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Sample records for adaptations impaired oxidative

  1. Elevated mitochondrial oxidative stress impairs metabolic adaptations to exercise in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Justin D Crane

    Full Text Available Mitochondrial oxidative stress is a complex phenomenon that is inherently tied to energy provision and is implicated in many metabolic disorders. Exercise training increases mitochondrial oxidative capacity in skeletal muscle yet it remains unclear if oxidative stress plays a role in regulating these adaptations. We demonstrate that the chronic elevation in mitochondrial oxidative stress present in Sod2 (+/- mice impairs the functional and biochemical mitochondrial adaptations to exercise. Following exercise training Sod2 (+/- mice fail to increase maximal work capacity, mitochondrial enzyme activity and mtDNA copy number, despite a normal augmentation of mitochondrial proteins. Additionally, exercised Sod2 (+/- mice cannot compensate for their higher amount of basal mitochondrial oxidative damage and exhibit poor electron transport chain complex assembly that accounts for their compromised adaptation. Overall, these results demonstrate that chronic skeletal muscle mitochondrial oxidative stress does not impact exercise induced mitochondrial biogenesis, but impairs the resulting mitochondrial protein function and can limit metabolic plasticity.

  2. Adaptive behavior of children with visual impairment

    Directory of Open Access Journals (Sweden)

    Anđelković Marija

    2014-01-01

    Full Text Available Adaptive behavior includes a wide range of skills necessary for independent, safe and adequate performance of everyday activities. Practical, social and conceptual skills make the concept of adaptive behavior. The aim of this paper is to provide an insight into the existing studies of adaptive behavior in persons with visual impairment. The paper mainly focuses on the research on adaptive behavior in children with visual impairment. The results show that the acquisition of adaptive skills is mainly low or moderately low in children and youth with visual impairment. Children with visual impairment achieve the worst results in social skills and everyday life skills, while the most acquired are communication skills. Apart from the degree of visual impairment, difficulties in motor development also significantly influence the acquisition of practical and social skills of blind persons and persons with low vision.

  3. Addition of Hyperoxic Component to Adaptation to Hypoxia Prevents Impairments Induced by Low Doses of Toxicants (Free Radical Oxidation and Proteins of HSP Family).

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    Sazontova, T G; Stryapko, N V; Arkhipenko, Yu V

    2016-01-01

    We studied the possibility of preventing disturbances caused by administration of low doses of toxicants by adaptation to interval hypoxia and hyperoxia. The preventive protective effect of adaptation to hypoxia-hyperoxia manifested in suppression of free radical oxidation, decrease in the levels of HIF-1α and inducible HOx-1, and improvement of tolerance to physical exercises.

  4. Serosal patching impairs intestinal adaptation following enterectomy.

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    Bragg, L E; Thompson, J S

    1992-02-01

    Increasing intestinal absorptive surface by mucosal regeneration on serosal patched intestinal defects is a potential surgical treatment for the short bowel syndrome. We previously found in long-term studies that serosal patching in dogs undergoing 75% enterectomy was deleterious to intestinal adaptation and absorption. Our aim was to evaluate the effect of serosal patching on the early morphologic and functional changes in postresectional adaptation and to examine the role of polyamine metabolic pathways in this process. Five unoperated New Zealand white rabbits (GP I) served as controls. Twelve other rabbits underwent either 50% distal enterectomy alone (GP II) or simultaneously had two 2 x 5-cm full-thickness ileal defects patched with adjacent cecal serosa (GP III). Animals in GP II gained an average of 7.2 +/- 5.3% body weight, whereas GP III animals lost 5.6 +/- 9.0% body weight (P less than 0.05). Intestinal remnant length was significantly less in GP III 3 weeks postoperatively (66 +/- 11 vs 85 +/- 8 cm, P less than 0.05) as was mucosal protein content (4.1 +/- 1.8% vs 6.2 +/- 1.9%) but villus height was similar in GPs II and III (505 +/- 131 vs 508 +/- 110 microns). In vitro mucosal function was similar in all three groups. Crypt cell production rate was significantly lower while ornithine decarboxylase and diamine oxidase activity were higher in GP III compared to GP II. However, polyamine levels were similar in all three groups. Serosal patching impairs intestinal adaptation following massive enterectomy. This is due in part to a decrease in proliferative activity which is not directly related to altered polyamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Oxidation of multiple methionine residues impairs rapid sodium channel inactivation

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    Kassmann, Mario; Hansel, Alfred; Leipold, Enrico; Birkenbeil, Jan; Lu, Song-Qing; Hoshi, Toshinori; Heinemann, Stefan H.

    2010-01-01

    Reactive oxygen species (ROS) readily oxidize the sulfur-containing amino acids cysteine and methionine (Met). The impact of Met oxidation on the fast inactivation of the skeletal muscle sodium channel NaV1.4 expressed in human embryonic kidney cells was studied by applying the Met-preferring oxidant chloramine-T (ChT) or by irradiating the ROS-producing dye Lucifer Yellow in the patch pipettes. Both interventions dramatically slowed down inactivation of the sodium channels. Replacement of Met in the Ile-Phe-Met inactivation motif with Leu (M1305L) strongly attenuated the oxidizing effect on inactivation but did not eliminate it completely. Mutagenesis of conserved Met residues in the intracellular linkers connecting the membrane-spanning segments of the channel (M1469L and M1470L) also markedly diminished the oxidation sensitivity of the channel, while that of other conserved Met residues (442, 1139, 1154, 1316) were without any noticeable effect. The results of mutagenesis of results, assays of other NaV channel isoforms (NaV1.2, NaV1.5, NaV1.7) and the kinetics of the oxidation-induced removal of inactivation collectively indicate that multiple Met target residues need to be oxidized to completely impair inactivation. This arrangement using multiple Met residues confers a finely graded oxidative modulation of NaV channels and allows organisms to adapt to a variety of oxidative stress conditions, such as ischemic reperfusion. PMID:18369661

  6. Adapting the Brief COPE for Chinese Adolescents with Visual Impairments

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    Yuan, Wei; Zhang, Li-fang; Li, Bing

    2017-01-01

    Introduction: The present research pioneered the effort in assessing adolescents' coping with visual impairment through adapting the Brief COPE in an eastern context. The first study preliminarily explored the applicability of the Brief COPE to Chinese adolescent students with visual impairments. Based on the results, the Brief COPE was modified…

  7. Loneliness, adaptation to vision impairment, social support and depression among visually impaired elderly

    NARCIS (Netherlands)

    Verstraten, P.F.J.; Brinkmann, W.L.J.H.; Stevens, N.L.; Schouten, J.S.A.G.

    2006-01-01

    The purpose of this study is to investigate the prevalence of loneliness among visually impaired elderly, and its relations with adaptation to vision loss, received social support and depression. Clients aged 55 years or older who contacted Sensis, a rehabilitation centre for visually impaired

  8. Adapting to the Hearing Impaired Dental Student.

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    Javid, Nikzad S.; And Others

    1986-01-01

    The curricular adaptations made at the University of Florida College of Dentistry to accommodate a deaf student are described. Because most of the didactic instructional material was presented in a self-paced audiovisual format, all videotapes were either transcribed or outlined. (MLW)

  9. Automatically Adapting Home Lighting to Assist Visually Impaired Children

    OpenAIRE

    Freeman, Euan; Wilson, Graham; Brewster, Stephen

    2016-01-01

    For visually impaired children, activities like finding everyday items, locating favourite toys and moving around the home can be challenging. Assisting them during these activities is important because it promotes independence and encourages them to use and develop their remaining visual function. We describe our work towards a system that adapts the lighting conditions at home to help visually impaired children with everyday tasks. We discuss scenarios that show how they may benefit from ad...

  10. Familiar Sports and Activities Adapted for Multiply Impaired Persons.

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    Schilling, Mary Lou, Ed.

    1984-01-01

    Means of adapting some familiar and popular physical activities for multiply impaired persons are described. Games reviewed are dice baseball, one base baseball, in-house bowling, wheelchair bowling, ramp bowling, swing-ball bowling, table tennis, shuffleboard, beanbag bingo and tic-tac-toe, balloon basketball, circle football, and wheelchair…

  11. Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Christiansen, Liselotte Bruun; Dela, Flemming; Koch, Jørgen

    2015-01-01

    Mitochondrial dysfunction and oxidative stress are important players in the development of various cardiovascular diseases, but their roles in hypertrophic cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative phosphorylation (OXPHOS) capacity was impaired with enhanced...

  12. Nitric oxide in adaptation to altitude

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    Laskowski, Daniel; Erzurum, Serpil C.

    2012-01-01

    This review summarizes published information on levels of nitric oxide gas (NO) in the lungs and NO-derived liquid phase molecules in the acclimatization of visitors newly arrived at altitudes of 2500m or more and adaptation of populations whose ancestors arrived thousands of years ago. Studies of acutely exposed visitors to high altitude focus on the first 24–48 hours with just a few extending to days or weeks. Among healthy visitors, NO levels in the lung, plasma and/or red blood cells fell within three hours, but then returned toward baseline or slightly higher by 48 hours, and increased above baseline by 5 days. Among visitors ill with high-altitude pulmonary edema at the time of the study or in the past, NO levels were lower than their healthy counterparts. As for highland populations, Tibetans had NO levels in the lung, plasma and red blood cells that were at least double and in some cases orders of magnitude greater than other populations regardless of altitude. Red blood cell associated nitrogen oxides were more than two hundred times higher. Other highland populations had generally higher levels although not to the degree showed by Tibetans. Overall, responses of those acclimatized and those presumed to be adapted are in the same direction although the Tibetans have much larger responses. Missing are long-term data on lowlanders at altitude showing how similar they become to the Tibetan phenotype. Also missing are data on Tibetans at low altitude to see the extent to which their phenotype is a response to the immediate environment or expressed constitutively. The mechanisms causing the visitors’ and the Tibetans’ high levels of NO and NO-derived molecules at altitude remain unknown. Limited data suggest processes including hypoxic upregulation of NO synthase gene expression, hemoglobin-NO reactions and genetic variation. Gains in understanding will require integrating appropriate methods and measurement techniques with indicators of adaptive function

  13. Divided attention impairs human motor adaptation but not feedback control.

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    Taylor, Jordan A; Thoroughman, Kurt A

    2007-07-01

    When humans experience externally induced errors in a movement, the motor system's feedback control compensates for those errors within the movement. The motor system's predictive control then uses information about those errors to inform future movements. The role of attention in these two distinct motor processes is unclear. Previous experiments have revealed a role for attention in motor learning over the course of many movements; however, these experimental paradigms do not determine how attention influences within-movement feedback control versus across-movement adaptation. Here we develop a dual-task paradigm, consisting of movement and audio tasks, which can differentiate and expose attention's role in these two processes of motor control. Over the course of several days, subjects performed horizontal reaching movements, with and without the audio task; movements were occasionally subjected to transient force perturbations. On movements with a force perturbation, subjects compensated for the force-induced movement errors, and on movements immediately after the force perturbation subjects exhibited adaptation. On every movement trial, subjects performed a two-tone frequency-discrimination task. The temporal specificity of the frequency-discrimination task allowed us to divide attention within and across movements. We find that divided attention did not impair the within-movement feedback control of the arm, but did reduce subsequent movement adaptation. We suggest that the secondary task interfered with the encoding and transformation of errors into changes in predictive control.

  14. Adaptive changes in autophagy after UPS impairment in Parkinson's disease.

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    Shen, Yu-fei; Tang, Yu; Zhang, Xiao-jie; Huang, Kai-xing; Le, Wei-dong

    2013-05-01

    Ubiquitin-proteasome system (UPS) and autophagosome-lysosome pathway (ALP) are the most important machineries responsible for protein degradation in Parkinson's disease (PD). The aim of this study is to investigate the adaptive alterations in autophagy upon proteasome inhibition in dopaminergic neurons in vitro and in vivo. Human dopaminergic neuroblastoma SH-SY5Y cells were treated with the proteasome inhibitor lactacystin (5 μmol/L) for 5, 12, or 24 h. The expression of autophagy-related proteins in the cells was detected with immunoblotting. UPS-impaired mouse model of PD was established by microinjection of lactacystin (2 μg) into the left hemisphere of C57BL/6 mice that were sacrificed 2 or 4 weeks later. The midbrain tissues were dissected to assess alterations in autophagy using immunofluorescence, immunoblotting and electron microscopy assays. Both in SH-SY5Y cells and in the midbrain of UPS-impaired mouse model of PD, treatment with lactacystin significantly increased the expression levels of LC3-I/II and Beclin 1, and reduced the levels of p-mTOR, mTOR and p62/SQSTM1. Furthermore, lactacystin treatment in UPS-impaired mouse model of PD caused significant loss of TH-positive neurons in the substantia nigra, and dramatically increased the number of autophagosomes in the left TH-positive neurons. Inhibition of UPS by lactacystin in dopaminergic neurons activates another protein degradation system, the ALP, which includes both the mTOR signaling pathway and Beclin 1-associated pathway.

  15. Oxidation and Cognitive Impairment in the Aging Zebrafish.

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    Ruhl, Tim; Jonas, Annika; Seidel, Nathan Ian; Prinz, Nicole; Albayram, Onder; Bilkei-Gorzo, Andras; von der Emde, Gerhard

    2015-01-01

    The zebrafish has become an established model organism in aging research giving insight into general aging processes in vertebrates. Oxidative stress in aging may damage proteins and lipids in brain cells. Enhanced levels of oxidized macromolecules exert neurotoxic effects that could lead to disturbances in neuronal functioning and cognitive skills. This study aims to investigate a possible relation between oxidative stress and learning deficits during aging in zebrafish. We tested zebrafish of different ages in a color discrimination paradigm for associative learning and in a hole board task for spatial learning abilities. Afterwards, we determined the levels of oxidized lipids and proteins as well as the amount of lipofuscin in the learning-relevant brain regions of animals of the same age. While young zebrafish at the age of 1 year successfully completed both learning tasks, cognitive abilities were significantly impaired in older animals. Learning deficits occurred at the age of 2 years, where we also detected significantly increased levels of lipofuscin and oxidized proteins in the zebrafish medial and lateral pallial areas of the dorsal telencephalon. These data suggest that enhanced oxidative stress may contribute to behavioral and cognitive impairments in the aging zebrafish. © 2015 S. Karger AG, Basel.

  16. Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes.

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    Delmaghani, Sedigheh; Defourny, Jean; Aghaie, Asadollah; Beurg, Maryline; Dulon, Didier; Thelen, Nicolas; Perfettini, Isabelle; Zelles, Tibor; Aller, Mate; Meyer, Anaïs; Emptoz, Alice; Giraudet, Fabrice; Leibovici, Michel; Dartevelle, Sylvie; Soubigou, Guillaume; Thiry, Marc; Vizi, E Sylvester; Safieddine, Saaid; Hardelin, Jean-Pierre; Avan, Paul; Petit, Christine

    2015-11-05

    A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The impact of psychosocial adaptation status on quality of life for Chinese patients with visual impairments.

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    Zhang, Xiu-jie; Wang, Ai-ping; Yin, An-chun

    2014-01-01

    To analyse the association of psychosocial adaptation with quality of life and to examine the influential factors for Chinese people with visual impairments. The status of psychosocial adaptation is the main influential factor for quality of life. The correlation between psychosocial adaptation and quality of life for various diseases has been studied previously. However, there have been few reports on the impact of psychosocial adaptation on quality of life in people with visual impairments. Survey. In this study, subjects with visual impairment (n = 213) were interviewed to assess their demographics, disease-related information, psychosocial adaptation status and quality of life. The psychosocial adaptation questionnaire and quality of life scale for visually impaired patients were used to survey psychosocial adaptation and quality of life. Correlation and multiple stepwise regression analyses were used to study the association of psychosocial adaptation with quality of life in visually impaired patients. Psychosocial adaptation was significantly associated with quality of life, including the sense of belonging and psychological dimensions. The results also showed that there was statistical significance for the impact of occupational status, payment, monthly income (family), vision classification and psychosocial adaptation on quality of life, and the status of psychosocial adaptation was the main factor affecting the quality of life in people with visual impairments. It was found that the status of psychosocial adaptation was conspicuously associated with multiple dimensions of quality of life. Therefore, psychosocial adaptation status should be given close attention in clinical care. Our results could be used to guide nurses in making a plan for health education and nursing that improves the quality of life for the visually impaired. © 2012 Blackwell Publishing Ltd.

  18. 5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.

    Directory of Open Access Journals (Sweden)

    Adriana Secatto

    Full Text Available 5-Lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO(-/- mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO(-/- mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.

  19. A Defective Oxidative Burst and Impaired Antigen Presentation are Hallmarks of Human Visceral Leishmaniasis.

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    Roy, Susmita; Mukhopadhyay, Debanjan; Mukherjee, Shibabrata; Ghosh, Susmita; Kumar, Shishir; Sarkar, Kumkum; Pal, Dipankar; Bhowmik, Pratik; Mandal, Kausik; Modak, Dolanchampa; Guha, Subhasish Kamal; Pramanik, Netai; Goswami, Rama Prosad; Saha, Bibhuti; Chatterjee, Mitali

    2015-01-01

    Survival of the Leishmania parasite within monocytes hinges on its ability to effectively nullify their microbicidal effector mechanisms. Accordingly, this study aimed to delineate this biological niche in patients with visceral leishmaniasis (VL). In monocytes, the redox status, antigen presenting capacity, expression of Toll-like receptors (TLRs), co-stimulatory molecules (CD80/86) and generation of intracellular cytokines (IL-8, IL-1β, IL-10 and LAP-TGF-β1) was measured by flow cytometry, levels of circulating cytokines (IL-1β, IL-6, TNF-α, IL-8, IL-4, IL-13, IL-10 and GM-CSF) by ELISA and arginase activity by spectrophotometry. Within monocytes, generation of an oxidative burst was markedly attenuated as evident by decreased generation of nitric oxide and reactive oxygen species, concomitant with raised levels of thiols. This was accompanied by lowered frequency of TLR4(+) monocytes, but the arginase activity remained unaltered. Pathogen persistence was enhanced by the predominance of anti-inflammatory cytokines within monocytes, notably IL-10. Alongside, development of adaptive immunity was severely attenuated as manifested by a pronounced impairment of antigen presentation and co-stimulation evident by down regulation of CD54, HLA-DR and CD86. Treatment corrected the redox imbalance and reversed the impaired antigen presentation. In VL, monocyte functions were severely impaired facilitating parasite persistence; anti-leishmanial chemotherapy mediated parasite elimination through modulation of the macrophage microenvironment by restoring its redox status and antigen presenting capacity.

  20. Adaptability of the oxidative capacity of motoneurons

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    Chalmers, G. R.; Roy, R. R.; Edgerton, V. R.

    1992-01-01

    Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

  1. Systemic adaptation to oxidative challenge induced by regular exercise.

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    Radak, Zsolt; Chung, Hae Young; Goto, Sataro

    2008-01-15

    Exercise is associated with increased ATP need and an enhanced aerobic and/or anaerobic metabolism, which results in an increased formation of reactive oxygen species (ROS). Regular exercise seems to decrease the incidence of a wide range of ROS-associated diseases, including heart disease, type II diabetes, rheumatic arthritis, Alzheimer and Parkinson diseases, and certain cancers. The preventive effect of regular exercise, at least in part, is due to oxidative stress-induced adaptation. The oxidative challenge-related adaptive process of exercise is probably not just dependent upon the generated level of ROS but primarily on the increase in antioxidant and housekeeping enzyme activities, which involves the oxidative damage repair enzymes. Therefore, the effects of exercise resemble the characteristics of hormesis. In addition, it seems that the oxidative challenge-related effects of exercise are systemic. Skeletal muscle, liver, and brain have very different metabolic rates and functions during exercise, but the adaptive response is very similar: increased antioxidant/damage repair enzyme activity, lower oxidative damage, and increased resistance to oxidative stress, due to the changes in redox homeostasis. Hence, it is highly possible that the well-known beneficial effects of exercise are due to the capability of exercise to produce increased levels of ROS. Or in other words, it seems that the vulnerability of the body to oxidative stress and diseases is significantly enhanced in a sedentary compared to a physically active lifestyle.

  2. Parkinson's disease associated with impaired oxidative phosphorylation

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    Finsterer, J. [Ludwig Boltzmann Inst. for Research in Epilepsy and Neuromuscular Disorders and 2. Neurological Dept., Neurological Hospital Rosenhuegel, Vienna (Austria); Jarius, C. [Institute of Clinical Neurology, University of Vienna, Vienna (Austria); Baumgartner, M. [Radiological Dept., Municipal Hospital Lainz, Vienna (Austria)

    2001-11-01

    Parkinson's disease may be due to primary or secondary oxidative phosphorylation (OXPHOS) defects. In a 76-year-old man with Parkinson's disease since 1992, slightly but recurrently elevated creatine phosphokinase, recurrently elevated blood glucose, thickening of the left ventricular myocardium, bifascicular block and hypacusis were found. Cerebral MRI showed atrophy, periventricular demyelination, multiple, disseminated, supra- and infratentorial lacunas, and haemosiderin deposits in both posterior horns. Muscle biopsy showed typical features of an OXPHOS defect. Whether the association of Parkinson's disease and impaired OXPHOS was causative or coincidental remains unknown. Possibly, the mitochondrial defect acted as an additional risk factor for Parkinson's disease or the OXPHOS defect worsened the preexisting neurological impairments by a cumulative or synergistic mechanism. In conclusion, this case shows that Parkinson's disease may be associated with a mitochondrially or nuclearly encoded OXPHOS defect, manifesting as hypacusis, myopathy, axonal polyneuropathy, cardiomyopathy and recurrent subclinical ischaemic strokes and haemorrhages. (orig.)

  3. High glucose-mediated oxidative stress impairs cell migration.

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    Marcelo L Lamers

    Full Text Available Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit cell migration. Using CHO.K1 cells, NIH-3T3 fibroblasts, mouse embryonic fibroblasts and primary skin fibroblasts from control and diabetic rats cultured in 5 mM D-glucose (low glucose, LG, 25 mM D-glucose (high glucose, HG or 25 mM L-glucose medium (osmotic control--OC, we analyzed the migration speed, protrusion stability, cell polarity, adhesion maturation and the activity of the small Rho GTPase Rac1. We also analyzed the effects of reactive oxygen species by incubating cells with the antioxidant N-Acetyl-Cysteine (NAC. We observed that HG conditions inhibited cell migration when compared to LG or OC. This inhibition resulted from impaired cell polarity, protrusion destabilization and inhibition of adhesion maturation. Conversely, Rac1 activity, which promotes protrusion and blocks adhesion maturation, was increased in HG conditions, thus providing a mechanistic basis for the HG phenotype. Most of the HG effects were partially or completely rescued by treatment with NAC. These findings demonstrate that HG impairs cell migration due to an increase in oxidative stress that causes polarity loss, deficient adhesion and protrusion. These alterations arise, in large part, from increased Rac1 activity and may contribute to the poor wound healing observed in diabetic patients.

  4. Development of a psychosocial adaptation questionnaire for Chinese patients with visual impairments.

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    Zhang, Xiu-jie; Wang, Ai-ping

    2011-10-01

    To develop a psychosocial adaptation questionnaire for Chinese patients with visual impairments and to examine its reliability and validity. Psychosocial adaptation with disease has been studied, however, there have been few reports on the impact of visual impairment on psychosocial adaptation. An instrument has not been developed to assess psychosocial adaptation with visual impairment specifically for patients in China. Both qualitative and quantitative research methods were used. A questionnaire was developed based on the concept of psychosocial adaptation with visual impairment. Items for the questionnaire were developed by reviewing the literature and carrying out a semi-structured interview with 12 visually impaired patients. Five ophthalmologists and ten patients evaluated the content validity and face validity of the questionnaire, respectively. The method of convenient sampling was used to select 213 visually impaired patients in the Ophthalmology Department of the First Affiliated Hospital of China Medical University to participate in the study. Discriminative index and item-total correlation analyses were used to delete items that were lower than a set criterion. Regarding construct validity, factor analysis was performed. The Self-rating Anxiety Scale (SAS), General Self-Efficacy Scale (GSES) and Self Acceptance Questionnaire (SAQ) were used to evaluate criterion validity. Cronbach's alpha coefficient was used as an index of internal consistency. To evaluate test-retest reliability, 50 patients were re-evaluated after 24 hours. A total of 204 questionnaire items were created. 22 items were deleted by discriminative index and item-total correlation before factor analysis; 38 items were entered into the model for factor analysis. Seven factors were extracted by using principal factor analysis and varimax rotation, with a cumulative contribution of 59·18%. The correlation coefficients between the psychosocial adaptation questionnaire for visual impairment

  5. Yoga-teaching protocol adapted for children with visual impairment.

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    Mohanty, Soubhagyalaxmi; Hankey, Alex; Pradhan, Balaram; Ranjita, Rajashree

    2016-01-01

    Childhood visual deficiency impairs children's neuro-psychomotor development, considerably affecting physical, mental, social, and emotional health. Yoga's multifaceted approach may help children with visual impairment (VI) to cope with their challenges. This study aimed to develop a special protocol for teaching yoga to children with VI, and to evaluate their preferred method of learning. The study was carried out at Ramana Maharishi Academy for the Blind, Bengaluru, South India. Forty-one students volunteered to learn yoga practices, and classes were held weekly 5 days, 1 hr per session for 16 weeks. The study introduced a new method using a sequence of five teaching steps: verbal instructions, tactile modeling, step-by-step teaching, learning in a group, and physical guidance. A questionnaire concerning the preferred steps of learning was then given to each student, and verbal answers were obtained. A total of 33 (out of 41), aged 11.97 ± 1.94, 15 girls and 18 boys responded. Twenty-six (78.79%) chose physical guidance as their most favored learning mode. Specially designed protocol may pave the way to impart yoga in an exciting and comfortable way to children with VI. More studies are needed to further investigate the effectiveness of this new yoga protocol in similar settings.

  6. Exercise-induced oxidative stress: A tool for “hormesis” and “adaptive response”

    National Research Council Canada - National Science Library

    Koyama, Katsuhiro

    2014-01-01

    ... adaptation to physical exercise. It is becoming increasingly clear that exercise-related beneficial adaptations are strongly regulated by exercise-induced oxidative stress, consistent with hormesis theory...

  7. Sanation of carious and periapical foci in young athletes with impairment of cardiovascular adaptation

    Directory of Open Access Journals (Sweden)

    I. I. Belyaev

    2014-01-01

    Full Text Available The aim of this study was to evaluate the impact of sanation of oral cavity in young athletes on the course of adaptation of the cardiovascular system to the condition of sports activities. According to the research results, it was revealed that the optimal period for sanation of periapical odontogenic foci in athletes with clinical signs of impairment (dysfunction of cardiovascular system adaptation to exercise stress was a preparatory training period, while carious lesion sanation required preparatory or postcompetition periods.

  8. Cross-Cultural Adaptation of a Developmental Assessment for Arabic-Speaking Children with Visual Impairment

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    Macrine, Sheila L.; Heji, Hayat; Sabri, Amel; Dalton, Sara

    2015-01-01

    Developmental screening has become an established component of child health programs in many developed countries. The research objective of this project was to translate and adapt a developmental assessment (Oregon Project Skills Inventory) for use with young children with visual impairments who speak Arabic. The study was prompted by the lack of…

  9. Classification of the Hearing Impaired for Independent Living Using the Vineland Adaptive Behavior Scale.

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    Dunlap, William R.; Sands, Deanna Iceman

    1990-01-01

    The Vineland Adaptive Behavior Scale was used to classify 118 hearing-impaired persons (88 percent were ages 16-21) into groups based on their ability to be trained in independent living skills. Using cluster analysis, the subjects were placed into three groups according to four domains: communication, daily living, socialization, and maladaptive…

  10. Guidelines for Assessing the Need for Adaptive Devices for Visually Impaired Pedestrians at Signalized Intersections.

    Science.gov (United States)

    Gallagher, Brian R.; de Oca, Patricia Montes

    1998-01-01

    Presents guidelines for orientation and mobility instructors and traffic engineers to assess the need for adaptive devices to make crosswalks at signalized intersections accessible to pedestrians with visual impairments. The discussions of audible and tactile pedestrian devices, along with case examples, distinguish when each device should be…

  11. Guidelines for the Practice of Adaptive Diabetes Education for Visually Impaired Persons.

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    Berkowitz, Kathy

    1993-01-01

    This article presents guidelines developed by the American Association of Diabetes Educators concerning adaptive diabetes education for visually impaired persons (ADEVIP). The article discusses definitions, values, and assumptions; recommended professional educational background; role delineation; and process and content of ADEVIP. (DB)

  12. Nitrate tolerance impairs nitric oxide-mediated vasodilation in vivo

    DEFF Research Database (Denmark)

    Laursen, Jørn Bech; Boesgaard, Søren; Poulsen, Henrik E.

    1996-01-01

    Nitrates, Nitrate tolerence, Nitric oxide, acetylcholine, N-acetylcholine, N-acetylcysteine, L-NAME, Rat, Anesthetized......Nitrates, Nitrate tolerence, Nitric oxide, acetylcholine, N-acetylcholine, N-acetylcysteine, L-NAME, Rat, Anesthetized...

  13. Triiodothyronine activates lactate oxidation without impairing fatty acid oxidation and improves weaning from extracorporeal membrane oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Kajimoto, Masaki; Ledee, Dolena R.; Xu, Chun; Kajimoto, Hidemi; Isern, Nancy G.; Portman, Michael A.

    2014-01-01

    Background: Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. We previously showed that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study was focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. Methods: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 hours) and wean: normal circulation (Group-C);transient coronary occlusion (10 minutes) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon labeled lactate, medium-chain and long-chain FAs were infused as oxidative substrates. Substrate fractional contribution to the citric acid cycle (FC) was analyzed by 13-Carbon nuclear magnetic resonance. Results: ECMO depressed circulating T3 levels to 40% baseline at 4 hours and were restored in Group-IR-T3. Group-IR decreased cardiac power, which was not fully restorable and 2 pigs were lost because of weaning failure. Group-IR also depressed FC-lactate, while the excellent contractile function and energy efficiency in Group-IR-T3 occurred along with a marked FC-lactate increase and [ATP]/[ADP] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. Conclusions: T3 releases inhibition of lactate oxidation following ischemia-reperfusion injury without impairing FA oxidation. These findings indicate that T3 depression during ECMO is maladaptive, and that restoring levels improves metabolic flux and enhances contractile function during weaning.

  14. OXIDATIVE STRESS IN MUSCLE GROWTH AND ADAPTATION TO PHYSICAL EXERCISE

    Directory of Open Access Journals (Sweden)

    Ihor Yurkevych

    2015-05-01

    Full Text Available In a few last decades oxidative stress detected in a variety of physiological processes where reactive oxygen species (ROS and reactive nitrogen species (RNS play a central role. They are directly involved in oxidation of proteins, lipids and nucleic acids. In certain concentrations they are necessary for cell division, proliferation and apoptosis. Contractile muscle tissue at aerobic conditions form high ROS flow that may modulate a variety of cell functions, for example proliferation. However, slight increase in ROS level provide hormetic effect which may participate in adaptation to heavy weight training resulted in hypertrophy and proliferation of skeletal muscle fibers. This review will discuss ROS types, sites of generation, strategies to increase force production and achieve skeletal muscle hypertrophy.

  15. Perceptual Adaptation to Room Acoustics and Effects on Speech Intelligibility in Hearing-Impaired Populations

    Science.gov (United States)

    Zahorik, Pavel; Brandewie, Eugene

    2012-01-01

    Summary Recent evidence suggests that brief listening exposure to a reverberant room environment can improve closed-set speech intelligibility in that same environment. For normal-hearing populations, this room adaptation effect can result in improvements in intelligibility of as much as 20%, but depends strongly on the reverberation time of the room, and appears to require binaural input. Because poor speech intelligibility in reverberation is a common complaint for hearing-impaired listeners, it is important to determine how room adaptation might impact speech intelligibility for hearing-impaired populations. Here, room adaptation was quantified for a sample of listeners with sensorineural hearing loss that varied in severity and configuration. Speech reception thresholds (SRTs) were measured both with and without prior listening exposure to the room environment. Headphone-based auralization techniques were used to simulate the acoustics of various listening rooms, ranging from anechoic to highly reverberant space (broadband T60 = 3 s). Although SRTs both with and without prior room exposure were found to be generally elevated relative to normal-hearing listeners, the room adaptation effect, as defined by the relative decrease in SRT with room exposure, was comparable on average to that observed for normal-hearing listeners. This result is consistent with the view that room adaptation effects result from central auditory processing mechanisms. PMID:23455358

  16. Perceptual Adaptation to Room Acoustics and Effects on Speech Intelligibility in Hearing-Impaired Populations.

    Science.gov (United States)

    Zahorik, Pavel; Brandewie, Eugene

    2011-06-27

    Recent evidence suggests that brief listening exposure to a reverberant room environment can improve closed-set speech intelligibility in that same environment. For normal-hearing populations, this room adaptation effect can result in improvements in intelligibility of as much as 20%, but depends strongly on the reverberation time of the room, and appears to require binaural input. Because poor speech intelligibility in reverberation is a common complaint for hearing-impaired listeners, it is important to determine how room adaptation might impact speech intelligibility for hearing-impaired populations. Here, room adaptation was quantified for a sample of listeners with sensorineural hearing loss that varied in severity and configuration. Speech reception thresholds (SRTs) were measured both with and without prior listening exposure to the room environment. Headphone-based auralization techniques were used to simulate the acoustics of various listening rooms, ranging from anechoic to highly reverberant space (broadband T60 = 3 s). Although SRTs both with and without prior room exposure were found to be generally elevated relative to normal-hearing listeners, the room adaptation effect, as defined by the relative decrease in SRT with room exposure, was comparable on average to that observed for normal-hearing listeners. This result is consistent with the view that room adaptation effects result from central auditory processing mechanisms.

