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Zidovudine (AZT) is the most commonly prescribed antiviral drug for the treatment of human immunodeficiency virus (HIV) infection. However, its chronic administration causes toxic side effects limiting its use. This study aimed to evaluate the toxicity of different concentrations of AZT and novel chalcogen derivatives (7A, 7D, 7G, 7K, 7M) on locomotion, mitochondrial dysfunction, acetylcholinesterase (AChE) activity, and production of reactive oxygen species (ROS) in adult Drosophila melanogaster. Our results show that AZT and its derivative 7K at a concentration of 10 μM impaired flies' locomotor behavior. Furthermore, AZT and the derivatives 7K, 7A, and 7M induced mitochondrial dysfunction observed by a decrease in oxygen flux through mitochondrial complexes I and II. Neither of the compounds tested affected AChE activity or ROS production in flies. According to these data, AZT derivatives presented the following decreasing order of toxicity: 7K > AZT > 7G > 7A > 7M > 7D. Based on the chemical structure, it is possible to infer that the presence of the seleno-phenyl group in 7A and 7G increases their toxicity compared to compounds 7D and 7M. In addition, compounds 7G, 7M, and 7K with three carbon atoms as spacer were more toxic than analogs containing one carbon atom (7A and 7D). Finally, the insertion of a p-methoxyl group enhances toxicity (7K). Based on these results, excepting 7K, all other chalcogen derivatives presented lower toxicity than AZT and are potential drug candidates., (© 2023 Wiley Periodicals LLC.)

Mitochondrial dysfunction plays a central role in Parkinson's disease (PD) and can be triggered by xenobiotics and mutations in mitochondrial quality control genes, such as the PINK1 gene. Caffeine has been proposed as a secondary treatment to relieve PD symptoms mainly by its antagonistic effects on adenosine receptors (ARs). Nonetheless, the potential protective effects of caffeine on mitochondrial dysfunction could be a strategy in PD treatment but need further investigation. In this study, we used high-resolution respirometry (HRR) to test caffeine's effects on mitochondrial dysfunction in PINK1 B9 -null mutants of Drosophila melanogaster. PINK1 loss-of-function induced mitochondrial dysfunction in PINK1 B9 -null flies observed by a decrease in O 2 flux related to oxidative phosphorylation (OXPHOS) and electron transfer system (ETS), respiratory control ratio (RCR) and ATP synthesis compared to control flies. Caffeine treatment improved OXPHOS and ETS in PINK B9 -null mutant flies, increasing the mitochondrial O 2 flux compared to untreated PINK B9 -null mutant flies. Moreover, caffeine treatment increased O 2 flux coupled to ATP synthesis and mitochondrial respiratory control ratio (RCR) in PINK 1 B9 -null mutant flies. The effects of caffeine on respiratory parameters were abolished by rotenone co-treatment, suggesting that caffeine exerts its beneficial effects mainly by stimulating the mitochondrial complex I (CI). In conclusion, we demonstrate that caffeine may improve mitochondrial function by increasing mitochondrial OXPHOS and ETS respiration in the PD model using PINK1 loss-of-function mutant flies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Parkinson's disease (PD) is a common neurodegenerative disease characterized by movement disorders as well as loss of dopaminergic neurons. Moreover, genes affecting mitochondrial function, such as SNCA, Parkin, PINK1, DJ-1 and LRRK2, were demonstrated to be associated with PD and other neurodegenerative disease. Additionally, mitochondrial dysfunction and cellular energy imbalance are common markers found in PD. In this study, we used the pink1 null mutants of Drosophila melanogaster as a Parkinson's disease model to investigate how the energetic pathways and mitochondrial functions change during aging in a PD model. In our study, the loss of the pink1 gene decreased the survival percent and the decreased climbing index during aging in pink1 -/- flies. Furthermore, there was an impairment in mitochondrial function demonstrated by a decrease in OXPHOS CI&CII-Linked and ETS CI&CII-Linked in pink1 -/- flies at 3, 15 and 30 days of life. Interestingly, OXPHOS CII-Linked and ETS CII-Linked presented decreases only at 15 days of life