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This study aimed to report the effects of chronic exposure of zebrafish exposed to environmentally relevant concentrations of 0.5, 2.4, and 5.0 mg L -1 iron (Fe) and 0.2, 0.4, and 2.0 mg L -1 aluminum (Al). We also evaluated the reversal and generational transposition (F1) of possible histopathological, behavioral, and genotoxic changes in the species. Locomotion changes that may have been caused by the increase in the number of apoptotic cells and in the telencephalic mitochondrial activity were observed especially after the 30 days exposure to Al and persisted after recovery (30 days). We also observed histopathological changes, such as an increase in the number of intestinal goblet cells, even after the recovery period in these animals. Our results also showed that the Fe concentrations used were insufficient to cause genotoxicity, behavioral and intestinal epithelium changes. The adult offspring (F1) of animals exposed to Al showed changes in locomotion and in the amount of goblet cells, demonstrating that even in low concentrations this pollutant can harm subsequent generations in the aquatic biota. Animals demonstrate, in general, greater tolerance to Fe which may be related to the physiological demand of this metal by the body. Even so, all concentrations of both metals that caused some change in the species represent Brazilian environmental occurrences or Brazilian legislation. It highlights the need for updating the guidelines and constant monitoring of aquatic environments, since even in the face of a hypothetical decontamination of the environment, some changes could persist and affect different trophic levels., (© 2024 Wiley Periodicals LLC.)

Background: The etiology of preeclampsia (PE) may be associated with the increased of production of reactive species and decreased antioxidant activity of enzymes. Inadequate intake of Zn can affect gestational health due to its biological functions, such as its role in the antioxidant defense system. The study aimed to assess the nutritional status of Zn and antioxidant enzymes in postpartum women and its correlation with neonatal outcomes., Methods: A cross-sectional analytical study was carried out at a referral gynecology and obstetrics hospital. A total of 119 women (PE = 58, HP = 61) participated in the study. A quantitative food-frequency questionnaire was used to assess food consumption and further analyze the dietary Zn levels. Zinc levels in plasma and erythrocytes samples were analyzed by flame atomic absorption spectrometry, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were determined by UV-Vis spectrophotometry., Results: Plasma and dietary intake Zn results were considered adequate and without statistical difference between groups. SOD levels were significantly higher in the HP group (p = 0.011), and CAT levels were higher in the PE group (p = 0.050). There was a positive correlation between SOD activity in women with PE and the weight of their newborns (r = 0.336, p=0.021)., Conclusion: The results showed adequate Zn levels (consumption and serum levels) in the groups studied, although with a reduction of plasma Zn in the PE group compared to the PH group. Zinc in plasma fractions and erythrocytes are important markers for oxidative stress, in particular, plasma Zn seems to be related to the rapid response to preeclampsia. The activity of antioxidant enzymes was elevated in the groups studied. Better SOD activity improves birth weight in children of pregnant women with preeclampsia., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carla Soraya Costa Maia reports financial support was provided by Coordination of Higher Education Personnel Improvement. Thaynan C. Dias reports financial support was provided by National Council for Scientific and Technological Development. Daniela V. Azevedo reports financial support was provided by Foundation for Scientific and Technological Development and Support of Ceará. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Parkinson's disease (PD) can affect hand function since the beginning of the motor symptoms., Objective: To compare the ability of different hand function tests to: 1) distinguish individuals with PD from healthy controls; 2) differentiate stages of the disease; and 3) indicate changes over time due to disease progression., Methods: Twenty-four individuals with PD (Hoehn and Yahr: I-III) and 24 age- and sex-matched controls performed the Jebsen-Taylor Hand Function Test (JTHFT), the Nine-Hole Peg Test (9HPT), and the maximum grip and the maximum pinch strength tests using their right and left hands. Eight individuals with PD (six females and two males) were reassessed after 18 months. The ROC analyses and Mann-Whitney U tests (for disease progression) using the average performance of the hands were done., Results: Individuals with PD presented worse test performances than controls, except for the writing subtest of the JTHFT and the grip strength test. The JTHFT without the writing subtest (JTHFT noW ) was the most accurate to discriminate PD from controls (AUC = 0.899; sensitivity 75% and specificity 95.8%). The 9HPT and the simulated feeding and moving large, light objects JTHFT subtests were sensitive to distinguish stages, while the 9HPT, the moving small, common objects JTHFT subtest, and the grip strength were sensitive to changes with disease progression., Conclusion: The JTHFT noW was highly discriminative of the hand function impairments in PD. TwoJTHFT subtests were the most sensitives to distinguish PD stages (i.e. simulated feeding JTHFT subtest) and disease progression (i.e. moving small, common objects JTHFT subtest).

High ethanol (EtOH) consumption is a serious condition that induces tremors, alcoholic psychosis, and delirium, being considered a public health problem worldwide. Prolonged EtOH exposure promotes neurodegeneration, affecting several neurotransmitter systems and transduction signaling pathways. Glutamate is the major excitatory amino acid in the central nervous system (CNS) and the extracellular glutamatergic tonus is controlled by glutamate transporters mostly located in astrocytes. Here, we explore the effects of prolonged EtOH exposure on the glutamatergic uptake system and its relationship with astroglial markers (GFAP and S100B), neuroinflammation (IL-1β and TNF-α), and brain derived neurotrophic factor (BDNF) levels in the CNS of adult zebrafish. Animals were exposed to 0.5% EtOH for 7, 14, and 28 days continuously. Glutamate uptake was significantly decreased after 7 and 14 days of EtOH exposure, returning to baseline levels after 28 days of exposure. No alterations were observed in crucial enzymatic activities linked to glutamate uptake, like Na,K-ATPase or glutamine synthetase. Prolonged EtOH exposure increased GFAP, S100B, and TNF-α levels after 14 days. Additionally, increased BDNF mRNA levels were observed after 14 and 28 days of EtOH exposure, while BDNF protein levels increased only after 28 days. Collectively, our data show markedly brain astroglial, neuroinflammatory and neurotrofic responses after an initial impairment of glutamate uptake following prolonged EtOH exposure. This neuroplasticity event could play a key role in the modulatory effect of EtOH on glutamate uptake after 28 days of continuous exposure., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Study Objectives: Obstructive sleep apnea and short sleep duration have been separately associated with inadequate serum 25-hydroxyvitamin D [25(OH)D] levels. However, whether these 2 factors may concurrently influence 25(OH)D in the general population is unknown. We hypothesized that both obstructive sleep apnea and short sleep duration would be independently associated with lower concentrations of 25(OH)D in a sex-dependent manner., Methods: In this cross-sectional study, 712 individuals, part of the prospective EPISONO cohort (Brazil), underwent polysomnography, answered sleep questionnaires, and had their blood collected for serum 25(OH)D quantification., Results: Individuals with a sleep duration of < 6 hours had 2-fold increased odds of 25(OH)D < 20 ng/mL compared with those who reported 6 or more hours of sleep, even after adjusting for confounding factors. Subset sex analysis revealed that men with a sleep duration of < 6 hours had 4-fold increased odds of 25(OH)D < 20 ng/mL. In women, short sleep duration was not associated with lower 25(OH)D levels. The presence of obstructive sleep apnea (as classified according to the individual's apnea-hypopnea index) was not independently related to 25(OH)D concentrations in men or women. Sleep parameters, including sleep latency and sleep efficiency, had no association with 25(OH)D < 20 ng/mL., Conclusions: Short sleep, but not apnea-hypopnea index, was an independent factor associated with low 25(OH)D serum levels in men, but not in women. Apnea-hypopnea index scores were not associated with 25(OH)D levels in either sex. These results raise the possibility of investigating sex-specific characteristics, such as gonadal hormone regulation, and re-evaluating obstructive events by classifying them in mild, moderate, and severe obstructive sleep apnea., Citation: de Oliveira DL, Dokkedal-Silva V, Fernandes GL, Kim LJ, Tufik S, Andersen ML. Sleep duration as an independent factor associated with vitamin D levels in the EPISONO cohort. J Clin Sleep Med . 2021;17(12):2439-2449., (© 2021 American Academy of Sleep Medicine.)