  17. Adaptive control with state-dependent modeling of patient impairment for robotic movement therapy.

    Science.gov (United States)

    Bower, C; Taheri, H; Wolbrecht, E

    2013-06-01

    This paper presents an adaptive control approach for robotic movement therapy that learns a state-dependent model of patient impairment. Unlike previous work, this approach uses an unstructured inertial model that depends on both the position and direction of the desired motion in the robot's workspace. This method learns a patient impairment model that accounts for movement specific disability in neuro-muscular output (such as flexion vs. extension and slow vs. dynamic tasks). Combined with assist-as-needed force decay, this approach may promote further patient engagement and participation. Using the robotic therapy device, FINGER (Finger Individuating Grasp Exercise Robot), several experiments are presented to demonstrate the ability of the adaptive control to learn state-dependent abilities.

  18. Development of a School Adaptation Program for Elementary School Students with Hearing Impairment

    OpenAIRE

    Kim, Shin-Jeong; Kwon, Myung Soon; Han, Woojae

    2015-01-01

    Background and Objectives Although new technology of assistive listening device leads many hard of hearing children to be mainstreamed in public school programs, many clinicians and teachers still wonder whether the children are able to understand all instruction, access educational materials, and have social skills in the school. The purpose of this study is to develop a school adaptation program (SAP) for the hearing-impaired children who attend public elementary school. Subjects and Method...

  19. The impairment of glucose-stimulated insulin secretion in pancreatic β-cells caused by prolonged glucotoxicity and lipotoxicity is associated with elevated adaptive antioxidant response.

    Science.gov (United States)

    Fu, Jingqi; Cui, Qi; Yang, Bei; Hou, Yongyong; Wang, Huihui; Xu, Yuanyuan; Wang, Difei; Zhang, Qiang; Pi, Jingbo

    2017-02-01

    Type 2 diabetes (T2D) is a progressive disease characterized by sustained hyperglycemia and is frequently accompanied by hyperlipidemia. Deterioration of β-cell function in T2D patients may be caused, in part, by long-term exposure to high concentrations of glucose and/or lipids. We developed systems to study how chronic glucotoxicity and lipotoxicity might be linked to the impairment of glucose-stimulated insulin secretion (GSIS) machinery in pancreatic β-cells. INS-1 (832/13) were exposed to glucose and/or palmitate for up to 10 weeks. Chronic high glucose and/or palmitate exposure resulted in impaired GSIS accompanied by a dramatic increase in oxidative stress, as determined by basal intracellular peroxide levels. In addition, the GSIS-associated reactive oxygen species (ROS) signals, assessed as glucose-stimulated peroxide accumulation positively correlated with GSIS in glucose- and/or palmitate-exposed cells, as well as glucose-stimulated reductions in GSH/GSSG ratios. Furthermore, the impairment of GSIS caused by chronic high glucose and/or palmitate exposures were attributed to the induction of adaptive antioxidant response and mitochondrial uncoupling, which negatively regulates glucose-derived ROS generation. Taken together, persistent glucotoxicity- and/or lipotoxicity-mediated oxidative stress and subsequent adaptive antioxidant response impair glucose-derived ROS signaling and GSIS in pancreatic β-cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Fibrin self-assembly is adapted to oxidation.

    Science.gov (United States)

    Rosenfeld, Mark A; Bychkova, Anna V; Shchegolikhin, Alexander N; Leonova, Vera B; Kostanova, Elizaveta A; Biryukova, Marina I; Sultimova, Natalia B; Konstantinova, Marina L

    2016-06-01

    of the non-oxidized counterparts. Moreover, the γ and α polypeptide chains of the oxidized molecules were more readily crosslinked by the FXIIIa. Upon increasing the urea solution concentration to 4.20M, the cross-linked double-stranded desA fibrin protofibrils have dissociated into the single-stranded fibrin oligomers, whereas the fibers dissociated into both the double-stranded desA fibrin oligomers, the structural integrity of the latter being maintained by means of the intermolecular α polymers, and the single-stranded fibrin oligomers cross-linked only by γ-γ dimers. The data we have obtained in this study indicate that the FXIIIa-mediated process of assembling the cross-linked protofibrils and the fibers constructed from the oxidized monomeric fibrin molecules was facilitated due to the strengthening of D:D interactions. The findings infer that the enhanced longitudinal D:D interactions become more essential in the assembly of soluble protofibrils when the interactions knobs 'A': holes 'a' are injured by oxidation. The new experimental findings presented here could be of help for elucidating the essential adaptive molecular mechanisms capable of mitigating the detrimental action of ROS in the oxidatively damaged fibrin self-assemblage processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Correlation between Low Temperature Adaptation and Oxidative Stress in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Estéfani García-Rios

    2016-08-01

    Full Text Available Many factors, such as must composition, juice clarification, fermentation temperature or inoculated yeast strain, strongly affect the alcoholic fermentation and aromatic profile of wine. As fermentation temperature is effectively controlled by the wine industry, low-temperature fermentation (10-15 ºC is becoming more prevalent in order to produce white and rosé wines with more pronounced aromatic profiles. Elucidating the response to cold in Saccharomyces cerevisiae is of paramount importance for the selection or genetic improvement of wine strains. Previous research has shown the strong implication of oxidative stress response in adaptation to low temperature during the fermentation process. Here we aimed first to quantify the correlation between recovery after shock with different oxidants and cold, and then to detect the key genes involved in cold adaptation that belong to sulfur assimilation, peroxiredoxins, glutathione-glutaredoxins and thioredoxins pathways. To do so, we analyzed the growth of knockouts from the EUROSCARF collection S. cerevisiae BY4743 strain at low and optimal temperatures. The growth rate of these knockouts, compared with the control, enabled us to identify the genes involved, which were also deleted and validated as key genes in the background of two commercial wine strains with a divergent phenotype in their low-temperature growth. We identified three genes, AHP1, MUP1 and URM1, whose deletion strongly impaired low-temperature growth.

  2. Neuroprotective Effects of Centella asiatica against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2009-01-01

    Full Text Available Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of Centella asiatica against colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 μg/5 μL was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment with Centella asiatica extract (150 and 300 mg/kg, p.o. for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides, Centella asiatica significantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect of Centella asiatica against colchicine-induced cognitive impairment and associated oxidative damage.

  3. Neuroprotective Effects of Centella asiatica against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress

    Science.gov (United States)

    Kumar, Anil; Dogra, Samrita; Prakash, Atish

    2009-01-01

    Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of Centella asiatica against colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 μg/5 μL) was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment with Centella asiatica extract (150 and 300 mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides, Centella asiatica significantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect of Centella asiatica against colchicine-induced cognitive impairment and associated oxidative damage. PMID:20798885

  4. Application of adaptive digital signal processing to speech enhancement for the hearing impaired.

    Science.gov (United States)

    Chabries, D M; Christiansen, R W; Brey, R H; Robinette, M S; Harris, R W

    1987-01-01

    A major complaint of individuals with normal hearing and hearing impairments is a reduced ability to understand speech in a noisy environment. This paper describes the concept of adaptive noise cancelling for removing noise from corrupted speech signals. Application of adaptive digital signal processing has long been known and is described from a historical as well as technical perspective. The Widrow-Hoff LMS (least mean square) algorithm developed in 1959 forms the introduction to modern adaptive signal processing. This method uses a "primary" input which consists of the desired speech signal corrupted with noise and a second "reference" signal which is used to estimate the primary noise signal. By subtracting the adaptively filtered estimate of the noise, the desired speech signal is obtained. Recent developments in the field as they relate to noise cancellation are described. These developments include more computationally efficient algorithms as well as algorithms that exhibit improved learning performance. A second method for removing noise from speech, for use when no independent reference for the noise exists, is referred to as single channel noise suppression. Both adaptive and spectral subtraction techniques have been applied to this problem--often with the result of decreased speech intelligibility. Current techniques applied to this problem are described, including signal processing techniques that offer promise in the noise suppression application.

  5. Association between oxidized low-density lipoprotein and cognitive impairment in patients with ischemic stroke.

    Science.gov (United States)

    Wang, A; Liu, J; Meng, X; Li, J; Wang, H; Wang, Y; Su, Z; Zhang, N; Dai, L; Wang, Y; Wang, Y

    2018-01-01

    The association between oxidized low-density lipoprotein (oxLDL) and cognitive impairment is unclear. This study aimed to investigate the potential association between oxLDL and cognitive impairment among patients with acute ischemic stroke. We measured the levels of oxLDL and recorded the Mini-Mental State Examination (MMSE) score in patients with acute ischemic stroke who were recruited from the Study of Oxidative Stress in Patients with Acute Ischemic Stroke. Cognitive impairment was defined as an MMSE score of impairment was assessed by multivariate logistic or linear regression analysis. Other clinical variables of interest were also studied. A total of 3726 patients [1287 (34.54%) female] were included in this study, with a mean age of 63.62 ± 11.96 years. After adjusting for potential confounders in our logistic regression model, each SD increase in oxLDL was associated with a 26% increase in the prevalence of cognitive impairment (odds radio, 1.26; 95% confidence interval, 1.13-1.39; P impairment (all interactions, P > 0.05). Elevated levels of oxLDL were associated with a higher prevalence of cognitive impairment in patients with ischemic stroke. © 2017 EAN.

  6. Use of Adaptive Digital Signal Processing to Improve Speech Communication for Normally Hearing aand Hearing-Impaired Subjects.

    Science.gov (United States)

    Harris, Richard W.; And Others

    1988-01-01

    A two-microphone adaptive digital noise cancellation technique improved word-recognition ability for 20 normal and 12 hearing-impaired adults by reducing multitalker speech babble and speech spectrum noise 18-22 dB. Word recognition improvements averaged 37-50 percent for normal and 27-40 percent for hearing-impaired subjects. Improvement was best…

  7. Platelet hyperaggregability in obesity: is there a role for nitric oxide impairment and oxidative stress?

    Science.gov (United States)

    Leite, Natália Rodrigues Pereira; Siqueira de Medeiros, Mariana; Mury, Wanda Vianna; Matsuura, Cristiane; Perszel, Monique Bandeira Moss; Noronha Filho, Gerson; Brunini, Tatiana Mc; Mendes-Ribeiro, Antônio Claúdio

    2016-08-01

    Epidemiological evidence has shown that platelet activation markers are consistently elevated in obesity, contributing to its prothrombotic state. In order to improve the understanding of the regulation of platelet function in obesity, the aim of this study was to investigate the l-arginine-nitric oxide (NO) pathway in obese adults without other cardiovascular risk factor. Seventeen obese (body mass index [BMI] 35.9±1.0 kg/m(2) ) and eighteen age-matched normal weight subjects (BMI 22.0±0.6 kg/m(2) ) were included in this study. l-arginine influx was measured with incubation of l-[(3) H]-arginine. NO synthase (NOS) and arginase activities were determined by the citrulline assay and the conversion of l-[(14) C]-arginine to [(14) C]-urea, respectively. Cyclic guanosine monophosphate (cGMP) content was evaluated by enzyme-linked immunosorbent assay. In addition, the study analyzed: platelet aggregation; intraplatelet antioxidant enzymes, via superoxide dismutase (SOD) and catalase activities; and systemic levels of l-arginine, fibrinogen, and C-reactive protein (CRP). Obese patients presented a significant decrease of platelet l-arginine influx, NOS activity, and cGMP levels, along with platelet hyperaggregability. On the presence of NO donor, platelet aggregation was similar between the groups. The fibrinogen and CRP systemic levels were significantly higher and SOD activity was reduced in obesity. No significant differences were observed in plasma levels of l-arginine and intraplatelet arginase and catalase activities between groups. The diminished NO bioavailability associated with inflammatory status and impaired enzymatic antioxidant defence may contribute to future cardiovascular complications in obesity. © 2016 John Wiley & Sons Australia, Ltd.

  8. Centella asiatica Attenuates D-Galactose-Induced Cognitive Impairment, Oxidative and Mitochondrial Dysfunction in Mice

    Science.gov (United States)

    Kumar, Anil; Prakash, Atish; Dogra, Samrita

    2011-01-01

    D-galactose induced neurotoxicity is well known model for studying aging and related oxidative damage and memory impairment. Aging is a biological process, characterized by the gradual loss of physiological functions by unknown mechanism. Centella asiatica, Indian pennywort has been documented in the treatment of various neurological disorders including aging. Therefore, present study has been conducted in order to explore the possible role of Centella asiatica against D-galactose induced cognitive impairment, oxidative and mitochondrial dysfunction in mice. Chronic administration of D-galactose (100 mg/kg s.c.) for a period of six weeks significantly impaired cognitive task (both in both Morris water maze and elevated plus maze) and oxidative defense (Increased lipid peroxidation, nitrite concentration and decreased activity of superoxide dismutase, catalase and non-protein thiols) and impaired mitochondrial complex (I, II and III) enzymes activities as compared to sham group. Six weeks Centella asiatica (150 and 300 mg/kg, p.o) treatment significantly improved behavioral alterations, oxidative damage and mitochondrial enzyme complex activities as compared to contro l (D-galactose). Centella asiatica also attenuated enhanced acetylcholine esterase enzyme level in D-galactose senescence mice. Present study highlights the protective effect of Centella asiatica against D-galactose induced behavioral, biochemical and mitochondrial dysfunction in mice. PMID:21629743

  9. Molecular pathophysiology of impaired glucose metabolism, mitochondrial dysfunction, and oxidative DNA damage in Alzheimer's disease brain.

    Science.gov (United States)

    Abolhassani, Nona; Leon, Julio; Sheng, Zijing; Oka, Sugako; Hamasaki, Hideomi; Iwaki, Toru; Nakabeppu, Yusaku

    2017-01-01

    In normal brain, neurons in the cortex and hippocampus produce insulin, which modulates glucose metabolism and cognitive functions. It has been shown that insulin resistance impairs glucose metabolism and mitochondrial function, thus increasing production of reactive oxygen species. Recent progress in Alzheimer's disease (AD) research revealed that insulin production and signaling are severely impaired in AD brain, thereby resulting in mitochondrial dysfunction and increased oxidative stress. Among possible oxidative DNA lesions, 8-oxoguanine (8-oxoG) is highly accumulated in the brain of AD patients. Previously we have shown that incorporating 8-oxoG in nuclear and mitochondrial DNA promotes MUTYH (adenine DNA glycosylase) dependent neurodegeneration. Moreover, cortical neurons prepared from MTH1 (8-oxo-dGTPase)/OGG1 (8-oxoG DNA glycosylase)-double deficient adult mouse brains is shown to exhibit significantly poor neuritogenesis in vitro with increased 8-oxoG accumulation in mitochondrial DNA in the absence of antioxidants. Therefore, 8-oxoG can be considered involved in the neurodegenerative process in AD brain. In mild cognitive impairment, mitochondrial dysfunction and oxidative damage may induce synaptic dysfunction due to energy failures in neurons thus resulting in impaired cognitive function. If such abnormality lasts long, it can lead to vicious cycles of oxidative damage, which may then trigger the neurodegenerative process seen in Alzheimer type dementia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Neuropsychological presentation and adaptive skills in high-functioning adolescents with visual impairment: A preliminary investigation.

    Science.gov (United States)

    Greenaway, R; Pring, L; Schepers, A; Isaacs, D P; Dale, N J

    2017-01-01

    Studies in infants and young children with congenital visual impairment (VI) have indicated early developmental vulnerabilities, conversely research with older children and adults have highlighted areas of cognitive strength. A minimal amount is known, however, about the possible combination of strengths and weaknesses in adolescence, and this present study therefore aims to explore the neuropsychological presentation and adaptive behavior profile in high-functioning adolescents with congenital VI. Participants completed a battery of commonly used neuropsychological measures assessing memory, executive function, and attention. The measures utilized focused on auditory neuropsychological function, because only subtests that could be completed with auditory administration were suitable for this sample. Parents completed standardized measures of adaptive behavior, executive function, and social communication. Compared to aged-based norms for normal sight, adolescents with VI demonstrated strengths in aspects of working memory and verbal memory. Furthermore, performance across the neuropsychological battery was within or above the average range for the majority of the sample. In contrast, parent-report measures indicated areas of weakness in adaptive functioning, social communication, and behavioral executive functioning. Overall, this study provides preliminary evidence that relative to fully sighted peers, high-functioning adolescents with VI present with an uneven profile of cognitive and adaptive skills, which has important implications for assessment and intervention.

  11. Adaptation and validation into Portuguese language of the six-item cognitive impairment test (6CIT).

    Science.gov (United States)

    Apóstolo, João Luís Alves; Paiva, Diana Dos Santos; Silva, Rosa Carla Gomes da; Santos, Eduardo José Ferreira Dos; Schultz, Timothy John

    2017-07-25

    The six-item cognitive impairment test (6CIT) is a brief cognitive screening tool that can be administered to older people in 2-3 min. To adapt the 6CIT for the European Portuguese and determine its psychometric properties based on a sample recruited from several contexts (nursing homes; universities for older people; day centres; primary health care units). The original 6CIT was translated into Portuguese and the draft Portuguese version (6CIT-P) was back-translated and piloted. The accuracy of the 6CIT-P was assessed by comparison with the Portuguese Mini-Mental State Examination (MMSE). A convenience sample of 550 older people from various geographical locations in the north and centre of the country was used. The test-retest reliability coefficient was high (r = 0.95). The 6CIT-P also showed good internal consistency (α = 0.88) and corrected item-total correlations ranged between 0.32 and 0.90. Total 6CIT-P and MMSE scores were strongly correlated. The proposed 6CIT-P threshold for cognitive impairment is ≥10 in the Portuguese population, which gives sensitivity of 82.78% and specificity of 84.84%. The accuracy of 6CIT-P, as measured by area under the ROC curve, was 0.91. The 6CIT-P has high reliability and validity and is accurate when used to screen for cognitive impairment.

  12. Impairment of subendocardial perfusion reserve and oxidative metabolism in nonischemic dilated cardiomyopathy.

    Science.gov (United States)

    Bell, Susan P; Adkisson, Douglas W; Ooi, Henry; Sawyer, Douglas B; Lawson, Mark A; Kronenberg, Marvin W

    2013-12-01

    Cardiac magnetic resonance (CMR) and [(11)C]acetate positron emission tomography (PET) were used to assess the hypothesis that patients with nonischemic dilated cardiomyopathy (NIDCM) have decreased subendocardial perfusion reserve and impaired oxidative metabolism, consistent with the concept of "energy starvation" in heart failure (HF). CMR myocardial perfusion was evaluated in 13 NIDCM patients and 15 control subjects with coronary risk factors and normal myocardial perfusion. The NIDCM patients underwent [(11)C]acetate PET. The myocardial perfusion index (MPI) was calculated as the normalized rate of myocardial signal augmentation following gadolinium contrast injection. Hyperemic transmural, subendocardial, and subepicardial MPI were reduced in NIDCM compared with control subjects [0.13 vs 0.18 (P subendocardial perfusion reserve was 1.59 ± 0.21 vs 1.86 ± 0.32 for the subepicardium (P = .002), demonstrating reduced perfusion reserve. The myocardial oxidative metabolic rate (kmono) per unit demand (rate-pressure product) was reduced in proportion to perfusion reserve (P = .02) CONCLUSIONS: Impaired subendocardial perfusion reserve in NIDCM confirmed results previously attained only in animal models. Impaired perfusion and impaired oxidative metabolism are consistent with subendocardial energy starvation in HF. Published by Elsevier Inc.

  13. Impairment of Subendocardial Perfusion Reserve and Oxidative Metabolism in Non-Ischemic Dilated Cardiomyopathy

    Science.gov (United States)

    Bell, Susan P.; Adkisson, Douglas W.; Ooi, Henry; Sawyer, Douglas B.; Lawson, Mark A.; Kronenberg, Marvin W.

    2014-01-01

    Background Cardiac magnetic resonance (CMR) and [11C] acetate positron emission tomography (PET) were used to assess the hypothesis that patients with nonischemic dilated cardiomyopathy (NIDCM) have decreased subendocardial perfusion reserve and impaired oxidative metabolism, consistent with the concept of “energy starvation” in heart failure (HF). Methods and results CMR myocardial perfusion was evaluated in 13 NIDCM patients and 15 control subjects with coronary risk factors and normal myocardial perfusion. The NIDCM patients underwent [11C] acetate PET. The myocardial perfusion index (MPI) was calculated as the normalized rate of myocardial signal augmentation following gadolinium contrast injection. Hyperemic transmural, subendocardial and subepicardial MPI were reduced in NIDCM compared to control subjects [0.13 vs. 0.18 (Psubendocardial perfusion reserve was 1.59 ± 0.21 vs. 1.86 ± 0.32 for the subepicardium (P= 0.002) demonstrating reduced perfusion reserve. The myocardial oxidative metabolic rate (kmono) per unit demand (rate-pressure product) was reduced proportional to perfusion reserve (P=0.02) Conclusions Impaired subendocardial perfusion reserve in NIDCM confirmed results previously attained only in animal models. Impaired perfusion and impaired oxidative metabolism are consistent with subendocardial energy starvation in HF. PMID:24331202

  14. Impact of Adaptive Materials on Teachers and their Students with Visual Impairments in Secondary Science and Mathematics Classes

    Science.gov (United States)

    Rule, Audrey C.; Stefanich, Greg P.; Boody, Robert M.; Peiffer, Belinda

    2011-04-01

    Science, technology, engineering, and mathematics (STEM) fields, important in today's world, are underrepresented by students with disabilities. Students with visual impairments, although cognitively similar to sighted peers, face challenges as STEM subjects are often taught using visuals. They need alternative forms of access such as enlarged or audio-converted text, tactile graphics, and involvement in hands-on science. This project focused on increasing teacher awareness of and providing funds for the purchase of supplemental adaptive resources, supplies, and equipment. We examined attitude and instructional changes across the year of the programme in 15 science and mathematics teachers educating students with visual impairments. Positive changes were noted from pretest to posttest in student and teacher perspectives, and in teacher attitudes towards students with disabilities in STEM classes. Teachers also provided insights into their challenges and successes through a reflective narrative. Several adolescent students resisted accommodations to avoid appearing conspicuous to peers. Teachers implemented three strategies to address this: providing the adaptations to all students in the class; convincing the student of the need for adaptation; and involving the class in understanding and accepting the student's impairment. A variety of teacher-created adaptations for various science and mathematics labs are reported. Another finding was many adaptations provided for the student with visual impairment benefitted the entire class. This study supports the claim that given knowledgeable, supportive teachers, and with appropriate accommodations such as tactile or auditory materials, students with visual impairments can be as successful and engaged as other students in science and mathematics.

  15. Adaptation of sensorimotor coupling in postural control is impaired by sleep deprivation.

    Directory of Open Access Journals (Sweden)

    Stefane A Aguiar

    Full Text Available The purpose of the study was to investigate the effects of sleep deprivation (SD in adaptation of the coupling between visual information and body sway in young adults' postural control due to changes in optic flow characteristics. Fifteen young adults were kept awake for approximately 25 hours and formed the SD group, while fifteen adults who slept normally the night before the experiment participated as part of the control group. All participants stood as still as possible in a moving room before and after being exposed to one trial with higher amplitude and velocity of room movement. Postural performance and the coupling between visual information, provided by a moving room, and body sway were examined. Results showed that after an abrupt change in visual cues, larger amplitude, and higher velocity of the room, the influence of room motion on body sway was decreased in both groups. However, such a decrease was less pronounced in sleep deprived as compared to control subjects. Sleep deprived adults were able to adapt motor responses to the environmental change provided by the increase in room motion amplitude. Nevertheless, they were not as efficient as control subjects in doing so, which demonstrates that SD impairs the ability to adapt sensorimotor coupling while controlling posture when a perturbation occurs.

  16. Oxidative damage and photosynthetic impairment in tropical rice cultivars upon exposure to excess iron

    Directory of Open Access Journals (Sweden)

    Samuel de Souza Pinto

    2016-06-01

    Full Text Available ABSTRACT Iron plays a pivotal role in the redox reactions of photosynthesis and metabolic processes such as chlorophyll synthesis. Iron availability in waterlogged soils can reach toxic levels and promote oxidative stress. Fe toxicity is the most concerning of stresses for rice in many lowland environments around the world and may cause severe impairments in rice photosynthesis. This study aimed to investigate the extension of oxidative stress after excess Fe exposure and its effects on the photosynthesis of rice cultivars with differential sensitivity. Three Brazilian rice cultivars (EPAGRI 107, BRSMG SELETA and BR IRGA 409 were grown in Hoagland nutrient solution (pH 4.0 with two Fe-EDTA doses corresponding to excess Fe (7 mM and control (0.009 mM treatments. After just three days of excess Fe exposure, there was a significant increase in iron concentration in the shoots. The BR IRGA 409 cultivar exhibited higher Fe accumulation in its shoots, and the EPAGRI 107 cultivar recorded the lowest values, which were below the critical toxicity level, as a resistance strategy. Impairment in light energy partitioning and oxidative damage became evident before changes in stomatal resistance, chlorophyll content, maximal PSII quantum yield or visual symptoms for the most sensitive cultivar (BR IRGA 409. The photosynthesis limitations, in addition to the impairment of excess energy dissipation in rice from iron toxicity, are the results of oxidative damage.

  17. Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training.

    Directory of Open Access Journals (Sweden)

    Sellamuthu S Gounder

    Full Text Available Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2 through antioxidant response cis-elements (AREs and are impaired in the aging heart. Whereas acute exercise stress (AES activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (~2 months, aging mouse (>23 months hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES, but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day for ~6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases.

  18. Human skin penetration and local effects of topical nano zinc oxide after occlusion and barrier impairment.

    Science.gov (United States)

    Leite-Silva, V R; Sanchez, W Y; Studier, H; Liu, D C; Mohammed, Y H; Holmes, A M; Ryan, E M; Haridass, I N; Chandrasekaran, N C; Becker, W; Grice, J E; Benson, H A E; Roberts, M S

    2016-07-01

    Public health concerns continue to exist over the safety of zinc oxide nanoparticles that are commonly used in sunscreen formulations. In this work, we assessed the effects of two conditions which may be encountered in everyday sunscreen use, occlusion and a compromised skin barrier, on the penetration and local toxicity of two topically applied zinc oxide nanoparticle products. Caprylic/capric triglyceride (CCT) suspensions of commercially used zinc oxide nanoparticles, either uncoated or with a silane coating, were applied to intact and barrier impaired skin of volunteers, without and with occlusion for a period of six hours. The exposure time was chosen to simulate normal in-use conditions. Multiphoton tomography with fluorescence lifetime imaging was used to noninvasively assess zinc oxide penetration and cellular metabolic changes that could be indicative of toxicity. We found that zinc oxide nanoparticles did not penetrate into the viable epidermis of intact or barrier impaired skin of volunteers, without or with occlusion. We also observed no apparent toxicity in the viable epidermis below the application sites. These findings were validated by ex vivo human skin studies in which zinc penetration was assessed by multiphoton tomography with fluorescence lifetime imaging as well as Zinpyr-1 staining and toxicity was assessed by MTS assays in zinc oxide treated skin cryosections. In conclusion, applications of zinc oxide nanoparticles under occlusive in-use conditions to volunteers are not associated with any measurable zinc oxide penetration into, or local toxicity in the viable epidermis below the application site. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Impaired metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martin; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina

    2014-01-01

    is assured by resident adult stem cells known as satellite cells. During senescence their replication and differentiation is compromised contributing to sarcopenia. In this study we have addressed the impact of oxidatively modified proteins in the impaired metabolism of senescent human satellite cells....... By using a targeted proteomics analysis we have found that proteins involved in protein quality control and glycolytic enzymes are the main targets of oxidation (carbonylation) and modification with advanced glycation/lipid peroxidation end products during replicative senescence of satellite cells....... Inactivation of the proteasome in aged cells appeared as a key contributor to the accumulation of such damaged proteins. Untargeted metabolomic profiling and functional analyses indicated glucose metabolism impairment in senescent cells, although mitochondrial respiration remained unaffected. A metabolic shift...

  20. Impaired fatty acid oxidation as a cause for lipotoxicity in cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Haffar, T. [Université de Montreal (Canada); Montreal Heart Institute (Canada); Bérubé-Simard, F. [Montreal Heart Institute (Canada); Bousette, N., E-mail: nicolas.bousette@umontreal.ca [Université de Montreal (Canada); Montreal Heart Institute (Canada)

    2015-12-04

    A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring {sup 14}C–CO{sub 2} production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative and qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. - Highlights: • Palmitate had a slower clearance rate from NCMs than oleate. • Palmitate caused a significant decrease in fatty acid oxidation in cardiomyocytes. • Impaired FAO was not due to loss of Cpt1b protein or mitochondrial integrity. • Enhancing FAO

  1. Hyperthyroidism impairs pancreatic beta cell adaptations to late pregnancy and maternal liporegulation in the rat.

    Science.gov (United States)

    Holness, M J; Greenwood, G K; Smith, N D; Sugden, M C

    2005-11-01

    Hyperthyroidism modifies lipid dynamics (increased oxidation), impairs insulin action and can suppress insulin secretion. We therefore examined the impact of hyperthyroidism on the relationship between glucose-stimulated insulin secretion (GSIS) and insulin action, using late pregnancy as a model of physiological insulin resistance that is associated with compensatory insulin hypersecretion to maintain glucose tolerance. Our aim was to examine whether hyperthyroidism compromises the regulation of insulin secretion and the ability of insulin to modulate circulating lipid concentrations in late pregnancy. Hyperthyroidism was induced by tri-iodothyronine (T(3)) administration from day 17 to 19 of pregnancy. GSIS was assessed during an IVGTT and during hyperglycaemic clamps in vivo and in vitro, using step-up and -down islet perifusions. Hyperthyroidism in pregnancy elevated the glucose threshold for GSIS and impaired GSIS at low and high glucose concentrations in islet perifusions. In the intact animal, insulin secretion (after bolus glucose) was more rapidly curtailed following removal of the glucose stimulus to secretion. In contrast, GSIS was maintained during protracted hyperglycaemia (hyperglycaemic clamps) in the hyperthyroid pregnant state in vivo. Hyperthyroidism in vivo during late pregnancy blunts GSIS in subsequently isolated and perifused islets at low and high glucose concentrations. It also adversely affects GSIS under conditions of an acute glucose challenge in vivo. In contrast, GSIS is maintained during sustained hyperglycaemia in vivo, suggesting that in vivo factors can rescue GSIS. The ability of insulin to suppress systemic lipid levels during hyperglycaemic clamps was impaired. We therefore suggest that higher circulating lipids may preserve GSIS under conditions of sustained hyperglycaemia in the hyperthyroid pregnancy.

  2. Neutrophilic iron oxidizers adapted to highly oxic environments

    DEFF Research Database (Denmark)

    Gülay, Arda; Musovic, Sanin; Albrechtsen, Hans-Jørgen

    carbon) while oxygen (O2) is the electron acceptor provided during the aeration process. Numerous previous studies have described neutrophilic iron oxidizers as a bacterial guild with a special niche preference, especially the transition zone between aerobic and anoxic regions, where abiotic chemical...... oxidation of iron would be retarded. For that reason, no attempts have been documented to describe the density and diversity of iron oxidizing bacteria (FeOB) in oxic neutrophilic environments. Under low temperatures (5 to 10°C) conditions, as typically found in groundwater, extremely low rates of chemical...... iron oxidation (t1/2: 315min.) have been documented. This assumed slow chemical oxidation of Fe2 + in rapid sand filters may allow certain bacteria to oxidize iron concurrently with the ongoing slow chemical oxidation. Hence, we aimed to investigate the abundance, diversity, and spatial distribution...

  3. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Mercado, Nicolas [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Thimmulappa, Rajesh [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E. [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Ito, Kazuhiro [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Barnes, Peter J., E-mail: p.j.barnes@imperial.ac.uk [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom)

    2011-03-11

    Research highlights: {yields} Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. {yields} HDAC inhibition decreases Nrf2 protein stability. {yields} HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. {yields} HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H{sub 2}O{sub 2}) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H{sub 2}O{sub 2}-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  4. Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Alexis Mougeolle

    Full Text Available Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H2O2 at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H2O2 treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H2O2 treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H2O2 treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H2O2 decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.

  5. Special home adaptation grants for members of the Armed Forces and veterans with certain vision impairment. Final rule.

    Science.gov (United States)

    2014-09-12

    The Department of Veterans Affairs (VA) is issuing a final rule to amend its adjudication regulations regarding special home adaptation grants for members of the Armed Forces and veterans with certain vision impairment. This regulatory amendment is necessary to conform the regulations to changes mandated in the Honoring America's Veterans and Caring for Camp Lejeune Families Act of 2012.

  6. Development and Adaptation of an Employment-Integration Program for People Who Are Visually Impaired in Quebec, Canada

    Science.gov (United States)

    Wittich, Walter; Watanabe, Donald H.; Scully, Lizabeth; Bergevin , Martin

    2013-01-01

    Introduction: In the Province of Quebec, Canada, it is estimated that only about one-third of working-age adults with visual impairments are part of the workforce, despite ongoing efforts of rehabilitation and government agencies to integrate these individuals. The present article describes the development and adaptation of a pre-employment…

  7. Brain aging, memory impairment and oxidative stress: a study in Drosophila melanogaster.

    Science.gov (United States)

    Haddadi, Mohammad; Jahromi, Samaneh Reiszadeh; Sagar, B K Chandrasekhar; Patil, Rajashekhar K; Shivanandappa, T; Ramesh, S R

    2014-02-01

    Memory impairment during aging is believed to be a consequence of decline in neuronal function and increase in neurodegeneration. Accumulation of oxidative damage and reduction of antioxidant defense system play a key role in organismal aging and functional senescence. In our study, we examined the age-related memory impairment (AMI) in relation to oxidative stress using Drosophila model. We observed a decline in cognitive function in old flies with respect to both short-lived and consolidated forms of olfactory memory. Light and electron microscopy of mushroom bodies revealed a reduction in the number of synapses and discernible architectural defects in mitochondria. An increase in neuronal apoptosis in Kenyon cells was also evident in aged flies. Biochemical investigations revealed a comparable age-associated decrease in the activity of antioxidant enzymes such as catalase and superoxide dismutase as well as the GSH level, accompanied by an increase in the level of lipid peroxidation and generation of reactive oxygen species in the brain. There was no significant difference in the activity level of AChE and BChE enzymes between different age groups while immunohistochemical studies showed a significant decrease in the level of ChAT in 50-day-old flies. RNAi-mediated silencing of cat and sod1 genes caused severe memory impairment in 15-day-old flies, whereas, over-expression of cat gene could partially rescue the memory loss in the old flies. We demonstrated that a Drosophila long-lived strain, possessing enhanced activity of antioxidant enzymes and higher rate of resistance to oxidative stress, shows lower extent of AMI compared to normal lifespan strain. Present study provides evidence for involvement of oxidative stress in AMI in Drosophila. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Does Vitamin C and E Supplementation Impair the Favorable Adaptations of Regular Exercise?