in pink1 -/- flies. Moreover, there was an increase in peroxide (H 2 O 2 ) levels in pink1 -/- flies at 15 and 30 days of life. Loss of the pink1 gene also decreased the activity of citrate synthase (CS) and increased the activity of lactate dehydrogenase (LDH) in pink1 -/- flies head. Our results demonstrate a metabolic shift in ATP production in pink1 -/- flies, which changed from oxidative to glycolytic pathways from 15 days of age, and is apparently more pronounced in the central nervous system., (Copyright © 2022 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Toluene is an air pollutant widely used as an organic solvent in industrial production and emitted by fossil fuel combustion, in addition to being used as a drug of abuse. Its toxic effects in the central nervous system have not been well established, and how and which neurons are affected remains unknown. Hence, this study aimed to fill this gap by investigating three central questions: 1) How does toluene induce neurotoxicity? 2) Which neurons are affected? And 3) What are the long-term effects induced by airborne exposure to toluene? To this end, a Caenorhabditis elegans model was employed, in which worms at the fourth larval stage were exposed to toluene in the air for 24 h in a vapor chamber to simulate four exposure scenarios. After the concentration-response curve analysis, we chose scenarios 3 (E3: 792 ppm) and 4 (E4: 1094 ppm) for the following experiments. The assays were performed 1, 48, or 96 h after removal from the exposure environments, and an irreversible reduction in neuron fluorescence and morphologic alterations were observed in different neurons of exposed worms, particularly in the dopaminergic neurons. Moreover, a significant impairment in a dopaminergic-dependent behavior was also associated with negative effects in healthspan endpoints, and we also noted that mitochondria may be involved in toluene-induced neurotoxicity since lower adenosine 5'-triphosphate (ATP) levels and mitochondrial viability were observed. In addition, a reduction of electron transport chain activity was evidenced using ex vivo protocols, which were reinforced by in silico and in vitro analysis, demonstrating toluene action in the mitochondrial complexes. Based on these findings model, it is plausible that toluene neurotoxicity can be initiated by complex I inhibition, triggering a mitochondrial dysfunction that may lead to irreversible dopaminergic neuronal death, thus impairing neurobehavioral signaling., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The current pandemic associated with SARS-CoV-2 has negatively influenced several activities, including teaching in Operative Dentistry. The aim of this study was to evaluate the influence of knowledge in Operative Dentistry on undergraduate students' perception related to personal life and return to clinical practices classes during pandemic., Materials and Methods: The present research was a cross-sectional, observational, and qualitative survey. The 16-item based questionnaire was sent to undergraduate students in 2020, which were divided into two groups, according to the Operative Dentistry knowledge: G1-not started clinical practice; G2-already started or completed clinical practice. Questions were focused on the impact of the pandemic in relation to their personal lives and return to clinical practice classes. Chi-square association test was performed using the SigmaPlot 12.0 software ( P ≤ 0.05)., Results: The response rate was 55.5% for G1 and 44.4% for G2. Regarding the questions related to personal life, G1 demonstrated higher percentages of fear of contracting the virus during theoretical classes. Same observations were found when students answered about their fear of contracting coronavirus during the clinical practice classes. However, G2 presented the highest agreement responses for the preparedness feeling to return to theoretical classroom, clinical practice classes, and the possibility of applying online learning., Conclusions: In general, students' knowledge had little influence on perception of personal life. However, students who have more knowledge in operative dentistry presented more security about returning to clinical classes., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Education and Health Promotion.)