Mitochondria play key roles in brain metabolism. Not surprisingly, mitochondria dysfunction is a ubiquitous cause of neurodegenerative diseases. In turn, acquired forms of epilepsy etiology is specifically intriguing since mitochondria function and dysfunction remain not completely enlightened. Investigation in the field includes models of epileptic disorder using mainly rodents followed by mitochondrial function evaluation, which in general evidenced controversial data. So, we considered the efforts and limitations in this research field and we took into account that sample preparation and quality are critical for bioenergetics investigation. For these reasons the aim of the present study was to develop a thorough protocol for adult zebrafish brain-tissue dissociation to evaluate oxygen consumption flux and reach the bioenergetics profile in health and models of epileptic disorder in both, in vitro using pentylenetetrazole (PTZ) and N-methyl-D-Aspartic acid (NMDA), and in vivo after kainic acid (KA)-induced status epilepticus. In conclusion, we verify that fire-polished glass Pasteur pipette is eligible to brain-tissue dissociation and to study mitochondrial function and dysfunction in adult zebrafish. The results give evidence for large effect size in increase of coupling efficiency respiration (p/O 2 ) correlated to treatment with PTZ and spare respiratory capacity (SRC) in KA-induced model indicating oxidative phosphorylation (OXPHOS) variable alterations. Further investigation is needed in order to clarify the bioenergetics role as well as other mitochondrial functions in epilepsy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: This photoelastic analysis evaluated stress distribution in different osteosynthesis systems, conventional and locking, used for treatment of mandibular angle fractures with a single plate., Material and Methods: Angle fractures were simulated in mandibles made of photoelastic resin. Following Champy's method, plate osteosynthesis was performed. The samples were divided into five groups: Group 1, non-fractured mandible; Group 2, two screws were installed in each segment using a conventional system; Group 3, two screws were installed in each segment using a locking system; Group 4, three screws were installed in the proximal segment and four screws in the distal segment using a conventional plate; Group 5, three screws were installed in the proximal segment and four screws in the distal segment using a locking plate. In an universal testing machine coupled to a polariscope, a load was applied to the first molar 10 times. The 50 images were randomly numbered and analyzed qualitatively and quantitatively by two raters., Results: The locking system promoted better stress distribution along the osteosynthesis. The locking system reduced stress magnitude in the distal segment, with a significant between-group difference ( P ≤ 0.001)., Conclusions: The locking plate/screw system can distribute stress more evenly throughout the osteosynthesis, especially when long seven-hole plates are used. Key words: Internal fracture fixation, osteosynthesis, mandibular fracture, bone plates., Competing Interests: Conflicts of interest The authors have no conflicts of interest to disclose., (Copyright: © 2021 Medicina Oral S.L.)

Neuroinflammation has been associated to neurodegenerative disease development, with evidence suggesting that high levels of proinflammatory cytokines promote neuronal dysfunction and death. Therefore, it is necessary to study new compounds that may be used as adjuvant treatments of neurodegenerative diseases by attenuating the inflammatory response in the central nervous system (CNS). The aim of this study was to utilize the lipopolysaccharide (LPS) induction model of neuroinflammation to evaluate the modulation of inflammation by rosmarinic acid (RA) isolated from Blechnum brasiliense in adult zebrafish. First, we investigated the toxicity and antioxidant properties of fractionated B. brasiliense extract (ethyl acetate fraction- EAF) and the isolated RA in zebrafish embryos. Next, we developed a model of neuroinflammation induction by intraperitoneal (i.p.) injection of LPS to observe the RA modulation of proinflammatory cytokines. The median lethal concentration (LC 50 ) calculated was 185.2 ± 1.24 μg/mL for the ethyl acetate fraction (EAF) and 296.0 ± 1.27 μM for RA. The EAF showed free radical inhibition ranging from 23.09% to 63.44% at concentrations of 10-250 μg/mL. The RA presented a concentration-dependent response ranging from 18.24% to 47.63% at 10-250 μM. Furthermore, the RA reduced LPS induction of TNF-α and IL-1β levels, with the greatest effect observed 6 h after LPS administration. Thus, the data suggested an anti-inflammatory effect of RA isolated from B. brasiliense and reinforced the utility of the new model of neuroinflammation to test the possible neuroprotective effects of novel drugs or compounds., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Several studies have used zebrafish to investigate the effects of environmental enrichment on behavior and physiology. However, to date there are no studies evaluating the behavioral responses, such as habituation and exploration, of enriched-housed zebrafish when they are submitted to novelty paradigms. The present work was, therefore, designed to evaluate the habituation and exploratory responses of zebrafish exposed to enriched- (EE) and non-enriched (NE) environments when they face novelty. Adult wild-type zebrafish were used. Three different enriched contexts were designed. In Context 1, zebrafish was exposed to enrichment during 7 days, which reduced their total distance traveled in novel tank and social preference tests in comparison to the non-enriched animals. In Context 2, animals were exposed to same enrichment during 14 days. EE exposure did not alter the behavioral responses of zebrafish compared to NE. In Context 3, fish were exposed to enrichment during 14 days, with changing the enriching elements at day 8. Similarly to Context 1, total distance traveled was reduced by EE exposure when compared to NE. Our results suggest a modulatory effect of EE on adult zebrafish locomotion that may be dependent on the time of exposure and on the physical structure of the enriched environment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of the present study was to evaluate the effect of cryopreservation on the morphology of zebrafish sperm (Danio rerio). Sperm from 30 males were collected and divided in two treatments: fresh and cryopreserved semen. The following were measured sperm morphology, motility and membrane integrity. Cryopreservation reduced motility, the number of normal cells and the membrane integrity, as well as increased the percentage of sperm abnormalities. The most frequent types of morphological changes found in cryopreserved semen were macrocephaly, loose head, degenerated head, proximal gout, curled tail and short tail. This study opens the way for further investigations on morphological changes and for a new classification of these changes in fish semen due to cryopreservation., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/aim: Anti-allergic drugs can inhibit the hard tissue resorption process, and due to similarities between root resorption and bone mechanisms, it can be inferred that these drugs may also control root resorption. The aim of this study was to analyze the effects of anti-allergic drugs used systemically on the process of root resorption following delayed tooth replantation., Materials and Methods: Thirty-two maxillary right incisors of rats were extracted and subsequently replanted. Rats were divided into four groups according to the anti-allergic drug administered: the rats in groups DEX, Q, and MO were treated systemically with dexamethasone phosphate, quercetin, and montelukast, respectively, and no systemic medication was administered to rats in group C. After 60 days, the animals were euthanized, and the specimens were processed for histomorphometric and immunohistochemical analyses. Statistical significance was set at P < .05., Results: There were no significant differences between the groups in terms of inflammatory resorption, replacement resorption, or presence of tartrate-resistant acid phosphatase. In terms of events occurring in the periodontal ligament space, there was a difference between groups Q and MO due to the presence of dental ankylosis and inflammatory connective tissue (P < .05). A difference in inflammatory cells was also observed through CD45 immunolabeling between the DEX and Q groups when compared to the C group (P < .05)., Conclusion: The systemic administration of anti-allergic drugs did not have an effect on the process of root resorption following delayed tooth replantation., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Proanthocyanidins are phenolic compounds abundant in the diet, commonly found in grapes and derivatives, foods known for their health-promoting benefits. There is previous evidence showing the antidiabetic activity of proanthocyanidins, however, their mechanisms of action have not been fully elucidated. This study evaluated the capacity of grape seed proanthocyanidins extract (GSPE) to modulate oxidative stress, nitric oxide levels, mitochondrial dysfunction, apoptosis, and sirtuin expression in endothelial cells EA.hy926 under high glucose condition. In addition, the possible toxic effects of GSPE was evaluated in a zebrafish embryos model. The results showed that GSPE was able to enhance cell viability and avoid the disturbance in redox metabolism induced by high glucose. Moreover, GSPE was able to avoid mitochondria dysfunction and the increased in p53 and poly-(ADP-ribose) polymerase expression induced by high glucose exposition. These effects were attributed to the increase in expression of sirtuin 3, a protein able to regulate mitochondrial function. GSPE in an effective concentration did not show toxic effects in zebrafish embryos model. Taken together, these data elucidate the key molecular target of GSPE for future pharmacological interventions in diabetic patients.

