Maqui berry (Aristotelia chilensis) extract improves memory and decreases oxidative stress in male rat brain exposed to ozone.

Introduction: Prolonged ozone exposure can produce a state of oxidative stress, which in turn causes alterations in the dynamics of the brain and affects memory and learning. Moreover, different investigations have shown that high flavonoid content berries show a great antioxidant activity. The relationship between the protective effect of the maqui berry extract and its antioxidant properties in the brain has not been studied in depth. Objectives: The present study evaluated whether the protection exerted by the aqueous extract of maqui berry in brain regions associated with cognitive performance is due to its antioxidant capacity. Methods: Sprague Dawley rats were exposed to 0.25 ppm ozone and administered with maqui berry extracts. At the end of the treatments, spatial learning and short- and long-term memory were evaluated, as well as oxidative stress markers. Results: The administration of 50 and 100 mg/kg of the aqueous extract of maqui berry was effective in preventing the cognitive deficit caused by chronic exposure to ozone. The antioxidant effect of the administration of maqui berry was analyzed in the prefrontal cortex, hippocampus, and amygdala. Oxidative stress markers levels decreased and the enzymatic activity of superoxide dismutase diminished in animals exposed to ozone treated with the 50 mg/kg dose of maqui berry. Discussion: These results show a relationship between protection at the cognitive level and a decrease in oxidative stress markers, which suggests that the prevention of cognitive damage is due to the antioxidant activity of the maqui berry.

Acanthamoeba (T4) trophozoites cross the MDCK epithelium without cell damage but increase paracellular permeability and transepithelial resistance by modifying tight junction composition.

Free-living amoebae of the genus Acanthamoeba are protozoa ubiquitously found in nature. Some species of the genus are potentially pathogenic for humans provoking keratitis in healthy individuals, often in contact lens wearers and opportunistic infections such as pneumonitis, fatal granulomatous encephalitis and skin infections, particularly in immunocompromised individuals. The pathogenic mechanisms of these amoebae are poorly understood, however it had been suggested that contact dependent mechanisms are important during invasion, regardless of the epithelia type, since amoebae penetrate epithelia separating tight junction (TJ). This study was undertaken to determine whether Acanthamoeba sp. (T4) damages the barrier function of the TJ in MDCK epithelial monolayers. Actin cytoskeleton staining and electron microscopy analyses were performed; paracellular permeability and TJ sealing were evaluated by apicobasolateral diffusion of ruthenium red and transepithelial resistance (TER) measurements; immunofluorescence and Western blot assays were performed to locate and estimate expression of TJ protein claudins 2 (Cldn2) and 4 (Cldn4). The results show that Acanthamoeba sp. crosses the MDCK monolayer without altering the actin cytoskeleton or the morphology of the cells. When trophozoites or conditioned medium interact with the monolayer, paracellular diffusion of ruthenium red increases. After 6 h, the amoebae, but not their conditioned medium, increase the TER, and Cldn2 is removed from the TJ, and its overall content in the cells diminishes, while Cldn4 is targeted to the TJ without changing its expression level. In conclusion Acanthamoeba (T4) crosses MDCK monolayer without damaging the cells, increasing permeability and TER through Cldn2 degradation, and redirecting Cldn4 to TJ. These results strongly suggest that contact-dependent mechanisms are relevant during amoebae invasion.

Carotid intima media thickness, oxidative stress, and inflammation in children with chronic kidney disease.