Traumatic brain injury (TBI) is considered a public health problem and is often related to motor and cognitive disabilities, besides behavioral and emotional changes that may remain for the rest of the subject's life. Resident astrocytes and microglia are the first cell types to start the inflammatory cascades following TBI. It is widely known that continuous or excessive neuroinflammation may trigger many neuropathologies. Despite the large numbers of TBI cases, there is no effective pharmacological treatment available. This study aimed to investigate the effects of the new hybrid molecule 3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro1H-pyrido[2,3-b][1,5]benzodiazepine (JM-20) on TBI outcomes. Male Wistar rats were submitted to a weight drop model of mild TBI and treated with a single dose of JM-20 (8 mg/kg). Twenty-four hours after TBI, JM-20-treated animals showed improvements on locomotor and exploratory activities, and short-term memory deficits induced by TBI improved as well. Brain edema was present in TBI animals and the JM-20 treatment was able to prevent this change. JM-20 was also able to attenuate neuroinflammation cascades by preventing glial cells-microglia and astrocytes-from exacerbated activation, consequently reducing pro-inflammatory cytokine levels (TNF-α and IL-1β). BDNF mRNA level was decreased 24 h after TBI because of neuroinflammation cascades; however, JM-20 restored the levels. JM-20 also increased GDNF and NGF levels. These results support the JM-20 neuroprotective role to treat mild TBI by reducing the initial damage and limiting long-term secondary degeneration after TBI., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The skin injury healing process involves the main phases of homoeostasis, inflammation, proliferation, and remodeling. The present study aimed to analyze the effects of low-level laser therapy (LLLT) on hematological dynamics, oxidative stress markers, and its relation with tissue healing following skin injury. Wistar rats were divided into control, sham, skin injury, and skin injury LLLT. The biochemical and morphological analyses were performed in the inflammatory (1 and 3 days) and regenerative phases (7, 14, and 21 days) following injury. The skin injury was performed in the dorsal region, between the intrascapular lines, using a surgical punch. LLLT (Al-Ga-In-P, λ=660 nm, energy density of 20 J/cm2, 30 mW power, and a time of 40 s) was applied at the area immediately after injury and on every following day according to the experimental subgroups. LLLT maintained hematocrit and hemoglobin levels until the 3rd day of treatment. Surprisingly, LLLT increased total leukocytes levels compared to control until the 3rd day. The effects of LLLT on mitochondrial activity were demonstrated by the significant increase in MTT levels in both inflammatory and regenerative phases (from the 1st to the 7th day), but only when associated with skin injury. The results indicated that LLLT modulated the inflammatory response intensity and accelerated skin tissue healing by a mechanism that involved oxidative damage reduction mostly at early stages of skin healing (inflammatory phase).

Hepatic encephalopathy is a pathophysiological complication of acute liver failure, which may be triggered by hepatotoxic drugs such as acetaminophen (APAP). Although APAP is safe in therapeutic concentration, APAP overdose may induce neurotoxicity, which is mainly associated with oxidative stress. Caffeine is a compound widely found in numerous natural beverages. However, the neuroprotective effect of caffeine remains unclear during APAP intoxication. The present study aimed to investigate the possible modulatory effects of caffeine on brain after APAP intoxication. Mice received intraperitoneal injections of APAP (250 mg/kg) and/or caffeine (20 mg/kg) and, 4 h after APAP administration, samples of brain and blood were collected for the biochemical analysis. APAP enhanced the transaminase activity levels in plasma, increased oxidative stress biomarkers (lipid peroxidation and reactive oxygen species), promoted an imbalance in endogenous antioxidant system in brain homogenate and increased the mortality. In contrast, APAP did not induce dysfunction of the mitochondrial bioenergetics. Co-treatment with caffeine modulated the biomarkers of oxidative stress as well as antioxidant system in brain. Besides, survival assays demonstrated that caffeine protective effects could be dose- and time-dependent. In addition, caffeine promoted an increase of mitochondrial bioenergetics response in brain by the enhancement of the oxidative phosphorylation, which could promote a better energy supply necessary for brain recovery. In conclusion, caffeine prevented APAP-induced biochemical alterations in brain and reduced lethality in APAP-intoxicated mice, these effects may relate to the preservation of the cellular antioxidant status, and these therapeutic properties could be useful in the treatment of hepatic encephalopathy induced by APAP intoxication., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Traumatic brain injury (TBI) constitutes a heterogeneous cerebral insult induced by traumatic biomechanical forces. Mitochondria play a critical role in brain bioenergetics, and TBI induces several consequences related with oxidative stress and excitotoxicity clearly demonstrated in different experimental model involving TBI. Mitochondrial bioenergetics alterations can present several targets for therapeutics which could help reduce secondary brain lesions such as neuropsychiatric problems, including memory loss and motor impairment. Guanosine (GUO), an endogenous neuroprotective nucleoside, affords the long-term benefits of controlling brain neurodegeneration, mainly due to its capacity to activate the antioxidant defense system and maintenance of the redox system. However, little is known about the exact protective mechanism exerted by GUO on mitochondrial bioenergetics disruption induced by TBI. Thus, the aim of this study was to investigate the effects of GUO in brain cortical and hippocampal mitochondrial bioenergetics in the mild TBI model. Additionally, we aimed to assess whether mitochondrial damage induced by TBI may be related to behavioral alterations in rats. Our findings showed that 24 h post-TBI, GUO treatment promotes an adaptive response of mitochondrial respiratory chain increasing oxygen flux which it was able to protect against the uncoupling of oxidative phosphorylation (OXPHOS) induced by TBI, restored the respiratory electron transfer system (ETS) established with an uncoupler. Guanosine treatment also increased respiratory control ratio (RCR), an indicator of the state of mitochondrial coupling, which is related to the mitochondrial functionality. In addition, mitochondrial bioenergetics failure was closely related with locomotor, exploratory and memory impairments. The present study suggests GUO treatment post mild TBI could increase GDP endogenous levels and consequently increasing ATP levels promotes an increase of RCR increasing OXPHOS and in substantial improve mitochondrial respiration in different brain regions, which, in turn, could promote an improvement in behavioral parameters associated to the mild TBI. These findings may contribute to the development of future therapies with a target on failure energetic metabolism induced by TBI., (Copyright © 2020. Published by Elsevier Inc.)