Fetal alcohol spectrum disorders (FASD) describe a wide range of ethanol-induced developmental disabilities, including craniofacial dysmorphology, and neurochemical and behavioral impairments. Zebrafish has become a popular animal model to evaluate the long-lasting effects of, both, severe and milder forms of FASD, including alterations to neurotransmission. Glutamate is one of the most affected neurotransmitter systems in ethanol-induced developmental disabilities. Therefore, the aim of the present study was to evaluate the functionality of the glutamatergic neurotransmitter system in an adult zebrafish FASD model. Zebrafish larvae (24 h post-fertilization) were exposed to ethanol (0.1 %, 0.25 %, 0.5 %, and 1%) for 2 h. After 4 months, the animals were euthanized and their brains were removed. The following variables were measured: glutamate uptake, glutamate binding, glutamine synthetase activity, Na+/K + ATPase activity, and high-resolution respirometry. Embryonic ethanol exposure reduced Na+-dependent glutamate uptake in the zebrafish brain. This reduction was positively modulated by ceftriaxone treatment, a beta-lactam antibiotic that promotes the expression of the glutamate transporter EAAT2. Moreover, the 0.5 % and 1% ethanol groups demonstrated reduced glutamate binding to brain membranes and decreased Na+/K + ATPase activity in adulthood. In addition, ethanol reduced glutamine synthetase activity in the 1% EtOH group. Embryonic ethanol exposure did not alter the immunocontent of the glutamate vesicular transporter VGLUT2 and the mitochondrial energetic metabolism of the brain in adulthood. Our results suggest that embryonic ethanol exposure may cause significant alterations in glutamatergic neurotransmission in the adult zebrafish brain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Manganese is a metal often found as an environmental pollutant and very associated with neurological disorders when in high concentrations. However, little is known about the effects that this contaminant can cause when in environmentally relevant concentrations and occurrence, that is, much lower than those commonly studied. So, the aim of the study was to evaluate the effects that environmentally relevant concentrations of this metal would cause in different zebrafish organs (brain, liver, and blood). Acute 96-h and chronic 30-day exposures were performed using the manganese chloride salt as a pollutant. Behavioral alterations of anxiogenic type were observed in the animals after chronic exposures to 4.0 mg L -1 MnCl 2 , which traveled a greater distance at the bottom of the aquarium. This may be associated with neuronal damages in the telencephalic region responsible for motor and cognitive activity of the fish, observed in animals from the same exposure. In addition, hepatic histopathological damage as vacuolization of hepatocytes and genotoxic damage, identified by comet assay and micronucleus test, was also observed after acute and chronic exposure, especially at the highest pollutant concentrations (8.0 and 16.0 mg L -1 in acute exposure, and 4.0 mg L -1 in chronic exposure. The study reinforces the risk that environmental pollutants pose to the ecosystem, even in low concentrations., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Cancer is a multifactorial disease, representing one of the leading causes of death worldwide. On a global estimate, breast cancer is the most frequently occurring cancer in women and cervical cancer, the fourth most common. Both types of cancer remain the major cause of cancer-related mortality in developing countries. A strategy for rational drug design is hybridization, which aims to bring together in one molecule, two or more pharmacophores in order to reach several biological targets., Objective: The objective of this work was to develop new hybrids based on natural pharmacophores: Betulinic acid (1) and brosimine b (2), active in female cancer cell lines., Methods: The coupling reactions were carried out by Steglich esterification. Different compounds were designed for the complete and simplified structural hybridization of molecules. The anticancer activities of the compounds were evaluated in human cervical adenocarcinoma (HeLa), human cervical metastatic epidermoid carcinoma (ME-180), and human breast adenocarcinoma (MCF-7) cell lines., Results: Hybrid 3 presented higher potency (IC50 = 9.2 ± 0.5μM) and SI (43.5) selectively in MCF-7 cells (in relation to Vero cells) with its cytotoxic effect occurring via apoptosis. In addition, compound 6 showed activity in MCF-7 and HeLa cells with intermediate potency, but with high efficacy, acting via apoptosis as well., Conclusion: In this context, we showed that the combination of two complex structures generated the development of hybrids with differing inhibitory profiles and apoptotic modes of action, thus representing potential alternatives in female cancer treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Stress-related psychiatric disorders are mental conditions that affect mood, cognition and behavior and arise because of the impact of prolonged stress on the central nervous system (CNS). Acetyl-L-carnitine (ALC) is an acetyl ester of L-carnitine that easily crosses the blood-brain barrier and was recently found to be decreased in patients with major depressive disorder. ALC plays a role in energy metabolism and is widely consumed as a nutritional supplement to improve physical performance. In this study, our objective was to evaluate the effects of ALC treatment (0.1 mg/L, 10 min) for 7 days on behavior and oxidative stress in zebrafish subjected to unpredictable chronic stress (UCS) protocol. Behavioral outcomes were assessed in the novel tank test, and parameters of oxidative status (lipid peroxidation and antioxidant defenses) were evaluated in the brain using colorimetric methods. According to our previous findings, UCS increased anxiety-like behavior and lipid peroxidation, while it decreased non-protein thiol levels and superoxide dismutase activity. However, ALC reversed the anxiety-like behavior and oxidative damage in stressed animals, while it was devoid of effect in control animals. Although our data reinforce the neuroprotective potential of ALC in the treatment of psychiatric disorders related to stress, further investigations are required to clarify its mechanisms of action and confirm its efficacy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Fetal Alcohol Spectrum Disorders (FASD) is a syndrome characterized by neurological and behavioral impairments. A recently discovered hallmark of FASD is impaired social behavior. Avoidance of social interaction typical of FASD may be the result of increased anxiety. Previously, the zebrafish was successfully used to model embryonic alcohol induced social abnormalities. Here, we analyzed both anxiety and social responses using a zebrafish FASD model, in adult fish. We exposed zebrafish embryos to low concentrations of ethanol (0.1%; 0.25%; 0.5% and 1% v/v) for 2h at, 24h post-fertilization, to mimic the most prevalent milder FASD cases, and investigated the ensuing alterations in adult, 4-month-old, zebrafish. We studied social interaction in the social preference task and anxiety in the novel tank task. We observed an ethanol dose dependent reduction of time spend in the conspecific zone compared to control, corroborating prior findings. We also found significant changes in the novel tank (e.g. increased bottom dwell time, increased distance to top) suggesting elevated anxiety to control, but we also found, using an anxiolytic drug buspirone, that reduction of anxiety is associated with reduced shoaling. Our results confirm that embryonic alcohol exposure disrupts social behavior, and also show that its effects on anxiety related phenotypes may be genotype, alcohol administration method, experimental procedure and test-context dependent., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The development of new antiepileptic drugs is a high-risk/high-cost research field, which is made even riskier if the behavioral epileptic seizure profile is the unique approach on which the development is based. In order to increase the effectiveness of the screening conducted in the zebrafish model of status epilepticus (SE), the evaluation of neurochemical markers of SE would be of great relevance. Epilepsy is associated with changes in the glutamatergic system, and glutamate uptake is one of the critical parameters of this process. Therefore, we evaluated the levels of glutamate uptake in the zebrafish brain and analyzed its correlation with the progression of behavioral changes in zebrafish at different times after the administration of kainic acid (5 mg/kg). The results showed that the zebrafish suffered with lethargy while swimming for up to 72 h after SE, had reduced levels of GFAP cells 12 h after SE, reduced levels of S100B up to 72 h after SE, and reduced levels of glutamate uptake in the forebrain between 3 h and 12 h after SE. The forebrain region of adult zebrafish after SE present similar changes to the neurochemical limbic alterations that are seen in rodent models of SE. This study demonstrated that there is a time window in which to use the KA zebrafish model of SE to explore some of the known neurochemical alterations that have been observed in rodent models of epilepsy and epileptic human patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Several works have demonstrated that status epilepticus (SE) induced-neurodegeneration appears to involve an overactivation of N-methyl-d-aspartate receptors and treatment with high-affinity NMDAR antagonists is neuroprotective against this brain damage. However, these compounds display undesirable side effects for patients since they block physiological NMDA receptor dependent-activity. In this context, memantine (MN), a well tolerable low-affinity NMDAR channel blocker, will be a promising alternative, since it does not compromise the physiological role of NMDA receptors on synaptic transmission. The aim of the present study was to investigate if MN could attenuate seizure severity and neuronal cell death caused by SE induced early in life. Wistar rats (15 days old; n = 6-8 per group) received memantine (20 mg/kg i.p.) in six different treatments: 6 and 3 h before SE onset; concomitant with pilocarpine; 15min and 1h after SE onset; and four consecutive administrations (15 min, 6 h, 12 h, and 18 h) after pilocarpine injection. Neurodegeneration was quantified by fluoro-jade C staining. Treatment with memantine increase latency to SE onset only in groups treated 3 h before or concomitant with pilocarpine. In CA1 hippocampal subfield, memantine significantly reduced neurodegeneration at the following times: 3 h prior SE-onset, concomitant with pilocarpine, and 15 min after pilocarpine injection. For amygdala and thalamus, all post-SE onset treatments were able to decrease neurodegeneration. In conclusion, the present study showed that MN was neuroprotective against SE-induced neuronal death and this neuroprotection appears to be time- and region-dependent., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Most AED target neuronal activity modulated by ionic channels, and the steroid sensitivity of these channels has supported the use of corticosteroids as adjunctives to AED. Assuming the importance of astrocytes in neuronal activity, we investigated inflammatory and astroglial markers in the hippocampus, a key structure affected in TLE and in the Li-pilocarpine model of epilepsy., Methods: Initially, hippocampal slices were obtained from sham rats and rats subjected to the Li-pilocarpine model of epilepsy, at 1, 14, and 56 days after status epilepticus (SE), which correspond to the acute, silent, and chronic phases. Dexamethasone was added to the incubation medium to evaluate the secretion of S100B, an astrocyte-derived protein widely used as a marker of brain injury. In the second set of experiments, we evaluated the in vivo effect of dexamethasone, administrated at 2 days after SE, on hippocampal inflammatory (COX-1/2, PGE2, and cytokines) and astroglial parameters: GFAP, S100B, glutamine synthetase (GS) and water (AQP-4), and K + (Kir 4.1) channels., Results: Basal S100B secretion and S100B secretion in high-K + medium did not differ at 1, 14, and 56 days for the hippocampal slices from epileptic rats, in contrast to sham animal slices, where high-K + medium decreased S100B secretion. Dexamethasone addition to the incubation medium per se induced a decrease in S100B secretion in sham and epileptic rats (1 and 56 days after SE induction). Following in vivo dexamethasone administration, inflammatory improvements were observed, astrogliosis was prevented (based on GFAP and S100B content), and astroglial dysfunction was partially abrogated (based on Kir 4.1 protein and GSH content). The GS decrease was not prevented by dexamethasone, and AQP-4 was not altered in this epileptic model., Conclusions: Changes in astroglial parameters emphasize the importance of these cells for understanding alterations and mechanisms of epileptic disorders in this model. In vivo dexamethasone administration prevented most of the parameters analyzed, reinforcing the importance of anti-inflammatory steroid therapy in the Li-pilocarpine model and possibly in other epileptic conditions in which neuroinflammation is present.