OBJECTIVE: We evaluated the association between inflammation and oxidative stress with carotid intima media thickness (cIMT) and elasticity increment module (E(inc)) in pediatric patients with chronic kidney disease (CKD). METHODS: This analytical, cross-sectional study assessed 134 children aged 6-17 years with CKD. Anthropometric measurements and biochemistry of intact parathyroid hormone (iPTH), high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-1ß, reduced glutathione (GSH), malondialdehyde, nitric oxide, and homocysteine were recorded. Bilateral carotid ultrasound (US) was taken. Patients were compared with controls for cIMT and E(inc) using ≥ 75 percentile (PC). RESULTS: Mean cIMT was 0.528 ± 0.089 mm; E(inc) was 0.174 ± 0.121 kPa × 10(3); cIMT negatively correlated with phosphorus (r -0.19, p =0.028) and the calcium × phosphorus (Ca × P) product (r -0.26, p =0.002), and positively with iPTH (r 0.19,p =0.024). After adjusting for potential confounders, hemodialysis (HD) (ß=0.111, p =<0.001), automated peritoneal dialysis (APD) (ß=0.064, p =0.026), and Ca x P product(ß=-0.002, p =0.015) predicted cIMT (R(2)=0.296). In patients on dialysis, HD (ß=0.068, p =0.010), low-density lipoprotein cholesterol (LDL-C) (ß=0.001, p =0.048), and GSH(ß=-0.0001, p=0.041) independently predicted cIMT (R(2)=0.204); HD, hypoalbuminemia, and high iPTH increased the risk of increased cIMT. In dialysis, E(inc) was inversely associated with GSH, and in predialysis, Ca × P correlated with/predicted E(inc) (ß=0.001, p =0.009). CONCLUSIONS: cIMT and E(inc) strongly associate with several biochemical parameters and GSH but not with other oxidative stress or inflammation markers.

In Silico and In Vivo Evaluation of the Maqui Berry (Aristotelia chilensis (Mol.) Stuntz) on Biochemical Parameters and Oxidative Stress Markers in a Metabolic Syndrome Model.

Metabolic syndrome (MetS) is a complex disease that includes metabolic and physiological alterations in various organs such as the heart, pancreas, liver, and brain. Reports indicate that blackberry consumption, such as maqui berry, has a beneficial effect on chronic diseases such as cardiovascular disease, obesity, and diabetes. In the present study, in vivo and in silico studies have been performed to evaluate the molecular mechanisms implied to improve the metabolic parameters of MetS. Fourteen-day administration of maqui berry reduces weight gain, blood fasting glucose, total blood cholesterol, triacylglycerides, insulin resistance, and blood pressure impairment in the diet-induced MetS model in male and female rats. In addition, in the serum of male and female rats, the administration of maqui berry (MB) improved the concentration of MDA, the activity of SOD, and the formation of carbonyls in the group subjected to the diet-induced MetS model. In silico studies revealed that delphinidin and its glycosylated derivatives could be ligands of some metabolic targets such as α-glucosidase, PPAR-α, and PPAR-γ, which are related to MetS parameters. The experimental results obtained in the study suggest that even at low systemic concentrations, anthocyanin glycosides and aglycones could simultaneously act on different targets related to MetS. Therefore, these molecules could be used as coadjuvants in pharmacological interventions or as templates for designing new multitarget molecules to manage patients with MetS.

High Fructose and High Fat Diet Impair Different Types of Memory through Oxidative Stress in a Sex- and Hormone-Dependent Manner.

Metabolic syndrome (MetS) contributes to the spread of cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. Evaluation of sex- and hormone-dependent changes in body weight, blood pressure, blood lipids, oxidative stress markers, and alterations in different types of memory in Sprague-Dawley rats fed with a high fat and high fructose (HFHF) diet were evaluated. After 12 weeks of feeding the male and female rats with HFHF, body weight gain, increase in blood pressure, and generation of dyslipidemia compared to the animals fed with chow diet were observed. Regarding memory, it was noted that gonadectomy reverted the effects of HFHF in the 24 h novel object recognition task and in spatial learning/memory analyzed through Morris water maze, males being more affected than females. Nevertheless, gonadectomy did not revert long-term memory impairment in the passive avoidance task induced by HFHF nor in male or female rats. On the other hand, sex-hormone-diet interaction was observed in the plasma concentration of malondialdehyde and nitric oxide. These results suggest that the changes observed in the memory and learning of MetS animals are sex- and hormone-dependent and correlate to an increase in oxidative stress.