Fibromyalgia (FM) is one of the most common musculoskeletal pain conditions. Although the aetiology of FM is still unknown, mitochondrial dysfunction and the overproduction of reactive oxygen intermediates (ROI) are common characteristics in its pathogenesis. The reserpine experimental model can induce FM-related symptoms in rodents by depleting biogenic amines. However, it is unclear whether reserpine causes other pathophysiologic characteristics of FM. So far, no one has investigated the relevance of mitochondrial dysfunction in the reserpine-induced experimental FM model using protection- and insult-based mitochondrial modulators. Reserpine (1 mg/kg) was subcutaneously injected once daily for three consecutive days in male Swiss mice. We carried out analyses of reserpine-induced FM-related symptoms, and their modulation by using mitochondrial insult on ATP synthesis (oligomycin; 1 mg/kg, intraperitoneally) or mitochondrial protection (coenzyme Q10; 150 mg/kg/5 days, orally). We also evaluated the effect of reserpine on mitochondrial function using high-resolution respirometry and oxidative status. Reserpine caused nociception, loss in muscle strength, and anxiety- and depressive-like behaviours in mice that were consistent with clinical symptoms of FM, without inducing body weight and temperature alterations or motor impairment. Reserpine-induced FM-related symptoms were increased by oligomycin and reduced by coenzyme Q10 treatment. Reserpine caused mitochondrial dysfunction by negatively modulating the electron transport system and mitochondrial respiration (ATP synthesis) mainly in oxidative muscles and the spinal cord. These results support the role of mitochondria in mediating oxidative stress and FM symptoms in this model. In this way, reserpine-inducing mitochondrial dysfunction and increased production of ROI contribute to the development and maintenance of nociceptive, fatigue, and depressive-like behaviours.

Overweight stands out as a growing health problem in the population, resulting in individual and societal burdens. This study aimed to identify the association between reproductive factors and overweight in women of reproductive age attended by a Primary Health Care Unit (UAPS).This is a cross-sectional study with home capitation and data collection in two PHC Units, in the city of Juiz de Fora (MG), Brazil, in women aged 20 to 59 years, whose outcome was the overweight measured by the Body Mass Index. The prevalence of overweight was 61.0% among the 2,018 women included in the analysis. In the multivariate analysis, overweight was associated with the variables age at menarche before 12 years of age, having children, age greater than or equal to 30years, and hypertension. The prevalence of overweight in women who had menarche before 12 years of age was 12.4% higher than those who had menarche aged 12 years or more, and the prevalence of overweight in women who had children was 58.2% higher than those who never had any. There was a high prevalence of overweight in the adult female population, emphasizing the influence of reproductive factors.