Several studies have shown that manipulations to the housing environment modulate susceptibility to stress in laboratory animals, mainly in rodents. Environmental enrichment (EE) is one such manipulation that promotes neuroprotection and neurogenesis, besides affecting behaviors such as drug self-administration. Zebrafish are a popular and useful animal model for behavioral neuroscience studies; however, studies evaluating the impact of housing conditions in this species are scarce. In this study, we verified the effects of EE on behavioral (novel tank test) and biochemical [cortisol and reactive oxygen species (ROS)] parameters in zebrafish submitted to unpredictable chronic stress (UCS). Consistent with our previous findings, UCS increased anxiety-like behavior, cortisol and ROS levels in zebrafish. EE for 21 or 28 days attenuated the effects induced by UCS on behavior and cortisol, and prevented the effects on ROS levels. Our findings reinforce the idea that EE exerts neuromodulatory effects across species, reducing vulnerability to stress and its biochemical impact. Also, these results indicate that zebrafish is a suitable model animal to study the behavioral effects and neurobiological mechanisms related to EE., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Valproic acid (VPA) is an antiepileptic drug (AED) that has the broadest spectrum across all types of seizures and epileptic syndromes. Unfortunately, approximately 30% of epileptic patients are refractory to the classical AED. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and research. In this preliminary study, we assess the embryo toxicity and the anticonvulsant activity of 4 novel metallodrugs, with Zn +2 and Cu +2 , a derivative of valproic acid and the N-donor ligand in an adult zebrafish epileptic seizure model induced by pentylenetetrazole. The most toxic complex was [Cu(Valp) 2 Bipy], in which the LC 50 was 0.22 μM at 48 h post fertilization (HPF) and 0.12 μM at 96 HPF, followed by [Zn(Valp) 2 Bipy] (LC 50  = 10 μM). These same metallodrugs ([Cu(Valp) 2 Bipy] 10 mM/kg and [Zn(Valp) 2 Bipy] 30 mM and 100 mM/kg) displayed superior activity, thus reducing the seizure intensity by approximately 20 times compared to sodium valproate (175 mM/kg). Overall, [Cu(Valp) 2 Bipy] showed the best anticonvulsant effects. However, because of the toxicity of copper, [Zn(Valp) 2 Bipy] is considered the most promising anticonvulsant for future studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Epilepsy prevalence is high in infancy and in the elderly population. Lithium-pilocarpine is widely used to induce experimental animal models of epilepsy, leading to similar neurochemical and morphological alterations to those observed in temporal lobe epilepsy. As astrocytes have been implicated in epileptic disorders, we hypothesized that specific astroglial changes accompany and contribute to epileptogenesis. Herein, we evaluated time-dependent astroglial alterations in the hippocampus of young (27-day-old) rats at 1, 14 and 56 days after Li-pilocarpine-induced status epilepticus (SE), corresponding to different phases in this model of epilepsy. We determined specific markers of astroglial activation: GFAP, S100B, glutamine synthetase (GS), glutathione (GSH) content, aquaporin-4 (AQP-4) and potassium channel Kir 4.1; as well as epileptic behavioral, inflammatory and neurodegenerative changes. Phase-dependent signs of hippocampal astrogliosis were observed, as demonstrated by increments in GFAP, S100B and GS. Astrocyte dysfunction in the hippocampus was characterized, based on the decrease in GSH content, AQP-4 and Kir 4.1 channels. Degenerating neurons were identified by Fluoro-Jade C staining. We found a clear, early (at SE1) and persistent (at SE56) increase in cerebrospinal fluid (CSF) S100B levels. Additionally, serum S100B was found to decrease soon after SE induction, implicating a rapid-onset increase in the CSF/serum S100B ratio. However, serum S100B increased at SE14, possibly reflecting astroglial activation and/or long-term increase in cerebrovascular permeability. Moreover, we suggest that peripheral S100B levels may represent a useful marker for SE in young rats and for follow up during the chronic phases of this model of epilepsy. Together, results reinforce and extend the idea of astroglial involvement in epileptic disorders.