    Directory of Open Access Journals (Sweden)

    Michalis G. Nikolaidis

    2012-01-01

    Full Text Available The detrimental outcomes associated with unregulated and excessive production of free radicals remains a physiological concern that has implications to health, medicine and performance. Available evidence suggests that physiological adaptations to exercise training can enhance the body’s ability to quench free radicals and circumstantial evidence exists to suggest that key vitamins and nutrients may provide additional support to mitigate the untoward effects associated with increased free radical production. However, controversy has risen regarding the potential outcomes associated with vitamins C and E, two popular antioxidant nutrients. Recent evidence has been put forth suggesting that exogenous administration of these antioxidants may be harmful to performance making interpretations regarding the efficacy of antioxidants challenging. The available studies that employed both animal and human models provided conflicting outcomes regarding the efficacy of vitamin C and E supplementation, at least partly due to methodological differences in assessing oxidative stress and training adaptations. Based on the contradictory evidence regarding the effects of higher intakes of vitamin C and/or E on exercise performance and redox homeostasis, a permanent intake of non-physiological dosages of vitamin C and/or E cannot be recommended to healthy, exercising individuals.

  9. Impaired secondary oxidant deactivation capacity and enhanced oxidative stress in serum from alveld affected lambs

    DEFF Research Database (Denmark)

    Hegge, Anne Bee; Mysterud, Ivar; Karlsen, Jan

    2013-01-01

    to serum samples from control lambs (n=31) and exposed to a controlled amount of singlet oxygen ((1)O2). The sera from alveld lambs were found to have an impaired ability to deactivate reactive oxygen species (ROS) compared to control sera. A higher degree of initial hemolysis and a higher concentration...... in pooled serum from alveld lambs that showed a high degree of hemolysis. It was concluded that alveld photosensitivity is likely to be initiated by a photodynamic reaction involving PP and possibly also PP IX followed by a light-independent reaction involving hemoglobin-related products and catalysis...

  10. Puerarin attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice.

    Science.gov (United States)

    Zhao, Shan-shan; Yang, Wei-na; Jin, Hui; Ma, Kai-ge; Feng, Gai-feng

    2015-12-01

    Puerarin (PUE), an isoflavone purified from the root of Pueraria lobata (Chinese herb), has been reported to attenuate learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). In the present study, we tested PUE in a sporadic AD (SAD) mouse model which was induced by the intracerebroventricular injection of streptozotocin (STZ). The mice were administrated PUE (25, 50, or 100mg/kg/d) for 28 days. Learning and memory abilities were assessed by the Morris water maze test. After behavioral test, the biochemical parameters of oxidative stress (glutathione peroxidase (GSH-Px), superoxide dismutases (SOD), and malondialdehyde (MDA)) were measured in the cerebral cortex and hippocampus. The SAD mice exhibited significantly decreased learning and memory ability, while PUE attenuated these impairments. The activities of GSH-Px and SOD were decreased while MDA was increased in the SAD animals. After PUE treatment, the activities of GSH-Px and SOD were elevated, and the level of MDA was decreased. The middle dose PUE was more effective than others. These results indicate that PUE attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice. PUE may be a promising therapeutic agent for SAD. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Oxidative stress with tau hyperphosphorylation in memory impaired 1,2-diacetylbenzene-treated mice.

    Science.gov (United States)

    Kang, Sin-Woo; Kim, Sung Jin; Kim, Min-Sun

    2017-09-05

    Long-term exposure to organic solvent may be related to the incidence of neuronal diseases, such as, Alzheimer's disease, depression, multiple sclerosis, dementia, Parkinson's disease. Previously, the authors reported 1,2-diacetylbenzene (DAB; a neurotoxic metabolite of 1,2-diethylbenzene) causes central and peripheral neuropathies that lead to motor neuronal deficits. Furthermore, it is known DAB increases oxidative stress and protein adduct levels and impairs hippocampal neurogenesis in mice. The authors examined the relevance of oxidative stress and tau hyperphosphorylation in the hippocampus. Five-week-old male C57BL/6 mice were treated with 1 or 5mg/kg/day DAB for 2weeks. Neither overall body weight increases nor behavioral differences were observed after treatment, but kidney and liver weights decreased. Increased ROS production, activated glycogen synthase kinase-3β (GSK-3β) and tau hyperphosphorylation were observed in hippocampal homogenates. To assess memory impairment, the Morris Water Maze was used. Animals in the DAB-treated groups took longer to reach the platform. Movement patterns of DAB treated mice were more complicated and their swimming speeds were lower than those of controls. When SHSY5Y neuroblastoma cells were pretreated with NAC (an antioxidant) or a GSK-3β inhibitor, the expression of active GSK-3β and tau hyperphosphorylation were reduced. These results suggest ROS produced by DAB causes tau hyperphosphorylation via GSK-3β phosphorylation and it might be related to impaired memory deficit. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Peripheral leukocyte populations and oxidative stress biomarkers in aged dogs showing impaired cognitive abilities.

    Science.gov (United States)

    Mongillo, Paolo; Bertotto, Daniela; Pitteri, Elisa; Stefani, Annalisa; Marinelli, Lieta; Gabai, Gianfranco

    2015-06-01

    In the present study, the peripheral blood leukocyte phenotypes, lymphocyte subset populations, and oxidative stress parameters were studied in cognitively characterized adult and aged dogs, in order to assess possible relationships between age, cognitive decline, and the immune status. Adult (N = 16, 2-7 years old) and aged (N = 29, older than 8 years) dogs underwent two testing procedures, for the assessment of spatial reversal learning and selective social attention abilities, which were shown to be sensitive to aging in pet dogs. Based on age and performance in cognitive testing, dogs were classified as adult not cognitively impaired (ADNI, N = 12), aged not cognitively impaired (AGNI, N = 19) and aged cognitively impaired (AGCI, N = 10). Immunological and oxidative stress parameters were compared across groups with the Kruskal-Wallis test. AGCI dogs displayed lower absolute CD4 cell count (p dogs had higher CD8 cell percentage than ADNI (p dogs showed lower CD4/CD8 and CD21 count and percentage and higher neutrophil/lymphocyte and CD3/CD21 ratios (p dog as a model for studying the functional relationship between the nervous and immune systems during aging.

  13. Devices for visually impaired people: High technological devices with low user acceptance and no adaptability for children.

    Science.gov (United States)

    Gori, Monica; Cappagli, Giulia; Tonelli, Alessia; Baud-Bovy, Gabriel; Finocchietti, Sara

    2016-10-01

    Considering that cortical plasticity is maximal in the child, why are the majority of technological devices available for visually impaired users meant for adults and not for children? Moreover, despite high technological advancements in recent years, why is there still no full user acceptance of existing sensory substitution devices? The goal of this review is to create a link between neuroscientists and engineers by opening a discussion about the direction that the development of technological devices for visually impaired people is taking. Firstly, we review works on spatial and social skills in children with visual impairments, showing that lack of vision is associated with other sensory and motor delays. Secondly, we present some of the technological solutions developed to date for visually impaired people. Doing this, we highlight the core features of these systems and discuss their limits. We also discuss the possible reasons behind the low adaptability in children. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Oxidative signature of cerebrospinal fluid from mild cognitive impairment and Alzheimer disease patients.

    Science.gov (United States)

    Di Domenico, Fabio; Pupo, Gilda; Giraldo, Esther; Badìa, Mari-Carmen; Monllor, Paloma; Lloret, Ana; Schininà, Maria Eugenia; Giorgi, Alessandra; Cini, Chiara; Tramutola, Antonella; Butterfield, D Allan; Viña, José; Perluigi, Marzia

    2016-02-01

    Several studies suggest that pathological changes in Alzheimer's disease (AD) brain begin around 10-20 years before the onset of cognitive impairment. Biomarkers that can support early diagnosis and predict development of dementia would, therefore, be crucial for patient care and evaluation of drug efficacy. Although cerebrospinal fluid (CSF) levels of Aβ42, tau, and p-tau are well-established diagnostic biomarkers of AD, there is an urgent need to identify additional molecular alterations of neuronal function that can be evaluated at the systemic level. This study was focused on the analysis of oxidative stress-related modifications of the CSF proteome, from subjects with AD and amnestic mild cognitive impairment (aMCI). A targeted proteomics approach has been employed to discover novel CSF biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers. CSF samples from aMCI, AD and control individuals (CTR) were collected and analyzed using a combined redox proteomics approach to identify the specific oxidatively modified proteins in AD and aMCI compared with controls. The majority of carbonylated proteins identified by redox proteomics are found early in the progression of AD, i.e., oxidatively modified CSF proteins were already present in aMCI compared with controls and remain oxidized in AD, thus suggesting that dysfunction of selected proteins initiate many years before severe dementia is diagnosed. The above findings highlight the presence of early oxidative damage in aMCI before clinical dementia of AD is manifested. The identification of early markers of AD that may be detected peripherally may open new prospective for biomarker studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Manish Jaiswal

    2015-07-01

    Full Text Available Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration--defects in mitochondrial function and aberrant Rhodopsin trafficking. Although mitochondrial defects are often associated with oxidative stress, they have not been linked to Rhodopsin trafficking. In an unbiased forward genetic screen designed to isolate mutations that cause photoreceptor degeneration, we identified mutations in a nuclear-encoded mitochondrial gene, ppr, a homolog of human LRPPRC. We found that ppr is required for protection against light-induced degeneration. Its function is essential to maintain membrane depolarization of the photoreceptors upon repetitive light exposure, and an impaired phototransduction cascade in ppr mutants results in excessive Rhodopsin1 endocytosis. Moreover, loss of ppr results in a reduction in mitochondrial RNAs, reduced electron transport chain activity, and reduced ATP levels. Oxidative stress, however, is not induced. We propose that the reduced ATP level in ppr mutants underlies the phototransduction defect, leading to increased Rhodopsin1 endocytosis during light exposure, causing photoreceptor degeneration independent of oxidative stress. This hypothesis is bolstered by characterization of two other genes isolated in the screen, pyruvate dehydrogenase and citrate synthase. Their loss also causes a light-induced degeneration, excessive Rhodopsin1 endocytosis and reduced ATP without concurrent oxidative stress, unlike many other mutations in mitochondrial genes that are associated with elevated oxidative stress and light-independent photoreceptor demise.

  16. Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle

    DEFF Research Database (Denmark)

    Hütter, Eveline; Skovbro, Mette; Lener, Barbara

    2007-01-01

    According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain...... mitochondria and that the level of ROS production is higher in young compared to aged muscle. Accordingly, we could not find any increase in oxidative modification of proteins in muscle from elderly donors. However, the accumulation of lipofuscin was identified as a robust marker of human muscle aging....... However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated...

  17. Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction.

    Science.gov (United States)

    Turki, Ahmed; Hayot, Maurice; Carnac, Gilles; Pillard, Fabien; Passerieux, Emilie; Bommart, Sébastien; Raynaud de Mauverger, Eric; Hugon, Gérald; Pincemail, Joel; Pietri, Sylvia; Lambert, Karen; Belayew, Alexandra; Vassetzky, Yegor; Juntas Morales, Raul; Mercier, Jacques; Laoudj-Chenivesse, Dalila

    2012-09-01

    Facioscapulohumeral muscular dystrophy (FSHD), the most frequent muscular dystrophy, is an autosomal dominant disease. In most individuals with FSHD, symptoms are restricted to muscles of the face, arms, legs, and trunk. FSHD is genetically linked to contractions of the D4Z4 repeat array causing activation of several genes. One of these maps in the repeat itself and expresses the DUX4 (the double homeobox 4) transcription factor causing a gene deregulation cascade. In addition, analyses of the RNA or protein expression profiles in muscle have indicated deregulations in the oxidative stress response. Since oxidative stress affects peripheral muscle function, we investigated mitochondrial function and oxidative stress in skeletal muscle biopsies and blood samples from patients with FSHD and age-matched healthy controls, and evaluated their association with physical performances. We show that specifically, oxidative stress (lipid peroxidation and protein carbonylation), oxidative damage (lipofuscin accumulation), and antioxidant enzymes (catalase, copper-zinc-dependent superoxide dismutase, and glutathione reductase) were higher in FSHD than in control muscles. FSHD muscles also presented abnormal mitochondrial function (decreased cytochrome c oxidase activity and reduced ATP synthesis). In addition, the ratio between reduced (GSH) and oxidized glutathione (GSSG) was strongly decreased in all FSHD blood samples as a consequence of GSSG accumulation. Patients with FSHD also had reduced systemic antioxidative response molecules, such as low levels of zinc (a SOD cofactor), selenium (a GPx cofactor involved in the elimination of lipid peroxides), and vitamin C. Half of them had a low ratio of gamma/alpha tocopherol and higher ferritin concentrations. Both systemic oxidative stress and mitochondrial dysfunction were correlated with functional muscle impairment. Mitochondrial ATP production was significantly correlated with both quadriceps endurance (T(LimQ)) and maximal

  18. Antarctic Krill Oil Diet Protects against Lipopolysaccharide-Induced Oxidative Stress, Neuroinflammation and Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Ji Yeon Choi

    2017-11-01

    Full Text Available Oxidative stress and neuroinflammation are implicated in the development and pathogenesis of Alzheimer’s disease (AD. Here, we investigated the anti-inflammatory and antioxidative effects of krill oil. Oil from Euphausia superba (Antarctic krill, an Antarctic marine species, is rich in eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. We examined whether krill oil diet (80 mg/kg/day for one month prevents amyloidogenesis and cognitive impairment induced by intraperitoneal lipopolysaccharide (LPS (250 µg/kg, seven times daily injections in AD mice model and found that krill oil treatment inhibited the LPS-induced memory loss. We also found that krill oil treatment inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 and decreased reactive oxygen species (ROS and malondialdehyde levels. Krill oil also suppresses IκB degradation as well as p50 and p65 translocation into the nuclei of LPS-injected mice brain cells. In association with the inhibitory effect on neuroinflammation and oxidative stress, krill oil suppressed amyloid beta (1–42 peptide generation by the down-regulating APP and BACE1 expression in vivo. We found that eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA (50 and 100 µM dose-dependently decreased LPS-induced nitric oxide and ROS generation, and COX-2 and iNOS expression as well as nuclear factor-κB activity in cultured microglial BV-2 cells. These results suggest that krill oil ameliorated impairment via anti-inflammatory, antioxidative, and anti-amyloidogenic mechanisms.

  19. Antarctic Krill Oil Diet Protects against Lipopolysaccharide-Induced Oxidative Stress, Neuroinflammation and Cognitive Impairment.

    Science.gov (United States)

    Choi, Ji Yeon; Jang, Jun Sung; Son, Dong Ju; Im, Hyung-Sik; Kim, Ji Yeong; Park, Joung Eun; Choi, Won Rak; Han, Sang-Bae; Hong, Jin Tae

    2017-11-28

    Oxidative stress and neuroinflammation are implicated in the development and pathogenesis of Alzheimer's disease (AD). Here, we investigated the anti-inflammatory and antioxidative effects of krill oil. Oil from Euphausia superba (Antarctic krill), an Antarctic marine species, is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We examined whether krill oil diet (80 mg/kg/day for one month) prevents amyloidogenesis and cognitive impairment induced by intraperitoneal lipopolysaccharide (LPS) (250 µg/kg, seven times daily) injections in AD mice model and found that krill oil treatment inhibited the LPS-induced memory loss. We also found that krill oil treatment inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and decreased reactive oxygen species (ROS) and malondialdehyde levels. Krill oil also suppresses IκB degradation as well as p50 and p65 translocation into the nuclei of LPS-injected mice brain cells. In association with the inhibitory effect on neuroinflammation and oxidative stress, krill oil suppressed amyloid beta (1-42) peptide generation by the down-regulating APP and BACE1 expression in vivo. We found that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (50 and 100 µM) dose-dependently decreased LPS-induced nitric oxide and ROS generation, and COX-2 and iNOS expression as well as nuclear factor-κB activity in cultured microglial BV-2 cells. These results suggest that krill oil ameliorated impairment via anti-inflammatory, antioxidative, and anti-amyloidogenic mechanisms.

  20. Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver.

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    Veggi, Luis M; Pretto, Luciana; Ochoa, Elena J; Catania, Viviana A; Luquita, Marcelo G; Taborda, Diego R; Sánchez Pozzi, Enrique J; Ikushiro, Shin-ichi; Coleman, Michael D; Roma, Marcelo G; Mottino, Aldo D

    2008-08-01

    Dapsone (DDS) is currently used in the treatment of leprosy, malaria and in infections with Pneumocystis jirovecii and Toxoplasma gondii in AIDS patients. Adverse effects of DDS involve methemoglobinemia and hemolysis and, to a lower extent, liver damage, though the mechanism is poorly characterized. We evaluated the effect of DDS administration to male and female rats (30 mg/kg body wt, twice a day, for 4 days) on liver oxidative stress through assessment of biliary output and liver content of reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, and expression/activities of the main antioxidant enzymes glutathione peroxidase, superoxide dismutase, catalase and glutathione S-transferase. The influence of DDS treatment on expression/activity of the main DDS phase-II-metabolizing system, UDP-glucuronosyltransferase (UGT), was additionally evaluated. The involvement of dapsone hydroxylamine (DDS-NHOH) generation in these processes was estimated by comparing the data in male and female rats since N-hydroxylation of DDS mainly occurs in males. Our studies revealed an increase in the GSSG/GSH biliary output ratio, a sensitive indicator of oxidative stress, and in lipid peroxidation, in male but not in female rats treated with DDS. The activity of all antioxidant enzymes was significantly impaired by DDS treatment also in male rats, whereas UGT activity was not affected in any sex. Taken together, the evidence indicates that DDS induces oxidative stress in rat liver and that N-hydroxylation of DDS was the likely mediator. Impairment in the activity of enzymatic antioxidant systems, also associated with DDS-NHOH formation, constituted a key aggravating factor.

  1. Astaxanthin ameliorates aluminum chloride-induced spatial memory impairment and neuronal oxidative stress in mice.

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    Al-Amin, Md Mamun; Reza, Hasan Mahmud; Saadi, Hasan Mahmud; Mahmud, Waich; Ibrahim, Abdirahman Adam; Alam, Musrura Mefta; Kabir, Nadia; Saifullah, A R M; Tropa, Sarjana Tarannum; Quddus, A H M Ruhul

    2016-04-15

    Aluminum chloride induces neurodegenerative disease in animal model. Evidence suggests that aluminum intake results in the activation of glial cells and generation of reactive oxygen species. By contrast, astaxanthin is an antioxidant having potential neuroprotective activity. In this study, we investigate the effect of astaxanthin on aluminum chloride-exposed behavioral brain function and neuronal oxidative stress (OS). Male Swiss albino mice (4 months old) were divided into 4 groups: (i) control (distilled water), (ii) aluminum chloride, (iii) astaxanthin+aluminum chloride, and (iv) astaxanthin. Two behavioral tests; radial arm maze and open field test were conducted, and OS markers were assayed from the brain and liver tissues following 42 days of treatment. Aluminum exposed group showed a significant reduction in spatial memory performance and anxiety-like behavior. Moreover, aluminum group exhibited a marked deterioration of oxidative markers; lipid peroxidation (MDA), nitric oxide (NO), glutathione (GSH) and advanced oxidation of protein products (AOPP) in the brain. To the contrary, co-administration of astaxanthin and aluminum has shown improved spatial memory, locomotor activity, and OS. These results indicate that astaxanthin improves aluminum-induced impaired memory performances presumably by the reduction of OS in the distinct brain regions. We suggest a future study to determine the underlying mechanism of astaxanthin in improving aluminum-exposed behavioral deficits. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Oxidative stress caused by pyocyanin impairs CFTR Cl(-) transport in human bronchial epithelial cells.

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    Schwarzer, Christian; Fischer, Horst; Kim, Eun-Jin; Barber, Katharine J; Mills, Aaron D; Kurth, Mark J; Gruenert, Dieter C; Suh, Jung H; Machen, Terry E; Illek, Beate

    2008-12-15

    Pyocyanin (N-methyl-1-hydroxyphenazine), a redox-active virulence factor produced by the human pathogen Pseudomonas aeruginosa, is known to compromise mucociliary clearance. Exposure of human bronchial epithelial cells to pyocyanin increased the rate of cellular release of H(2)O(2) threefold above the endogenous H(2)O(2) production. Real-time measurements of the redox potential of the cytosolic compartment using the redox sensor roGFP1 showed that pyocyanin (100 microM) oxidized the cytosol from a resting value of -318+/-5 mV by 48.0+/-4.6 mV within 2 h; a comparable oxidation was induced by 100 microM H(2)O(2). Whereas resting Cl(-) secretion was slightly activated by pyocyanin (to 10% of maximal currents), forskolin-stimulated Cl(-) secretion was inhibited by 86%. The decline was linearly related to the cytosolic redox potential (1.8% inhibition/mV oxidation). Cystic fibrosis bronchial epithelial cells homozygous for DeltaF508 CFTR failed to secrete Cl(-) in response to pyocyanin or H(2)O(2), indicating that these oxidants specifically target the CFTR and not other Cl(-) conductances. Treatment with pyocyanin also decreased total cellular glutathione levels to 62% and cellular ATP levels to 46% after 24 h. We conclude that pyocyanin is a key factor that redox cycles in the cytosol, generates H(2)O(2), depletes glutathione and ATP, and impairs CFTR function in Pseudomonas-infected lungs.

  3. Oxidative Stress By Pyocyanin Impairs CFTR Cl- Transport In Human Bronchial Epithelial Cells

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    Schwarzer, Christian; Fischer, Horst; Kim, Eun-Jin; Barber, Katharine J.; Mills, Aaron D.; Kurth, Mark J.; Gruenert, Dieter C.; Suh, Jung H.; Machen, Terry E.; Illek, Beate

    2008-01-01

    Pyocyanin (N-methyl-1-hydroxyphenazine), a redox-active virulence factor produced by the human pathogen Pseudomonas aeruginosa, is known to compromise mucociliary clearance. Exposure of human bronchial epithelial cells to pyocyanin increased the rate of cellular release of H2O2 3-fold above the endogenous H2O2 production. Real-time measurements of the redox-potential of the cytosolic compartment using the redox sensor roGFP1 showed that pyocyanin (100 μM) oxidized the cytosol from a resting value of -318 ± 5 mV by 48.0 ± 4.6 mV within 2 hours; a comparable oxidation was induced by 100 μM H2O2. While resting Cl- secretion was slightly activated by pyocyanin (to 10% of maximal currents), forskolin-stimulated Cl- secretion was inhibited by 86%. The decline was linearly related to the cytosolic redox potential (1.8% inhibition/mV oxidation). CF bronchial epithelial cells homozygous for ΔF508 CFTR failed to secrete Cl- in response to pyocyanin or H2O2 indicating that these oxidants specifically target CFTR and not other Cl- conductances. Treatment with pyocyanin also decreased total cellular glutathione levels to 62% and cellular ATP levels to 46% after 24 hours. We conclude that pyocyanin is a key factor that redox cycles in the cytosol, generates H2O2, depletes glutathione and ATP, and impairs CFTR function in Pseudomonas infected lungs. PMID:18845244

  4. Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats

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    Yousef Baghcheghi

    Full Text Available ABSTRACT In this study, the effect of thymoquinone (TQ on propylthiouracil (PTU-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.

  5. Plant-adapted Escherichia coli show increased lettuce colonizing ability, resistance to oxidative stress and chemotactic response.

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    Maria de los Angeles Dublan

    Full Text Available Escherichia coli is a widespread gut commensal and often a versatile pathogen of public health concern. E. coli are also frequently found in different environments and/or alternative secondary hosts, such as plant tissues. The lifestyle of E. coli in plants is poorly understood and has potential implications for food safety.This work shows that a human commensal strain of E. coli K12 readily colonizes lettuce seedlings and produces large microcolony-like cell aggregates in leaves, especially in young leaves, in proximity to the vascular tissue. Our observations strongly suggest that those cell aggregates arise from multiplication of single bacterial cells that reach those spots. We showed that E. coli isolated from colonized leaves progressively colonize lettuce seedlings to higher titers, suggesting a fast adaptation process. E. coli cells isolated from leaves presented a dramatic rise in tolerance to oxidative stress and became more chemotactic responsive towards lettuce leaf extracts. Mutant strains impaired in their chemotactic response were less efficient lettuce colonizers than the chemotactic isogenic strain. However, acclimation to oxidative stress and/or minimal medium alone failed to prime E. coli cells for enhanced lettuce colonization efficiency.These findings help to understand the physiological adaptation during the alternative lifestyle of E. coli in/on plant tissues.

  6. Effects of imperatorin on scopolamine-induced cognitive impairment and oxidative stress in mice.

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    Budzynska, Barbara; Boguszewska-Czubara, Anna; Kruk-Slomka, Marta; Skalicka-Wozniak, Krystyna; Michalak, Agnieszka; Musik, Irena; Biala, Grazyna

    2015-03-01

    Imperatorin, a naturally occurring furanocoumarin, inactivates gamma-aminobutyric acid transaminase and inhibits acetylcholinesterase activity. The purpose of our experiment was to examine the influence of imperatorin on cognitive impairment and oxidative stress in the brain induced by scopolamine in male Swiss mice. In the present studies, we used scopolamine-invoke memory deficit measured in passive avoidance (PA) paradigm as an animal model of Alzheimer disease (AD). Our finding revealed that imperatorin administered acutely at the doses of 5 and 10 mg/kg prior to the injection of scopolamine (1 mg/kg) improved memory acquisition and consolidation impaired by scopolamine. Furthermore, repeatable (7 days, twice daily) administration of the highest dose of imperatorin (10 mg/kg) significantly attenuated the effects of scopolamine on memory acquisition, whereas the doses of 5 and 10 mg/kg of this furanocoumarin were effective when memory consolidation was measured. Imperatorin, administered with scopolamine, increased antioxidant enzymes activity and decreased concentration of malondiamide, an indicator of lipid peroxidation level. These results demonstrate that imperatorin may offer protection against scopolamine-induced memory impairments and possesses antioxidant properties, thus after further preclinical and clinical studies this compound may provide an interesting approach in pharmacotherapy, as well as prophylactics of AD.

  7. Neuroprotective effect of resveratrol against scopolamine-induced cognitive impairment and oxidative stress in rats

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    Pushpalatha Bunadri

    2013-01-01

    Full Text Available The objective of this study was to examine the neuroprotective effect of resveratrol on cognitive impairment induced by scopolamine, a muscarinic antagonist, in rats. Memory impairment was induced by administration of scopolamine (1 mg/kg intraperitoneally. Cognitive functions were assessed using radial arm maze, an active avoidance paradigm. Oxidative stress parameters like malondialdehyde, catalase and superoxide dismutase were assessed and acetylcholinesterase activity was estimated. More working and reference memory errors in the radial arm maze test and fewer avoidances in the active avoidance test were observed with scopolamine in the 1 mg/kg i.p.-treated animals. This phenomenon is a clear indication of memory impairment. Oral administration of resveratrol (20 mg/kg inhibited the occurrence of higher working, reference memory errors and prevented the incidence of less avoidances. Resveratrol appeared to have exerted memory-enhancing effects by inhibiting acetylcholinesterase activity and prevented the rise in malondialdehyde levels and loss of antioxidant enzymes catalase and superoxide dismutase, showing antioxidant potential. Based on the above results of behavioral and biochemical studies, it can be concluded that resveratrol protected against scopolamine-induced loss of cognition. The results also indicate that resveratrol is an antioxidant and an acetylcholinesterase inhibitor, and it is likely that resveratrol’s protective effect is related to its antioxidant and cholinesterase inhibitory effects.

  8. Relation of Oxidative Stress and Impaired Fibrinolysis with HDL Biogenesis in Indonesian Men with Metabolic Syndrome

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    Ida Paulina Sormin

    2010-04-01

    Full Text Available BACKGROUND: Biogenesis of HDL involves factors that regulate the synthesis, intravascular remodeling, and catabolism of HDL. Disturbance of these factors can lead to low concentration of HDL-C. Metabolic syndrome (MetS is characterized by low concentration of high-density lipoprotein cholesterol (HDL-C. In MetS occur several pathological conditions including oxidative stress and impaired fibrinolysis, which contribute to the risk of atherosclerosis process. The correlation between oxidative stress and impaired fibrinolysis with HDL biogenesis dysfunction and its correlation with low concentration of HDL-C has not been well understood and therefore needs to be further investigated. METHODS: This study was an observational study with crosssectional design, involving 163 adult men, aged 25-60 years with metabolic syndrome. Concentration of apoA-1, prebeta-1 HDL, CETP, F2-isoprostan, PAI-1, and HDL-C were measured. The apo A1/HDL ratio indicated HDL maturation, whereas the CETP/HDL-C and CETP/TG ratios indicated HDL catabolism. RESULTS: The study showed that there were a positive correlation between PAI-1 with apoA1/HDL-C ratios (r=0.226, p=0.005 and a negative correlation with the CETP/TG ratios (r=-0.215, p=0.007, whereas F2-isoprostan did not have correlation with HDL biogenesis factors. CONCLUSIONS: We concluded that there was correlation between impaired fibrinolysis with decreased HDL maturation and there was increased HDL catabolism leading to low HDL-C concentration in men with metabolic syndrome. KEYWORDS: F2-isoprostan, PAI-1, apoA-1, prebeta-1 HDL, CETP, metabolic syndrome.

  9. Nitric oxide plasma concentration associated with cognitive impairment in patients with recurrent depressive disorder.

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    Talarowska, Monika; Gałecki, Piotr; Maes, Michael; Orzechowska, Agata; Chamielec, Marcelina; Bartosz, Grzegorz; Kowalczyk, Edward

    2012-02-29

    Depressive disorders are multifactorial diseases, in which cognitive impairment is one of the characteristic feature. One of the molecules that regulate of various cognitive, emotional and behavioural processes is nitric oxide (NO), synthesized from l-arginine by a family of isoformic enzymes known as nitric oxide synthases (NOS). NO is a gaseous compounds that acts as a biological second messenger in a number of organ system. In addition, NO is a ubiquitous free radical (NO) that affects many normal physiologic functions but is also implicated in the etiology and progression of many diseases. The aim of the study was to determine the concentration of NO in patients with recurrent depressive disorder (rDD) and to define relationship between plasma NO levels and the cognitive performance. The study comprised 78 subjects: patients with rDD (n=45), healthy controls (CG, n=33). Cognitive function assessment was based on: TMT, The Stroop Test, VFT, AVLT. Statistically significant differences were found among patients with rDD in the intensity of depression symptoms, measured by the HDRS on therapy onset vs. the examination results after 8 weeks of treatment (pdepressive symptoms measured by HDRS (p=0.03). (1) Higher concentration of plasma NO in rDD patients is associated with the severity of depressive symptoms. (2) Elevated levels of plasma NO are related to impairment of visual-spatial and auditory-verbal working memory as well as to impairment of short-term declarative memory. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Increase in oxidative stress and mitochondrial impairment in hypothalamus of streptozotocin treated diabetic rat: Antioxidative effect of Withania somnifera.

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    Parihar, P; Shetty, R; Ghafourifar, P; Parihar, M S

    2016-01-22

    Hypothalamus, the primary brain region for glucose sensing, is severely affected by oxidative stress in diabetes mellitus. Oxidative stress in this region of brain may cause severe impairment in neuronal metabolic functions. Mitochondria are prominent targets of oxidative stress and the combination of increased oxidative stress and mitochondrial dysfunctions may further decline hypothalamic neuronal functions. In the present study we examined the oxidative damage response, antioxidative responses and mitochondrial membrane permeability transition in hypothalamus of streptozotocin-treated diabetic rats. Our results show that streptozotocin significantly increases hypothalamic lipid peroxidation, protein carbonyl content while glutathione peroxidase and reduced glutathione were declined. Mitochondrial impairment marked by an increase in mitochondrial membrane permeabilization was seen following streptozotocin treatment in the hypothalamus. The oral administration of Withania somnifera root extract stabilized mitochondrial functions and prevented oxidative damage in the hypothalamus of diabetic rat. These findings suggest an increase in the oxidative stress and decline in antioxidative responses in the hypothalamus of streptozotocin treated diabetic rats. Withania somnifera root extract was found useful in reducing oxidative stress and mitochondrial impairment in hypothalamus of diabetic rat.

  11. Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection.

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    Justin M Richner

    2015-07-01

    Full Text Available Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV, an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN. Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naïve CD4+ T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection.