Organic selenium compounds are widely associated with numerous pharmacological properties. However, selenium compounds, such as Ebselen (Ebs) and Diphenyl Diselenide (DPDS), could interact with mitochondrial respiratory complexes, especially with thiol groups. The present study evaluated whether the insertion of functional groups, o-methoxy, and p-methyl on organic selenium compounds promotes changes in mitochondrial functioning parameters and whether this is related to antibacterial activity. Here we tested some in vitro parameters after the exposure of mitochondria to different concentrations of β-selenoamines 1-phenyl-3-(p-tolylselanyl)propan-2-amine (C1) and 1-(2-methoxyphenylselanyl)-3-phenylpropan-2-amine (C2) and analogs of DPDS 1,2-bis(2-methoxyphenyl)diselenide (C3) and 1,2-bisp-tolyldiselenide (C4). We also evaluated the antibacterial activity of β-selenoamines and diselenides against Methicillin-resistant Staphylococcus aureus and Escherichia coli. Our results showed that o-methoxy insertion increased the antioxidant properties, without affecting the mitochondrial membrane potential. The compounds with a p-methyl insertion affected the mitochondrial membrane potential and significantly decreased the State III respiration and RCR. Besides, the p-methyl compounds presented antibacterial activity at lower concentrations than those shown in o-methoxy, precisely by the same mechanism that promotes damage to thiol groups and better absorption in gram-positive bacteria due to their relationship with cell wall constituents. Finally, our study confirms that structural modifications in organic selenium compounds provide changes in mitochondrial functioning but also raise their antibacterial effect. This strategy can be used as a target for the development of new enough potent antibacterial to restrict the advance of resistant bacterial infections., 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 the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Skeletal muscle is the most abundant tissue in the human body and mechanical injuries are common; these are frequently of mechanical origins, such as contusion. However, the immediate mitochondrial response to injury and energetic substrate utilisation is still unclear. We evaluated the acute response in mitochondrial function after a single muscle contusion, either in fast twitch fibres (glycolytic metabolism), fast and slow twitch (oxidative and glycolytic metabolism), or slow twitch fibres (oxidative metabolism). Rats were assigned to two groups: control and Lesion (muscle contusion). We collected the gastrocnemius and soleus muscles. The fibres were analysed for mitochondrial respiration, lactate dehydrogenase (LDH), citrate synthase (CS) activity, Ca 2+ uptake, and H 2 O 2 production. We found that muscle injury was able to increase ATP synthesis-dependent and OXPHOS oxygen flux in the oxidative fibres when stimulated by complex I + II substrates. On the other hand, the muscle injury increased hydrogen peroxide (H 2 O 2 ) production when compared to control fibres, and reduced citrate synthase activity; however, it did not change Ca 2+ uptake. Surprisingly, injury in mixed fibres increased the OXPHOS and ATP synthesis oxygen consumption, and H 2 O 2 production, but it reduced Ca 2+ uptake. The injury in glycolytic fibres did not affect oxygen flux coupled to ATP synthesis, citrate synthase, and lactate dehydrogenase activity, but did reduce Ca 2+ uptake. Finally, we demonstrated distinct mitochondrial responses between the different muscle fibres, indicating that the mitochondrial dynamics is related to flexibilities in metabolism, and that reactive oxygen species directly affect physiology and normal function.

Mitochondria play an important role in cell life and in the regulation of cell death. In addition, mitochondrial dysfunction contributes to a wide range of neuropathologies. The nucleoside Guanosine (GUO) is an endogenous molecule, presenting antioxidant properties, possibly due to its direct scavenging ability and/or from its capacity to activate the antioxidant defense system. GUO demonstrate a neuroprotective effect due to the modulation of the glutamatergic system and maintenance of the redox system. Thus, considering the few studies focused on the direct effects of GUO on mitochondrial bioenergetics, we designed a study to evaluate the in vitro effects of GUO on rat mitochondrial function, as well as against Ca 2+ -induced impairment. Our results indicate that GUO prevented mitochondrial dysfunction induced by Ca 2+ misbalance, once GUO was able to reduce mitochondrial swelling in the presence of Ca 2+ , as well as ROS production and hydrogen peroxide levels, and to increase manganese superoxide dismutase activity, oxidative phosphorylation and tricarboxylic acid cycle activities. Our study indicates for the first time that GUO