Palicourea genus is chemically and taxonomically close to Psychotria genus, a well-known source of neuroactive alkaloids. It has been previously reported the pharmacological potential of these alkaloids in some targets related to the neurodegenerative process. In this context, this study was carried out in order to evaluate the toxic effects and acetylcholinesterase (AChE) inhibitory potential of Palicourea deflexa fraction of total alkaloids (FTA). P. deflexa FTA was analyzed by means of HPLC-DAD and HRMS-ESI. We performed toxicological screening through Fish Embryo Toxicity (FET) test using zebrafish embryo and abnormal developmental phenotypes were recorded daily. For AChE inhibition, zebrafish brains were used as enzymatic source and formation of thiolate dianion of 5,5'-Dithiobis(2-nitrobenzoic acid) (DTNB) was used to monitor acetylthiocholine hydrolysis. Lineaweaver-Burk double reciprocal plots were used to indicate mode of inhibition. Chemical analysis of the P. deflexa FTA allowed the identification of the main compound as harman-3-carboxylic acid. This fraction was evaluated in vivo for its toxicological effect. The zebrafish embryo test indicated that the FTA has a lethal concentration of 50% (LC 50 )=72.18μg/mL. Further, the FTA was evaluated for its AChE inhibitory profile, demonstrating an inhibitory concentration of 50% (IC 50 ) of 50.65μg/mL. Lineaweaver-Burk double reciprocal plots indicated a mixed mode of inhibition. It is reported for the first time the toxicological and pharmacological profile of the alkaloid fraction of Palicourea deflexa in zebrafish models., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Sports' practitioners are vulnerable to dental trauma; if this occurs, the emergency treatment should be fast and efficient. This may be performed by any person at the site of the accident, not only by dental professionals. Physical educators may face dental trauma and should be able to provide proper care. This study had the objective evaluated the knowledge of physical education graduates on dental trauma., Materials and Methods: A questionnaire containing questions on dental trauma was applied to 199 physical education students; after collection of the questionnaires, data were tabulated and processed on the software Epi Info 2000 (Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333, USA). As a result, only 36.7% of participants would take the individual suffering trauma to the dental professional, 56.8% believe that the avulsed tooth should be replanted, and 42.2% would replant it. Only 7.5% would store the avulsed tooth in an ideal storage medium for transportation., Conclusion: It was concluded that there is a lack of knowledge on dental trauma among physical education graduates, evidencing the need of public policies to allow education on this issue., Competing Interests: There are no conflicts of interest.

Purpose: This study aimed to quantify, using cone-beam computed tomography (CBCT) in patients who underwent a mandibular advancement surgery associated with genioplasty, three-dimensional changes in airway space and to evaluate whether these changes differ between men and women., Materials and Methods: Preoperative and 8-month postoperative CBCT scans of 38 patients aged 18-45 years of either sex and any ethnicity who underwent mandibular advancement surgery associated with genioplasty were analyzed using the Xoran software (Xoran Technologies, Ann Arbor, MI, USA). The linear distances gonion-gnathion (Go-Gn) and condylion-menton (Co-Me) were obtained. Airway volume was measured using the Dolphin Imaging software, version 11.0. Then, data were tabulated and analyzed using Student's t -test., Results: Mean patient age was 30.3 years; 39.47% were men and 60.63% were women. The mean Go-Gn distance was 72.05 mm before surgery and 78.56 mm after surgery, with a mean gain of 6.51 mm. The mean Co-Me distance was 113.47 mm before surgery and 119.89 mm after surgery, with a mean increase of 6.42 mm. Both differences were statistically significant. The mean volume of airway space was 17,272.92 mm 3 before surgery and 24,173.74 mm 3 after surgery, with a statistically significant mean increase of 6900.82 mm 3 . There was no statistically significant difference in mean volumetric gain between men (7566.69 mm 3 ) and women (7456.69 mm 3 )., Conclusion: Mandibular advancement surgery results in significant increase of airway space, and there is no difference in airway volume between men and women., Competing Interests: There are no conflicts of interest.

The role of vitamin D in osteomineral metabolism is well known. Several studies have suggested its action on different biological mechanisms, such as nociceptive sensitivity and sleep-wake cycle modulation. Sleep is an important biological process regulated by different regions of the central nervous system, mainly the hypothalamus, in combination with several neurotransmitters. Pain, which can be classified as nociceptive, neuropathic and psychological, is regulated by both the central and peripheral nervous systems. In the peripheral nervous system, the immune system participates in the inflammatory process that contributes to hyperalgesia. Sleep deprivation is an important condition related to hyperalgesia, and recently it has also been associated with vitamin D. Poor sleep efficiency and sleep disorders have been shown to have an important role in hyperalgesia, and be associated with different vitamin D values. Vitamin D has been inversely correlated with painful manifestations, such as fibromyalgia and rheumatic diseases. Studies have demonstrated a possible action of vitamin D in the regulatory mechanisms of both sleep and pain. The supplementation of vitamin D associated with good sleep hygiene may have a therapeutic role, not only in sleep disorders but also in the prevention and treatment of chronic pain conditions., (© 2017 Society for Endocrinology.)

Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands. In addition to the growing number of studies reporting mGluR gene or protein expression in glioma samples (resections, lineages, and primary cultures), pharmacological blockade in vitro of mGluR1 and mGluR3 by selective ligands has been shown to be anti-proliferative and anti-migratory, decreasing activation of MAPK and PI3K pathways. In addition, mGluR3 antagonists promoted astroglial differentiation of GBM cells and also enabled cytotoxic action of temozolomide (TMZ). mGluR3-dependent TMZ toxicity was supported by increasing levels of MGMT transcripts through an intracellular signaling pathway that sequentially involves PI3K and NF-κB. Further, continuous pharmacological blockade of mGluR1 and mGluR3 have been shown to reduced growth of GBM tumor in two independent in vivo xenograft models. In parallel, low levels of mGluR3 mRNA in GBM resections may be a predictor for long survival rate of patients. Since several Phase I, II and III clinical trials are being performed using group I and II mGluR modulators, there is a strong scientifically-based rationale for testing mGluR antagonists as an adjuvant therapy for malignant brain tumors.

Objective: This work evaluated histologic and biochemically the effect of magnetic field buried in bone repair after autogenous bone graft and calcium phosphate cement implants., Methodology: Bone defects with 5,0 mm of diameter in the cranium of Wistar mice were used to analyse. These mice were submitted to different interventions: autogenous bone graft and calcium phosphate cement implants, both with and without magnetic stimulation. Longitudinal and transversal histometric and biochemistry analysis were made in times of 15, 30 and 60 post-operative days., Results: The histometric transversal analysis did not show significant differences in the bone repair between groups. Longitudinally, significant difference were found in the quantity of neoformed bone between the times 15 and 60 post-operative days in the autogenous bone graft group under magnetic stimulation. The alkaline phosphatase enzyme presented a higher activity in 30 post-operative days and the groups under magnetic stimulation presented reduced enzymatic activity in comparison to the other groups., Conclusion: The permanent and static magnetic field promoted significant differences in the neoformed bone in the groups autogenous bone graft., Competing Interests: There are no conflicts of interest.