  12. Impairment of PPARαand the Fatty Acid Oxidation Pathway Aggravates Renal Fibrosis during Aging.

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    Chung, Ki Wung; Lee, Eun Kyeong; Lee, Mi Kyung; Oh, Goo Taeg; Yu, Byung Pal; Chung, Hae Young

    2018-02-12

    Defects in the renal fatty acid oxidation (FAO) pathway have been implicated in the development of renal fibrosis. Although, compared with young kidneys, aged kidneys show significantly increased fibrosis with impaired kidney function, the mechanisms underlying the effects of aging on renal fibrosis have not been investigated. In this study, we investigated peroxisome proliferator-activated receptor α (PPAR α ) and the FAO pathway as regulators of age-associated renal fibrosis. The expression of PPAR α and the FAO pathway-associated proteins significantly decreased with the accumulation of lipids in the renal tubular epithelial region during aging in rats. In particular, decreased PPAR α protein expression associated with increased expression of PPAR α -targeting microRNAs. Among the microRNAs with increased expression during aging, miR-21 efficiently decreased PPAR α expression and impaired FAO when ectopically expressed in renal epithelial cells. In cells pretreated with oleic acid to induce lipid stress, miR-21 treatment further enhanced lipid accumulation. Furthermore, treatment with miR-21 significantly exacerbated the TGF- β -induced fibroblast phenotype of epithelial cells. We verified the physiologic importance of our findings in a calorie restriction model. Calorie restriction rescued the impaired FAO pathway during aging and slowed fibrosis development. Finally, compared with kidneys of aged littermate controls, kidneys of aged PPAR α -/- mice showed exaggerated lipid accumulation, with decreased activity of the FAO pathway and a severe fibrosis phenotype. Our results suggest that impaired renal PPAR α signaling during aging aggravates renal fibrosis development, and targeting PPAR α is useful for preventing age-associated CKD. Copyright © 2018 by the American Society of Nephrology.

  13. Impaired fatty acid oxidation as a cause for lipotoxicity in cardiomyocytes.

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    Haffar, T; Bérubé-Simard, F; Bousette, N

    A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring (14)C-CO2 production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative and qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Oxidative stress impairs the heat stress response and delays unfolded protein recovery.

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    Masaaki Adachi

    2009-11-01

    Full Text Available Environmental changes, air pollution and ozone depletion are increasing oxidative stress, and global warming threatens health by heat stress. We now face a high risk of simultaneous exposure to heat and oxidative stress. However, there have been few studies investigating their combined adverse effects on cell viability.Pretreatment of hydrogen peroxide (H(2O(2 specifically and highly sensitized cells to heat stress, and enhanced loss of mitochondrial membrane potential. H(2O(2 exposure impaired the HSP40/HSP70 induction as heat shock response (HSR and the unfolded protein recovery, and enhanced eIF2alpha phosphorylation and/or XBP1 splicing, land marks of ER stress. These H(2O(2-mediated effects mimicked enhanced heat sensitivity in HSF1 knockdown or knockout cells. Importantly, thermal preconditioning blocked H(2O(2-mediated inhibitory effects on refolding activity and rescued HSF1 +/+ MEFs, but neither blocked the effects nor rescued HSF1 -/- MEFs. These data strongly suggest that inhibition of HSR and refolding activity is crucial for H(2O(2-mediated enhanced heat sensitivity.H(2O(2 blocks HSR and refolding activity under heat stress, thereby leading to insufficient quality control and enhancing ER stress. These uncontrolled stress responses may enhance cell death. Our data thus highlight oxidative stress as a crucial factor affecting heat tolerance.

  15. Potential oxidative stress biomarkers of mild cognitive impairment due to Alzheimer disease.

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    García-Blanco, Ana; Baquero, Miguel; Vento, Máximo; Gil, Esperanza; Bataller, Luis; Cháfer-Pericás, Consuelo

    2017-02-15

    The high and increasing incidence of Alzheimer Disease (AD) worldwide is a major global concern. Classical diagnosis is carried out in the dementia phase, often in the moderate stages when treatment efficacy is limited. Nowadays, early diagnosis, even in pre-dementia stages, is possible in selected cases within an appropriate clinical setting, employing cerebral spinal fluid (CSF) sample analysis and neuroimaging procedures. In spite of the accurate diagnosis achieved by novel CSF biomarkers or positron emission tomography beta-amyloid tracers, these tests are invasive and expensive. Therefore, important work is being carried out to discover reliable biomarkers in peripheral biofluids (blood, plasma, urine) to be incorporated in clinical routine for early AD diagnosis. Although the nature of AD pathogenesis is complex, it is known that oxidative stress plays a key role, for which biomarkers are easily determined in peripheral biofluids. This review summarizes recent research on oxidative stress biomarkers in mild cognitive impairment due to AD. Among them, a promising research line is the study of the relationship between lipid peroxidation biomarkers and early AD clinical features. Results show a pronounced imbalance between scientific production and clinical reality due to the lack of clinical validation. We conclude that an important field in oxidative stress biomarkers could be developed with the aim to help clinicians in early disease diagnosis, effective treatment initiation and reliable disease monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial SIRT3 expression in rat offspring at weaning.

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    Sarah J Borengasser

    Full Text Available In utero exposure to maternal obesity increases the offspring's risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND21. In the current study, we examined systemic and hepatic adaptations in male Sprague-Dawley offspring from lean and obese dams at PND21. Indirect calorimetry revealed decreases in energy expenditure (p<0.001 and increases in RER values (p<0.001, which were further exacerbated by high fat diet (45% kcals from fat consumption indicating an impaired ability to utilize fatty acids in offspring of obese dams as analyzed by PRCF. Mitochondrial function is known to be associated with fatty acid oxidation (FAO in the liver. Several markers of hepatic mitochondrial function were reduced in offspring of obese dams. These included SIRT3 mRNA (p = 0.012 and mitochondrial protein content (p = 0.002, electron transport chain complexes (II, III, and ATPase, and fasting PGC-1α mRNA expression (p<0.001. Moreover, hepatic LCAD, a SIRT3 target, was not only reduced 2-fold (p<0.001 but was also hyperacetylated in offspring of obese dams (p<0.005 suggesting decreased hepatic FAO. In conclusion, exposure to maternal obesity contributes to early perturbations in whole body and liver energy metabolism. Mitochondrial dysfunction may be an underlying event that reduces hepatic fatty acid oxidation and precedes the development of detrimental obesity associated co-morbidities such as insulin resistance and NAFLD.

  17. Lipotoxic Palmitate Impairs the Rate of β-Oxidation and Citric Acid Cycle Flux in Rat Neonatal Cardiomyocytes

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    Taha Haffar

    2016-12-01

    Full Text Available Background/Aims: Diabetic hearts exhibit intracellular lipid accumulation. This suggests that the degree of fatty acid oxidation (FAO in these hearts is insufficient to handle the elevated lipid uptake. We previously showed that palmitate impaired the rate of FAO in primary rat neonatal cardiomyocytes. Here we were interested in characterizing the site of FAO impairment induced by palmitate since it may shed light on the metabolic dysfunction that leads to lipid accumulation in diabetic hearts. Methods: We measured fatty acid oxidation, acetyl-CoA oxidation, and carnitine palmitoyl transferase (Cpt1b activity. We measured both forward and reverse aconitase activity, as well as NAD+ dependent isocitrate dehydrogenase activity. We also measured reactive oxygen species using the 2', 7'-Dichlorofluorescin Diacetate (DCFDA assay. Finally we used thin layer chromatography to assess diacylglycerol (DAG levels. Results: We found that palmitate significantly impaired mitochondrial β-oxidation as well as citric acid cycle flux, but not Cpt1b activity. Palmitate negatively affected net aconitase activity and isocitrate dehydrogenase activity. The impaired enzyme activities were not due to oxidative stress but may be due to DAG mediated PKC activation. Conclusion: This work demonstrates that palmitate, a highly abundant fatty acid in human diets, causes impaired β-oxidation and citric acid cycle flux in primary neonatal cardiomyocytes. This metabolic defect occurs prior to cell death suggesting that it is a cause, rather than a consequence of palmitate mediated lipotoxicity. This impaired mitochondrial metabolism can have important implications for metabolic diseases such as diabetes and obesity.

  18. Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy.

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    Hassanzadeh, Parichehr; Arbabi, Elham; Atyabi, Fatemeh; Dinarvand, Rassoul

    2017-06-15

    Some conventional antiepileptic drugs induce oxidative stress and cognitive impairment which may limit their clinical applications. Ferulic acid is a phenolic phytochemical with antioxidant and neuroprotective properties that prompted us to evaluate its therapeutic potential in epilepsy which is usually associated with oxidative stress and cognitive decline. Male Wistar rats received 30mg/kg of pentylenetetrazole (PTZ) intraperitoneally (i.p.) once every alternate day until the development of kindling. The locomotor activity, elevated plus maze, and passive avoidance tests were performed. Oxidative stress was evaluated by the determination of brain malondialdehyde and reduced glutathione. The effects of pre-treatment with ferulic acid (25, 50, 75, and 100mg/kg, i.p.) against PTZ-kindled seizures, cognitive impairment, and oxidative stress were investigated. Kindling was developed 34.18±1.54days after PTZ treatment which was associated with generalized tonic-clonic seizures (GTCS), myoclonic jerks, cognitive deficit, and oxidative stress. Ferulic acid at doses of 75 and 100mg/kg significantly reduced the seizure score, number of myoclonic jerks, cognitive decline and oxidative stress. Spontaneous locomotor activity did not significantly differ between the groups. Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment induced by PTZ kindling. Therefore, this phenolic phytochemical appears as a promising adjuvant for antiepileptic drugs. Meanwhile, further experimental and clinical studies are required to provide insights into the cellular/molecular mechanism(s) underlying the action of ferulic acid. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

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    Tatiana Barichello

    2011-01-01

    Full Text Available Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day. The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction.

  20. Impaired endothelial nitric oxide bioavailability: a common link between aging, hypertension, and atherogenesis?

    LENUS (Irish Health Repository)

    Walsh, Thomas

    2012-01-31

    Endothelial-derived nitric oxide (NO) is responsible for maintaining continuous vasodilator tone and for regulating local perfusion and systemic blood pressure. It also has significant antiproliferative effects on vascular smooth muscle and platelet anti-aggregatory effects. Impaired endothelial-dependent (NO mediated) vasorelaxation is observed in most animal and human models of healthy aging. It also occurs in age-associated conditions such as atherosclerosis and hypertension. Such "endotheliopathy" increases vascular risk in older adults. Studies have indicated that pharmacotherapeutic intervention with angiotensin-converting enzyme inhibitors and 3-hydroxy-3-methyl-glutaryl coenzyme-A reductase inhibitors may improve NO-mediated vasomotor function. This review, evaluates the association between impaired endothelial NO bioavailability, accelerated vascular aging, and the age-associated conditions hypertension and atherogenesis. This is important, because pharmacotherapy aimed at improving endothelial NO bioavailability could modify age-related vascular disease and transform age into a potentially modifiable vascular risk factor, at least in a subpopulation of older adults.

  1. Adaptive Blood Glucose Monitoring and Insulin Measurement Devices for Visually Impaired Persons.

    Science.gov (United States)

    Petzinger, R. A.

    1993-01-01

    This article describes devices that people with visual impairments and diabetes can use to monitor blood glucose levels and measure insulin. A table lists devices, their manufacturers (including address and telephone number), and comments about the devices. (DB)

  2. Adaptation of intertidal biofilm communities is driven by metal ion and oxidative stresses

    KAUST Repository

    Zhang, Weipeng

    2013-11-11

    Marine organisms in intertidal zones are subjected to periodical fluctuations and wave activities. To understand how microbes in intertidal biofilms adapt to the stresses, the microbial metagenomes of biofilms from intertidal and subtidal zones were compared. The genes responsible for resistance to metal ion and oxidative stresses were enriched in both 6-day and 12-day intertidal biofilms, including genes associated with secondary metabolism, inorganic ion transport and metabolism, signal transduction and extracellular polymeric substance metabolism. In addition, these genes were more enriched in 12-day than 6-day intertidal biofilms. We hypothesize that a complex signaling network is used for stress tolerance and propose a model illustrating the relationships between these functions and environmental metal ion concentrations and oxidative stresses. These findings show that bacteria use diverse mechanisms to adapt to intertidal zones and indicate that the community structures of intertidal biofilms are modulated by metal ion and oxidative stresses.

  3. Ethylene oxide sterilization: how hospitals can adapt to the changes.

    Science.gov (United States)

    1994-12-01

    Ethylene oxide (EtO) gas sterilizers have been used by hospitals for over 40 years to sterilize surgical equipment and supplies that are heat sensitive or that cannot tolerate excessive moisture. However, in recent decades, EtO has been recognized as a potential mutagenic, reproductive, neurologic, and fire and explosion hazard to workers, and one agency has reportedly voted to classify EtO as carcinogenic to humans. Strict regulations concerning EtO exposure have been imposed by the Occupational Safety and Health Administration (OSHA), and the use of EtO, along with other toxic pollutants, is also being monitored by the Environmental Protection Agency (EPA) under the Clean Air Act. In addition, the use of chlorofluorocarbons (CFCs) as EtO diluents has focused attention on the EtO-CFC mixtures used in many sterilizers because CFCs have been linked to destruction of the ozone layer. Concerns about restrictive regulations related to these issues have prompted many hospitals to examine their use of EtO sterilization and propagated the misinformation that EtO sterilization is being phased out. In this article, we address some commonly asked questions regarding the use and regulation of EtO mixtures, as well as alternative sterilization agents and methods; provide two case studies illustrating how hospitals can evaluate various sterilization options; and summarize our conclusions and recommendations for hospitals facing decisions about sterilization techniques. For related topics, also see our Evaluation Update on endoscope reprocessors and our Hazard Report on improperly connected EtO-CFC cylinders to EtO sterilizers in this issue.

  4. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.

    Science.gov (United States)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner; Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M; De Sousa-Coelho, Ana Luisa; Daher, Grace; Manoli, Irini; Sysol, Justin R; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J; Beebe, Kirk; Gall, Walt; Venditti, Charles P; Patti, Mary-Elizabeth

    2016-10-01

    Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  5. Involvement of oxidative stress and impaired lysosomal degradation in amiodarone-induced schwannopathy.

    Science.gov (United States)

    Niimi, Naoko; Yako, Hideji; Tsukamoto, Masami; Takaku, Shizuka; Yamauchi, Junji; Kawakami, Emiko; Yanagisawa, Hiroko; Watabe, Kazuhiko; Utsunomiya, Kazunori; Sango, Kazunori

    2016-07-01

    Amiodarone hydrochloride (AMD), an anti-arrhythmic agent, has been shown to cause peripheral neuropathy; however, its pathogenesis remains unknown. We examined the toxic effects of AMD on an immortalized adult rat Schwann cell line, IFRS1, and cocultures of IFRS1 cells and adult rat dorsal root ganglion neurons or nerve growth factor-primed PC12 cells. Treatment with AMD (1, 5, and 10 μm) induced time- and dose-dependent cell death, accumulation of phospholipids and neutral lipids, upregulation of the expression of gangliosides, and oxidative stress (increased nuclear factor E2-related factor in nuclear extracts and reduced GSH/GSSG ratios) in IFRS1 cells. It also induced the upregulation of LC3-II and p62 expression, with phosphorylation of p62, suggesting that deficient autolysosomal degradation is involved in AMD-induced IFRS1 cell death. Furthermore, treatment of the cocultures with AMD induced detachment of IFRS1 cells from neurite networks in a time- and dose-dependent manner. These findings suggest that AMD-induced lysosomal storage accompanied by enhanced oxidative stress and impaired lysosomal degradation in Schwann cells might be a cause of demyelination in the peripheral nervous system. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. Transfer RNAs Mediate the Rapid Adaptation of Escherichia coli to Oxidative Stress

    Science.gov (United States)

    Du, Gaofei; Sun, Xuesong; He, Qing-Yu; Zhang, Gong

    2015-01-01

    Translational systems can respond promptly to sudden environmental changes to provide rapid adaptations to environmental stress. Unlike the well-studied translational responses to oxidative stress in eukaryotic systems, little is known regarding how prokaryotes respond rapidly to oxidative stress in terms of translation. In this study, we measured protein synthesis from the entire Escherichia coli proteome and found that protein synthesis was severely slowed down under oxidative stress. With unchanged translation initiation, this slowdown was caused by decreased translation elongation speed. We further confirmed by tRNA sequencing and qRT-PCR that this deceleration was caused by a global, enzymatic downregulation of almost all tRNA species shortly after exposure to oxidative agents. Elevation in tRNA levels accelerated translation and protected E. coli against oxidative stress caused by hydrogen peroxide and the antibiotic ciprofloxacin. Our results showed that the global regulation of tRNAs mediates the rapid adjustment of the E. coli translation system for prompt adaptation to oxidative stress. PMID:26090660

  7. alpha-Synuclein budding yeast model: toxicity enhanced by impaired proteasome and oxidative stress.

    Science.gov (United States)

    Sharma, Nijee; Brandis, Katrina A; Herrera, Sara K; Johnson, Brandon E; Vaidya, Tulaza; Shrestha, Ruja; Debburman, Shubhik K

    2006-01-01

    Parkinson's disease (PD) is a common neurodegenerative disorder that results from the selective loss of midbrain dopaminergic neurons. Misfolding and aggregation of the protein alpha-synuclein, oxidative damage, and proteasomal impairment are all hypotheses for the molecular cause of this selective neurotoxicity. Here, we describe a Saccharomyces cerevisiae model to evaluate the misfolding, aggregation, and toxicity-inducing ability of wild-type alpha-synuclein and three mutants (A30P, A53T, and A30P/A53T), and we compare regulation of these properties by dysfunctional proteasomes and by oxidative stress. We found prominent localization of wild-type and A53T alpha-synuclein near the plasma membrane, supporting known in vitro lipid-binding ability. In contrast, A30P was mostly cytoplasmic, whereas A30P/A53T displayed both types of fluorescence. Surprisingly, alpha-synuclein was not toxic to several yeast strains tested. When yeast mutants for the proteasomal barrel (doa3-1) were evaluated, delayed alpha-synuclein synthesis and membrane association were observed; yeast mutant for the proteasomal cap (sen3-1) exhibited increased accumulation and aggregation of alpha-synuclein. Both sen3-1and doa3-1 mutants exhibited synthetic lethality with alpha-synuclein. When yeasts were challenged with an oxidant (hydrogen peroxide), alpha-synuclein was extremely lethal to cells that lacked manganese superoxide dismutase Mn-SOD (sod2Delta) but not to cells that lacked copper, zinc superoxide dismutase Cu,Zn-SOD (sod1Delta). Despite the toxicity, sod2Delta cells never displayed intracellular aggregates of alpha-synuclein. We suggest that the toxic alpha-synuclein species in yeast are smaller than the visible aggregates, and toxicity might involve alpha-synuclein membrane association. Thus, yeasts have emerged effective organisms for characterizing factors and mechanisms that regulate alpha-synuclein toxicity.

  8. Effect of Cinnamomum zeylanicum extract on scopolamine-induced cognitive impairment and oxidative stress in rats.

    Science.gov (United States)

    Jain, Seema; Sangma, Tultul; Shukla, Santosh Kumar; Mediratta, Pramod Kumari

    2015-07-01

    Cinnamomum zeylanicum (CZ) is commonly known as cinnamon in traditional system of medicine having antibacterial, antioxidant, antidiabetic, hypolipidemic, and other activities. The present study was designed to assess the effect of extract of CZ bark on cognitive performance of scopolamine (SCOP)-treated rats and on associated altered oxidative stress markers in the brain of rats. The extract was administered orally in three doses (100, 200, and 400 mg/kg) for a period of 21 days. SCOP was administered in the dose of 1.0 mg/kg intraperitoneally. The Morris water maze and passive avoidance step-down tasks were performed to assess cognitive functions. At the end of the study, oxidative stress parameters namely, malondialdehyde (MDA) and reduced glutathione (GSH) were also analyzed in the brain tissue of rats. SCOP-treated group showed significantly impaired acquisition and retention of memory as compared to the saline- and vehicle-treated groups. Pretreatment with CZ extract (200 and 400 mg/kg) for 21 days significantly reversed SCOP-induced amnesia as evidenced by increased step-down latency in passive avoidance and decreased latency in Morris water maze test compared to the SCOP-treated group. SCOP administration also caused the increase of MDA and reduction of GSH levels. Pretreatment with CZ extract (200 and 400 mg/kg) resulted in a significant decrease in MDA levels and increase in GSH levels as compared to the SCOP-treated animals. The results suggest that CZ can induce cognitive improvement in SCOP-treated rats and this effect can be attributed to a certain extent to decreased oxidative stress.

  9. The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: the role of oxidative stress.

    Science.gov (United States)

    Alzoubi, Karem H; Khabour, Omar F; Rashid, Baraa Abu; Damaj, Imad M; Salah, Heba A

    2012-01-01

    Sleep deprivation induces oxidative stress and impairs learning and memory processes. Vitamin E, on the other hand, is a strong antioxidant that has neuroprotective effect on the brain. In this study, we examined the potential protective effect of chronic administration of vitamin E on chronic sleep deprivation-induced cognitive impairment. In addition, possible molecular targets for vitamin E effects on chronic sleep deprivation-induced cognitive impairment were determined. Sleep deprivation was induced in rats using modified multiple platform model. Vitamin E (100mg/kg) was administered to animals by oral gavage. Behavioral study was conducted to test the spatial learning and memory using the radial arm water maze (RAWM). In addition, the hippocampus was dissected out and antioxidant markers including glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) were assessed. The results of this project revealed that chronic sleep deprivation impaired both (short- and long-term) memories (Psleep deprivation-induced reduction in the hippocampus GSH/GSSG ratio, and activity of catalase, SOD, and GPx. In conclusion, sleep deprivation induces memory impairment, and treatment with vitamin E prevented this impairment probably through its antioxidant action in the hippocampus. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Sexual dimorphism in oxidant-induced adaptive homeostasis in multiple wild-type D. melanogaster strains.

    Science.gov (United States)

    Pomatto, Laura C D; Wong, Sarah; Tower, John; Davies, Kelvin J A

    2017-12-15

    Sexual dimorphism includes the physical and reproductive differences between the sexes, including differences that are conserved across species, ranging from the common fruit fly, Drosophila melanogaster, to humans. Sex-dependent variations in adaptive homeostasis, and adaptive stress responses may offer insight into the underlying mechanisms for male and female survival differences and into differences in chronic disease incidence and severity in humans. Earlier work showed sex-specific differences in adaptive responses to oxidative stressors in hybrid laboratory strains of D. melanogaster. The present study explored whether this phenomenon is also observed in wild-type D. melanogaster strains Oregon-R (Or-R) and Canton-S (Ca-S), as well as the common mutant reference strain w[1118], in order to better understand whether such findings are descriptive of D. melanogaster in general. Flies of each strain were pretreated with non-damaging, adaptive concentrations of hydrogen peroxide (H2O2) or of different redox cycling agents (paraquat, DMNQ, or menadione). Adaptive homeostasis, and changes in the expression of the Proteasome and overall cellular proteasomal proteolytic capacity were assessed. Redox cycling agents exhibited a male-specific adaptive response, whereas H2O2 exposure provoked female-specific adaptation. These findings demonstrate that different oxidants can elicit sexually dimorphic adaptive homeostatic responses in multiple fly strains. These results (and those contained in a parallel study [1]) highlight the need to address sex as a biological variable in fundamental science, clinical research, and toxicology. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Vitamin B12 deficiency results in severe oxidative stress, leading to memory retention impairment in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Tomohiro Bito

    2017-04-01

    Full Text Available Oxidative stress is implicated in various human diseases and conditions, such as a neurodegeneration, which is the major symptom of vitamin B12 deficiency, although the underlying disease mechanisms associated with vitamin B12 deficiency are poorly understood. Vitamin B12 deficiency was found to significantly increase cellular H2O2 and NO content in Caenorhabditis elegans and significantly decrease low molecular antioxidant [reduced glutathione (GSH and L-ascorbic acid] levels and antioxidant enzyme (superoxide dismutase and catalase activities, indicating that vitamin B12 deficiency induces severe oxidative stress leading to oxidative damage of various cellular components in worms. An NaCl chemotaxis associative learning assay indicated that vitamin B12 deficiency did not affect learning ability but impaired memory retention ability, which decreased to approximately 58% of the control value. When worms were treated with 1 mmol/L GSH, L-ascorbic acid, or vitamin E for three generations during vitamin B12 deficiency, cellular malondialdehyde content as an index of oxidative stress decreased to the control level, but the impairment of memory retention ability was not completely reversed (up to approximately 50%. These results suggest that memory retention impairment formed during vitamin B12 deficiency is partially attributable to oxidative stress.

  12. Adaptation of office workers to a new building - impaired well-being as part of the sick-building-syndrome.

    Science.gov (United States)

    Neuner, Ralf; Seidel, Hans-Joachim

    2006-07-01

    The focus of our study was the assessment of the effects of spatial relocation on office staff. Our aim was to investigate whether psychosocial or personal factors are better predictors of the occurrence of impaired well-being. Before relocation the administration of the university hospital of Ulm (Germany) was located in ten different buildings. Chemical and physical parameters of the indoor air were measured. The employees were surveyed with a questionnaire for their health status and psychosocial determinants. After moving to a new wide-spaced building, the same procedure was reapplied shortly afterwards and half a year later. Only respondents who had taken part in all three surveys are taken into account (n=84). The definition of impaired well-being as defined by the ProKlimA-study group was used as the criterion variable. The overall prevalence of impaired well-being rose from 24% to 36% after relocation. Contrarily, persons who were formerly accommodated in a wide spaced-building showed a reduced risk (OR(post1)=0.3). Affected persons had at all times a more negative response pattern. Chemical and physical parameters did not have any influence in this context. The adaptation to a new environment is influenced by the old "socialization" of the former buildings. Impaired well-being is not limited to bodily complaints, it rather has a systemic character in the form of a distinctive overall response pattern. For an adequate analysis of impaired well-being - and the sick-building-syndrome in consequence - the elucidation of individual and other potentially intervening factors is essential. Taking this into consideration, the search for norm values or a framework seems to be of limited value.

  13. Investigating low adaptive behaviour and presence of the triad of impairments characteristic of autistic spectrum disorder as indicators of risk for challenging behaviour among adults with intellectual disabilities.

    Science.gov (United States)

    Felce, D; Kerr, M

    2013-02-01

    Identification of possible personal indicators of risk for challenging behaviour has generally been through association in cross-sectional prevalence studies, but few analyses have controlled for intercorrelation between potential risk factors. The aim was to investigate the extent to which gender, age, presence of the triad of impairments characteristic of autism and level of adaptive behaviour were independently associated with level of challenging behaviour among adults with intellectual disabilities. Five datasets were merged to produce information on challenging behaviour, adaptive behaviour, presence of the triad of impairments, gender and age of 818 adults. Variables were entered into a multivariate linear regression, which also tested the interaction between the presence of the triad of impairments and level of adaptive behaviour. Presence of the triad of impairments, level of adaptive behaviour, their interaction, and age, but not gender, significantly and independently contributed to the prediction of challenging behaviour. Presence/absence of the triad of impairments moderated the effect of adaptive behaviour on challenging behaviour. The inverse relationship found in the absence of the triad of impairments was virtually removed when present. This study has shown that it is necessary to control for intercorrelation between potential risk factors for challenging behaviour and to explore how interaction between them might moderate associations. © 2012 The Author. Journal of Intellectual Disability Research © 2012 Blackwell Publishing Ltd.

  14. Individuals with medial knee osteoarthritis show neuromuscular adaptation when perturbed during walking despite functional and structural impairments.

    Science.gov (United States)

    Kumar, Deepak; Swanik, Charles Buz; Reisman, Darcy S; Rudolph, Katherine S

    2014-01-01

    Neuromuscular control relies on sensory feedback that influences responses to changing external demands, and the normal response is for movement and muscle activation patterns to adapt to repeated perturbations. People with knee osteoarthritis (OA) are known to have pain, quadriceps weakness, and neuromotor deficits that could affect adaption to external perturbations. The aim of this study was to analyze neuromotor adaptation during walking in people with knee OA (n = 38) and controls (n = 23). Disability, quadriceps strength, joint space width, malalignment, and proprioception were assessed. Kinematic and EMG data were collected during undisturbed walking and during perturbations that caused lateral translation of the foot at initial contact. Knee excursions and EMG magnitudes were analyzed. Subjects with OA walked with less knee motion and higher muscle activation and had greater pain, limitations in function, quadriceps weakness, and malalignment, but no difference was observed in proprioception. Both groups showed increased EMG and decreased knee motion in response to the first perturbation, followed by progressively decreased EMG activity and increased knee motion during midstance over the first five perturbations, but no group differences were observed. Over 30 trials, EMG levels returned to those of normal walking. The results illustrate that people with knee OA respond similarly to healthy individuals when exposed to challenging perturbations during functional weight-bearing activities despite structural, functional, and neuromotor impairments. Mechanisms underlying the adaptive response in people with knee OA need further study.

  15. Quercetin ameliorates hypobaric hypoxia-induced memory impairment through mitochondrial and neuron function adaptation via the PGC-1α pathway.

    Science.gov (United States)

    Liu, Peng; Zou, Dan; Yi, Long; Chen, Mingliang; Gao, Yanxiang; Zhou, Rui; Zhang, Qianyong; Zhou, Yong; Zhu, Jundong; Chen, Ka; Mi, Mantian

    2015-01-01

    Acute hypobaric hypoxia (HH) causes persistent cognitive impairment, affecting memory function specifically. Mitochondrial dysfunction and synaptic morphological change were the prominent pathological features of HH exposure on brain. Quercetin, a flavonoid found in fruits, vegetables, leaves and grains, is reported to prevent ischemia induced by neuronal injury. This study investigated the efficacy of quercetin to ameliorate HH-induced memory deficit. Rats were exposed to HH equivalent to 5000 m for 7 days in a decompression chamber and received quercetin daily (50, 75 or 100 mg/kg·bw) via gavage during the period of exposure. Cognitive performance was assessed by the Morris water maze test. In vitro, the effect of quercetin was tested in hippocampus tissue. Quercetin, especially at 100 mg/kg·bw, significantly reduced HH-induced memory decline. Meanwhile, HH-induced hippocampus mitochondrial and synaptic lesions were ameliorated by quercetin. Furthermore, quercetin regulated the expression of sirtuin 1(Sirt1), PGC-1α, and the proteins related with mitochondrial biogenesis and dynamics. Moreover, quercetin increased expression of fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF), showing the PGC-1α/FNDC5/BNDF pathways might be involved in neuronal adaptation. The results suggest quercetin has prophylactic potential for amelioration of HH-induced memory impairment, which is associated with the mitochondrial and neuronal adaptation in hippocampus.

  16. Energy Efficient Glazing for Adaptive Solar Control Fabricated with Photothermotropic Hydrogels Containing Graphene Oxide

    OpenAIRE

    Kim, Dowan; Lee, Eunsu; Lee, Heon Sang; Yoon, Jinhwan

    2015-01-01

    Glazing for adaptive solar control is the most promising for energy efficient development, because the use of this technology in buildings can be expected to significantly impact energy use and efficiency by screening sunlight that enters a building in summer. To achieve autonomous adjustable transparency, we have developed photothermotropic material system by combining photothermal materials with thermotropic hydrogels. We found that graphene oxide dispersed within a hydrogel matrix effectiv...

  17. Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.

    Science.gov (United States)

    Glorieux, Christophe; Sandoval, Juan Marcelo; Fattaccioli, Antoine; Dejeans, Nicolas; Garbe, James C; Dieu, Marc; Verrax, Julien; Renard, Patricia; Huang, Peng; Calderon, Pedro Buc

    2016-10-01

    Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H 2 O 2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation and repression, respectively, by controlling chromatin remodeling through a histone deacetylases-dependent mechanism. This regulatory mechanism plays an important role in redox adaptation to chronic exposure to H 2 O 2 in breast cancer cells. Our study suggests that cancer adaptation to oxidative stress may be regulated by transcriptional factors through chromatin remodeling, and reveals a potential new mechanism to target cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Phytomedicinal Role of Pithecellobium dulce against CCl4-mediated Hepatic Oxidative Impairments and Necrotic Cell Death

    Directory of Open Access Journals (Sweden)

    Prasenjit Manna

    2011-01-01

    Full Text Available Present study investigates the beneficial role of the aqueous extract of the fruits of Pithecellobium dulce (AEPD against carbon tetrachloride (CCl4-induced hepatic injury using a murine model. AEPD has been found to possess free radical (DPPH, hydroxyl and superoxide scavenging activity in cell-free system. CCl4 exposure increased the activities of various serum maker enzymes and intracellular reactive oxygen species (ROS production. In line with these findings, we also observed that CCl4 intoxication increased the lipid peroxidation and protein carbonylation accompanied by decreased intracellular antioxidant defense, activity of cytochrome P450 and CYP2E1 expression. DNA fragmentation and flow cytometric analyses revealed that CCl4 exposure caused hepatic cell death mainly via the necrotic pathway. Treatment with AEPD both pre- and post-toxin exposure protected the organ from CCl4-induced hepatic damage. Histological findings also support our results. A well-known antioxidant vitamin C was included in this study to compare the antioxidant potency of AEPD. Combining all, results suggest that AEPD protects murine liver against CCl4-induced oxidative impairments probably via its antioxidative property.

  19. Cadmium sulfide quantum dots induce oxidative stress and behavioral impairments in the marine clam Scrobicularia plana.

    Science.gov (United States)

    Buffet, Pierre-Emmanuel; Zalouk-Vergnoux, Aurore; Poirier, Laurence; Lopes, Christelle; Risso-de-Faverney, Christine; Guibbolini, Marielle; Gilliland, Douglas; Perrein-Ettajani, Hanane; Valsami-Jones, Eugenia; Mouneyrac, Catherine

    2015-07-01

    Cadmium sulfide (CdS) quantum dots have a number of current applications in electronics and solar cells and significant future potential in medicine. The aim of the present study was to examine the toxic effects of CdS quantum dots on the marine clam Scrobicularia plana exposed for 14 d to these nanomaterials (10 µg Cd L(-1) ) in natural seawater and to compare them with soluble Cd. Measurement of labile Cd released from CdS quantum dots showed that 52% of CdS quantum dots remained in the nanoparticulate form. Clams accumulated the same levels of Cd regardless of the form in which it was delivered (soluble Cd vs CdS quantum dots). However, significant changes in biochemical responses were observed in clams exposed to CdS quantum dots compared with soluble Cd. Increased activities of catalase and glutathione-S-transferase were significantly higher in clams exposed in seawater to Cd as the nanoparticulate versus the soluble form, suggesting a specific nano effect. The behavior of S. plana in sediment showed impairments of foot movements only in the case of exposure to CdS quantum dots. The results show that oxidative stress and behavior biomarkers are sensitive predictors of CdS quantum dots toxicity in S. plana. Such responses, appearing well before changes might occur at the population level, demonstrate the usefulness of this model species and type of biomarker in the assessment of nanoparticle contamination in estuarine ecosystems. © 2015 SETAC.