could direct prevent the mitochondrial damage induced by Ca 2+ and that these effects were not related to its scavenging properties. Our data indicates that GUO could be included as a new pharmacological strategy for diseases linked to mitochondrial dysfunction., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Mitochondrial dysfunction has been demonstrated to have a central role in Parkinson Disease (PD) pathophysiology. Some studies have indicated that PD causes an impairment in mitochondrial bioenergetics; however, the effects of PD on brain-region specific bioenergetics was never investigated before. This study aimed to evaluate mitochondrial bioenergetics in different rat brain structures in an in vitro model of PD using 6-OHDA. Rat brain slices of hippocampus, striatum, and cortex were exposed to 6-OHDA (100 μM) for 1 h and mitochondrial bioenergetic parameters, peroxide production, lactate dehydrogenase (LDH) and citrate synthase (CS) activities were analyzed. Hippocampus slices exposed to 6-OHDA presented increased peroxide production but, no mitochondrial adaptive response against 6-OHDA damage. Cortex slices exposed to 6-OHDA presented increased oxygen flux related to oxidative phosphorylation and energetic pathways exchange demonstrated by the increase in LDH activity, suggesting a mitochondrial compensatory response. Striatum slices exposed to 6-OHDA presented a decrease of oxidative phosphorylation and decrease of oxygen flux related to ATP-synthase indicating an impairment in the respiratory chain. The co-incubation of 6-OHDA with n-acetylcysteine (NAC) abolished the effects of 6-OHDA on mitochondrial function in all brain regions tested, indicating that the increased reactive oxygen species (ROS) production is responsible for the alterations observed in mitochondrial bioenergetics. The present results indicate a brain-region specific response against 6-OHDA, providing new insights into brain mitochondrial bioenergetic function in PD. These findings may contribute to the development of future therapies with a target on energy metabolism., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Drosophila melanogaster is a suitable model for toxicological studies of environmental pollutants including pesticides, which are known to produce adverse effects on the ecosystem. The aim of the present study was to investigate the adverse influence of the pesticide Palace®, a mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and picloram, using D. melanogaster as a model organism. D. melanogaster larvae were exposed to 0.011%, 0.022%, 0.112%, 0.224%, and 1.12% of Palace® and development examined. Adult flies were treated with 0.224%, 1.12%, 2.24%, 11.2%, and 22.4% of Palace® and the following analyzed survival, locomotor behavior, acetylcholinesterase (AchE) activity, reactive oxygen species (ROS) production, total and non-protein thiol levels, and mitochondrial function. Data demonstrated that exposure of flies during larval stage to Palace® significantly affected development of larvae to the adult stage. In adults, treatment with Palace® resulted in dose-dependent progressive adverse effects on survival and behavior with males more sensitive than females. In both males and females, ROS production and AchE activity were not markedly affected by Palace®. However, total thiol levels increased in female heads treated with highest dilution of Palace®, while decreased levels of non-protein thiols were detected in heads of male flies following Palace® exposure. In females and males flies exposed to Palace® reduced mitochondrial oxygen consumption related to oxidative phosphorylation (OXPHOS) state, mitochondrial capacity of excess (E-P) and respiratory control ratio (RCR) was noted, indicating that the pesticide mixture altered mitochondrial complexes functionality with consequences on bioenergetics. In summary, Palace® exposure produced adverse effects on D. melanogaster affecting survival, development, behavior and mitochondrial function, which may exert ecotoxicological consequences which poses risks to different organisms in the ecosystem.

Aims: Many studies have been demonstrating the role of mitochondrial function in acetaminophen (APAP) hepatotoxicity. Since APAP is commonly consumed with caffeine, this work evaluated the effects of the combination of APAP and caffeine on hepatic mitochondrial bioenergetic function in mice., Main Methods: Mice were treated with caffeine (20mg/kg, intraperitoneal (i.p.)) or its vehicle and, after 30minutes, APAP (250mg/kg, i.p.) or its vehicle. Four hours later, livers were removed, and the parameters associated with mitochondrial function and oxidative stress were evaluated. Hepatic cellular oxygen consumption was evaluated by high-resolution respirometry (HRR)., Key Findings: APAP treatment decreased cellular oxygen consumption and mitochondrial complex