Ethanol is a widely consumed substance throughout the world. During development it can substantially damage the human fetus, whereas the developing brain is particularly vulnerable. The brain damage induced by prenatal alcohol exposure may lead to a variety of long-lasting behavioral and neurochemical problems. However, there are no data concerning the effects of developmental ethanol exposure on the glutamatergic system, where extracellular glutamate acts as signaling molecule. Here we investigated the effect of ethanol exposure for 2h (concentrations of 0.0%, 0.1%, 0.25%, 0.50%, and 1.00%) in embryos at 24h post-fertilization (hpf) by measuring the functionality of glutamate transporters in the brain of adult (4 months) zebrafish. However, ethanol 0.1%, 0.25% and 0.50% decreased transport of glutamate to 81.96%, 60.65% and 45.91% respectively, when compared with the control group. Interestingly, 1.00% was able to inhibit the transport activity to 68.85%. In response to the embryonic alcohol exposure, we found impairment in the function of cerebral glutamate transport in adult fish, contributing to long-term alteration in the homeostasis glutamatergic signaling., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Acacia is an important forest species of rapid growth whose seeds have tegument dormancy. In this work it was intended to characterize water absorption pattern after seed dormancy break, and to determine the amount of water, container size and the need of breaking the tegument dormancy, as to perform electrical conductivity test in small and large seeds of Acacia mangium (Fabaceae). The seeds were collected from 10, 8 and 6 years old trees established in poor yielding-capacity soils on savannah areas of Roraima, Brazil; seeds were classified in six lots concerning to seed size and tree age. Germination tests (50 seeds and four replications per lot) were carried out on germitest® paper maintained on gerbox at 25 °C. Imbibition was verified by seed weighing at different times (0, 2, 5, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96 and 120 hours). The electrical conductivity test consisted of three experiments, distinguished by the amount of water used and by the container size in which seeds were immersed. Seeds of A. mangium coming from 10 years old trees presented increased germination percent and germination speed than seeds of six-year old trees. Small seeds presented increased in electrical conductivity and water absorption until 120 hours when compared to large seeds. The immersion of seeds of A. mangium in 40 mL of distilled water into 180 mL plastic containers, after dormancy break, it is indicated for the determination of electrical conductivity test. The ratio of electrolytes by seed mass, after 24 hours of immersion in water, turns electrical conductivity test more accurate concerning A. mangium seeds.

Objective:: Wake-up stroke (WUS) is defined when the exact time of the beginning of the symptoms cannot be determined, for the deficits are perceived upon awakening. Sleep alterations are important risk factors for stroke and cardiovascular diseases. This study evaluates the characteristics of patients with and without WUS, the presence of daytime sleepiness, and associated risk factors., Method:: Patients with ischemic stroke were investigated about the presence of WUS. Clinical and demographic characteristics were evaluated. Stroke severity was studied by the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Scale (MRS), and daytime sleepiness severity was studied by the Epworth Sleepiness Scale (ESS)., Results:: Seventy patients (57.1% men) aged from 32 to 80 years (58.5±13.3) were studied. WUS was observed in 24.3%. Arterial hypertension (67.1%), type 2 diabetes (27.1%), and hyperlipidemia (22.8%) were frequent. Type 2 diabetes and sedentary lifestyle were more common in patients with WUS (p<0.05). Overall, mild, moderate or very few symptoms of stroke (NIHSS<5) were predominant (62.3%). Among all cases, 20% had excessive daytime sleepiness (ESS>10). No differences were found between patients with and without WUS as regards stroke severity or excessive daytime sleepiness. Patients with excessive daytime sleepiness were younger and had more sedentary lifestyle (p<0.05). Individuals with previous history of heavy drinking had more daytime sleepiness (p=0.03)., Conclusion:: Wake-up stroke occurs in approximately 25% of stroke cases. In this study, patients with WUS had more diabetes and sedentary lifestyle. Daytime sleepiness is frequent and is associated with sedentary lifestyle and heavy drinking.

The understanding of the consequences of chronic treatment with methylphenidate is very important since this psychostimulant is extensively prescribed to preschool age children, and little is known about the mechanisms underlying the persistent changes in behavior and neuronal function related with the use of methylphenidate. In this study, we initially investigate the effect of early chronic treatment with methylphenidate on amino acids profile in cerebrospinal fluid and prefrontal cortex of juvenile rats, as well as on glutamatergic homeostasis, Na(+),K(+)-ATPase function, and balance redox in prefrontal cortex of rats. Wistar rats at early age received intraperitoneal injections of methylphenidate (2.0 mg/kg) or an equivalent volume of 0.9% saline solution (controls), once a day, from the 15th to the 45th day of age. Twenty-four hours after the last injection, the animals were decapitated and the cerebrospinal fluid and prefrontal cortex were obtained. Results showed that methylphenidate altered amino acid profile in cerebrospinal fluid, increasing the levels of glutamate. Glutamate uptake was decreased by methylphenidate administration, but GLAST and GLT-1 were not altered by this treatment. In addition, the astrocyte marker GFAP was not altered by MPH. The activity and immunocontent of catalytic subunits (α1, α2, and α3) of Na(+),K(+)-ATPase were decreased in prefrontal cortex of rats subjected to methylphenidate treatment, as well as changes in α1 and α2 gene expression of catalytic α subunits of Na(+),K(+)-ATPase were also observed. CAT activity was increased and SOD/CAT ratio and sulfhydryl content were decreased in rat prefrontal cortex. Taken together, our results suggest that chronic treatment with methylphenidate at early age induces excitotoxicity, at least in part, due to inhibition of glutamate uptake probably caused by disturbances in the Na(+),K(+)-ATPase function and/or in protein damage observed in the prefrontal cortex.

Currently, the black/white preference test has been used to evaluate anxiety-like behaviors in zebrafish. However, several inconsistent results have been reported across literature. Since animal behavior can be influenced by several environmental factors, the main goal of the present study was to investigate the influence of different water column depths and light intensities on zebrafish behavioral responses in the black/white test. On a 4cm water column depth, animals spent more time in the black than in the white compartment. However, when animals were tested in an 8cm water column, no significant difference was found. Using an inclined acrylic floor inside the aquarium, animals spent more time in the deep compartment when this was black. However, there is no difference in time spent in each compartment when the deeper compartment was white. For light intensity test, animals showed preference for the white compartment only when both compartments were illuminated with 100lx. For the others illumination settings, there was no difference in the compartment preference. In conclusion, our results suggest that variations in water column depth and light intensity can modulate zebrafish preference in the black/white test. These variations may be implicated in the discrepancies observed in literature., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Hyperprolinemias are inherited disorder of proline (Pro) metabolism. Patients affected may present neurological manifestations, but the mechanisms of neural excitotoxicity elicited by hyperprolinemia are far from being understood. Considering that the astrocytes are important players in neurological disorders, the aim of the present work was to study the effects 1 mM Pro on glutamatergic and inflammatory parameters in cultured astrocytes from cerebral cortex of rats, exploring some molecular mechanisms underlying the disrupted homeostasis of astrocytes exposed to this toxic Pro concentration. We showed that cortical astrocytes of rats exposed to 1 mM Pro presented significantly elevated extracellular glutamate and glutamine levels, suggesting glutamate excitotoxicity. The excess of glutamate elicited by Pro together with increased glutamate uptake and upregulated glutamine synthetase (GS) activity supported misregulated glutamate homeostasis in astrocytic cells. High Pro levels also induced production/release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. We also evidenced misregulation of cholinergic anti-inflammatory system with increased acetylcholinesterase (AChE) activity and decreased acetylcholine (ACh) levels, contributing to the inflammatory status in Pro-treated astrocytes. Our findings highlighted a crosstalk among disrupted glutamate homeostasis, cholinergic mechanisms, and inflammatory cytokines, since ionotropic (DL-AP5 and CNQX) and metabotropic (MCPG and MPEP) glutamate antagonists were able to restore the extracellular glutamate and glutamine levels; downregulate TNFα and IL6 production/release, modulate GS and AChE activities; and restore ACh levels. Otherwise, the non-steroidal anti-inflammatory drugs nimesulide, acetylsalicylic acid, ibuprofen, and diclofenac sodium decreased the extracellular glutamate and glutamine levels, downregulated GS and AChE activities, and restored ACh levels in Pro-treated astrocytes. Altogether, our results evidence that the vulnerability of metabolic homeostasis in cortical astrocytes might have important implications in the neurotoxicity of Pro.

