provide the bioenergetics and growth requirements for tumour growth progression. Currently, the mitochondrial physiology and dynamic shift during pituitary tumour development are not well understood. Pituitary tumours present endocrine neoplastic benign growth which, in previous reports, we had shown that in addition to increased proliferation, these tumours were also characterized by cellular senescence signs with no indication of apoptosis. Here, we show clear evidence of oxidative stress in pituitary cells, accompanied by bigger and round mitochondria during tumour development, associated with augmented biogenesis and an increased fusion process. An activation of the Nrf2 stress response pathway together with the attenuation of the oxidative damage signs occurring during tumour development were also observed which will probably provide survival advantages to the pituitary cells. These neoplasms also presented a progressive increase in lactate production, suggesting a metabolic shift towards glycolysis metabolism. These findings might imply an oxidative stress state that could impact on the pathogenesis of pituitary tumours. These data may also reflect that pituitary cells can modulate their metabolism to adapt to different energy requirements and signalling events in a pathophysiological situation to obtain protection from damage and enhance their survival chances. Thus, we suggest that mitochondria function, oxidative stress or damage might play a critical role in pituitary tumour progression.

Neuropsychological functioning and brain energetics of drug resistant mesial temporal lobe epilepsy patients.

Interictal hypometabolism is commonly measured by 18-fluoro-deoxyglucose Positron Emission Tomography (FDG-PET) in the temporal lobe of patients with mesial temporal lobe epilepsy (MTLE-HS). Left temporal lobe interictal FDG-PET hypometabolism has been associated with verbal memory impairment, while right temporal lobe FDG-PET hypometabolism is associated with nonverbal memory impairment. The biochemical mechanisms involved in these findings remain unknown. In comparison to healthy controls (n=21), surgically treated patients with MTLE-HS (n=32, left side=17) had significant lower scores in the Rey Auditory Verbal Learning Test (RAVLT retention and delayed), Logical Memory II (LMII), Boston Naming test (BNT), Letter Fluency and Category Fluency. We investigated whether enzymatic activities of the mitochondrial enzymes Complex I (C I), Complex II (C II), Complex IV (C IV) and Succinate Dehydrogenase (SDH) from the resected samples of the middle temporal neocortex (mTCx), amygdala (AMY) and hippocampus (HIP) were associated with performance in the RAVLT, LMII, BNT and fluency tests of our patients. After controlling for the side of hippocampus sclerosis, years of education, disease duration, antiepileptic treatment and seizure outcome after surgery, no independent associations were observed between the cognitive test scores and the analyzed mitochondrial enzymatic activities (p>0.37). Results indicate that memory and language impairment observed in MTLE-HS patients are not strongly associated with the levels of mitochondrial CI, CII, SDH and C IV enzymatic activities in the temporal lobe structures ipsilateral to the HS lesion.

Ergophthalmology in accounting offices: the computer vision syndrome (CVS) / Ergoftalmologia em escritórios de contabilidade: a síndrome visual do computador (SVC)

Abstract Purpose: This study aimed to determine the presence of the symptoms of computer vision syndrome (CVS) accounting office employees. Methods: The research tools used were a questionnaire based on the set of symptoms of CVS rated by Likert scale (1-5) and workplace observations based on Ergonomic Workplace Analysis (EWA). Results: The participants who worked with a viewing angle of less than 10º relative to the screen had more symptoms, particularly of pain in the back of the neck and back (p = 0.0460). The participants who used lighting other than 450 and 699 lux reported significant headache (p = 0.0045) and dry eye (p = 0.0329) symptoms. Younger workers had more headaches (p = 0.0182), and workers with fewer years of employment had more headaches and dry eyes symptoms (p = 0.0164 and p = 0.0479, respectively). A total of 37% of the participants reported a lack of guidance regarding prevention and painful symptoms in the back of the neck and back (p = 0.0936). Conclusion: Younger participants with fewer years of employment, who had not received information regarding proper computer use, who did not use lighting between 450 and 699 lux or who worked with viewing angles of less than 10º had more computer vision syndrome symptoms.

Resumo Objetivo: Este trabalho objetivou averiguar a presença dos sintomas da Síndrome Visual dos Computadores (SVC) trabalhadores de escritórios de contabilidade. Métodos: Como instrumentos de pesquisa utilizou-se um questionário baseado no conjunto de sintomas da SVC, avaliado por Escala Likert (1-5), e foram realizadas observações no local de trabalho baseadas na Avaliação Ergonômica de Postos de Trabalho. Resultados: Os participantes que trabalhavam com o ângulo de visão menor do que 10º em relação à tela foram os que apresentaram mais sintomas sobretudo de dor na parte posterior do pescoço e nas costas (p=0,0460). Aqueles que usavam iluminação diferente de 450 e 699 lux reportaram sintomas significativos para dor de cabeça (p=0,0045) e ressecamento ocular (p=0,0329). Os mais jovens apresentaram mais dor de cabeça (p=0,0182) e aqueles com menor tempo de trabalho mais sintomas de dor de cabeça e ressecamento ocular (respectivamente p=0,0164 e p=0,0479). A falta de recebimento de orientações sobre prevenção foi confirmada por 37% participantes que referiram mais sintomas de dor na parte posterior do pescoço e nas costas (p=0,0936). Conclusão: Os participantes mais jovens, com menor tempo de trabalho, que não haviam recebido informações sobre o uso de computador, não utilizavam iluminação entre 450 e 699 lux ou trabalhavam com o ângulo de visão menor do que 10º apresentaram mais sintomas da síndrome visual do computador.

Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney.

Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT) in kidney. Wistar rats were fed with oxonic acid 2% and UA 2% (OXA + U), OXA + U plus allopurinol (ALL) or regular chow (C) for 7 weeks. We analyzed the presence of EMT markers, the expression of NLRP3, ASC, Caspase-1 and Smad 2/3 molecules and the mitochondrial morphological and functional characteristics. High UA induced renal fibrosis, mild chronic inflammation, as well as morphological and biochemical evidence of EMT. High UA also increased the expression of NLRP3/ASC with activation of both inflammasome related caspase-1 and inflammasome unrelated Smad 2/3 pathways. Ultrastructural co-localization of NLRP3 and Smad 2/3 indicated physical interaction between the two molecules. No morphological or functional changes were found between mitochondria exposed to high UA. In conclusion, kidney epithelial NLRP3/ASC expression was increased in high UA state in rats and both inflammasome related caspase-1 and non-inflammasome related P-Smad 2/3 pathways were associated with the observed EMT, inflammation and fibrosis induced by UA in the kidney.