  20. Impaired Cerebral Mitochondrial Oxidative Phosphorylation Function in a Rat Model of Ventricular Fibrillation and Cardiopulmonary Resuscitation

    Directory of Open Access Journals (Sweden)

    Jun Jiang

    2014-01-01

    Full Text Available Postcardiac arrest brain injury significantly contributes to mortality and morbidity in patients suffering from cardiac arrest (CA. Evidence that shows that mitochondrial dysfunction appears to be a key factor in tissue damage after ischemia/reperfusion is accumulating. However, limited data are available regarding the cerebral mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR and its relationship to the alterations of high-energy phosphate. Here, we sought to identify alterations of mitochondrial morphology and oxidative phosphorylation function as well as high-energy phosphates during CA and CPR in a rat model of ventricular fibrillation (VF. We found that impairment of mitochondrial respiration and partial depletion of adenosine triphosphate (ATP and phosphocreatine (PCr developed in the cerebral cortex and hippocampus following a prolonged cardiac arrest. Optimal CPR might ameliorate the deranged phosphorus metabolism and preserve mitochondrial function. No obvious ultrastructural abnormalities of mitochondria have been found during CA. We conclude that CA causes cerebral mitochondrial dysfunction along with decay of high-energy phosphates, which would be mitigated with CPR. This study may broaden our understanding of the pathogenic processes underlying global cerebral ischemic injury and provide a potential therapeutic strategy that aimed at preserving cerebral mitochondrial function during CA.

  1. Sulforaphane induces oxidative stress and death by p53-independent mechanism: implication of impaired glutathione recycling.

    Directory of Open Access Journals (Sweden)

    José Miguel P Ferreira de Oliveira

    Full Text Available Sulforaphane (SFN is a naturally-occurring isothiocyanate best known for its role as an indirect antioxidant. Notwithstanding, in different cancer cell lines, SFN may promote the accumulation of reactive oxygen species (ROS and cause cell death e.g. by apoptosis. Osteosarcoma often becomes chemoresistant, and new molecular targets to prevent drug resistance are needed. Here, we aimed to determine the effect of SFN on ROS levels and to identify key biomarkers leading to ROS unbalance and apoptosis in the p53-null MG-63 osteosarcoma cell line. MG-63 cells were exposed to SFN for up to 48 h. At 10 μM concentration or higher, SFN decreased cell viability, increased the%early apoptotic cells and increased caspase 3 activity. At these higher doses, SFN increased ROS levels, which correlated with apoptotic endpoints and cell viability decline. In exposed cells, gene expression analysis revealed only partial induction of phase-2 detoxification genes. More importantly, SFN inhibited ROS-scavenging enzymes and impaired glutathione recycling, as evidenced by inhibition of glutathione reductase (GR activity and combined inhibition of glutathione peroxidase (GPx gene expression and enzyme activity. In conclusion, SFN induced oxidative stress and apoptosis via a p53-independent mechanism. GPx expression and activity were found associated with ROS accumulation in MG-63 cells and are potential biomarkers for the efficacy of ROS-inducing agents e.g. as co-adjuvant drugs in osteosarcoma.

  2. Systemic Oxidative Stress and Conversion to Dementia of Elderly Patients with Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Carlo Cervellati

    2014-01-01

    Full Text Available Mild cognitive impairment (MCI is regarded as a prodromal phase of late onset Alzheimer’s disease (LOAD. It has been proposed that oxidative stress (OxS might be implicated in the pathogenesis of LOAD. The aim of this study was to investigate whether a redox imbalance measured as serum level of hydroperoxides (i.e., by-products of lipid peroxidation and/or serum antioxidant capacity might be predictive of the clinical progression of MCI to LOAD. The levels of these two markers were measured in 111 patients with MCI (follow-up: 2.0 ± 0.6 years, 105 patients with LOAD, and 118 nondemented healthy controls. Multivariate analysis adjusted for potential confounding factors, including age, gender, smoking, and comorbidities, showed a significant increase (P<0.05 in baseline levels of OxS in MCI and LOAD as compared to cognitive healthy controls. No differences in either of OxS markers were found by comparing MCI patients who converted (n = 29 or not converted (n = 82 to LOAD. Overall, these results suggest that systemic OxS might be a precocious feature of MCI and LOAD. However, the role of OxS as an early prognostic marker of progression to LOAD needs further investigations.

  3. Impaired Healing of a Cutaneous Wound in an Inducible Nitric Oxide Synthase-Knockout Mouse

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    Takashi Kitano

    2017-01-01

    Full Text Available Background. We investigated the effects of loss of inducible nitric oxide synthase (iNOS on the healing process of cutaneous excisional injury by using iNOS-null (KO mice. Population of granulation tissue-related cell types, that is, myofibroblasts and macrophages, growth factor expression, and reepithelialization were evaluated. Methods. KO and wild type (WT mice of C57BL/6 background were used. Under general anesthesia two round full-thickness excision wounds of 5.0 mm in diameter were produced in dorsal skin. After specific intervals of healing, macroscopic observation, histology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction (RT-PCR were employed to evaluate the healing process. Results. The loss of iNOS retards granulation tissue formation and reepithelialization in excision wound model in mice. Detailed analyses showed that myofibroblast appearance, macrophage infiltration, and mRNA expression of transforming growth factor b and of collagen 1α2 were all suppressed by lacking iNOS. Conclusions. iNOS is required in the process of cutaneous wound healing. Lacking iNOS retards macrophage invasion and its expression of fibrogenic components that might further impair fibrogenic behaviors of fibroblasts.

  4. Role of oxidative stress in impaired insulin signaling associated with exercise-induced muscle damage.

    Science.gov (United States)

    Aoi, Wataru; Naito, Yuji; Yoshikawa, Toshikazu

    2013-12-01

    Skeletal muscle is a major tissue that utilizes blood glucose. A single bout of exercise improves glucose uptake in skeletal muscle through insulin-dependent and insulin-independent signal transduction mechanisms. However, glucose utilization is decreased in muscle damage induced by acute, unaccustomed, or eccentric exercise. The decrease in glucose utilization is caused by decreased insulin-stimulated glucose uptake in damaged muscles with inhibition of the membrane translocation of glucose transporter 4 through phosphatidyl 3-kinase/Akt signaling. In addition to inflammatory cytokines, reactive oxygen species including 4-hydroxy-2-nonenal and peroxynitrate can induce degradation or inactivation of signaling proteins through posttranslational modification, thereby resulting in a disturbance in insulin signal transduction. In contrast, treatment with factors that attenuate oxidative stress in damaged muscle suppresses the impairment of insulin sensitivity. Muscle-damaging exercise may thus lead to decreased endurance capacity and muscle fatigue in exercise, and it may decrease the efficiency of exercise therapy for metabolic improvement. © 2013 Elsevier Inc. All rights reserved.

  5. Lycopene protects against memory impairment and mito-oxidative damage induced by colchicine in rats: an evidence of nitric oxide signaling.

    Science.gov (United States)

    Prakash, Atish; Kumar, Anil

    2013-12-05

    Oxidative-nitrosative stress and mitochondrial dysfunction plays an important role in the onset of various neurodegenerative diseases. Lycopene, a carotenoid antioxidant, has received considerable scientific interest in recent years. Present study was designed to evaluate the possible nitric oxide mechanism in protective effects of lycopene against the colchicine induced cognitive impairment and mito-oxidative damage in rats. Wistar rats were received i.c.v. colchicine (15 µg/5 µl). Lycopene (2.5 and 5mg/kg), NO modulators e.g. l-Arginine (50mg/kg) l-NAME (5mg/kg) administered for 21 days. Behavioural alterations were assessed in between study period. Animals were killed immediately following the last behavioral session, and mitochondrial enzymes, oxidative parameters, inflammatory mediators (TNF-α, IL-6) and caspase-3 activity were measured. I.C.V. administration of colchicine impaired memory performance in Morris water maze, oxidative defense and mitochondrial complex enzymes activities as compared to sham group. A significant increase of TNF-α, IL-6 and caspase-3 activity in hippocampus and cortex was also noted. Chronic treatment lycopene significantly improved memory retention and attenuated mito-oxidative damage parameters, inflammatory markers and apoptosis in colchicine treated rats. Further, l-arginine pretreatment with sub effective dose of lycopene significantly reversed the protective effect of lycopene. However, l-NAME pretreatment with sub effective dose of lycopene significantly potentiated the protective effect of lycopene which was significant as compared to their effect per se. These results suggest that lycopene exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down regulating nitric oxide pathways. Thus, lycopene may be used as therapeutic agent in preventing complications in memory dysfunction. © 2013 Elsevier B.V. All rights reserved.

  6. Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle

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    Malkus Kristen A

    2009-06-01

    Full Text Available Abstract While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with oxidative stress, contribute to neuron death. Using Parkinson's disease (PD as the paradigm, this review explores the hypothesis that oxidative modifications, mitochondrial functional disruption, and impairment of protein degradation constitute three interrelated molecular pathways that execute neuron death. These intertwined events are the consequence of environmental exposure, genetic factors, and endogenous risks and constitute a "Bermuda triangle" that may be considered the underlying cause of neurodegenerative pathogenesis.

  7. Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle.

    Science.gov (United States)

    Malkus, Kristen A; Tsika, Elpida; Ischiropoulos, Harry

    2009-06-05

    While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with oxidative stress, contribute to neuron death. Using Parkinson's disease (PD) as the paradigm, this review explores the hypothesis that oxidative modifications, mitochondrial functional disruption, and impairment of protein degradation constitute three interrelated molecular pathways that execute neuron death. These intertwined events are the consequence of environmental exposure, genetic factors, and endogenous risks and constitute a "Bermuda triangle" that may be considered the underlying cause of neurodegenerative pathogenesis.

  8. Effect of Lactobacillus pentosus-Fermented Artemisiae Argi Folium on Nitric Oxide Production of Macrophage impaired with Various Toxicants

    Directory of Open Access Journals (Sweden)

    Wansu Park

    2009-12-01

    Full Text Available Objectives : The purpose of this study is to investigate the effect of Water Extract from Lactobacillus pentosus-fermented ARTEMISIAE ARGI FOLIUM (AFL on nitric oxide production of mouse macrophage Raw 264.7 cells impaired by various toxicants such as gallic acid, EtOH, nicotine, acetaminophen, and acetaldehyde. Methods : ARTEMISIAE ARGI FOLIUM was fermented with Lactobacillus pentosus and extracted by water. Nitric oxide production of mouse macrophage Raw 264.7 cells was measured by Griess reagent assay. Examined concentrations of AFL were 10, 50, 100, 200, 400 ug/mL. Results : The results of the experiment are as below. 1. AFL at the concentration of 400 ug/mL significantly recovered nitric oxide production which was reduced by gallic acid (100 uM in Raw 264.7 cells. 2. AFL at the concentration of 200, 400 ug/mL significantly recovered nitric oxide production which was reduced by EtOH (100 uM in Raw 264.7 cells. 3. AFL at the concentration of 400 ug/mL significantly recovered nitric oxide production which was reduced by nicotine (1mM in Raw 264.7 cells. 4. AFL at the concentration of 200, 400 ug/mL significantly recovered nitric oxide production which was reduced by acetaminophen(2mM in Raw 264.7 cells. 5. AFL at the concentration of 200, 400 ug/mL significantly recovered nitric oxide production which was reduced by acetaldehyde (200 uM in Raw 264.7 cells. Conclusions : AFL could be supposed to have the immune-enhancing activity related with nitric oxide production of macrophage impaired by various toxicants.

  9. Nitric oxide pathway activity modulation alters the protective effects of (-)Epigallocatechin-3-gallate on reserpine-induced impairment in rats.

    Science.gov (United States)

    Chen, Cheng-Neng; Chang, Kuo-Chi; Lin, Rui-Feng; Wang, Mao-Hsien; Shih, Ruoh-Lan; Tseng, Hsiang-Chien; Soung, Hung-Sheng; Tsai, Cheng-Chia

    2016-05-15

    Reserpine (RES) has been reported to increase the brain's neural oxidative stress and cause cognitive dysfunction. Having powerful antioxidative properties, green tea catechins, especially (-)epigallocatechin-3-gallate (EGCG), are able to protect against many oxidative injuries. In this study, we examined the protecting properties of EGCG on RES-induced impairment of short-term memory in three-month-old male Wistar rats. RES (1mg/kg i.p.) induced memory impairment (p<0.001) as evaluated by the social recognition task. EGCG treatment (100mg/kg i.p. for 7days, starting 6days before RES injection) was able to improve the impaired memory caused by RES. RES treatment increased the nitric oxide (NO) level and lipid peroxidation (LPO) production, and decreased the antioxidation power in hippocampi. EGCG treatment was able to counteract the RES-induced NO level and LPO production, as well as enhanced the hippocampal antioxidation power in RES-treated rats. In order to examine the implication of NO pathway activity in RES treatment, either NO precursor (L-arginine; L-A) or NO synthase inhibitor (L-NAME; L-N) was co-pretreated with EGCG; NO precursor treatment eliminated the protective effect of EGCG, in contrast to that NO synthase inhibitor treatment significantly increased the EGCG effects on cognitive and biochemical protection in RES-treated rats. These results suggested that the NO pathway was implicated, at least in part, in the RES-induced impairment, as well as in the protective effect of EGCG in treating RES-induced impairment of memory. The above evidence provides a clinically relevant value for EGCG in preventing RES-induced cognitive dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Calpain-3 impairs cell proliferation and stimulates oxidative stress-mediated cell death in melanoma cells.

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    Daniele Moretti

    Full Text Available Calpain-3 is an intracellular cysteine protease, belonging to Calpain superfamily and predominantly expressed in skeletal muscle. In human melanoma cell lines and biopsies, we previously identified two novel splicing variants (hMp78 and hMp84 of Calpain-3 gene (CAPN3, which have a significant lower expression in vertical growth phase melanomas and, even lower, in metastases, compared to benign nevi. In the present study, in order to investigate the pathophysiological role played by the longer Calpain-3 variant, hMp84, in melanoma cells, we over-expressed it in A375 and HT-144 cells. In A375 cells, the enforced expression of hMp84 induces p53 stabilization, and modulates the expression of a few p53- and oxidative stress-related genes. Consistently, hMp84 increases the intracellular production of ROS (Reactive Oxygen Species, which lead to oxidative modification of phospholipids (formation of F2-isoprostanes and DNA damage. Such events culminate in an adverse cell fate, as indicated by the decrease of cell proliferation and by cell death. To a different extent, either the antioxidant N-acetyl-cysteine or the p53 inhibitor, Pifithrin-α, recover cell viability and decrease ROS formation. Similarly to A375 cells, hMp84 over-expression causes inhibition of cell proliferation, cell death, and increase of both ROS levels and F2-isoprostanes also in HT-144 cells. However, in these cells no p53 accumulation occurs. In both cell lines, no significant change of cell proliferation and cell damage is observed in cells over-expressing the mutant hMp84C42S devoid of its enzymatic activity, suggesting that the catalytic activity of hMp84 is required for its detrimental effects. Since a more aggressive phenotype is expected to benefit from down-regulation of mechanisms impairing cell growth and survival, we envisage that Calpain-3 down-regulation can be regarded as a novel mechanism contributing to melanoma progression.

  11. Gamma radiation induces growth retardation, impaired egg production, and oxidative stress in the marine copepod Paracyclopina nana

    Energy Technology Data Exchange (ETDEWEB)

    Won, Eun-Ji; Lee, Jae-Seong, E-mail: jslee2@skku.edu

    2014-05-01

    Highlights: • Mortality was increased with a dose dependent manner in ovigerous females of Paracyclopina nana. • Developmental impairments were observed in gamma irradiated nauplii. • Ovigerous females exposed to more than 50 Gy could not have normal two bilateral egg sacs. • Oxidative levels increased with antioxidant enzyme activities in the gamma irradiated P. nana. • The molecular indices (antioxidant enzymes and heat shock protein) were also increased. - Abstract: Accidental nuclear radioisotope release into the ocean from nuclear power plants is of concern due to ecological and health risks. In this study, we used the marine copepod Paracyclopina nana to examine the effects of radioisotopes on marine organisms upon gamma radiation, and to measure the effects on growth and fecundity, which affect population and community structure. Upon gamma radiation, mortality (LD50 – 96 h = 172 Gy) in P. nana was significantly increased in a dose-dependent manner in ovigerous P. nana females. For developmental impairment of gamma-irradiated nauplii, we observed growth retardation; in over 30 Gy-irradiated groups, offspring did not grow to adults. Particularly, over 50 Gy-irradiated ovigerous P. nana females did not have normal bilateral egg sacs, and their offspring did not develop normally to adulthood. Additionally, at over 30 Gy, we found dose-dependent increases in oxidative levels with elevated antioxidant enzyme activities and DNA repair activities. These findings indicate that gamma radiation can induce oxidative stress and DNA damage with growth retardation and impaired reproduction.

  12. Adaptation of ammonia-oxidizing microorganisms to environment shift of paddy field soil.

    Science.gov (United States)

    Ke, Xiubin; Lu, Yahai

    2012-04-01

    Adaptation of microorganisms to the environment is a central theme in microbial ecology. The objective of this study was to investigate the response of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) to a soil medium shift. We employed two rice field soils collected from Beijing and Hangzhou, China. These soils contained distinct AOB communities dominated by Nitrosomonas in Beijing rice soil and Nitrosospira in Hangzhou rice soil. Three mixtures were generated by mixing equal quantities of Beijing soil and Hangzhou soil (BH), Beijing soil with sterilized Hangzhou soil (BSH), and Hangzhou soil with sterilized Beijing soil (HSB). Pure and mixed soils were permanently flooded, and the surface-layer soil where ammonia oxidation occurred was collected to determine the response of AOB and AOA to the soil medium shift. AOB populations increased during the incubation, and the rates were initially faster in Beijing soil than in Hangzhou soil. Nitrosospira (cluster 3a) and Nitrosomonas (communis cluster) increased with time in correspondence with ammonia oxidation in the Hangzhou and Beijing soils, respectively. The 'BH' mixture exhibited a shift from Nitrosomonas at day 0 to Nitrosospira at days 21 and 60 when ammonia oxidation became most active. In 'HSB' and 'BSH' mixtures, Nitrosospira showed greater stimulation than Nitrosomonas, both with and without N amendment. These results suggest that Nitrosospira spp. were better adapted to soil environment shifts than Nitrosomonas. Analysis of the AOA community revealed that the composition of AOA community was not responsive to the soil environment shifts or to nitrogen amendment. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  13. Preliminary Data on the Interaction between Some Biometals and Oxidative Stress Status in Mild Cognitive Impairment and Alzheimer's Disease Patients.

    Science.gov (United States)

    Balmuș, Ioana-Miruna; Strungaru, Stefan-Adrian; Ciobica, Alin; Nicoara, Mircea-Nicusor; Dobrin, Romeo; Plavan, Gabriel; Ștefănescu, Cristinel

    2017-01-01

    Increased interest regarding the biometal mechanisms of action and the pathways in which they have regulatory roles was lately observed. Particularly, it was shown that biometal homeostasis dysregulation may lead to neurodegeneration including Alzheimer's disease, Parkinson disease, or prion protein disease, since important molecular signaling mechanisms in brain functions implicate both oxidative stress and redox active biometals. Oxidative stress could be a result of a breakdown in metal-ion homeostasis which leads to abnormal metal protein chelation. In our previous work, we reported a strong correlation between Alzheimer's disease and oxidative stress. Consequently, the aim of the present work was to evaluate some of the biometals' levels (magnesium, manganese, and iron), the specific activity of some antioxidant enzymes (superoxide dismutase and glutathione peroxidase), and a common lipid peroxidation marker (malondialdehyde concentration), in mild cognitive impairment (n = 15) and Alzheimer's disease (n = 15) patients, compared to age-matched healthy subjects (n = 15). We found increased lipid peroxidation effects, low antioxidant defense, low magnesium and iron concentrations, and high manganese levels in mild cognitive impairment and Alzheimer's disease patients, in a gradual manner. These data could be relevant for future association studies regarding the prediction of Alzheimer's disease development risk or circling through stages by analyzing both active redox metals, oxidative stress markers, and the correlations in between.

  14. Inhibitory effect of ethanol extract of Nannochloropsis oceanica on lipopolysaccharide-induced neuroinflammation, oxidative stress, amyloidogenesis and memory impairment.

    Science.gov (United States)

    Choi, Ji Yeon; Hwang, Chul Ju; Lee, Hee Pom; Kim, Hee Sik; Han, Sang-Bae; Hong, Jin Tae

    2017-07-11

    Oxidative stress and neuroinflammation is implicated in the pathogenesis and development of Alzheimer's disease (AD). Here, we investigated the suppressive possibility of ethanol extract of Nannochloropsis oceanica (N. oceanica) on memory deficiency along with the fundamental mechanisms in lipopolysaccharide (LPS)-treated mice model. Among several extracts of 32 marine microalgae, ethanol extract of N. oceanica showed the most significant inhibitory effect on nitric oxide (NO) generation, NF-κB activity and β-secretase activity in cultured BV-2 cells, neuronal cells and Raw 264.7 cells. Ethanol extract of N. oceanica (50, 100 mg/kg) also ameliorated LPS (250 μg/kg)-induced memory impairment. We also found that ethanol extract of N. oceanica inhibited the LPS-induced expression of iNOS and COX-2. Furthermore, the production of reactive oxygen species (ROS), malondialdehyde (MDA) level as well as glutathione (GSH) level was also decreased by treatment of ethanol extract of N.oceanica. The ethanol extract of N. oceanica also suppresses IκB degradation as well as p50 and p65 translocation into the nucleus in LPS-treated mice brain. Associated with the inhibitory effect on neuroinflammation and oxidative stress, ethanol extract of N. oceanica suppressed Aβ1-42 generation through down-regulation of APP and BACE1 expression in in vivo. These results suggest that ethanol extract of N. oceanica ameliorated memory impairment via anti-inflammatory, anti-oxidant and anti-amyloidogenic mechanisms.

  15. Complete genome sequence of Nitrosomonas sp. Is79, an ammonia oxidizing bacterium adapted to low ammonium concentrations

    OpenAIRE

    Bollmann, A.; Sedlacek, C.J.; Norton, J.; Laanbroek, H.J.; Suwa, Y.; Stein, L.Y.; Klotz, M.G.; Arp, D.; Sayavedra-Soto, L.; Lu, M.; Bruce, D.; Detter, C.; Tapia, R.; Han, J.; Woyke, T.

    2013-01-01

    Nitrosomonas sp. Is79 is a chemolithoautotrophic ammonia-oxidizing bacterium that belongs to the family Nitrosomonadaceae within the phylum Proteobacteria. Ammonia oxidation is the first step of nitrification, an important process in the global nitrogen cycle ultimately resulting in the production of nitrate. Nitrosomonas sp. Is79 is an ammonia oxidizer of high interest because it is adapted to low ammonium and can be found in freshwater environments around the world. The 3,783,444-bp chromos...

  16. The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress.

    Science.gov (United States)

    Pomatto, Laura C D; Carney, Caroline; Shen, Brenda; Wong, Sarah; Halaszynski, Kelly; Salomon, Matthew P; Davies, Kelvin J A; Tower, John

    2017-01-09

    Multiple human diseases involving chronic oxidative stress show a significant sex bias, including neurodegenerative diseases, cancer, immune dysfunction, diabetes, and cardiovascular disease. However, a possible molecular mechanism for the sex bias in physiological adaptation to oxidative stress remains unclear. Here, we report that Drosophila melanogaster females but not males adapt to hydrogen peroxide stress, whereas males but not females adapt to paraquat (superoxide) stress. Stress adaptation in each sex requires the conserved mitochondrial Lon protease and is associated with sex-specific expression of Lon protein isoforms and proteolytic activity. Adaptation to oxidative stress is lost with age in both sexes. Transgenic expression of transformer gene during development transforms chromosomal males into pseudo-females and confers the female-specific pattern of Lon isoform expression, Lon proteolytic activity induction, and H2O2 stress adaptation; these effects were also observed using adult-specific transformation. Conversely, knockdown of transformer in chromosomal females eliminates the female-specific Lon isoform expression, Lon proteolytic activity induction, and H2O2 stress adaptation and produces the male-specific paraquat (superoxide) stress adaptation. Sex-specific expression of alternative Lon isoforms was also observed in mouse tissues. The results develop Drosophila melanogaster as a model for sex-specific stress adaptation regulated by the Lon protease, with potential implications for understanding sexual dimorphism in human disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Vanillin Attenuated Behavioural Impairments, Neurochemical Deficts, Oxidative Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Dhanalakshmi, Chinnasamy; Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed; Kalandar, Ameer; Khan, Mohammed Abdul Sattar; Guillemin, Gilles J

    2016-08-01

    Vanillin (4-hydroxy-3-methoxybenzaldehyde), a pleasant smelling organic aromatic compound, is widely used as a flavoring additive in food, beverage, cosmetic and drug industries. It is reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. We previously reported the neuroprotective effect of vanillin against rotenone induced in in vitro model of PD. The present experiment was aimed to analyze the neuroprotective effect of vanillin on the motor and non-motor deficits, neurochemical variables, oxidative, anti-oxidative indices and the expression of apoptotic markers against rotenone induced rat model of Parkinson's disease (PD). Rotenone treatment exhibited motor and non-motor impairments, neurochemical deficits, oxidative stress and apoptosis, whereas oral administration of vanillin attenuated the above-said indices. However further studies are needed to explore the mitochondrial protective and anti-inflammatory properties of vanillin, as these processes play a vital role in the cause and progression of PD.

  18. Piperine potentiates the protective effects of curcumin against chronic unpredictable stress-induced cognitive impairment and oxidative damage in mice.

    Science.gov (United States)

    Rinwa, Puneet; Kumar, Anil

    2012-12-07

    Life event stressors are the major vulnerability factors for the development of cognitive disorders. A vital therapeutic for stress related disorders is curcumin, derived from curry spice turmeric. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study was designed to investigate the effect of curcumin and its co-administration with piperine against chronic unpredictable stress (CUS)-induced cognitive impairment and oxidative stress in mice. Male Laca mice were subjected to undergo a battery of stressors for a period of 28 days. Vehicle/drugs were administered daily 30mins before CUS procedure. Chronic stress significantly impaired memory performance (delayed latency time to reach platform in Morris water maze as well as to reach closed arm in elevated plus maze test) and decreased locomotor activity along with sucrose consumption. Further, there was a significant impairment in oxidative parameters (elevated malondialdehyde, nitrite concentration and decreased reduced glutathione, catalase levels) and mitochondrial enzyme complex activities, along with raised acetylcholinesterase and serum corticosterone levels. Chronic treatment with curcumin (200 and 400mg/kg, p.o.) significantly improved these behavioral and biochemical alterations, restored mitochondrial enzyme complex activities and attenuated increased acetylcholinesterase and serum corticosterone levels. In addition, co-administration of piperine (20mg/kg; p.o.) with curcumin (100 and 200mg/kg, p.o.) significantly elevated the protective effect as compared to their effects alone. The results clearly suggest that piperine enhanced the bioavailability of curcumin and potentiated its protective effects against CUS induced cognitive impairment and associated oxidative damage in mice. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Aerobic and Anaerobic Thiosulfate Oxidation by a Cold-Adapted, Subglacial Chemoautotroph

    Science.gov (United States)

    Harrold, Zoë R.; Skidmore, Mark L.; Hamilton, Trinity L.; Desch, Libby; Amada, Kirina; van Gelder, Will; Glover, Kevin; Roden, Eric E.

    2015-01-01

    Geochemical data indicate that protons released during pyrite (FeS2) oxidation are important drivers of mineral weathering in oxic and anoxic zones of many aquatic environments, including those beneath glaciers. Oxidation of FeS2 under oxic, circumneutral conditions proceeds through the metastable intermediate thiosulfate (S2O32−), which represents an electron donor capable of supporting microbial metabolism. Subglacial meltwaters sampled from Robertson Glacier (RG), Canada, over a seasonal melt cycle revealed concentrations of S2O32− that were typically below the limit of detection, despite the presence of available pyrite and concentrations of the FeS2 oxidation product sulfate (SO42−) several orders of magnitude higher than those of S2O32−. Here we report on the physiological and genomic characterization of the chemolithoautotrophic facultative anaerobe Thiobacillus sp. strain RG5 isolated from the subglacial environment at RG. The RG5 genome encodes genes involved with pathways for the complete oxidation of S2O32−, CO2 fixation, and aerobic and anaerobic respiration with nitrite or nitrate. Growth experiments indicated that the energy required to synthesize a cell under oxygen- or nitrate-reducing conditions with S2O32− as the electron donor was lower at 5.1°C than 14.4°C, indicating that this organism is cold adapted. RG sediment-associated transcripts of soxB, which encodes a component of the S2O32−-oxidizing complex, were closely affiliated with soxB from RG5. Collectively, these results suggest an active sulfur cycle in the subglacial environment at RG mediated in part by populations closely affiliated with RG5. The consumption of S2O32− by RG5-like populations may accelerate abiotic FeS2 oxidation, thereby enhancing mineral weathering in the subglacial environment. PMID:26712544

  20. Adaptive Immune Response Impairs the Efficacy of Autologous Transplantation of Engineered Stem Cells in Dystrophic Dogs

    Science.gov (United States)

    Sitzia, Clementina; Farini, Andrea; Jardim, Luciana; Razini, Paola; Belicchi, Marzia; Cassinelli, Letizia; Villa, Chiara; Erratico, Silvia; Parolini, Daniele; Bella, Pamela; da Silva Bizario, Joao Carlos; Garcia, Luis; Dias-Baruffi, Marcelo; Meregalli, Mirella; Torrente, Yvan

    2016-01-01

    Duchenne muscular dystrophy is the most common genetic muscular dystrophy. It is caused by mutations in the dystrophin gene, leading to absence of muscular dystrophin and to progressive degeneration of skeletal muscle. We have demonstrated that the exon skipping method safely and efficiently brings to the expression of a functional dystrophin in dystrophic CD133+ cells injected scid/mdx mice. Golden Retriever muscular dystrophic (GRMD) dogs represent the best preclinical model of Duchenne muscular dystrophy, mimicking the human pathology in genotypic and phenotypic aspects. Here, we assess the capacity of intra-arterial delivered autologous engineered canine CD133+ cells of restoring dystrophin expression in Golden Retriever muscular dystrophy. This is the first demonstration of five-year follow up study, showing initial clinical amelioration followed by stabilization in mild and severe affected Golden Retriever muscular dystrophy dogs. The occurrence of T-cell response in three Golden Retriever muscular dystrophy dogs, consistent with a memory response boosted by the exon skipped-dystrophin protein, suggests an adaptive immune response against dystrophin. PMID:27506452

  1. Oxidation of KCNB1 Potassium Channels Causes Neurotoxicity and Cognitive Impairment in a Mouse Model of Traumatic Brain Injury.

    Science.gov (United States)

    Yu, Wei; Parakramaweera, Randika; Teng, Shavonne; Gowda, Manasa; Sharad, Yashsavi; Thakker-Varia, Smita; Alder, Janet; Sesti, Federico

    2016-10-26

    The delayed rectifier potassium (K + ) channel KCNB1 (Kv2.1), which conducts a major somatodendritic current in cortex and hippocampus, is known to undergo oxidation in the brain, but whether this can cause neurodegeneration and cognitive impairment is not known. Here, we used transgenic mice harboring human KCNB1 wild-type (Tg-WT) or a nonoxidable C73A mutant (Tg-C73A) in cortex and hippocampus to determine whether oxidized KCNB1 channels affect brain function. Animals were subjected to moderate traumatic brain injury (TBI), a condition characterized by extensive oxidative stress. Dasatinib, a Food and Drug Administration-approved inhibitor of Src tyrosine kinases, was used to impinge on the proapoptotic signaling pathway activated by oxidized KCNB1 channels. Thus, typical lesions of brain injury, namely, inflammation (astrocytosis), neurodegeneration, and cell death, were markedly reduced in Tg-C73A and dasatinib-treated non-Tg animals. Accordingly, Tg-C73A mice and non-Tg mice treated with dasatinib exhibited improved behavioral outcomes in motor (rotarod) and cognitive (Morris water maze) assays compared to controls. Moreover, the activity of Src kinases, along with oxidative stress, were significantly diminished in Tg-C73A brains. Together, these data demonstrate that oxidation of KCNB1 channels is a contributing mechanism to cellular and behavioral deficits in vertebrates and suggest a new therapeutic approach to TBI. This study provides the first experimental evidence that oxidation of a K + channel constitutes a mechanism of neuronal and cognitive impairment in vertebrates. Specifically, the interaction of KCNB1 channels with reactive oxygen species plays a major role in the etiology of mouse model of traumatic brain injury (TBI), a condition associated with extensive oxidative stress. In addition, a Food and Drug Administration-approved drug ameliorates the outcome of TBI in mouse, by directly impinging on the toxic pathway activated in response to

  2. Early-Life Exposure to Lead Induces Cognitive Impairment in Elder Mice Targeting SIRT1 Phosphorylation and Oxidative Alterations

    Directory of Open Access Journals (Sweden)

    Lijie Zhang

    2017-06-01

    Full Text Available Pb is a potential risk factor for cognition, mainly mediated by enhanced oxidative stress. Resveratrol, a natural polyphenol with crucial anti-oxidative property, is recently implicated in preventing cognitive deficits in normal aging and neurodegenerative disorders. Its beneficial effects have been linked to sirtuin 1(SIRT1 activation. The aim of this work is to investigate the possible linkage between alterations in Pb-induced oxidative damage and cognitive impairment by prolonged treatment of resveratrol. Male C57BL/6 mice were given Pb(Ac2 treatment or deionized H2O for 12 weeks, and subjected to resveratrol gavage at the dose of 50 mg/kgBw•d or vehicle after Pb exposure. Results from biochemical analysis and immunohistofluorescence showed that Pb induced oxidative DNA damage and decreased cortical antioxidant biomarker. As expected, these abnormalities were improved by resveratrol treatment. Morris water maze test, Western blotting, immunohistofluorescence staining and RT-qPCR indicated that resveratrol ameliorated spatial learning and memory deficits with alterations in hippocampal BDNF-TrkB signaling, promoted nuclear localization and phosphorylation of hippocampal SIRT1, partly increased protein levels of AMPK and PGC-1α involving in modulation of antioxidant response in Pb-exposed mice. Our results support the hypothesis that resveratrol could attenuate Pb-induced cognitive impairment which was associated with activating SIRT1 via modulation of oxidative stress. Additionally, resveratrol also repressed the Pb-induce amyloidogenic processing with resultant decline in cortical Aβ1−−40. Noteworthy, such effects were not mediated by resveratrol treatment alone. These findings emphasize the potential of SIRT1 activator as an efficacious dietary intervention to downgrade the Pb-induced neurotoxic lesion.