Ethanol is a widely consumed drug, which acts on the central nervous system to induce behavioral alterations ranging from disinhibition to sedation. Recent studies have produced accumulating evidence for the therapeutic role of probiotic bacteria in behavior. We aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) on the behavior of adult zebrafish chronically exposed to ethanol. Adult wild-type zebrafish were randomly divided into four groups, each containing 15 fish. The following groups were formed: Control (C), received unsupplemented feed during the trial period; Probiotic (P), fed with feed supplemented with LGG; Ethanol (E), received unsupplemented feed and 0.5% of ethanol directly added to the tank water; and Probiotic+Ethanol (P+E), group under ethanol exposure (0.5%) and fed with LGG supplemented feed. After 2 weeks of exposure, the novel tank test was used to evaluate fish behavior, which was analyzed using computer-aided video tracking. LGG alone did not alter swimming behavior of the fish. Ethanol exposure led to robust behavioral effects in the form of reduced anxiety levels, as indicated by increased vertical exploration and more time spent in the upper region of the novel tank. The group exposed to ethanol and treated with LGG behaved similarly to animals exposed to ethanol alone. Taken together, these results show that zebrafish behavior was not altered by LGG per se, as seen in murine models. This was the first study to investigate the effects of a probiotic diet on behavior after a chronic ethanol exposure.

Hypermethioninemic patients may exhibit different neurological dysfunctions, and the mechanisms underlying these pathologies remain obscure. Glutamate and ATP are important excitatory neurotransmitters co-released at synaptic clefts, and whose activities are intrinsically related. Adenosine-the final product of ATP breakdown-is also an important neuromodulator. Here, we investigated the effects of long-term (7-day) exposure to 1.5 or 3 mM methionine (Met) on glutamate uptake in brain tissues (telencephalon, optic tectum, and cerebellum) and on ATP, ADP, and AMP catabolism by ecto-nucleotidases found in brain membrane samples, using a zebrafish model. Also, we evaluated the expression of ecto-nucleotidase (ntdp1, ntdp2mg, ntdp2mq, ntdp2mv, ntdp3, and nt5e) and adenosine receptor (adora1, adora2aa, adora2ab, adora2b) genes in the brain of zebrafish exposed to Met. In animals exposed to 3.0 mM Met, glutamate uptake in the telencephalon decreased significantly. Also, ATP and ADP (but not AMP) catabolism decreased significantly at both Met concentrations tested. The messenger RNA (mRNA) levels of ntpd genes and of the adenosine receptors adora1 and adora2aa increased significantly after Met exposure. In contrast, adora2ab mRNA levels decreased after Met exposure. Our data suggest that glutamate and ATP accumulate at synaptic clefts after Met exposure, with potential detrimental effects to the nervous system. This phenomenon might explain, at least in part, the increased susceptibility of hypermethioninemic patients to neurological symptoms.

Açai (Euterpe oleracea Mart.), a highly consumed fruit in Amazon, is from a common palm with remarkable antioxidant properties. Because oxidative stress and seizures are intimately linked, this study investigated the potential neuroprotective and anticonvulsant effects of commercial clarified açai juice (EO). EO did not alter spontaneous locomotor activity. Four doses of EO were sufficient to increase latencies to both first myoclonic jerk and first generalized tonic-clonic seizure and significantly decrease the total duration of tonic-clonic seizures caused by pentylenetetrazol administration. Also, electrocortical alterations provoked by pentylenetetrazol were prevented, significantly decreasing amplitude of discharges and frequencies above 50 Hz. EO was also able to completely prevent lipid peroxidation in the cerebral cortex, showing a potent direct scavenging property. These results demonstrate for the first time that E. oleracea significantly protects against seizures and seizure-related oxidative stress, indicating an additional protection for humans who consume this fruit., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Environmental enrichment (EE) is a non-pharmacological manipulation that promotes diverse forms of benefits in the central nervous system of captive animals. It is thought that EE influences animal behavior in a specie-(strain)-specific manner. Since rodents in general present different behaviors during distinct periods of the day, in this study we aimed to investigate the influence of time-of-day on behavioral repertoire of Swiss mice that reared in EE. Forty male Swiss mice (21days old) were housed in standard (SC) or enriched conditions (EC) for 60days. Behavioral assessments were conducted during the light phase (in presence of light) or dark phase (in absence of light) in the following tasks: open field, object recognition and elevated plus maze. First, we observed that the locomotor and exploratory activities are distinct between SC and EC groups only during the light phase. Second, we observed that "self-protective behaviors" were increased in EC group only when mice were tested during the light phase. However, "less defensive behaviors" were not affected by both housing conditions and time-of-day. Third, we showed that the performance of EE animals in object recognition task was improved in both light and dark conditions. Our findings highlight that EE-induced alterations in exploratory and emotional behaviors are just evident during light conditions. However, EE-induced cognitive benefits are remarkable even during dark conditions, when exploratory and emotional behaviors were similar between groups., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This study investigated the variability by considering an action programme as hierarchically organized, which reconciles invariant and variant features of motor skills at the macro- and microstructural level of analysis. It was assumed that invariant aspects of skilled actions express the macrostructure and therefore measures of sequencing, relative size, relative timing, relative force and relative pause time. The microstructure was related to the variant aspects so that total size, total movement time, total force, and total pause time were selected as its measures. These propositions were tested in an experimental design comprised by three learning phases: a stabilisation phase that entailed a given number of trials to achieve the functional stabilization on a graphic task, followed by transfer and retention phases. In the transfer phase, the graphic task was modified to yield different demands upon skill reorganization. Two such modifications demanded parametric changes (i.e. microstructure changes), in which graphic size and drawing speed were altered. Another modification demanded structural alterations (i.e. macrostructure change), in which drawing was changed. Overall, results supported the main predictions by showing that parametric changes in the task affected the microstructure, but did not affect the macrostructure consistently. Furthermore, a structural change affected both macro- and microstructure.