Remote cerebellar hemorrhage after lumbar spinal surgery.

Remote cerebellar hemorrhage (RCH) is a rare complication after supratentorial or spinal surgery. RCH is poorly known and hence probably underdiagnosed. Diminished consciousness and headache are the most common clinical features. Computed tomography and magnetic resonance reveal a characteristic pattern of linear bleeding between the cerebellar folia. The pathophysiological mechanism is disputed but is probably venous bleeding secondary to significant intraoperative or postoperative loss of cerebrospinal fluid. Multiple risk factors have been described, but postsurgical negative pressure drainage of cerebrospinal fluid is the only clearly predisposing factor. We present a case of RCH after spinal surgery with a literature review.

The Importance of Natural Antioxidants in the Treatment of Spinal Cord Injury in Animal Models: An Overview.

Patients with spinal cord injury (SCI) face devastating health, social, and financial consequences, as well as their families and caregivers. Reducing the levels of reactive oxygen species (ROS) and oxidative stress are essential strategies for SCI treatment. Some compounds from traditional medicine could be useful to decrease ROS generated after SCI. This review is aimed at highlighting the importance of some natural compounds with antioxidant capacity used in traditional medicine to treat traumatic SCI. An electronic search of published articles describing animal models of SCI treated with natural compounds from traditional medicine was conducted using the following terms: Spinal Cord Injuries (MeSH terms) AND Models, Animal (MeSH terms) AND [Reactive Oxygen Species (MeSH terms) AND/OR Oxidative Stress (MeSH term)] AND Medicine, Traditional (MeSH terms). Articles reported from 2010 to 2018 were included. The results were further screened by title and abstract for studies performed in rats, mice, and nonhuman primates. The effects of these natural compounds are discussed, including their antioxidant, anti-inflammatory, and antiapoptotic properties. Moreover, the antioxidant properties of natural compounds were emphasized since oxidative stress has a fundamental role in the generation and progression of several pathologies of the nervous system. The use of these compounds diminishes toxic effects due to their high antioxidant capacity. These compounds have been tested in animal models with promising results; however, no clinical studies have been conducted in humans. Further research of these natural compounds is crucial to a better understanding of their effects in patients with SCI.

Acute Administration of Tibolone Prevents Oxidative Stress in Ovariectomized Rats Fed High-Fat-and-Fructose Diet.

In addition to oxidative stress due to the increase of free radicals, estrogen deficiency is associated with changes in enzymatic activity, glutathione redox ratio (GSH/GSSG), and the content of oxidative markers such as malondialdehyde. Tibolone, a synthetic steroid, has been used as an elective treatment for the relief of menopausal symptoms. However, the acute effects of hormonal therapy with tibolone on metabolic parameters and oxidative stress markers associated with the first stages of estrogen deficiency are still unknown. The study aimed to evaluate if the acute administration of tibolone reduces oxidative stress in ovariectomized rats fed high-fat-and-fructose diet. Rats were fed a standard diet or a diet consisting of 10% lard-supplemented chow and 20% high-fructose syrup in the drinking water plus tibolone or vehicle for seven days. Weight, cholesterol, triglycerides, and glucose levels, as well as antioxidant enzymes and oxidative stress markers were quantified in the serum of each experimental group. It was observed that seven days of diet and tibolone treatment in the ovariectomized group reduced weight, triglycerides, cholesterol, glucose levels and advanced glycation end products but did not change GSH/GSSG ratio nor the enzymatic activity of superoxide dismutase. Also, both glutathione peroxidase and glutathione reductase activity decreased, as well as malondialdehyde levels. These results suggest that the acute treatment with tibolone prevented the changes in the metabolic parameters analyzed as well as the increase in the levels of malondialdehyde and AGEs induced by ovariectomy and high-fat diet.