  3. Apnea stimulates the adaptive response to oxidative stress in elephant seal pups.

    Science.gov (United States)

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Tift, Michael S; Forman, Henry Jay; Crocker, Daniel E; Ortiz, Rudy M

    2011-12-15

    Extended breath-hold (apnea) bouts are routine during diving and sleeping in seals. These apneas result in oxygen store depletion and blood flow redistribution towards obligatory oxygen-dependent tissues, exposing seals to critical levels of ischemia and hypoxemia. The subsequent reperfusion/reoxygenation has the potential to increase oxidant production and thus oxidative stress. The contributions of extended apnea to oxidative stress in adapted mammals are not well defined. To address the hypothesis that apnea in seals is not associated with increased oxidative damage, blood samples were collected from northern elephant seal pups (N=6) during eupnea, rest- and voluntary submersion-associated apneas, and post-apnea (recovery). Plasma 4-hydroxynonenal (HNE), 8-isoprostanes (8-isoPGF(2α)), nitrotyrosine (NT), protein carbonyls, xanthine and hypoxanthine (HX) levels, along with xanthine oxidase (XO) activity, were measured. Protein content of XO, superoxide dismutase 1 (Cu,ZnSOD), catalase and myoglobin (Mb), as well as the nuclear content of hypoxia inducible factor 1α (HIF-1α) and NF-E2-related factor 2 (Nrf2), were measured in muscle biopsies collected before and after the breath-hold trials. HNE, 8-iso PGF(2α), NT and protein carbonyl levels did not change among eupnea, apnea or recovery. XO activity and HX and xanthine concentrations were increased at the end of the apneas and during recovery. Muscle protein content of XO, CuZnSOD, catalase, Mb, HIF-1α and Nrf2 increased 25-70% after apnea. Results suggest that rather than inducing the damaging effects of hypoxemia and ischemia/reperfusion that have been reported in non-diving mammals, apnea in seals stimulates the oxidative stress and hypoxic hormetic responses, allowing these mammals to cope with the potentially detrimental effects associated with this condition.

  4. Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver.

    Science.gov (United States)

    Ferreira, Andréa G K; da Cunha, Aline A; Machado, Fernanda R; Pederzolli, Carolina D; Dalazen, Giovana R; de Assis, Adriano M; Lamers, Marcelo L; dos Santos, Marinilce F; Dutra-Filho, Carlos S; Wyse, Angela T S

    2012-01-01

    The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation. Copyright © 2011 Wiley Periodicals, Inc.

  5. Macrophage Depletion Impairs Skeletal Muscle Regeneration: the Roles of Pro-fibrotic Factors, Inflammation, and Oxidative Stress.

    Science.gov (United States)

    Xiao, Weihua; Liu, Yu; Chen, Peijie

    2016-12-01

    Muscle contusion is one of the most common muscle injuries in sports medicine. Macrophages play complex roles in the regeneration of skeletal muscle. However, the roles of macrophages, especially the mechanisms involved, in the regeneration of muscle contusion are still not fully understood. We hypothesize that the depletion of macrophages impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may be involved in the process. To test these hypotheses, we constructed a muscle contusion injury and a macrophage depletion model and followed it up with morphological and gene expression analyses. The data showed that fibrotic scars were formed in the muscle of contusion injury, and they deteriorated in the mice of macrophage depletion. Furthermore, the sizes of regenerating myofibers were significantly reduced by macrophage depletion. Pro-fibrotic factors, inflammatory cytokines, chemokines, and oxidative stress-related enzymes increased significantly after muscle injury. Moreover, the expression of these factors was delayed by macrophage depletion. Most of them were still significantly higher in the later stage of regeneration. These results suggest that macrophage depletion impairs skeletal muscle regeneration and that pro-fibrotic factors, inflammation, and oxidative stress may play important roles in the process.

  6. Anticonvulsant effect of piperine ameliorates memory impairment, inflammation and oxidative stress in a rat model of pilocarpine-induced epilepsy.

    Science.gov (United States)

    Mao, Ke; Lei, Ding; Zhang, Heng; You, Chao

    2017-02-01

    The primary active component of black pepper is piperine, which is purified and used to treat epilepsy, achieving higher efficiency when purified. The present study was conducted to evaluate whether the anticonvulsant effect of piperine ameliorates pilocarpine-induced epilepsy, and to investigate the mechanism underlying these effects. Epilepsy was induced in Sprague Dawley rats using pilocarpine. Pilocarpine-induced epilepsy in the rats was treated with 40 mg/kg piperine for 45 consecutive days. Status epilepticus and a Morris water maze test were used to analyze the anticonvulsant effects of piperine in the epileptic rats. Inflammation and oxidative stress were then measured using commercially-available kits following piperine treatment. Lastly, the activity of caspase-3 and the protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were evaluated using commercially-available kits and western blot analysis, respectively. The results demonstrated that treatment with piperine was able to reduce the status epilepticus and prevented memory impairment following pilocarpine-induced epilepsy in rats. The anticonvulsant effects of piperine decreased inflammation and oxidative stress following pilocarpine-induced epilepsy in rats. The upregulated activity of caspase-3 and expression levels of Bax/Bcl-2 were suppressed following treatment with piperine in the rats with pilocarpine-induced epilepsy. These results suggest that the anticonvulsant effects of piperine ameliorate memory impairment, inflammation and oxidative stress in a rat model of pilocarpine-induced epilepsy.

  7. Oxidative stress-mediated thrombospondin-2 upregulation impairs bone marrow-derived angiogenic cell function in diabetes mellitus.

    Science.gov (United States)

    Bae, Ok-Nam; Wang, Jie-Mei; Baek, Seung-Hoon; Wang, Qingde; Yuan, Hong; Chen, Alex F

    2013-08-01

    Circulating angiogenic cells play an essential role in angiogenesis but are dysfunctional in diabetes mellitus characterized by excessive oxidative stress. We hypothesize that oxidative stress-mediated upregulation of thrombospondin-2 (TSP-2), a potent antiangiogenic protein, contributes to diabetic bone marrow-derived angiogenic cell (BMAC) dysfunction. BMACs were isolated from adult male type 2 diabetic db/db mice and control db/+ (C57BLKS/J) mice. In Matrigel tube formation assay, angiogenic function was impaired in diabetic BMACs, accompanied by increased oxidative stress and nicotinamide adenine dinucleotide phosphate oxidase activity. BMAC angiogenic function was restored by overexpression of dominant negative Rac1 or by overexpression of manganese superoxide dismutase. TSP-2 mRNA and protein were both significantly upregulated in diabetic BMACs, mediated by increased oxidative stress as shown by a decrease in TSP-2 level after overexpression of dominant negative Rac1 or manganese superoxide dismutase. Silencing TSP-2 by its small interfering RNA in diabetic BMACs improved BMAC function in tube formation, adhesion, and migration assays. Notably, the upregulation of TSP-2 was also found in BMACs from streptozotocin-induced type 1 diabetic mice, and normal BMACs with high glucose treatment. let-7f, a microRNA which has been related to endothelial angiogenic function, is found to play key role in TSP-2 increase, but let-7f did not directly interact with TSP-2 mRNA. The upregulation of TSP-2 mediated by increased oxidative stress contributes to angiogenesis dysfunction in diabetic BMACs.

  8. Targeting ABL1-mediated oxidative stress adaptation in fumarate hydratase-deficient cancer.

    Science.gov (United States)

    Sourbier, Carole; Ricketts, Christopher J; Matsumoto, Shingo; Crooks, Daniel R; Liao, Pei-Jyun; Mannes, Philip Z; Yang, Youfeng; Wei, Ming-Hui; Srivastava, Gaurav; Ghosh, Sanchari; Chen, Viola; Vocke, Cathy D; Merino, Maria; Srinivasan, Ramaprasad; Krishna, Murali C; Mitchell, James B; Pendergast, Ann Marie; Rouault, Tracey A; Neckers, Len; Linehan, W Marston

    2014-12-08

    Patients with germline fumarate hydratase (FH) mutation are predisposed to develop aggressive kidney cancer with few treatment options and poor therapeutic outcomes. Activity of the proto-oncogene ABL1 is upregulated in FH-deficient kidney tumors and drives a metabolic and survival signaling network necessary to cope with impaired mitochondrial function and abnormal accumulation of intracellular fumarate. Excess fumarate indirectly stimulates ABL1 activity, while restoration of wild-type FH abrogates both ABL1 activation and the cytotoxicity caused by ABL1 inhibition or knockdown. ABL1 upregulates aerobic glycolysis via the mTOR/HIF1α pathway and neutralizes fumarate-induced proteotoxic stress by promoting nuclear localization of the antioxidant response transcription factor NRF2. Our findings identify ABL1 as a pharmacologically tractable therapeutic target in glycolytically dependent, oxidatively stressed tumors. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Aminoguanidine alleviated MMA-induced impairment of cognitive ability in rats by downregulating oxidative stress and inflammatory reaction.

    Science.gov (United States)

    Li, Qiliang; Song, Wenqi; Tian, Ze; Wang, Peichang

    2017-03-01

    Methylmalonic acidemia (MMA) is the most common organic acidemia in childhood. Many "treated" patients continued to display various degrees of mental retardation and psychomotor delay, which could be caused by brain damage from elevated oxidative stress. Aminoguanidine (AG), a synthetic antioxidant, was tested in a MMA rat model for its potential therapeutic effects on memory impairment. The effects of AG on MMA-induced cognitive impairment in Wistar rats were evaluated with Morris Water Maze. The levels of nerve cell apoptosis and microglial activation were investigated to illustrate the mechanisms of the improvement of cognition with AG treatment in MMA rats. To further explore the mechanism of neuroprotection induced by AG, several biomarkers including free radicals and inflammatory cytokines in the hippocampus were quantified. The results showed that the rats treated with AG exhibited better neurological behavior performances than MMA model rats. The AG-treated rats had a decreased level of apoptosis of the hippocampal neurons, which could be the structural basis of the observed neural behavior protection. In addition, AG treatment significantly inhibited the activation of microglia. The AG-treated rats had decreased levels of IL-1β, IL-6, TNF-α, NO, malonaldehyde and iNOS activities in the hippocampus. The level of glutathione and superoxide dismutase activity in the hippocampus of the AG-treated rats increased significantly. In conclusion, AG could alleviate the MMA-induced cognitive impairment via down-regulating of oxidative stress and inflammatory reaction and provide a basis as a therapeutic potential against MMA-induced cognitive impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Distinct transthyretin oxidation isoform profile in spinal fluid from patients with Alzheimer’s disease and mild cognitive impairment

    DEFF Research Database (Denmark)

    Poulsen, Keld; Bahl, Justyna Mc; Simonsen, Anja H

    2014-01-01

    such as Alzheimer's disease (AD) it is of interest to characterize CSF-TTR isoform distribution in AD patients and controls. Here, TTR isoforms are profiled directly from CSF by an optimized immunoaffinity-mass spectrometry method in 76 samples from patients with AD (n = 37), mild cognitive impairment (MCI, n = 17...... diagnostic information in patients with dementia symptoms but this should be explored in larger studies including prospective studies of MCI patients. The development of methods for simple, robust, and reproducible inhibition of in vitro oxidation during CSF sampling and sample handling is highly warranted...

  11. Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet.

    Directory of Open Access Journals (Sweden)

    Gaetano Serviddio

    Full Text Available There is growing evidence that mitochondrial dysfunction, and more specifically fatty acid β-oxidation impairment, is involved in the pathophysiology of non-alcoholic steatohepatitis (NASH. The goal of the present study was to achieve more understanding on the modification/s of carnitinepalmitoyltransferase-I (CPT-I, the rate-limiting enzyme of the mitochondrial fatty acid β-oxidation, during steatohepatitis. A high fat/methionine-choline deficient (MCD diet, administered for 4 weeks, was used to induce NASH in rats.We demonstrated that CPT-I activity decreased, to the same extent, both in isolated liver mitochondria and in digitonin-permeabilized hepatocytes from MCD-diet fed rats.At the same time, the rate of total fatty acid oxidation to CO(2 and ketone bodies, measured in isolated hepatocytes, was significantly lowered in treated animals when compared to controls. Finally, an increase in CPT-I mRNA abundance and protein content, together with a high level of CPT-I protein oxidation was observed in treated rats. A posttranslational modification of rat CPT-I during steatohepatitis has been here discussed.

  12. Neuronal nitric oxide synthase-deficient mice have impaired Renin release but normal blood pressure

    DEFF Research Database (Denmark)

    Sällström, Johan; Carlström, Mattias; Jensen, Boye L

    2008-01-01

    BackgroundNitric oxide deficiency is involved in the development of hypertension, but the mechanisms are currently unclear. This study was conducted to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood pressure regulation and renin release in relation to different sodiu...

  13. Modulating Oxidative Stress Relieves Stress-Induced Behavioral and Cognitive Impairments in Rats

    OpenAIRE

    Solanki, Naimesh; Salvi, Ankita; Patki, Gaurav; Salim, Samina

    2017-01-01

    Abstract Background: Persistent psychological stress often leads to anxiety disorders and depression. Benzodiazepines and selective serotonin reuptake inhibitors are popular treatment options but have limited efficacy, supporting the need for alternative treatment. Based on our recent preclinical work suggesting a causal link between neurobehavioral deficits and elevated oxidative stress, we hypothesized that interventions that mitigate oxidative stress can attenuate/overcome neurobehavioral ...

  14. Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response

    Science.gov (United States)

    Blasco-Baque, Vincent; Garidou, Lucile; Pomié, Céline; Escoula, Quentin; Loubieres, Pascale; Le Gall-David, Sandrine; Lemaitre, Mathieu; Nicolas, Simon; Klopp, Pascale; Waget, Aurélie; Azalbert, Vincent; Colom, André; Bonnaure-Mallet, Martine; Kemoun, Philippe; Serino, Matteo; Burcelin, Rémy

    2017-01-01

    Objective To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. Design We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis (Pg), Fusobacterium nucleatum and Prevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. Results Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. Conclusions We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. PMID:26838600

  15. Reduced carbohydrate availability does not modulate training-induced heat shock protein adaptations but does upregulate oxidative enzyme activity in human skeletal muscle

    National Research Council Canada - National Science Library

    James P. Morton; Louise Croft; Jonathan D. Bartlett; Don P. M. MacLaren; Thomas Reilly; Louise Evans; Anne McArdle; Barry Drust

    2009-01-01

    ... for training-induced heat shock protein (HSP) adaptations of skeletal muscle. A secondary aim was to investigate the influence of reduced carbohydrate availability on oxidative adaptations and exercise performance...

  16. Eph-B4 mediates vein graft adaptation by regulation of endothelial nitric oxide synthase.

    Science.gov (United States)

    Wang, Mo; Collins, Michael J; Foster, Trenton R; Bai, Hualong; Hashimoto, Takuya; Santana, Jeans M; Shu, Chang; Dardik, Alan

    2017-01-01

    Vein graft adaptation is characterized by loss of expression of the tyrosine kinase receptor Eph-B4, the embryonic determinant of venous identity, without increased expression of its ligand ephrin-B2, the embryonic determinant of arterial identity. Endothelial nitric oxide synthase (eNOS) is an important mediator of vessel remodeling. We hypothesized that the mechanism of action of Eph-B4 during vein graft adaptation might be through regulation of downstream eNOS activity. Mouse lung endothelial cells were stimulated with ephrin-B2/Fc, without and with preclustering, without and with the eNOS inhibitor Nω-nitro-l-arginine methyl ester hydrochloride or the Eph-B4 inhibitor NVP-BHG712, and assessed by Western blot and immunofluorescence for eNOS and Eph-B4 phosphorylation. Nitric oxide (NO) production was assessed using an NO-specific chemiluminescence analyzer. Cell migration was assessed using a Transwell assay. Human and mouse vein graft specimens were examined for eNOS activity by Western blot, and vessel remodeling was assessed in vein grafts in wild-type or eNOS knockout mice. Ephrin-B2/Fc stimulated both Eph-B4 and eNOS phosphorylation in a bimodal temporal distribution (n = 4; P < .05), with preclustered ephrin-B2/Fc causing prolonged peak Eph-B4 and eNOS phosphorylation as well as altered subcellular localization (n = 4; P < .05). Ephrin-B2/Fc increased NO release (n = 3; P < .01) as well as increased endothelial cell migration (n = 6; P < .05) in an eNOS-dependent fashion. Both human and mouse vein grafts showed increased eNOS phosphorylation compared with normal veins (n = 3; P < .05). Vein grafts from eNOS knockout mice showed less dilation and less wall thickening compared with wild-type vein grafts (n = 7; P < .05). eNOS is a mediator of vein graft adaptation to the arterial environment. Eph-B4 stimulates eNOS phosphorylation in vitro and may mediate vein graft adaptation by regulation of eNOS activity in vivo. Published by Elsevier Inc.

  17. Effect of hesperidin on neurobehavioral, neuroinflammation, oxidative stress and lipid alteration in intracerebroventricular streptozotocin induced cognitive impairment in mice.

    Science.gov (United States)

    Javed, Hayate; Vaibhav, Kumar; Ahmed, M Ejaz; Khan, Andleeb; Tabassum, Rizwana; Islam, Farah; Safhi, Mohammed M; Islam, Fakhrul

    2015-01-15

    Recent attention is given to the influence of dietary supplementation on health and mental well-being. Oxidative stress is associated with many diseases including neurodegenerative disorders. Dietary flavonoids exert chemopreventive and neuroprotective effects and comprise the most common group of plant polyphenols that provide much of the flavour and colour of the vegetables and fruits. Hesperidin is a flavanone glycoside found abundantly in citrus fruits, has been reported to have antioxidant, hypolipidaemic, analgesic and anti-hypertensive activity. Pretreatment of hesperidin (100 and 200mg/kg body weight orally once daily for 15 days) to Swiss male albino mice has prevented the cognitive impairment. The cognitive impairment was developed by giving single intracerebroventricular-streptozotocin (ICV-STZ) injection (2.57 mg/kg body weight each side) bilaterally. Hesperidin pretreatment improved memory consolidation process as tested by Morris water maze possibly through modulation of acetylcholine esterase activity (AChE). Moreover, hesperidin attenuated the depleted content of reduced glutathione (GSH) and elevated level of thiobarbituric acid reactive substances (TBARS) and also augmented lipid alteration significantly following ICV-STZ injection. We also demonstrated that the flavonoid hesperidin modulates neuronal cell death by inhibiting the overexpression of inflammatory markers like nuclear factor κB, inducible nitric oxide synthase, cyclooxygenase-2 and glial fibrillary acidic protein positive astrocytes. The results from the present study open the possibility of using flavonoids for potential new therapeutic strategies for sporadic dementia of Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Endomembrane Ca2+-AtPases play a significant role in virus-induced adaptation to oxidative stress

    DEFF Research Database (Denmark)

    Shabala, Sergey; Bækgaard, Lone; Shabala, Lana

    2011-01-01

    in adaptive responses to oxidative stress by removing excessive Ca2+ from the cytosol, and that their functional expression is significantly altered in PVX-inoculated plants. These findings highlight the crucial role of Ca2+ efflux systems in acquired tolerance to oxidative stress and open up prospects...... for practical applications in agriculture, after in-depth comprehension of the fundamental mechanisms involved in common responses to environmental factors at the genomic, cellular and organismal levels....

  19. Free radicals impair the anti-oxidative stress activity of DJ-1 through the formation of SDS-resistant dimer.

    Science.gov (United States)

    Yasuda, Tatsuki; Niki, Takeshi; Ariga, Hiroyoshi; Iguchi-Ariga, Sanae M M

    2017-04-01

    DJ-1 is a causative gene for familial Parkinson's disease (PD). Loss-of-function of DJ-1 protein is suggested to contribute to the onset of PD, but the causes of DJ-1 dysfunction remain insufficiently elucidated. In this study, we found that the SDS-resistant irreversible dimer of DJ-1 protein was formed in human dopaminergic neuroblastoma SH-SY5Y cells when the cells were exposed to massive superoxide inducers such as paraquat and diquat. The dimer was also formed in vitro by superoxide in PQ redox cycling system and hydroxyl radical produced in Fenton reaction. We, thus, found a novel phenomenon that free radicals directly affect DJ-1 to form SDS-resistant dimers. Moreover, the formation of the SDS-resistant dimer impaired anti-oxidative stress activity of DJ-1 both in cell viability assay and H 2 O 2 -elimination assay in vitro. Similar SDS-resistant dimers were steadily formed with several mutants of DJ-1 found in familial PD patients. These findings suggest that DJ-1 is impaired due to the formation of SDS-resistant dimer when the protein is directly attacked by free radicals yielded by external and internal stresses and that the DJ-1 impairment is one of the causes of sporadic PD.

  20. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    Directory of Open Access Journals (Sweden)

    Carles Lerin

    2016-10-01

    Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  1. Nitric oxide-mediated cutaneous microvascular function is impaired in polycystic ovary sydrome but can be improved by exercise training.

    Science.gov (United States)

    Sprung, V S; Cuthbertson, D J; Pugh, C J A; Daousi, C; Atkinson, G; Aziz, N F; Kemp, G J; Green, D J; Cable, N T; Jones, H

    2013-03-15

    Polycystic ovary syndrome (PCOS) is associated with cardiovascular disease. The contribution of the nitric oxide (NO) dilator system to cutaneous endothelial dysfunction is currently unknown in PCOS. Our aim was to examine whether women with PCOS demonstrate impaired cutaneous microvascular NO function and whether exercise training can ameliorate any impairment. Eleven women with PCOS (age, 29 ± 7 years; body mass index, 34 ± 6 kg m(-2)) were compared with six healthy obese control women (age, 29 ± 7 years; body mass index, 34 ± 5 kg m(-2)). Six women with PCOS (30 ± 7 years; 31 ± 6 kg m(-2)) then completed 16 weeks of exercise training. Laser Doppler flowmetry, combined with intradermal microdialysis of l-N(G)-monomethyl-l-arginine, a nitric oxide antagonist, in response to incremental local heating of the forearm was assessed in women with PCOS and control women, and again in women with PCOS following exercise training. Cardiorespiratory fitness, homeostasis model assessment for insulin resistance, hormone and lipid profiles were also assessed. Differences between women with PCOS and control women and changes with exercise were analysed using Student's unpaired t tests. Differences in the contribution of NO to cutaneous blood flow [expressed as a percentage of maximal cutaneous vasodilatation (CVCmax)] were analysed using general linear models. At 42°C heating, cutaneous NO-mediated vasodilatation was attenuated by 17.5%CVCmax (95% confidence interval, 33.3, 1.7; P = 0.03) in women with PCOS vs. control women. Exercise training improved cardiorespiratory fitness by 5.0 ml kg(-1) min(-1) (95% confidence interval, 0.9, 9.2; P = 0.03) and NO-mediated cutaneous vasodilatation at 42°C heating by 19.6% CVCmax (95% confidence interval, 4.3, 34.9; P = 0.02). Cutaneous microvascular NO function is impaired in women with PCOS compared with obese matched control women but can be improved with exercise training.

  2. Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Subbuswamy K. Prabu

    2011-05-01

    Full Text Available We have previously shown a tissue-specific increase in oxidative stress in the early stages of streptozotocin (STZ-induced diabetic rats. In this study, we investigated oxidative stress-related long-term complications and mitochondrial dysfunctions in the different tissues of STZ-induced diabetic rats (>15 mM blood glucose for 8 weeks. These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively production. Oxidative protein carbonylation was also increased with the maximum effect observed in the pancreas of diabetic rats. The activities of mitochondrial respiratory enzymes ubiquinol: cytochrome c oxidoreductase (Complex III and cytochrome c oxidase (Complex IV were significantly decreased while that of NADH:ubiquinone oxidoreductase (Complex I and succinate:ubiquinone oxidoreductase (Complex II were moderately increased in diabetic rats, which was confirmed by the increased expression of the 70 kDa Complex II sub-unit. Mitochondrial matrix aconitase, a ROS sensitive enzyme, was markedly inhibited in the diabetic rat tissues. Increased expression of oxidative stress marker proteins Hsp-70 and HO-1 was also observed along with increased expression of nitric oxide synthase. These results suggest that mitochondrial respiratory complexes may play a critical role in ROS/RNS homeostasis and oxidative stress related changes in type 1 diabetes and may have implications in the etiology of diabetes and its complications.

  3. Executive functioning, concern about falling and quadriceps strength mediate the relationship between impaired gait adaptability and fall risk in older people.

    Science.gov (United States)

    Caetano, Maria Joana D; Lord, Stephen R; Brodie, Matthew A; Schoene, Daniel; Pelicioni, Paulo H S; Sturnieks, Daina L; Menant, Jasmine C

    2018-01-01

    Reduced ability to adapt gait, particularly under challenging conditions, may be an important reason why older adults have an increased risk of falling. This study aimed to identify cognitive, psychological and physical mediators of the relationship between impaired gait adaptability and fall risk in older adults. Fifty healthy older adults (mean±SD: 74±7years) were categorised as high or low fall risk, based on past falls and their performance in the Physiological Profile Assessment. High and low-risk groups were then compared in the gait adaptability test, i.e. an assessment of the ability to adapt gait in response to obstacles and stepping targets under single and dual task conditions. Quadriceps strength, concern about falling and executive function were also measured. The older adults who made errors on the gait adaptability test were 4.76 (95%CI=1.08-20.91) times more likely to be at high risk of falling. Furthermore, each standard deviation reduction in gait speed while approaching the targets/obstacle increased the odds of being at high risk of falling approximately three fold: single task - OR=3.10,95%CI=1.43-6.73; dual task - 3.42,95%CI=1.56-7.52. Executive functioning, concern about falling and quadriceps strength substantially mediated the relationship between the gait adaptability measures and fall risk status. Impaired gait adaptability is associated with high risk of falls in older adults. Reduced executive function, increased concern about falling and weaker quadriceps strength contribute significantly to this relationship. Training gait adaptability directly, as well as addressing the above mediators through cognitive, behavioural and physical training may maximise fall prevention efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Aging impairs myocardial fatty acid and ketone oxidation and modifies cardiac functional and metabolic responses to insulin in mice.

    Science.gov (United States)

    Hyyti, Outi M; Ledee, Dolena; Ning, Xue-Han; Ge, Ming; Portman, Michael A

    2010-09-01

    Aging presumably initiates shifts in substrate oxidation mediated in part by changes in insulin sensitivity. Similar shifts occur with cardiac hypertrophy and may contribute to contractile dysfunction. We tested the hypothesis that aging modifies substrate utilization and alters insulin sensitivity in mouse heart when provided multiple substrates. In vivo cardiac function was measured with microtipped pressure transducers in the left ventricle from control (4-6 mo) and aged (22-24 mo) mice. Cardiac function was also measured in isolated working hearts along with substrate and anaplerotic fractional contributions to the citric acid cycle (CAC) by using perfusate containing (13)C-labeled free fatty acids (FFA), acetoacetate, lactate, and unlabeled glucose. Stroke volume and cardiac output were diminished in aged mice in vivo, but pressure development was preserved. Systolic and diastolic functions were maintained in aged isolated hearts. Insulin prompted an increase in systolic function in aged hearts, resulting in an increase in cardiac efficiency. FFA and ketone flux were present but were markedly impaired in aged hearts. These changes in myocardial substrate utilization corresponded to alterations in circulating lipids, thyroid hormone, and reductions in protein expression for peroxisome proliferator-activated receptor (PPAR)alpha and pyruvate dehydrogenase kinase (PDK)4. Insulin further suppressed FFA oxidation in the aged. Insulin stimulation of anaplerosis in control hearts was absent in the aged. The aged heart shows metabolic plasticity by accessing multiple substrates to maintain function. However, fatty acid oxidation capacity is limited. Impaired insulin-stimulated anaplerosis may contribute to elevated cardiac efficiency, but may also limit response to acute stress through depletion of CAC intermediates.

  5. Aging Impairs Myocardial Fatty Acid and Ketone Oxidation and Modifies Cardiac Functional and Metabolic Responses to Insulin in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Hyyti, Outi M.; Ledee, Dolena; Ning, Xue-Han; Ge, Ming; Portman, Michael A.

    2010-07-02

    Aging presumably initiates shifts in substrate oxidation mediated in part by changes in insulin sensitivity. Similar shifts occur with cardiac hypertrophy and may contribute to contractile dysfunction. We tested the hypothesis that aging modifies substrate utilization and alters insulin sensitivity in mouse heart when provided multiple substrates. In vivo cardiac function was measured with microtipped pressure transducers in the left ventricle from control (4–6 mo) and aged (22–24 mo) mice. Cardiac function was also measured in isolated working hearts along with substrate and anaplerotic fractional contributions to the citric acid cycle (CAC) by using perfusate containing 13C-labeled free fatty acids (FFA), acetoacetate, lactate, and unlabeled glucose. Stroke volume and cardiac output were diminished in aged mice in vivo, but pressure development was preserved. Systolic and diastolic functions were maintained in aged isolated hearts. Insulin prompted an increase in systolic function in aged hearts, resulting in an increase in cardiac efficiency. FFA and ketone flux were present but were markedly impaired in aged hearts. These changes in myocardial substrate utilization corresponded to alterations in circulating lipids, thyroid hormone, and reductions in protein expression for peroxisome proliferator-activated receptor (PPAR)α and pyruvate dehydrogenase kinase (PDK)4. Insulin further suppressed FFA oxidation in the aged. Insulin stimulation of anaplerosis in control hearts was absent in the aged. The aged heart shows metabolic plasticity by accessing multiple substrates to maintain function. However, fatty acid oxidation capacity is limited. Impaired insulin-stimulated anaplerosis may contribute to elevated cardiac efficiency, but may also limit response to acute stress through depletion of CAC intermediates.

  6. Anhydroecgonine Methyl Ester (AEME), a Product of Cocaine Pyrolysis, Impairs Spatial Working Memory and Induces Striatal Oxidative Stress in Rats.

    Science.gov (United States)

    Gomes, Elisa Fraga; Lipaus, Ingryd Fortes Souza; Martins, Cleciane Waldetário; Araújo, Andrezza Menezes; Mendonça, Josidéia Barreto; Pelição, Fabrício Souza; Lebarch, Evandro Carlos; de Melo Rodrigues, Lívia Carla; Nakamura-Palacios, Ester Miyuki

    2017-09-15

    When burning crack cocaine, the pyrolysis of cocaine generates anhydroecgonine methyl ester (AEME). AEME has been shown to be highly neurotoxic but its effects on cognitive function and oxidative stress are still unknown. Thus, this study investigated the effects of AEME on spatial working memory and on parameters of oxidative stress in the prefrontal cortex, hippocampus, and striatum. First, 18 well-trained rats in 8-arm radial maze (8-RM) procedures received acute intracerebroventricular (icv) administration of AEME at doses of 10, 32, or 100 μg or saline (SAL) in a counterbalanced order and were tested 5 min later in 1-h delayed tasks in the 8-RM. Secondly, separated animals received acute icv administration of AEME at doses of 10 (n = 5), 32 (n = 5), or 100 μg (n = 5) or SAL (n = 5) for analysis of advanced oxidation protein products, thiobarbituric acid, catalase, glutathione peroxidase, and superoxide dismutase. A higher number of errors were seen in the 1-h post-delay performance after AEME 32 μg and AEME 100 μg when compared to SAL. In the striatum, animals receiving AEME 100 μg icv showed increased advanced oxidation protein products levels when compared to 10 μg, and also showed increased activity of glutathione peroxidase enzyme when compared to SAL but also comparing to AEME 32 μg and AEME 10 μg. These results showed that AEME impairs long-term spatial working memory and also induces greater protein oxidation and increased levels of antioxidant enzymes in the striatum.

  7. Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats.