activities in the livers of mice. Additionally, treatment with APAP increased swelling of isolated mitochondria from mice livers. On the other hand, caffeine administered with APAP was able to improve hepatic mitochondrial bioenergetic function. Treatment with APAP increased lipid peroxidation and reactive oxygen species (ROS) production and decreased glutathione levels in the livers of mice. Caffeine administered with APAP was able to prevent lipid peroxidation and the ROS production in mice livers, which may be associated with the improvement of mitochondrial function caused by caffeine treatment., Significance: We suggest that the antioxidant effects of caffeine and/or its interactions with mitochondrial bioenergetics may be involved in its beneficial effects against APAP hepatotoxicity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: This in situ study evaluated the effect of the association of low-F (4500μg F/g) gel containing TMP and FT (1100μg F/g) on enamel demineralization., Methods: This crossover and double-blind study consisted of five phases of seven days each. Volunteers (n=12) wore palatal appliances containing four enamel blocks. The cariogenic challenge was performed with 30% sucrose solution (six times/day). Treatments were: placebo toothpaste (PT, no fluoride/TMP); 1100μg F/g toothpaste (FT); FT+4500μg F/g+5%TMP gel (FT+TMP gel); FT+9000μg F/g gel (FT+9000 gel) and FT+12,300μg F/g (FT+Acid gel). After topical application of treatments for one min, two blocks were removed for analysis of loosely bound fluoride (CaF 2 ), calcium (Ca), phosphorus (P) and firmly bound fluoride (FA) formed in enamel. After the seven-day experimental periods, the percentage of surface hardness loss (%SH), integrated subsurface hardness loss (ΔKHN), CaF 2 , Ca, P and FA retained were determined. Moreover, the biofilms formed on the blocks were analyzed for F, Ca, P and insoluble extracellular polysaccharide (EPS) concentrations., Results: FT+TMP gel promoted the lowest%SH and ΔKHN (p<0.001). The highest concentration of CaF 2 formed was observed for the FT+Acid gel (p<0.001), followed by FT+9000 gel > FT+TMP gel > FT > PT. CaF 2 retained on the blocks was reduced across all groups (p<0.001). Similar values were observed for the Ca/P/F and EPS in enamel and biofilm for all fluoride groups., Conclusion: The association of FT+TMP gel significantly reduced enamel demineralization in situ., Clinical Significance: The association of treatments may be an alternative for patients with high caries risk., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Thioacetamide (TAA) is a hepatotoxin that rapidly triggers the necrotic process and oxidative stress in the liver. Nevertheless, organic selenium compounds, such as β-selenoamines, can be used as pharmacological agents to diminish the oxidative damage. Thus, the aim of this study was to investigate the protective effect of the antioxidant β-selenoamines on TAA-induced oxidative stress in mice. Here, we observed that a single intraperitoneal injection of TAA (200 mg/kg) dramatically elevated some parameters of oxidative stress, such as lipid peroxidation and reactive oxygen species (ROS) production, as well as depleted cellular antioxidant defenses. In addition, TAA-induced edema and morphological changes in the liver, which correlate with high serum aspartate and alanine aminotransferase enzyme activities, and a decrease in cell viability. Conversely, a significant reduction in liver lipid peroxidation, ROS production, and edema was observed in animals that received an intraperitoneal injection of β-selenoamines (15.6 mg/kg) 1 h after TAA administration., (© 2017 Wiley Periodicals, Inc.)

The role of physical exercise as a neuroprotective agent against ischemic injury has been extensively discussed. Nevertheless, the mechanisms underlying the effects of physical exercise on cerebral ischemia remain poorly understood. Here, we investigate the hypothesis that physical exercise increases ischemic tolerance by decreasing the induction of cellular apoptosis and glutamate release. Rats (n = 50) were submitted to a swimming exercise protocol for 8 weeks. Hippocampal slices were then submitted to oxygen and glucose deprivation. Cellular viability, pro-apoptotic markers (Caspase 8, Caspase 9, Caspase 3, and apoptosis-inducing factor), and glutamate release were analyzed. The percentage of cell death, the amount of glutamate release, and the expression of the apoptotic markers were all decreased in the exercise group when compared to the sedentary group after oxygen and glucose deprivation. Our results suggest that physical exercise protects hippocampal slices from the effects of oxygen and glucose deprivation, probably by a mechanism involving both the decrease of glutamatergic excitotoxicity and apoptosis induction., (© 2014 International Society for Neurochemistry.)