Recommendations for the use of ultrasound and magnetic resonance in patients with rheumatoid arthritis. / Recomendaciones para el uso de la ecografía y la resonancia magnética en pacientes con artritis reumatoide.

OBJECTIVE: To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA). METHODS: Recommendations were generated following a nominal group technique. A panel of experts, consisting of 15 rheumatologists and 3 radiologists, was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents). A first draft of recommendations and text was generated. Then, an electronic Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of experts voted ≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. The full text was circulated and reviewed by the panel. The consensus was coordinated by an expert methodologist. RESULTS: A total of 20 recommendations were proposed. They include the validity of US and MRI regarding inflammation and damage detection, diagnosis, prediction (structural damage progression, flare, treatment response, etc.), monitoring and the use of US guided injections/biopsies. CONCLUSIONS: These recommendations will help clinicians use US and MRI in RA patients.

Recommendations for the Use of Ultrasound and Magnetic Resonance in Patients With Spondyloarthritis, Including Psoriatic Arthritis, and Patients With Juvenile Idiopathic Arthritis. / Recomendaciones para el uso de la ecografía y la resonancia magnética en pacientes con espondiloartritis, incluyendo la artritis psoriásica, y en pacientes con artritis idiopática juvenil.

OBJECTIVE: To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging in patients with spondyloarthritis, including psoriatic arthritis, and juvenile idiopathic arthritis. METHODS: Recommendations were generated following a nominal group technique. A panel of experts (15 rheumatologists and 3 radiologists) was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents). A first draft of recommendations and text was generated. Then, an electronic Delphi process (2 rounds) was carried out. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% of participants voted≥7. The level of evidence and grade or recommendation was assessed using the Oxford Centre for Evidence Based Medicine levels of evidence. The full text was circulated and reviewed by the panel. The consensus was coordinated by an expert methodologist. RESULTS: A total of 12 recommendations were proposed for each disease. They include, along with explanations of the validity of US and magnetic resonance imaging regarding inflammation and damage detection, diagnosis, prediction (structural damage progression, flare, treatment response, etc.), monitoring and the use of US guided injections/biopsies. CONCLUSIONS: These recommendations will help clinicians use US and magnetic resonance imaging in patients with spondyloarthritis and juvenile idiopathic arthritis.

Tibolone modulates neuronal plasticity through regulating Tau, GSK3ß/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice.

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3ß involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone (TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB (0.01 mg/kg and 1 mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau (PHF-1) proteins and the regulation of GSK3ß/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3ß or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3ß/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

[Hematological changes induced by erythrocytapheresis]. / Cambios hematológicos inducidos por la eritroféresis.

BACKGROUND: Although automated cell separators (apheresis) have undergone a lot of technical refinements, the effect of the procedure on hematological indices of donors is rarely taken into account. The purpose of this study is to identify potential hematologic changes in donors undergoing erythrocytapheresis. METHODS: 30 apparently healthy adult donors were evaluated. Erythrocytapheresis procedure was performed using automated equipment. Hematologic measurements (hemoglobin, hematocrit, white blood cells counts and platelets) were analyzed before and after erythrocytapheresis in all donors. RESULTS: We observed a significant decrease in the donors in hemoglobin (p <0.0001), hematocrit (p <0.0001), leukocytes (p <0.0001), lymphocytes (p = 0.0267), and platelets (p <0.0001). On the other hand, we found no changes in segmented, monocytes, eosinophils and basophils post erythrocytapheresis. CONCLUSION: In this study we found a significant drop in complete blood count in blood donation procedure by erythrocytapheresis; there are hematological changes in both red and white cells in all donors; however, none of donors manifested symptoms of thrombocytopenia or anemia. This study demonstrates hematological changes post-donation and therefore requires larger multicenter studies, in order to establish guidelines for donors' safety in apheresis and also help in assessing donor suitability, especially given the present trend of double product apheresis collections.