    Science.gov (United States)

    Hajiluian, Ghazaleh; Abbasalizad Farhangi, Mahdieh; Nameni, Ghazaleh; Shahabi, Parviz; Megari-Abbasi, Mehran

    2017-07-06

    There is evidence that obesity leads to cognitive impairments via several markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase and malondialdehyde (MDA) in the hippocampus. Increased inflammatory markers in the brain have obesity triggering effects. In the current study we aimed to investigate the effects of vitamin D on cognitive function, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α concentration and markers of oxidative stress in the hippocampus of high-fat diet-induced obese rats. Forty male Wistar rats were divided into two groups: control diet (CD) and high-fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: CD, CD + vitamin D, HFD and HFD + vitamin D. Vitamin D was administered at 500 IU/kg dosage for 5 weeks. Four weeks after supplementation, Morris water maze test was performed. NF-κB and TNF-α concentration in the hippocampus were determined using ELISA kits. Moreover, oxidative stress markers in the hippocampus including GPx, SOD, MDA and CAT concentrations were measured by spectrophotometry methods. HFD significantly increased TNF-α (P = 0.04) and NF-κB (P = 0.01) concentrations in the hippocampus compared with CD. Vitamin D treatment led to a significant reduction in hippocampus NF-κB concentrations in HFD + vitamin D group (P = 0.001); however, vitamin D had no effect on TNF-α concentrations. Moreover, HFD significantly induced oxidative stress by reducing GPx, SOD and increasing MDA concentrations in the hippocampus. Vitamin D supplementation in HFD group also significantly increased GPx, SOD and reduced MDA concentrations. Vitamin D improved hippocampus oxidative stress and inflammatory markers in HFD-induced obese rats and improved cognitive performance. Further studies are needed to better clarify the underlying mechanisms.

  8. Vitamin D status and oxidative stress markers in the elderly with impaired fasting glucose and type 2 diabetes mellitus.

    Science.gov (United States)

    Gradinaru, Daniela; Borsa, Claudia; Ionescu, Cristina; Margina, Denisa; Prada, Gabriel I; Jansen, Eugène

    2012-12-01

    Vitamin D deficiency has been identified in the elderly as a potential risk factor for cardiovascular disease development, possibly through its association with other risk factors, such as type 2 diabetes mellitus (T2DM), hypercholesterolemia and hypertension. The aim of this cross-sectional study was to evaluate the vitamin D status in elderly subjects with impaired fasting glucose (IFG) or T2DM, and to examine its relationships to systemic oxidative stress and biochemical markers of endothelial dysfunction. Serum 25-hydroxyvitamin D [25(OH)D], fasting glucose, insulin, lipid profile, advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), low-density lipoprotein susceptibility to oxidation (oxLDL) and nitric oxide metabolic pathway products (NOx) were analyzed in elderly subjects with IFG (n=30) and T2DM (n=35) compared with aged-matched controls (n=25). 25(OH)D levels in the IFG and T2DM groups were significantly lower than in controls (31.9±1.9 and 28.5±1.9 vs 39.4±2.4 ng/mL, poxidative stress parameters AGEs, AOPPs, oxLDL and NOx. Hypovitaminosis D [25(OH)D)oxidative stress and cardiovascular risk in hyperglycemic subjects compared with sufficient vitamin D [25(OH)D)≥30 ng/mL] status subjects. In subjects with IFG and T2DM (n=65), the vitamin D status was significantly inversely correlated both with oxLDL (r=-0.413, p=0.001) and AOPPs (r=-0.475, poxidative stress and endothelial dysfunction, especially in subjects with hypovitaminosis D.

  9. Roles of Fatty Acid Oversupply and Impaired Oxidation in Lipid Accumulation in Tissues of Obese Rats

    Directory of Open Access Journals (Sweden)

    Nicholas D. Oakes

    2013-01-01

    Full Text Available To test the roles of lipid oversupply versus oxidation in causing tissue lipid accumulation associated with insulin resistance/obesity, we studied in vivo fatty acid (FA metabolism in obese (Obese and lean (Lean Zucker rats. Indices of local FA utilization and storage were calculated using the partially metabolizable [9,10-3H]-(R-2-bromopalmitate (3H-R-BrP and [U-14C]-palmitate (14C-P FA tracers, respectively. Whole-body FA appearance (Ra was estimated from plasma 14C-P kinetics. Whole-body FA oxidation rate (Rox was assessed using 3H2O production from 3H-palmitate infusion, and tissue FA oxidative capacity was evaluated ex vivo. In the basal fasting state Obese had markedly elevated FA levels and Ra, associated with elevated FA utilization and storage in most tissues. Estimated rates of muscle FA oxidation were not lower in obese rats and were similarly enhanced by contraction in both lean and obese groups. At comparable levels of FA availability, achieved by nicotinic acid, Rox was lower in Obese than Lean. In Obese rats, FA oxidative capacity was 35% higher than that in Lean in skeletal muscle, 67% lower in brown fat and comparable in other organs. In conclusion, lipid accumulation in non-adipose tissues of obese Zucker rats appears to result largely from systemic FA oversupply.

  10. Periodontitis induced byPorphyromonas gingivalisdrives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response.

    Science.gov (United States)

    Blasco-Baque, Vincent; Garidou, Lucile; Pomié, Céline; Escoula, Quentin; Loubieres, Pascale; Le Gall-David, Sandrine; Lemaitre, Mathieu; Nicolas, Simon; Klopp, Pascale; Waget, Aurélie; Azalbert, Vincent; Colom, André; Bonnaure-Mallet, Martine; Kemoun, Philippe; Serino, Matteo; Burcelin, Rémy

    2017-05-01

    To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis ( Pg ), Fusobacterium nucleatum and Prevotella intermedia . The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Escin attenuates behavioral impairments, oxidative stress and inflammation in a chronic MPTP/probenecid mouse model of Parkinson's disease.

    Science.gov (United States)

    Selvakumar, Govindasamy Pushpavathi; Janakiraman, Udaiyappan; Essa, Musthafa Mohamed; Justin Thenmozhi, Arokiasamy; Manivasagam, Thamilarasan

    2014-10-17

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that results mainly due to the death of dopaminergic neurons in the substantia nigra (SN), and subsequently has an effect on one's motor function and coordination. The current investigation explored the neuroprotective potential of escin, a natural triterpene-saponin on chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced mouse model of PD. Administration of MPTP led to the depleted striatal dopamine content, impaired patterns of behavior, enhanced oxidative stress and diminished expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2). The expressions of interleukin-6 and -10, glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (IBA-1), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in SN were also enhanced. Oral treatment of escin significantly attenuated MPTP/p induced dopaminergic markers depletion, physiological abnormalities, oxidative stress and inhibit neuroinflammatory cytokine expressions in SN. The result of our study confirmed that escin mediated its protection against experimental PD through its antioxidant and anti-inflammatory properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Nicotine versus 6-hydroxy-l-nicotine against chlorisondamine induced memory impairment and oxidative stress in the rat hippocampus.

    Science.gov (United States)

    Hritcu, Lucian; Ionita, Radu; Motei, Diana Elena; Babii, Cornelia; Stefan, Marius; Mihasan, Marius

    2017-02-01

    6-Hydroxy-l-nicotine (6HLN), a nicotine derivative from nicotine degradation by Arthrobacter nicotinovorans pAO1 strain was found to improve behavioral deficits and to reverse oxidative stress in the rat hippocampus. Rats were given CHL (10mg/kg, i.p.) were used as an Alzheimer's disease-like model. The nicotine (0.3mg/kg) and 6HLN (0.3mg/kg) were administered alone or in combination in the CHL-treated rats. Memory-related behaviors were evaluated using Y-maze and radial arm-maze tests. The antioxidant enzymes activity and the levels of the biomarkers of oxidative stress were measured in the hippocampus. Statistical analyses were performed using two-way ANOVA and Tukey's post hoc test. F values for which pnicotine and 6HLN administration attenuated the cognitive deficits and recovered the antioxidant capacity in the rat hippocampus of the CHL rat model. Our results suggest that 6HLN versus nicotine confers anti-amnesic properties in the CHL-induced a rat model of memory impairment via reversing cholinergic function and decreasing brain oxidative stress, suggesting the use of this compound as an alternative agent in AD treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Modulating Oxidative Stress Relieves Stress-Induced Behavioral and Cognitive Impairments in Rats.

    Science.gov (United States)

    Solanki, Naimesh; Salvi, Ankita; Patki, Gaurav; Salim, Samina

    2017-07-01

    Persistent psychological stress often leads to anxiety disorders and depression. Benzodiazepines and selective serotonin reuptake inhibitors are popular treatment options but have limited efficacy, supporting the need for alternative treatment. Based on our recent preclinical work suggesting a causal link between neurobehavioral deficits and elevated oxidative stress, we hypothesized that interventions that mitigate oxidative stress can attenuate/overcome neurobehavioral deficits. Here, we employed the rat social defeat model of psychological stress to determine whether increasing antioxidant levels using grape powder would prevent and/or reverse social defeat-induced behavioral and cognitive deficits. Furthermore, a hippocampal-derived HT22 cell culture model of oxidative stress was employed to identify the individual beneficial constituent(s) of grape powder and the underlying mechanism(s) of action. Grape powder treatment prevented and reversed social defeat-induced behavioral and cognitive deficits and also decreased social defeat-induced increase in plasma corticosterone and 8-isoprostane (systemic and oxidative stress markers, respectively). And grape powder treatment replenished social defeat-induced depleted pool of key antioxidant enzymes glyoxalase-1, glutathione reducatse-1, and superoxide dismutase. Grape powder constituents, quercetin and resveratrol, were most effective in preventing oxidative stress-induced decreased cellular antioxidant capacity. Grape powder protected oxidative stress-induced cell death by preventing calcium influx, mitochondrial dysfunction, and release of cytochrome c. Grape powder treatment by increasing antioxidant pool and preventing cell damage and death prevented and reversed social defeat-induced behavioral and cognitive deficits in rats. Quercetin and resveratrol are the major contributors towards beneficial effects of grape powder.

  14. Oxidized VLDL induces less triglyceride accumulation in J774 macrophages than native VLDL due to an impaired extracellular lipolysis.

    Science.gov (United States)

    Jong, M C; Hendriks, W L; van Vark, L C; Dahlmans, V E; Groener, J E; Havekes, L M

    2000-01-01

    The present study examined the relative contributions of the different pathways by which oxidatively modified VLDL (oxVLDL) promotes the uptake and intracellular accumulation of lipids in J774 macrophages. VLDL was oxidized for a maximum of 4 hours, resulting in an increase in thiobarbituric acid-reactive substances and an increased electrophoretic mobility on agarose gel. The lipid composition of the relatively moderately oxidized VLDL samples did not differ significantly from that of nonoxidized VLDL samples. The uptake of (125)I-labeled VLDL by the J774 cells increased with oxidation time and was completely blocked on coincubation with polyinosinic acid (PolyI), indicating that oxVLDL is taken up by the cells via the scavenger receptor only. Despite the 2-fold increased uptake of oxVLDL protein, the cell association of triglyceride (TG)-derived fatty acids by the J774 macrophages after incubation with oxVLDL was only 50% of that with native VLDL. In line with these observations, the induction of de novo synthesis of TG by J774 cells was approximately 3-fold less efficient after incubation with oxVLDL than after incubation with native VLDL. The induction of de novo synthesis of TG with oxVLDL was even further decreased on simultaneous incubation with PolyI, whereas PolyI did not affect the native VLDL-induced TG synthesis. These results indicate that oxVLDL induces endogenous TG synthesis predominantly through particle uptake via the scavenger receptor and much less via the extracellular lipoprotein lipase (LPL)-mediated hydrolysis of TG, as is the case for native VLDL. In line with these observations, we showed that the suitability of VLDL as a substrate for LPL decreases with oxidation time. Addition of oxVLDL to the LPL assay did not interfere with the lipolysis of native VLDL. However, enrichment of the oxidized lipoprotein particle with native apoC2 was able to fully restore the impaired lipolysis. Thus, from these studies it can be concluded that on

  15. Impaired amino acid metabolism contributes to fasting-induced hypoglycemia in fatty acid oxidation defects

    NARCIS (Netherlands)

    Houten, S.M.; Herrema, H.; Brinke, te H.; Denis, S.; Ruiter, J.P.N.; Dijk, van Th.; Argmann, C.A.; Ottenhoff, R.; Müller, M.R.; Groen, A.K.; Kuipers, F.; Reijngoud, D.J.; Wanders, R.J.A.

    2013-01-01

    The importance of mitochondrial fatty acid beta-oxidation (FAO) as a glucose-sparing process is illustrated by patients with inherited defects in FAO, who may present with life-threatening fasting-induced hypoketotic hypoglycemia. It is unknown why peripheral glucose demand outpaces hepatic

  16. Impaired amino acid metabolism contributes to fasting-induced hypoglycemia in fatty acid oxidation defects

    NARCIS (Netherlands)

    Houten, Sander M.; Herrema, Hilde; te Brinke, Heleen; Denis, Simone; Ruiter, Jos P. N.; van Dijk, Theo H.; Argmann, Carmen A.; Ottenhoff, Roelof; Müller, Michael; Groen, Albert K.; Kuipers, Folkert; Reijngoud, Dirk-Jan; Wanders, Ronald J. A.

    2013-01-01

    The importance of mitochondrial fatty acid β-oxidation (FAO) as a glucose-sparing process is illustrated by patients with inherited defects in FAO, who may present with life-threatening fasting-induced hypoketotic hypoglycemia. It is unknown why peripheral glucose demand outpaces hepatic

  17. Impaired energy metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes

    DEFF Research Database (Denmark)

    Baraibar, Martín A; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina

    2016-01-01

    Accumulation of oxidized proteins is a hallmark of cellular and organismal aging. Adult muscle stem cell (or satellite cell) replication and differentiation is compromised with age contributing to sarcopenia. However, the molecular events related to satellite cell dysfunction during aging are not...

  18. A stimulatory effect of FFA on glycolysis unmasked in cells with impaired oxidative capacity

    Energy Technology Data Exchange (ETDEWEB)

    Blackard, W.G.; Clore, J.N.; Powers, L.P. (Virginia Commonwealth Univ., Richmond (USA))

    1990-09-01

    The physiological importance of the glucose fatty acid cycle has been controversial. Many studies have failed to demonstrate an inhibitory effect of free fatty acids (FFA) on glucose utilization. Using both hepatoma cells (Hep G2) and human erythrocytes, which have poor oxidative capacity and metabolize glucose primarily anaerobically, we have demonstrated a unique stimulatory effect of FFA on glycolysis. Fructose 2,6-bisphosphate (F-2,6-P2) concentrations also increased significantly in Hep G2 cells incubated with palmitic acid. In contrast, F-2,6-P2 concentrations fell in primary cultured hepatocytes incubated with palmitic acid in association with increased oxidation of FFA and accumulation of beta-hydroxybutyrate. We propose that a stimulatory effect of FFA on glycolysis reported here for the first time may have been masked in previous studies performed in tissues in which the oxidation of FFA and the accumulation of intermediates such as citrate may have decreased F-2,6-P2 concentrations. We conclude that the spectrum of FFA effects in glycolysis probably depends on tissue oxidative capacity.

  19. Induction and stability of oxidative stress adaptation in Listeria monocytogenes EGD (Bug600) and F1057 in sublethal concentrations of H2O2 and NaOH

    Science.gov (United States)

    Food processing and food handling environments may contain residual levels of sanitizers or cleaners which may trigger oxidative stress adaptation in Listeria monocytogenes. The aim of this study was to determine the induction and stability of oxidative stress adaptation in L. monocytogenes EGD (Bug...

  20. Impairment of mitochondrial β-oxidation in rats under cold-hypoxic environment

    Science.gov (United States)

    Dutta, Arkadeb; Vats, Praveen; Singh, Vijay K.; Sharma, Yogendra K.; Singh, Som N.; Singh, Shashi B.

    2009-09-01

    Mitochondrial ß-oxidation of fatty acid provides a major source of energy in mammals. High altitude (HA), characterized by hypobaric hypoxia and low ambient temperatures, causes alteration in metabolic homeostasis. Several studies have depicted that hypoxic exposure in small mammals causes hypothermia due to hypometabolic state. Moreover, cold exposure along with hypoxia reduces hypoxia tolerance in animals. The present study investigated the rate of β-oxidation and key enzymes, carnitine palmitoyl transferase-I (CPT-I) and hydroxyacyl CoA dehydrogenase (HAD), in rats exposed to cold-hypobaric hypoxic environment. Male Sprague Dawley rats (190-220 g) were randomly divided into eight groups ( n = 6 rats in each group): 1 day hypoxia (H1); 7 days hypoxia (H7); 1 day cold (C1); 7 days cold (C7); 1 day cold-hypoxia (CH1); 7 days cold-hypoxia (CH7) exposed; and unexposed control for 1 and 7 days (UC1 and UC7). After exposure, animals were anaesthetized with ketamine (50 mg/kg body weight) and xylazine (10 mg/kg body weight) intraperitonialy and sacrificed. Mitochondrial CPT-I, HAD, 14C-palmitate oxidation in gastrocnemius muscle and liver, and plasma leptin were measured. Mitochondrial CPT-I was significantly reduced in muscle and liver in CH1 and CH7 as compared to respective controls. HAD activity was significantly reduced in H1 and CH7, and in H1, H7, CH1, and CH7 as compared to unexposed controls in muscle and liver, respectively. A concomitant decrease in 14C-palmitate oxidation was found. Significant reduction in plasma leptin in hypoxia and cold-hypoxia suggested hypometabolic state. It can be concluded that ß-oxidation of fatty acids is reduced in rats exposed to cold-hypoxic environment due to the persisting hypometabolic state in cold-hypoxia exposure.

  1. Impairment of fat oxidation under high- vs. low-glycemic index diet occurs before the development of an obese phenotype.

    Science.gov (United States)

    Isken, F; Klaus, S; Petzke, K J; Loddenkemper, C; Pfeiffer, A F H; Weickert, M O

    2010-02-01

    Exposure to high vs. low glycemic index (GI) diets increases fat mass and insulin resistance in obesity-prone C57BL/6J mice. However, the longer-term effects and potentially involved mechanisms are largely unknown. We exposed four groups of male C57BL/6J mice (n = 10 per group) to long-term (20 wk) or short-term (6 wk) isoenergetic and macronutrient matched diets only differing in starch type and as such GI. Body composition, liver fat, molecular factors of lipid metabolism, and markers of insulin sensitivity and metabolic flexibility were investigated in all four groups of mice. Mice fed the high GI diet showed a rapid-onset (from week 5) marked increase in body fat mass and liver fat, a gene expression profile in liver consistent with elevated lipogenesis, and, after long-term exposure, significantly reduced glucose clearance following a glucose load. The long-term high-GI diet also led to a delayed switch to both carbohydrate and fat oxidation in the postprandial state, indicating reduced metabolic flexibility. In contrast, no difference in carbohydrate oxidation was observed after short-term high- vs. low-GI exposure. However, fatty acid oxidation was significantly blunted as early as 3 wk after beginning of the high-GI intervention, at a time where most measured phenotypic markers including body fat mass were comparable between groups. Thus long-term high-GI feeding resulted in an obese, insulin-resistant, and metabolically inflexible phenotype in obesity-prone C57BL/6J mice. Early onset and significantly impaired fatty acid oxidation preceded these changes, thereby indicating a potentially causal involvement.

  2. Elevated level of DNA damage and impaired repair of oxidative DNA damage in patients with recurrent depressive disorder.

    Science.gov (United States)

    Czarny, Piotr; Kwiatkowski, Dominik; Kacperska, Dagmara; Kawczyńska, Daria; Talarowska, Monika; Orzechowska, Agata; Bielecka-Kowalska, Anna; Szemraj, Janusz; Gałecki, Piotr; Śliwiński, Tomasz

    2015-02-06

    Depressive disorder (DD), including recurrent DD (rDD), is a severe psychological disease, which affects a large percentage of the world population. Although pathogenesis of the disease is not known, a growing body of evidence shows that inflammation together with oxidative stress may contribute to development of DD. Since reactive oxygen species produced during stress may damage DNA, we wanted to evaluate the extent of DNA damage and efficiency of DNA repair in patients with depression. We measured and compared the extent of endogenous DNA damage--single- and double-strand breaks, alkali-labile sites, and oxidative damage of the pyrimidines and purines--in peripheral blood mononuclear cells isolated from rDD patients (n=40) and healthy controls (n=46) using comet assay. We also measured DNA damage evoked by hydrogen peroxide and monitored changes in DNA damage during repair incubation. We found an increased number DNA breaks, alkali-labile sites, and oxidative modification of DNA bases in the patients compared to the controls. Exposure to hydrogen peroxide evoked the same increased damage in both groups. Examination of the repair kinetics of both groups revealed that the lesions were more efficiently repaired in the controls than in the patients. For the first time we showed that patients with depression, compared with non-depresses individuals, had more DNA breaks, alkali-labile sites, and oxidative DNA damage, and that those lesions may be accumulated by impairments of the DNA repair systems. More studies must be conducted to elucidate the role of DNA damage and repair in depression.

  3. Impaired oxidative capacity due to decreased CPT1b levels as a contributing factor to fat accumulation in obesity

    DEFF Research Database (Denmark)

    Ratner, Cecilia; Madsen, Andreas Nygaard; Kristensen, Line Vildbrad

    2015-01-01

    In order to characterize mechanisms responsible for fat accumulation we used a selectively bred obesity-prone (OP) and obesity-resistant (OR) rat model, where the rats were fed a Western diet for 76 days. Body composition was assessed by MRI scans and as expected the OP rats developed a higher...... likewise had higher RER values indicating that this trait may be a primary and contributing factor to their obese phenotype. When the adult obese rats were exposed to the orexigenic and adipogenic hormone ghrelin, we observed increased RER values in both OP and OR rats, while OR rats were more sensitive...... to ghrelin's orexigenic effects as well as ghrelin-induced attenuation of activity and energy expenditure. Thus, increased fat accumulation characterizing obesity may be caused by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b levels in the white adipose tissue, while ghrelin...

  4. Inhaled Nitric Oxide for the Prevention of Impaired Arterial Oxygenation during Myocardial Revascularization with Extracorporeal Circulation

    Directory of Open Access Journals (Sweden)

    I. A. Kozlov

    2011-01-01

    Full Text Available Objective: to study the efficacy of inhaled nitric oxide used intraoperatively to prevent lung oxygenating dysfunction in patients with coronary heart disease after myocardial revascularization under extracorporeal circulation (EC. Subjects and methods. Thirty-two patients aged 55.0±2.0 years were examined. The inclusion criteria were the standard course of surgical intervention (the absence of hemorrhage, acute cardiovascular insufficiency, perioperative myocardial infarction, etc., a pulmonary artery wedge pressure of less than 15 – mm Hg throughout the study, and the baseline arterial partial oxygen tension/inspired mixture oxygen fraction (PaO2/FiO2 ratio of at least 350 mm Hg. There was a control group (n=21; Group 1 that used no special measures to prevent and/or to correct lung oxygenating dysfunction and Group 2 (n=11 that received inhaled nitric oxide. Ihe administration of inhaled nitric oxide at a concentration of 10 ppm was initiated after water anesthesia, stopped during EC, and resumed in the postperfusion period. Results. At the end, PaO2/FiO2 and intrapulmonary shunt fraction did not differ between the groups (p>0.05. Before EC, the patients receiving inhaled nitric oxide had a lower intrapulmonary blood shunting (8.9±0.7 and 11.7±1.0%; p<0.05. There were no intergroup differences in the values of PaO2/FiO2 at this stage. In the earliest postperfusion period, PaO2/FiO2 was higher in Group 2 than that in Group 1. At the end of operations, Groups 1 and 2 had a PaO2/FiO2 of 336.0±16.8 and 409.0±24.3 mm Hg, respectively (p<0.05 and an intrapulmonary shunt fraction of 14.5±1.0 and 10.4±1.0% (p<0.05. At the end of surgery, the rate of a reduction in PaO2/FiO2 to the level below 350 mm Hg was 52.4±11.1% in Group 1 and 18.2±11.6% in Group 2 (p<0.05. Six hours after surgery, PaO2/FiO2 values less than 300 mm Hg were diagnosed in 61.9±10.5% of Group 1 patients and in 27.3±13.4% of Group 2 ones (p<0.05. Conclusion. The

  5. Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Wang, Dongmei; Liu, Ling; Zhu, Xiaoying; Wu, Wenlan; Wang, Yong

    2014-11-01

    The role of mitochondrial dysfunction and oxidative stress has been well-documented in Alzheimer's disease (AD). Bioflavonoids are being utilised as neuroprotectants in the treatment of various neurological disorders, including AD. Therefore, we conducted this current study in order to explore the effects of hesperidin (a flavanone glycoside) against amyloid-β (Aβ)-induced cognitive dysfunction, oxidative damage and mitochondrial dysfunction in mice. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two hesperidin (either 50 or 100 mg/kg per day) groups, or an Aricept (2.5 mg/kg per day) group. After 16 weeks of treatment, although there was no obvious change in Aβ deposition in the hesperidin-treated (100 mg/kg per day) group, however, we found that the administration of hesperidin (100 mg/kg per day) resulted in the reduction of learning and memory deficits, improved locomotor activity, and the increase of anti-oxidative defense and mitochondrial complex I-IV enzymes activities. Furthermore, Glycogen synthase kinase-3β (GSK-3β) phosphorylation significantly increased in the hesperidin-treated (100 mg/kg per day) group. Taken together, these findings suggest that a reduction in mitochondrial dysfunction through the inhibition of GSK-3β activity, coupled with an increase in anti-oxidative defense, may be one of the mechanisms by which hesperidin improves cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD.

  6. Assessment of benzene induced oxidative impairment in rat isolated pancreatic islets and effect on insulin secretion.

    Science.gov (United States)

    Bahadar, Haji; Maqbool, Faheem; Mostafalou, Sara; Baeeri, Maryam; Rahimifard, Mahban; Navaei-Nigjeh, Mona; Abdollahi, Mohammad

    2015-05-01

    Benzene (C6H6) is an organic compound used in petrochemicals and numerous other industries. It is abundantly released to our environment as a chemical pollutant causing widespread human exposure. This study mainly focused on benzene induced toxicity on rat pancreatic islets with respect to oxidative damage, insulin secretion and glucokinase (GK) activity. Benzene was dissolved in corn oil and administered orally at doses 200, 400 and 800mg/kg/day, for 4 weeks. In rats, benzene significantly raised the concentration of plasma insulin. Also the effect of benzene on the release of glucose-induced insulin was pronounced in isolated islets. Benzene caused oxidative DNA damage and lipid peroxidation, and also reduced the cell viability and total thiols groups, in the islets of exposed rats. In conclusion, the current study revealed that pancreatic glucose metabolism is susceptible to benzene toxicity and the resultant oxidative stress could lead to functional abnormalities in the pancreas. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

    Directory of Open Access Journals (Sweden)

    Francisco Bruno Teixeira

    Full Text Available Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies, GFAP (a marker of astrocytes and Iba1 (microglia marker in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

  8. Skiing across the Greenland icecap: divergent effects on limb muscle adaptations and substrate oxidation

    DEFF Research Database (Denmark)

    Helge, Jørn W; Lundby, Carsten; Christensen, Dirk L

    2003-01-01

    This study investigates the adaptive response of the lower limb muscles and substrate oxidation during submaximal arm or leg exercise after a crossing of the Greenland icecap on cross-country skies. Before and after the 42-day expedition, four male subjects performed cycle ergometer and arm......-cranking exercise on two separate days. On each occasion, the subjects exercised at two submaximal loads (arm exercise, 45 W and 100 W; leg exercise, 100 W and 200 W). In addition, peak oxygen uptake ((VO(2max))) was determined for both leg and arm exercise. Before and after the crossing, a muscle biopsy...... was obtained from the vastus lateralis and the triceps brachii muscles prior to exercise (N=3). After the crossing, body mass decreased by 5.7+/-0.5 kg (in four of four subjects), whereas (VO(2max)) was unchanged in the arm (3.1+/-0.2 l min(-1)) and leg (4.0+/-0.1 l min(-1)). Before the crossing, respiratory...

  9. Successive deep dives impair endothelial function and enhance oxidative stress in man.

    Science.gov (United States)

    Obad, Ante; Marinovic, Jasna; Ljubkovic, Marko; Breskovic, Toni; Modun, Darko; Boban, Mladen; Dujic, Zeljko

    2010-11-01

    The aim of this study was to assess the effects of successive deep dives on endothelial function of large conduit arteries and plasma pro-oxidant and antioxidant activity. Seven experienced divers performed six dives in six consecutive days using a compressed mixture of oxygen, helium and nitrogen (trimix) with diving depths ranging from 55 to 80 m. Before and after first, third and sixth dive, venous gas emboli formation and brachial artery function (flow-mediated dilation, FMD) was assessed by ultrasound. In addition, plasma antioxidant capacity (AOC) was measured by ferric reducing antioxidant power, and the level of oxidative stress was assessed by thiobarbituric acid-reactive substances (TBARS) method. Although the FMD was reduced to a similar extent after each dive, the comparison of predive FMD showed a reduction from 8.6% recorded before the first dive to 6.3% before the third (P = 0.03) and 5.7% before the sixth dive (P = 0.003). A gradual shift in baseline was also detected with TBARS assay, with malondialdehyde values increasing from 0.10 ± 0.02 μmol l⁻¹ before the first dive to 0.16 ± 0.03 before the sixth (P = 0.005). Predive plasma AOC values also showed a decreasing trend from 0.67 ± 0.20 mmol l⁻¹ trolox equivalents (first day) to 0.56 ± 0.12 (sixth day), although statistical significance was not reached (P = 0.08). This is the first documentation of acute endothelial dysfunction in the large conduit arteries occurring after successive deep trimix dives. Both endothelial function and plasma pro-oxidant and antioxidant activity did not return to baseline during the course of repetitive dives, indicating possible cumulative and longer lasting detrimental effects. © 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  10. Allicin ameliorates cognitive impairment in APP/PS1 mice via Suppressing oxidative stress by Blocking JNK Signaling Pathways.

    Science.gov (United States)

    Zhang, Hao; Wang, Ping; Xue, Yixue; Liu, Libo; Li, Zhen; Liu, Yunhui

    2018-02-01

    In middle and old age, Alzheimer's disease (AD) is a progressive neurodegenerative disorder of brain. As an increasingly aging population, AD represents a huge burden for the patients' family and the country. However, current therapeutical strategies have shown limited effectiveness. Allicin, which is the main composition of garlic, was reported to prevent the learning and memory impairment of AD mouse model. As the mechanism is not clear, in this study, we used the APP (amyloid precursor protein)/PS1 (presenilin 1) double transgenic mice, which express human mutant APP and PS1, to determine the protective effect of allicin on neurons. AD involves a broad range of clinical, cellular, and biochemical manifestations. This has led to many views of AD, e.g. the amyloid, presenilin, oxidative stress, and mitochondrial dysfunction. We confirmed that allicin improves the cognitive function of APP/PS1 double transgenic mice by reducing the expression levels of Aβ, oxidative stress, and improving mitochondrial dysfunction. Application of behavioral, morphological and molecular biology, and other means were conducted to investigate the effect of allicin, which provide an experimental basis for the reliable application of allicin in the treatment of neurodegenerative diseases. Copyright © 2017. Published by Elsevier Ltd.

  11. Beneficial Effects of Teucrium polium and Metformin on Diabetes-Induced Memory Impairments and Brain Tissue Oxidative Damage in Rats

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    S. Mojtaba Mousavi

    2015-01-01

    Full Text Available Objective. The effects of hydroalcoholic extract of Teucrium polium and metformin on diabetes-induced memory impairment and brain tissues oxidative damage were investigated. Methods. The rats were divided into: (1 Control, (2 Diabetic, (3 Diabetic-Extract 100 (Dia-Ext 100, (4 Diabetic-Extract 200 (Dia-Ext 200, (5 Diabetic-Extract 400 (Dia-Ext 400, and (6 Diabetic-Metformin (Dia-Met. Groups 3–6 were treated by 100, 200, and 400 mg/kg of the extract or metformin, respectively, for 6 weeks (orally. Results. In passive avoidance test, the latency to enter the dark compartment in Diabetic group was lower than that of Control group (P<0.01. In Dia-Ext 100, Dia-Ext 200, and Dia-Ext 400 and Metformin groups, the latencies were higher than those of Diabetic group (P<0.01. Lipid peroxides levels (reported as malondialdehyde, MDA, concentration in the brain of Diabetic group were higher than Control (P<0.001. Treatment by all doses of the extract and metformin decreased the MDA concentration (P<0.01. Conclusions. The results of present study showed that metformin and the hydroalcoholic extract of Teucrium polium prevent diabetes-induced memory deficits in rats. Protection against brain tissues oxidative damage might have a role in the beneficial effects of the extract and metformin.

  12. Isolation, cultivation, and characterization of ammonia-oxidizing bacteria and archaea adapted to low ammonium concentrations

    NARCIS (Netherlands)

    Bollmann, A.; French, A.; Laanbroek, H.J.

    2011-01-01

    Ammonia-oxidizing microorganisms (AOM) generate their energy by the oxidation of ammonia (NH3) to nitrite (NO2−). This process can be carried out by ammonia-oxidizing bacteria (AOB) as well as by the recently discovered ammonia-oxidizing archaea (AOA). In the past, AOB were enriched in batch

  13. Aging and SKN-1-dependent Loss of 20S Proteasome Adaptation to Oxidative Stress in C. elegans.

    Science.gov (United States)

    Raynes, Rachel; Juarez, Crystal; Pomatto, Laura C D; Sieburth, Derek; Davies, Kelvin J A

    2017-02-01

    Aging is marked by a collapse of protein homeostasis and deterioration of adaptive stress responses that often lead to disease. During aging, the induction of stress responses decline along with protein quality control. Here, we have shown that the ability to mount an adaptive response by pretreatment with minor oxidative stress is abrogated in aged Caenorhabditis elegans We have identified a defect in SKN-1 signaling sensitivity during aging and have also found an aging-related increase in basal proteasome expression and in vitro activity, however, adaptation of the 20S proteasome in response to stress is lost in old animals. Interestingly, increased activation of SKN-1 promotes stress resistance, but is unable to rescue declining adaptation during aging. Our data demonstrate that the aging-dependent decline in SKN-1 signaling negatively impacts adaptation of the 20S proteasome in response to acute oxidative stress. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Homocysteine Exposure Impairs Myocardial Resistance to Ischaemia Reperfusion and Oxidative Stress

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    Amer Almashhadany

    2015-12-01

    Full Text Available Background/Aims: Hyperhomocysteinaemia is recognised as a strong independent risk factor for developing cardiovascular disease. This study investigated how an acute homocysteine dose affected cardiac performance during ischaemia reperfusion and cardiomyocyte contractility and morphology under normal conditions and during oxidative stress. Methods: Cardiac function was measured in isolated and perfused rat hearts before and after 40 minutes' global normothermic ischaemia. Where used, 0.1 mM L-homocysteine was present prior to, and throughout ischaemia, before wash out after 10 minutes' reperfusion. Calcium transients under normal conditions and changes in contractile synchronicity during oxidative stress (exposure to 0.2 mM H2O2 were measured in freshly isolated rat cardiomyocytes incubated for 60 minutes ± 0.1 mM L-homocysteine. Results: During ischaemia reperfusion 0.1 mM L-homocysteine significantly reduced the rate pressure product during reperfusion (10,038 ± 749 vs. 5955 ± 567 mmHg bpm, p Conclusions: These findings suggest that homocysteine exposure affected myocardial recovery from ischaemia and contractile homeostasis although the exact mechanisms for these changes remain to be determined.