Tissue pH is an indicator of altered cellular metabolism in diseases including stroke and cancer. Ischemic tissue often becomes acidic due to increased anaerobic respiration leading to irreversible cellular damage. Chemical exchange saturation transfer (CEST) effects can be used to generate pH-weighted magnetic resonance imaging (MRI) contrast, which has been used to delineate the ischemic penumbra after ischemic stroke. In the current study, a novel MRI ratiometric technique is presented to measure absolute pH using the ratio of CEST-mediated contrast from amine and amide protons: amine/amide concentration-independent detection (AACID). Effects of CEST were observed at 2.75 parts per million (p.p.m.) for amine protons and at 3.50 p.p.m. for amide protons downfield (i.e., higher frequency) from bulk water. Using numerical simulations and in vitro MRI experiments, we showed that pH measured using AACID was independent of tissue relaxation time constants, macromolecular magnetization transfer effects, protein concentration, and temperature within the physiologic range. After in vivo pH calibration using phosphorus ((31)P) magnetic resonance spectroscopy ((31)P-MRS), local acidosis is detected in mouse brain after focal permanent middle cerebral artery occlusion. In summary, our results suggest that AACID represents a noninvasive method to directly measure the spatial distribution of absolute pH in vivo using CEST MRI.

Quantitative study aimed to identify the enterprising tendency of nurses at a university hospital and to relate them with age, length of work in the hospital and conclusion of the nursing course. This cross-sectional quantitative study was developed in 2010. All 60 nurses from the hospital answered the questionnaire General measure of Enterprising Tendency, which contains five categories. In the creativity category one nurse obtained two points; in need for achievement one nurse totaled 12 points; one nurse obtained two points; in motivation four nurses achieved higher scores; in taking calculated risks, the highest score was 10 points, in autonomy, nine nurses obtained one point each. Individuals aged between 27 and 33 years showed higher enterprising tendencies. Reduced enterprising tendencies were found for nurses aged between 43 and 56 years, graduated more than 17 years ago and with a greater length of work. Actions are necessary to encourage nurses in the age range of enterprising tendency decline and those who graduated longer ago and who have worked for a longer period of time in the hospital.

Basal forebrain cholinergic neurons, which innervate the hippocampus and cortex, have been implicated in many forms of cognitive function. Immunolesion-based methods in animal models have been widely used to study the role of acetylcholine (ACh) neurotransmission in these processes, with variable results. Cholinergic neurons have been shown to release both glutamate and ACh, making it difficult to deduce the specific contribution of each neurotransmitter on cognition when neurons are eliminated. Understanding the precise roles of ACh in learning and memory is critical because drugs that preserve ACh are used as treatment for cognitive deficits. It is therefore important to define which cholinergic-dependent behaviors could be improved pharmacologically. Here we investigate the contributions of forebrain ACh on hippocampal synaptic plasticity and cognitive behavior by selective elimination of the vesicular ACh transporter, which interferes with synaptic storage and release of ACh. We show that elimination of vesicular ACh transporter in the hippocampus results in deficits in long-term potentiation and causes selective deficits in spatial memory. Moreover, decreased cholinergic tone in the forebrain is linked to hyperactivity, without changes in anxiety or depression-related behavior. These data uncover the specific contribution of forebrain cholinergic tone for synaptic plasticity and behavior. Moreover, these experiments define specific cognitive functions that could be targeted by cholinergic replacement therapy.

We intended to identify and evaluate the association between the socio-demographic and epidemiological characteristics of elderly people with their nutritional characteristics. This is a transversal study PMTI (from the Portuguese name of "Programa Municipal da Terceira Idade"), conducted at Viçosa, MG, Brazil. We analyzed 93 records of elderly people registered since 2006 and who underwent nutritional care. After having analyzed the questionnaire, we performed the descriptive and association analyses in the Epi Info (version 6.04) and Minitab softwares. Of the 93 analyzed records, most elderly people were women (80.4%), with an average of 72 years of age, of which 13.0% were long-lived people. The mean body mass index (BMI) was 27.4 kg/m(2), and 50.5% were overweight. We have found 26.8% elderly patients with hypertension, and 31.6% took antihypertensives. Elderly patients who were overweight are 4.54 times more likely to have arterial hypertension (odds ratio (OR)=4.54; 95% confidence interval (CI)=1.2-2.45). Only 7.5% smoked, 30.1% were alcoholics and 60.2% made physical activities. Inadequacies were found regarding the servings of fruits, dairy products, vegetables and sugars consumed. However, the servings of cereals, leguminous, meat and fat consumed were appropriate. This study showed that the nutritional diagnosis and the epidemiological and socio-demographic studies are critical tools to understand this population group, in addition to being important to the planning of health actions., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)