Cadmium (Cd) is a known hepato- and nephrotoxic pollutant and zinc (Zn) metalloproteins are important targets of Cd. Hence, the administration of Zn may mitigate Cd toxic effects. However, the interaction of Cd and Zn has been little investigated in the brain. Previously, we reported a protective effect of Zn on mortality caused by Cd in rats. Here, we tested whether the protective effect of Zn could be related to changes in brain Zn-proteins, metallothionein (MT) and δ-aminolevulinate dehydratse (δ-ALA-D). Male adult rats were daily administered for 10 days with Zn (2 mg kg -1 ), Cd (0.25 and 1 mg kg -1 ) and 0.25 mg kg -1 of Cd plus Zn and 1 mg kg -1 of Cd plus Zn. The body weight loss, food intake deprivation, and mortality occurred in 1 mg kg -1 of Cd, but Zn co-administration did mitigate these effects. The brain Zn content was not modified by treatment with Cd, whereas cerebral Cd levels increased in animals exposed to Cd. The administration of 0.25 mg kg -1 of Cd (with or without Zn) induced lipid peroxidation and decreased MT concentration, but 2 mg kg -1 of Zn and 1 mg kg -1 of Cd did not change these parameters. Brain δ-ALA-D was not modified by Cd and/or Zn treatments. Since the co-administration of Zn did not attenuate the changes induced by Cd in the brain, our results suggest that the protective effect of Zn on impairments caused by Cd in animal status is weakly related to a cerebral interaction of these metals.

Anxiety-related disorders are frequently observed in the population. Because the available pharmacotherapies for anxiety can cause side effects, new anxiolytic compounds have been screened using behavioral tasks. For example, diphenyl diselenide (PhSe)2, a simple organoselenium compound with neuroprotective effects, has demonstrated anxiolytic effects in rodents. However, this compound has not yet been tested in a novelty-based paradigm in non-mammalian animal models. In this study, we assessed the potential anxiolytic effects of (PhSe)2 on the behavior of adult zebrafish under novelty-induced stress. The animals were pretreated with 0.1, 0.25, 0.5, and 1μM (PhSe)2 in the aquarium water for 30min. The fish were then exposed to a novel tank, and their behavior was quantified during a 6-min trial. (PhSe)2 treatment altered fish behavior in a concentration-dependent manner. At 0.01 and 0.25μM, (PhSe)2 did not elicit effects on fish behavior. At 0.5μM, moderate behavioral side effects (e.g., lethargy and short episodic immobility) were noted. At the highest concentration tested (1μM), dramatic side effects were observed, such as burst behavior and longer periods of immobility. The results were confirmed by spatiotemporal analysis of each group. Occupancy plot data showed dispersed homebase formation in the 0.25μM (PhSe)2-treated group compared with the control group (treated with 0.04% DMSO). Furthermore, animals treated with 0.25μM (PhSe)2 showed a reduction in latency to enter the top and spent more time in the upper area of the tank. These data suggest that (PhSe)2 may induce an anxiolytic-like effect in situations of anxiety evoked by novelty., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Biodentine (Septodont, St-Maur-des-Fossés, France) is a new material suitable for various clinical situations in endodontics, such as perforation repair, retrograde filling, pulp capping, and others. Because it is a new material, its properties should be analyzed before routine clinical use. Thus, this study evaluated the biocompatibility of Biodentine in the subcutaneous tissue of rats., Methods: This study was conducted on 15 male rats. Two incisions were made on the dorsal region of each animal for the introduction of 4 tubes. One tube was empty, 1 was filled with zinc oxide-eugenol cement, 1 was filled with mineral trioxide aggregate, and the last tube was filled with Biodentine. After 7, 14, and 30 days, the animals were sacrificed, and the specimens were submitted to histotechnical preparation. The histologic sections were stained with hematoxylin-eosin and analyzed using light microscopy. Scores were established according to the inflammatory process and were statistically compared using the Kruskal-Wallis test (P < .05)., Results: The analysis of the histologic sections evidenced a nonsignificant or mild presence of inflammatory reaction in the connective tissue in contact with the empty tube and the tube containing MTA, which was different from the tube containing zinc oxide eugenol. The connective tissue was moderately inflamed at 7 days when in contact with Biodentine; however, at 14 and 30 days, the inflammatory process was mild or nonsignificant., Conclusions: Biodentine was biocompatible with tissue after the 14th day., (Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Ethanol (EtOH) and its metabolite, acetaldehyde (ALD), induce deleterious effects on central nervous system (CNS). Here we investigate the in vitro toxicity of EtOH and ALD (concentrations of 0.25%, 0.5%, and 1%) in zebrafish brain structures [telencephalon (TE), opticum tectum (OT), and cerebellum (CE)] by measuring the functionality of glutamate transporters, MTT reduction, and extracellular LDH activity. Both molecules decreased the activity of the Na(+)-dependent glutamate transporters in all brain structures. The strongest glutamate uptake inhibition after EtOH exposure was 58% (TE-1%), and after ALD, 91% (CE-1%). The results of MTT assay and LDH released demonstrated that the actions of EtOH and its metabolite are concentration and structure-dependent, in which ALD was more toxic than EtOH. In summary, our findings demonstrate a differential toxicity in vitro of EtOH and ALD in zebrafish brain structures, which can involve changes on glutamatergic parameters. We suggest that this species may be an interesting model for assessing the toxicological actions of alcohol and its metabolite in CNS., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Several researchers have recently used C6 cells to evaluate functional properties of high-affinity glutamate transporters. However, it has been demonstrated that this lineage suffers several morphological and biochemical alterations according to the number of passages in culture. Currently, there are no reports showing whether functional properties of high-affinity glutamate transporters comply with these sub culturing-dependent modifications. The present study aimed to compare the functional properties of high-affinity glutamate transporters expressed in early (EPC6) and late (LPC6) passage C6 cells through a detailed pharmacological and biochemical characterization. Between 60-180 min of L-[(3)H]glu incubation, LPC6 presented an intracellular [(3)H] 55% lower than EPC6. Both cultures showed a time-dependent increase of intracellular [(3)H] reaching maximal levels at 120 min. Cultures incubated with D-[(3)H]asp showed a time-dependent increase of [(3)H] until 180 min. Moreover, LPC6 have a D-[(3)H]asp-derived intracellular [(3)H] 30-45% lower than EPC6 until 120 min. Only EAAT3 was immunodetected in cultures and its total content was equal between them. PMA-stimulated EAAT3 trafficking to membrane increased 50% of L-[(3)H]glu-derived intracellular [(3)H] in EPC6 and had no effect in LPC6. LPC6 displayed characteristics that resemble senescence, such as high β-Gal staining, cell enlargement and increase of large and regular nuclei. Our results demonstrated that LPC6 exhibited glutamate uptake impairment, which may have occurred due to its inability to mobilize EAAT3 to cell membrane. This profile might be related to senescent process observed in this culture. Our results suggest that LPC6 cells are an inappropriate glial cellular model to investigate the functional properties of high-affinity glutamate transporters.

This paper analyzes from the users' perception adherent to treatment, the meanings attributed to the risks of the disease. The qualitative study was developed from the Grounded Theory. Data collection occurred through semi-structured interviews, with 19 users as subjects adhering to tuberculosis treatment. The project was approved by the research ethics committee of UFRGS. Survey participants indicate relational risks such as the possibility of harms that tuberculosis is the interaction of the patient with society, with interference with public and private dimensions of everyday life. The recognition of the participants as subjects of risks was part of a process that is producing identities, making them sought an image of the subject concerned with his care and the care of the other, preserving their personal relationships and interaction in society.

The objective was to analyze an intervention in the traditional way of teaching nursing consultation and its potential for nurses' education aiming for the practice of integrality in health. This is a participative research carried out from August to November 2011 with eight students attending the School of Nursing in a public university from the south of Brazil. The study context comprised outpatient consultations and daily life experiences of the patients. Data were collected through focus group and submitted to thematic analysis, in which two categories emerged: "The interactivity between the traditional and the extended scenario:possibilities for the integrality in education" and "The extended nursing consultation, knowledge from experience". The analysis evidenced that the experience produced knowledge coherent with the integrality in education. We conclude that the diversification of learning scenarios may configure a pedagogical strategy with potential to foster changes in the existing health care and education model.