Introducción: El efecto del procedimiento en los índices hematológicos del donador rara vez se determina al finalizar una sesión de donación. El propósito de este estudio es identificar las posibles alteraciones hematológicas en los donadores sometidos a eritroféresis. Métodos: Se evaluaron 30 donadores adultos, aparentemente sanos. El procedimiento de eritroféresis se realizó utilizando un equipo automatizado. Las mediciones hematológicas (hemoglobina, hematocrito, células blancas y plaquetas) se realizaron antes y después de la eritroféresis. Resultados: Existe disminución significativa en hemoglobina (p < 0.0001), hematocrito (p < 0.0001), leucocitos totales (p < 0.0001), linfocitos (p = 0.0267), y plaquetas (p < 0.0001) tras el procedimiento de donación. Por otro lado, los segmentados tienen un ligero aumento. No se encontraron cambios en monocitos, eosinófilos ni en basófilos poseritroféresis. Conclusiones: durante el procedimiento de donación sanguínea mediante eritroféresis se producen cambios hematológicos tanto en la formula roja como blanca en los donadores estudiados, a pesar de ello, ninguno de los donadores manifestaron signos de trombocitopenia o anemia. Este trabajo demuestra que existen cambios hematológicos postdonación y por ello se requiere de estudios amplios y multicéntricos, con el fin de establecer directrices para establecer un procedimiento seguro para el donador y mejorar la evaluación de idoneidad de los donadores.

Maternal obesity increases oxidative stress in the newborn.

OBJECTIVE: Obesity before pregnancy is associated with a greater risk for the offspring to develop obesity and diabetes in childhood and adulthood. The aim of the present study was to determine the association between maternal overweight or obesity before pregnancy and newborn oxidative stress (OS). METHODS: Seventy-two mother-child pairs were divided according to the pre-gestational body mass index (BMI) of the mothers as follows: eutrophic (n = 21), overweight (n = 32), and obese (n = 19). Malondialdehyde (MDA) and nitric oxide (NO) were measured in the plasma of a blood sample from the newborn's umbilical cord. RESULTS: The MDA levels of newborns increased with maternal BMI (P = 0.001), as did the levels of NO (P = 0.019). There was a direct correlation between MDA and NO levels in each of the three groups (eutrophic: R(2) = 0.59, P < 0.001; overweight: R(2) = 0.45, P < 0.001; and obese: R(2) = 0.26, P = 0.024). CONCLUSIONS: Maternal overweight and obesity before pregnancy are associated with increased OS in the offspring.

Metabolic syndrome in children with chronic kidney disease: PON1 and treatment modality.

BACKGROUND AND AIMS: We undertook this study to evaluate the relationship between PON1, SOD and metabolic syndrome (MetS) in pediatric patients undergoing peritoneal dialysis, hemodialysis and patients in early stages of CKD. METHODS: We carried out an analytical cross-sectional study of 134 children 6-17 years old. We registered anthropometric variables, vital signs, basic biochemical parameters, intact PTH (iPTH), high sensitivity CRP (hs-CRP), paraoxonase-1; SOD; PON1/HDL-cholesterol and homocysteine. For statistical analyses we used t test, Mann Whitney U test, χ(2), Fisher exact test, linear or logistic regression models, using SPSS v.16.0. p values <0.05 were considered as significant. RESULTS: There were 66 (49.3%) females; 39 (29.1%) had CKD stages 2-4 (predialysis), 42 (31.3%) on hemodialysis (HD) and 53 (39.6%) on automated peritoneal dialysis (PD). Time from diagnosis was 26 months. Significant differences were observed in mean, systolic and diastolic blood pressure, C-peptide, triglycerides, and HDL-cholesterol as well as PON1/HDL-cholesterol ratio and SOD. CONCLUSIONS: This study demonstrates that PON1 and SOD may be predictors for the presence of MetS in pediatric patients under treatment with peritoneal dialysis. The positive correlation observed in PON1/HDL-cholesterol ratio may reflect the protector effect of HDL-cholesterol in patients with CKD according with the modality of treatment.