  15. Nitric oxide agents impair insulin-mediated signal transduction in rat skeletal muscle

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    Ragoobirsingh Dalip

    2006-05-01

    Full Text Available Abstract Background Evidence demonstrates that exogenously administered nitric oxide (NO can induce insulin resistance in skeletal muscle. We have investigated the modulatory effects of two NO donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP and S-nitrosoglutathione (GSNO on the early events in insulin signaling in rat skeletal myocytes. Results Skeletal muscle cells from 6–8 week old Sprague-Dawley rats were treated with SNAP or GSNO (25 ng/ml in the presence or absence of glucose (25 mM and insulin (100 nM. Cellular insulin receptor-β levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Reversal to near normal levels was achieved using the NO scavenger, 2-(4-carboxyphenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO. Conclusion These data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.

  16. Neuroprotective effect of Rhodiola rosea Linn against MPTP induced cognitive impairment and oxidative stress.

    Science.gov (United States)

    Jacob, Reenu; Nalini, G; Chidambaranathan, N

    2013-04-01

    Ageing and age-related neurodegenerative changes including Parkinson's disease are characterized by an important role of reactive oxygen species. It is characterized by signs of major oxidative stress and mitochondrial damage in the pars compacta of substantia nigra. Present study was designed to investigate whether Rhodiola rosea extract would prevent MPTP induced neurotoxicity in Male wistar rats. Male Wistar rats were divided into following five groups: Group I received vehicle (saline (10 ml/kg for 21 days) orally); Group II received Rhodiola rosea extract (250 mg/kg for 21 days) orally; Group III was treated with 20 mg/kg MPTP i.p. for 21 days; Group IV received 20 mg/kg MPTP, i.p. along with 100 mg/kg Rhodiola rosea orally for 21 days. Group V received 20 mg/kg MPTP i.p. along with 250 mg/kg Rhodiola rosea orally for 21 days. MPTP induced rats showed behavioral alterations in elevated plus maze testing. Group III rats elicited significant increase in lipid hydroperoxide along with reduction in level of glutathione peroxidase, catalase, superoxide dismutase and total antioxidants. Histological evidence revealed that MPTP treated rats shown pathological changes like cellular inflammation and vascular degeneration in brain tissue. The oxidative stress and related biochemical alteration by MPTP were attenuated by Rhodiola rosea treatment. However, further studies may be necessary to elucidate the precise mechanism to support the clinical use of a plant source as antiparkinsonism drug.

  17. S100A1 deficiency impairs postischemic angiogenesis via compromised proangiogenic endothelial cell function and nitric oxide synthase regulation.

    Science.gov (United States)

    Most, Patrick; Lerchenmüller, Carolin; Rengo, Giuseppe; Mahlmann, Adrian; Ritterhoff, Julia; Rohde, David; Goodman, Chelain; Busch, Cornelius J; Laube, Felix; Heissenberg, Julian; Pleger, Sven T; Weiss, Norbert; Katus, Hugo A; Koch, Walter J; Peppel, Karsten

    2013-01-04

    Mice lacking the EF-hand Ca2+ sensor S100A1 display endothelial dysfunction because of distorted Ca2+ -activated nitric oxide (NO) generation. To determine the pathophysiological role of S100A1 in endothelial cell (EC) function in experimental ischemic revascularization. Patients with chronic critical limb ischemia showed almost complete loss of S100A1 expression in hypoxic tissue. Ensuing studies in S100A1 knockout (SKO) mice subjected to femoral artery resection unveiled insufficient perfusion recovery and high rates of autoamputation. Defective in vivo angiogenesis prompted cellular studies in SKO ECs and human ECs, with small interfering RNA-mediated S100A1 knockdown demonstrating impaired in vitro and in vivo proangiogenic properties (proliferation, migration, tube formation) and attenuated vascular endothelial growth factor (VEGF)-stimulated and hypoxia-stimulated endothelial NO synthase (eNOS) activity. Mechanistically, S100A1 deficiency compromised eNOS activity in ECs by interrupted stimulatory S100A1/eNOS interaction and protein kinase C hyperactivation that resulted in inhibitory eNOS phosphorylation and enhanced VEGF receptor-2 degradation with attenuated VEGF signaling. Ischemic SKO tissue recapitulated the same molecular abnormalities with insufficient in vivo NO generation. Unresolved ischemia entailed excessive VEGF accumulation in SKO mice with aggravated VEGF receptor-2 degradation and blunted in vivo signaling through the proangiogenic phosphoinositide-3-kinase/Akt/eNOS cascade. The NO supplementation strategies rescued defective angiogenesis and salvaged limbs in SKO mice after femoral artery resection. Our study shows for the first time downregulation of S100A1 expression in patients with critical limb ischemia and identifies S100A1 as critical for EC function in postnatal ischemic angiogenesis. These findings link its pathological plasticity in critical limb ischemia to impaired neovascularization, prompting further studies to probe the

  18. Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling

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    Bruno Pereira Carreira

    2014-10-01

    Full Text Available Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO, which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSC, and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an inflammatory stimulus (LPS plus IFN-γ, using a culture system of subventricular zone (SVZ-derived NSC mixed with microglia cells obtained from wild-type mice (iNOS+/+ or from iNOS knockout mice (iNOS-/-. We found an impairment of NSC cell proliferation in iNOS+/+ mixed cultures, which was not observed in iNOS-/- mixed cultures. Furthermore, the increased release of NO by activated iNOS+/+ microglial cells decreased the activation of the ERK/MAPK signaling pathway, which was concomitant with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive species formation with MnTBAP, a scavenger of peroxynitrite, or using the peroxynitrite degradation catalyst FeTMPyP, cell proliferation and ERK signaling were restored to basal levels in iNOS+/+ mixed cultures. Moreover, exposure to the NO donor NOC-18 (100 µM, for 48 h, inhibited SVZ-derived NSC proliferation. Regarding the antiproliferative effect of NO, we found that NOC-18 caused the impairment of signaling through the ERK/MAPK pathway, which may be related to increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO from inflammatory origin leads to a decreased function of the EGF receptor, which compromised proliferation of NSC. We also demonstrated that NO-mediated nitration of the EGF receptor caused a decrease in its phosphorylation, thus preventing regular proliferation signaling through the

  19. Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice

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    Choi Youkyung

    2011-02-01

    Full Text Available Abstract Aging is a progressive process related to the accumulation of oxidative damage and neuroinflammation. We tried to find the anti-amnesic effect of the Scutellaria baicalens Georgia (SBG ethanol extract and its major ingredients. The antioxidative effect of SBG on the mice model with memory impairment induced by chronic injection of D-galactose and sodium nitrate was studied. The Y-maze test was used to evaluate the learning and memory function of mice. The activities of superoxide dismutase, catalase and the content of malondialdehyde in brain tissue were used for the antioxidation activities. Neuropathological alteration and expression of bcl-2 protein were investigated in the hippocampus by immunohistochemical staining. ROS, neuroinflammation and apoptosis related molecules expression such as Cox-2, iNOS, procaspase-3, cleaved caspase-3, 8 and 9, bcl-2 and bax protein and the products of iNOS and Cox-2, NO, PGE2, were studied using LPS-activated Raw 264.7 cells and microglia BV2 cells. The cognition of mice was significantly improved by the treatment of baicalein and 50 and 100 mg/kg of SBG in Y-maze test. Both SBG groups showed strong antioxidation, antiinflammation effects with significantly decreased iNOS and Cox-2 expression, NO and PGE2 production, increased bcl-2 and decreased bax and cleaved caspase-3 protein expression in LPS induced Raw 264.7 and BV2 cells. We also found that apoptotic pathway was caused by the intrinsic mitochondrial pathway with the decreased cleaved caspase-9 and unchanged cleaved caspase-8 expression. These findings suggest that SBG, especially high dose, 100 mg/kg, improved the memory impairments significantly and showed antioxidation, antiinflammation and intrinsic caspase-mediated apoptosis effects.

  20. The ‘Goldilocks Zone’ from a redox perspective - Adaptive versus deleterious responses to oxidative stress in striated muscle

    Directory of Open Access Journals (Sweden)

    Rick J Alleman

    2014-09-01

    Full Text Available Consequences of oxidative stress may be beneficial or detrimental in physiological systems. An organ system’s position on the ‘hormetic curve’ is governed by the source and temporality of reactive oxygen species (ROS production, proximity of ROS to moieties most susceptible to damage, and the capacity of the endogenous cellular ROS scavenging mechanisms. Most importantly, the resilience of the tissue (the capacity to recover from damage is a decisive factor, and this is reflected in the disparate response to ROS in cardiac and skeletal muscle. In myocytes, a high oxidative capacity invariably results in a significant ROS burden which in homeostasis, is rapidly neutralized by the robust antioxidant network. The up-regulation of key pathways in the antioxidant network is a central component of the hormetic response to ROS. Despite such adaptations, persistent oxidative stress over an extended time-frame (e.g. months to years inevitably leads to cumulative damages, maladaptation and ultimately the pathogenesis of chronic diseases. Indeed, persistent oxidative stress in heart and skeletal muscle has been repeatedly demonstrated to have causal roles in the etiology of heart disease and insulin resistance, respectively. Deciphering the mechanisms that underlie the divergence between adaptive and maladaptive responses to oxidative stress remains an active area of research for basic scientists and clinicians alike, as this would undoubtedly lead to novel therapeutic approaches. Here, we provide an overview of major types of ROS in striated muscle and the divergent adaptations that occur in response to them. Emphasis is placed on highlighting newly uncovered areas of research on this topic, with particular focus on the mitochondria, and the diverging roles that ROS play in muscle health (e.g., exercise or preconditioning and disease (e.g., cardiomyopathy, ischemia, metabolic syndrome.

  1. Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress

    Directory of Open Access Journals (Sweden)

    Patrizia Ferroni

    2015-01-01

    Full Text Available Metabolic disorders, especially type 2 diabetes and its associated complications, represent a growing public health problem. Epidemiological findings indicate a close relationship between diabetes and many types of cancer (including breast cancer risk, which regards not only the dysmetabolic condition, but also its underlying risk factors and therapeutic interventions. This review discusses the advances in understanding of the mechanisms linking metabolic disorders and breast cancer. Among the proposed mechanisms to explain such an association, a major role is played by the dysregulated glucose metabolism, which concurs with a chronic proinflammatory condition and an associated oxidative stress to promote tumour initiation and progression. As regards the altered glucose metabolism, hyperinsulinaemia, both endogenous due to insulin-resistance and drug-induced, appears to promote tumour cell growth through the involvement of innate immune activation, platelet activation, increased reactive oxygen species, exposure to protumorigenic and proangiogenic cytokines, and increased substrate availability to neoplastic cells. In this context, understanding the relationship between metabolic disorders and cancer is becoming imperative, and an accurate analysis of these associations could be used to identify biomarkers able to predict disease risk and/or prognosis and to help in the choice of proper evidence-based diagnostic and therapeutic protocols.

  2. An aminoglycoside antibiotic gentamycin induces oxidative stress, reduces antioxidant reserve and impairs spermatogenesis in rats.

    Science.gov (United States)

    Narayana, Kilarkaje

    2008-02-01

    Gentamycin (GS) is an aminoglycoside antibiotic used to treat infections of various Gram-negative organisms. The present study was designed to investigate the effects of GS on oxidative stress, antioxidant levels, testicular structure and sperm parameters in the rat. Adult Wistar rats (12 week old; N=7/group) were treated (i. p.) with 0 mg/kg, 3 mg/kg and 5 mg/kg for 10 days at an interval of 24 hr between subsequent treatments. Animals were sacrificed on days 1 and 35 after the last treatment, and the reproductive organs were removed and weights of testis and seminal vesicle were recorded. The right testis was processed for light microscopic analysis. The left testis was homogenized and step 19 spermatids were counted to determine the daily sperm production (DSP) and daily abnormal sperm production (DASP). The sperm count, sperm motility and incidence of abnormal sperms were estimated in the epididymis. In testicular sections, along with the evaluation of qualitative changes, the seminiferous tubule diameter (STD) and the epithelial height (SE) were measured. The incidence of stage XIV tubules in testicular sections, meiotic figures and step 14 spermatids/stage XIV tubule, and step 19 spermatids/stage VII tubule were estimated. Intra-testicular levels of superoxide anion, lipid peroxidation and antioxidants-superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and ascorbic acid were measured. GS did not affect the body weight, but the testis weight and DSP were decreased at 5 mg/kg dose-level on both days (p<0.05), and the weight of seminal vesicle decreased on day 35 at both dose-levels. The DASP was increased in a dose-dependent manner (p<0.05) on days 1 and 35 at both dose-levels. The sperm count was decreased at both dose-levels on day 35, whereas the sperm motility was decreased and sperm abnormality was increased on day 1 at 5 mg/kg and on day 35 at both dose-levels. GS induced structural changes such as sloughing of seminiferous epithelium

  3. Ficus sycomorus extract reversed behavioral impairment and brain oxidative stress induced by unpredictable chronic mild stress in rats.

    Science.gov (United States)

    Foyet, Harquin Simplice; Tchinda Deffo, Serge; Koagne Yewo, Pascaline; Antioch, Iulia; Zingue, Stéphane; Asongalem, Emmanuel Acha; Kamtchouing, Pierre; Ciobica, Alin

    2017-11-28

    Stress, regardless of its nature is nowadays recognized as one of the major risk factors for neuropsychiatric diseases, such as mood and anxiety disorders. The brain compared with other organs is more vulnerable to oxidative damage mainly due to its high rate of oxygen consumption, abundant lipid content, and relative insufficiency of antioxidant enzymes. Thus, the identification of neural mechanisms underlying resistance and vulnerability to stress is of crucial importance in understanding the pathophysiology of neuropsychiatric disorders and in developing new treatments, since the existing ones are for several reasons subject to increasing limitations. This study was aimed to assess the effects of hydromethanolic extract of Ficus sycomorus stem bark on depression, anxiety and memory impairment induced by unpredictable chronic mild stress (UCMS) in rats. These effects were studied using anxiety-related behavior, depression-related behavior, anhedonia-like behavior and the Y maze task. Sucrose test was performed twice (before and after UCMS) to assess anhedonia in rats. Liquid chromatography-mass spectrometry analysis of the extract were performed. The antioxidant activities of the extract were assessed using total glutathione (GSH) content and malondialdehyde (MDA) level (lipid peroxidation) in the rat temporal lobe homogenates. The extract of F. sycomorus in a dose of 100 mg/kg significantly increased the sucrose consumption and the swimming time which had been reduced by the unpredictable chronic mild stress (p extract also significantly reduced (p extract (100 and 200 mg/kg) significantly reduced (p extracts also significantly increased alternation in the Y-maze (p extract significantly increased the total GSH content and reduced MDA level in rat temporal lobe. For the LC-MS analysis, the major compound in the extract was a flavonoid with formula C22H28O14. F. sycomorus reversed the harmful effects of UCMS on mood and behaviors in rats and it

  4. Gross motor function in children with spastic Cerebral Palsy and Cerebral Visual Impairment: A comparison between outcomes of the original and the Cerebral Visual Impairment adapted Gross Motor Function Measure-88 (GMFM-88-CVI).

    Science.gov (United States)

    Salavati, M; Rameckers, E A A; Waninge, A; Krijnen, W P; Steenbergen, B; van der Schans, C P

    2017-01-01

    To investigate whether the adapted version of the Gross Motor Function Measure-88 (GMFM-88) for children with Cerebral Palsy (CP) and Cerebral Visual Impairment (CVI) results in higher scores. This is most likely to be a reflection of their gross motor function, however it may be the result of a better comprehension of the instruction of the adapted version. The scores of the original and adapted GMFM-88 were compared in the same group of children (n=21 boys and n=16 girls), mean (SD) age 113 (30) months with CP and CVI, within a time span of two weeks. A paediatric physical therapist familiar with the child assessed both tests in random order. The GMFCS level, mental development and age at testing were also collected. The Wilcoxon signed-rank test was used to compare two different measurements (the original and adapted GMFM-88) on a single sample, (the same child with CP and CVI; pchildren with CP and CVI showed a positive difference in percentage score on at least one of the five dimensions and positive percentage scores for the two versions differed on all five dimensions for fourteen children. For six children a difference was seen in four dimensions and in 10 children difference was present in three dimensions (GMFM dimension A, B& C or C, D & E) (pchildren with CP and CVI that is not adversely impacted bytheir visual problems. On the basis of these findings, we recommend using the adapted GMFM-88 to measure gross motor functioning in children with CP and CVI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Cobalt Oxide Nanoparticles: Behavior towards Intact and Impaired Human Skin and Keratinocytes Toxicity

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    Marcella Mauro

    2015-07-01

    Full Text Available Skin absorption and toxicity on keratinocytes of cobalt oxide nanoparticles (Co3O4NPs have been investigated. Co3O4NPs are commonly used in industrial products and biomedicine. There is evidence that these nanoparticles can cause membrane damage and genotoxicity in vitro, but no data are available on their skin absorption and cytotoxicity on keratinocytes. Two independent 24 h in vitro experiments were performed using Franz diffusion cells, using intact (experiment 1 and needle-abraded human skin (experiment 2. Co3O4NPs at a concentration of 1000 mg/L in physiological solution were used as donor phase. Cobalt content was evaluated by Inductively Coupled–Mass Spectroscopy. Co permeation through the skin was demonstrated after 24 h only when damaged skin protocol was used (57 ± 38 ng·cm−2, while no significant differences were shown between blank cells (0.92 ± 0.03 ng cm−2 and those with intact skin (1.08 ± 0.20 ng·cm−2. To further investigate Co3O4NPs toxicity, human-derived HaCaT keratinocytes were exposed to Co3O4NPs and cytotoxicity evaluated by MTT, Alamarblue® and propidium iodide (PI uptake assays. The results indicate that a long exposure time (i.e., seven days was necessary to induce a concentration-dependent cell viability reduction (EC50 values: 1.3 × 10−4 M, 95% CL = 0.8–1.9 × 10−4 M, MTT essay; 3.7 × 10−5 M, 95% CI = 2.2–6.1 × 10−5 M, AlamarBlue® assay that seems to be associated to necrotic events (EC50 value: 1.3 × 10−4 M, 95% CL = 0.9–1.9 × 10−4 M, PI assay. This study demonstrated that Co3O4NPs can penetrate only damaged skin and is cytotoxic for HaCat cells after long term exposure.

  6. Impact of Adaptive Materials on Teachers and Their Students with Visual Impairments in Secondary Science and Mathematics Classes

    Science.gov (United States)

    Rule, Audrey C.; Stefanich, Greg P.; Boody, Robert M.; Peiffer, Belinda

    2011-01-01

    Science, technology, engineering, and mathematics (STEM) fields, important in today's world, are underrepresented by students with disabilities. Students with visual impairments, although cognitively similar to sighted peers, face challenges as STEM subjects are often taught using visuals. They need alternative forms of access such as enlarged or…

  7. Induction and stability of oxidative stress adaptation in Listeria monocytogenes EGD (Bug600) and F1057 in sublethal concentrations of H2O2 and NaOH.

    Science.gov (United States)

    De Abrew Abeysundara, Piumi; Nannapaneni, Ramakrishna; Soni, Kamlesh A; Sharma, Chander S; Mahmoud, Barakat

    2016-12-05

    Food processing and food handling environments may contain residual levels of sanitizers or cleaners which may trigger oxidative stress adaptation in Listeria monocytogenes. The aim of this study was to determine the induction and stability of oxidative stress adaptation in L. monocytogenes EGD (Bug600) (serotype 1/2a) and F1057 (serotype 4b) at different concentrations and times of sublethal oxidative stress induced by H2O2 or sublethal alkali stress induced by NaOH at 37°C. Both L. monocytogenes Bug600 and F1057 strains showed significantly higher survival in lethal oxidative stress (1000ppm H2O2) after pre-exposure to 50ppm H2O2 for 30min compared to control cells (no pre-exposure to H2O2). When the cells were pre-exposed to sublethal alkali stress by NaOH, the oxidative stress adaptation was induced within 5min in L. monocytogenes. The survival of both L. monocytogenes strains was increased by 2 to 4.5 logs in lethal oxidative stress when the cells were pre-exposed to sublethal alkali stress at pH9 from 5 to 120min by NaOH compared to control cells (no pre-exposure to sublethal alkali pH). Two other alkali reagents tested (KOH and NH4OH) also induced oxidative stress adaptation in L. monocytogenes. For both L. monocytogenes strains, the oxidative stress adaptation induced by sublethal H2O2 was reversible in 30min and that induced by sublethal alkali stress was reversible within 60min at 37°C in the absence of such sublethal stress. These findings show that sublethal oxidative or alkali stress conditions can induce oxidative stress adaptation that may increase the risk of survival of L. monocytogenes cells in lethal oxidative stress. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Effect of Capparis spinosa L. on cognitive impairment induced by D-galactose in mice via inhibition of oxidative stress.

    Science.gov (United States)

    Turgut, Nergiz Hacer; Kara, Haki; Arslanbaş, Emre; Mert, Derya Güliz; Tepe, Bektaş; Güngör, Hüseyin

    2015-01-01

    To determine the phenolic acid levels and DNA damage protection potential of Capparis spinosa L. seed extract and to investigate the effect of the extract on cognitive impairment and oxidative stress in an Alzheimer disease mice model. Thirty BALB/c mice divided into 5 groups (control, D-galactose, D-galactose + C. spinosa 50, D-galactose + C. spinosa 100, D-galactose + C. spinosa 200) were used. Mice were administered an injection of D-galactose (100 mg/kg, subcutaneous) and orally administered C. spinosa (50, 100, or 200 mg/kg) daily for 8 weeks. Syringic acid was detected and the total amount was 204.629 µg/g. Addition of 0.05 mg/mL C. spinosa extract provided significant protection against the damage of DNA bands. C. spinosa attenuated D-galactose-induced learning dysfunctions in mice and significantly increased memory retention. Malondialdehyde (MDA) levels increased and superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities decreased in the D-galactose group. C. spinosa (200 mg/kg body weight) significantly decreased MDA level and increased SOD, GPx, and CAT activities. These results show that C. spinosa has the potential in ameliorating cognitive deficits induced by D-galactose in mice and the antioxidant activity may partially account for the improvement of learning and memory function.

  9. The chalcone derivative Chana 1 protects against amyloid β peptide-induced oxidative stress and cognitive impairment.

    Science.gov (United States)

    Kwak, Jieun; Kim, Mi-Jeong; Choi, Kyung-Chul; Choi, Hyo-Kyung; Jun, Woojin; Park, Hyun-Jin; Lee, Yoo-Hyun; Yoon, Ho-Geun

    2012-07-01

    Alzheimer's disease (AD) is the most common neurodegenerative disease to cause dementia in the elderly. Amyloid β (Aβ)-peptide induced oxidative stress causes the initiation and progression of AD. Recently, new chalcone derivatives termed the Chana series were synthesized. Among them, Chana 1 showed high free radical scavenging activity (72.5%), as measured by a DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. In this study, we investigated the effect of Chana 1 against Aβ-induced cytotoxicity and cognitive deficits. Additionally, we sought to estimate the lethal dose, 50% (LD50) of Chana 1 in mice using an acute oral toxicity test. We found that Chana 1 significantly protected against Aβ-induced neuronal cell death in PC12 cells. Oral administration of Chana 1 at a dose of 50 mg/kg body weight/day significantly improved Aβ-induced learning and memory impairment in mice, as measured in Y-maze and passive avoidance tests. In acute toxicity tests, the LD50 in mice was determined to be 520.44 mg/kg body weight. The data are valuable for future studies and suggest that Chana 1 has therapeutic potential for the management of neurodegenerative disease.

  10. Oxidative stress in mouse sperm impairs embryo development, fetal growth and alters adiposity and glucose regulation in female offspring.

    Directory of Open Access Journals (Sweden)

    Michelle Lane

    Full Text Available Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investigated whether a chemically induced increase of ROS in sperm impairs embryo, pregnancy and offspring health. Mouse sperm was exposed to 1500 µM of hydrogen peroxide (H2O2, which induced oxidative damage, however did not affect sperm motility or the ability to bind and fertilize an oocyte. Sperm treated with H2O2 delayed on-time development of subsequent embryos, decreased the ratio of inner cell mass cells (ICM in the resulting blastocyst and reduced implantation rates. Crown-rump length at day 18 of gestation was also reduced in offspring produced by H2O2 treated sperm. Female offspring from H2O2 treated sperm were smaller, became glucose intolerant and accumulated increased levels of adipose tissue compared to control female offspring. Interestingly male offspring phenotype was less severe with increases in fat depots only seen at 4 weeks of age, which was restored to that of control offspring later in life, demonstrating sex-specific impacts on offspring. This study implicates elevated sperm ROS concentrations, which are common to many paternal health pathologies, as a mediator of programming offspring for metabolic syndrome and obesity.

  11. Liver-specific knockdown of IGF-1 decreases vascular oxidative stress resistance by impairing the Nrf2-dependent antioxidant response: a novel model of vascular aging.

    Science.gov (United States)

    Bailey-Downs, Lora C; Mitschelen, Matthew; Sosnowska, Danuta; Toth, Peter; Pinto, John T; Ballabh, Praveen; Valcarcel-Ares, M Noa; Farley, Julie; Koller, Akos; Henthorn, Jim C; Bass, Caroline; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2012-04-01

    Recent studies demonstrate that age-related dysfunction of NF-E2-related factor-2 (Nrf2)-driven pathways impairs cellular redox homeostasis, exacerbating age-related cellular oxidative stress and increasing sensitivity of aged vessels to oxidative stress-induced cellular damage. Circulating levels of insulin-like growth factor (IGF)-1 decline during aging, which significantly increases the risk for cardiovascular diseases in humans. To test the hypothesis that adult-onset IGF-1 deficiency impairs Nrf2-driven pathways in the vasculature, we utilized a novel mouse model with a liver-specific adeno-associated viral knockdown of the Igf1 gene using Cre-lox technology (Igf1(f/f) + MUP-iCre-AAV8), which exhibits a significant decrease in circulating IGF-1 levels (~50%). In the aortas of IGF-1-deficient mice, there was a trend for decreased expression of Nrf2 and the Nrf2 target genes GCLC, NQO1 and HMOX1. In cultured aorta segments of IGF-1-deficient mice treated with oxidative stressors (high glucose, oxidized low-density lipoprotein, and H(2)O(2)), induction of Nrf2-driven genes was significantly attenuated as compared with control vessels, which was associated with an exacerbation of endothelial dysfunction, increased oxidative stress, and apoptosis, mimicking the aging phenotype. In conclusion, endocrine IGF-1 deficiency is associated with dysregulation of Nrf2-dependent antioxidant responses in the vasculature, which likely promotes an adverse vascular phenotype under pathophysiological conditions associated with oxidative stress (eg, diabetes mellitus, hypertension) and results in accelerated vascular impairments in aging.

  12. The influence of gender, age and treatment time on brain oxidative stress and memory impairment induced by D-galactose in mice.

    Science.gov (United States)

    Hao, Ling; Huang, Huang; Gao, Junying; Marshall, Charles; Chen, Yali; Xiao, Ming

    2014-06-13

    Chronic exposure to d-galactose (d-gal) serves as a model for age-related oxidative damage and cognitive dysfunction. However, methods used, including the dose and treatment time of d-gal as well as the gender, age and strain of animals used, vary greatly among published articles. In this study, we investigate the effect of gender, age and treatment time on brain oxidative stress and spatial memory deficits induced by d-gal in mice, respectively. Eight-week-old female mice injected with 100mg/kg d-gal per day, for 6 weeks, did not show spatial memory impairment or high levels of hydroxyl radical, protein carbonyl and malondialdehyde in brain homogenates, although brain reactive oxygen species were increased when compared with saline control mice. In contrast, both 8-week-old male mice and 24-week-old female mice receiving 100mg/kg d-gal for 6 weeks, or 8-week-old female mice receiving 100mg/kg d-gal for 10 weeks showed spatial memory deficits and significant increases in the above oxidative markers, compared with their corresponding controls. These results demonstrate that d-gal-induced brain oxidative stress and spatial memory impairment are dependent upon exposure time of d-gal, plus gender and age of the animals used. The findings can serve as a useful guide for successfully establishing d-gal induced age-related oxidative damage models. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. The effects of captopril on lipopolysaccharide induced learning and memory impairments and the brain cytokine levels and oxidative damage in rats.

    Science.gov (United States)

    Abareshi, Azam; Hosseini, Mahmoud; Beheshti, Farimah; Norouzi, Fatemeh; Khazaei, Majid; Sadeghnia, Hamid Reza; Boskabady, Mohammad Hossein; Shafei, Mohammad Naser; Anaeigoudari, Akbar

    2016-12-15

    Renin-angiotensin system has a role in inflammation and also involves in learning and memory. In the present study, the effects of captopril on lipopolysaccharide (LPS) induced learning and memory impairments, hippocampal cytokine levels and brain tissues oxidative damage was investigated. The rats were divided and treated : [1] saline (Control), [2] LPS (1mg/kg), [3-5] 10, 50 or 100mg/kg captopril 30min before LPS. The treatment was started since six days before the behavioral experiments and continued during the behavioral tests (LPS injection two h before each behavioral experiment). Administration of LPS prolonged the escape latency and traveled path to find the platform in Morris water maze (MWM) test (Plearning and memory impairments in rats which were accompanied with attenuating hippocampal cytokine levels and improving the brain tissues oxidative damage criteria. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling.

    Science.gov (United States)

    Chen, Long; Ding, Mei-Lin; Wu, Fang; He, Wen; Li, Jin; Zhang, Xiao-Yu; Xie, Wen-Li; Duan, Sheng-Zhong; Xia, Wen-Hao; Tao, Jun

    2016-02-01

    Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5

  15. Adaptability as the key to success for the ubiquitous marine nitrite oxidizer Nitrococcus.

    Science.gov (United States)

    Füssel, Jessika; Lücker, Sebastian; Yilmaz, Pelin; Nowka, Boris; van Kessel, Maartje A H J; Bourceau, Patric; Hach, Philipp F; Littmann, Sten; Berg, Jasmine; Spieck, Eva; Daims, Holger; Kuypers, Marcel M M; Lam, Phyllis

    2017-11-01

    Nitrite-oxidizing bacteria (NOB) have conventionally been regarded as a highly specialized functional group responsible for the production of nitrate in the environment. However, recent culture-based studies suggest that they have the capacity to lead alternative lifestyles, but direct environmental evidence for the contribution of marine nitrite oxidizers to other processes has been lacking to date. We report on the alternative biogeochemical functions, worldwide distribution, and sometimes high abundance of the marine NOB Nitrococcus. These largely overlooked bacteria are capable of not only oxidizing nitrite but also reducing nitrate and producing nitrous oxide, an ozone-depleting agent and greenhouse gas. Furthermore, Nitrococcus can aerobically oxidize sulfide, thereby also engaging in the sulfur cycle. In the currently fast-changing global oceans, these findings highlight the potential functional switches these ubiquitous bacteria can perform in various biogeochemical cycles, each with distinct or even contrasting consequences.

  16. Natural thermal adaptation increases heat shock protein levels and decreases oxidative stress

    Directory of Open Access Journals (Sweden)

    Niku K.J. Oksala

    2014-01-01

    Full Text Available Heat shock proteins (HSPs, originally identified as heat-inducible gene products, are a family of highly conserved proteins that respond to a wide variety of stress including oxidative stress. Although both acute and chronic oxidative stress have been well demonstrated to induce HSP responses, little evidence is available whether increased HSP levels provide enhanced protection against oxidative stress under elevated yet sublethal temperatures. We studied relationships between oxidative stress and HSPs in a physiological model by using Garra rufa (doctor fish, a fish species naturally acclimatized to different thermal conditions. We compared fish naturally living in a hot spring with relatively high water temperature (34.4±0.6 °C to those living in normal river water temperature (25.4±4.7 °C, and found that levels of all the studied HSPs (HSP70, HSP60, HSP90, HSC70 and GRP75 were higher in fish living in elevated water temperature compared with normal river water temperature. In contrast, indicators of oxidative stress, including protein carbonyls and lipid hydroperoxides, were decreased in fish living in the elevated temperature, indicating that HSP levels are inversely associated with oxidative stress. The present results provide evidence that physiologically increased HSP levels provide protection against oxidative stress and enhance cytoprotection.

  17. Adaptive control paradigm for photovoltaic and solid oxide fuel cell in a grid-integrated hybrid renewable energy system.

    Science.gov (United States)

    Mumtaz, Sidra; Khan, Laiq

    2017-01-01

    The hybrid power system (HPS) is an emerging power generation scheme due to the plentiful availability of renewable energy sources. Renewable energy sources are characterized as highly intermittent in nature due to meteorological conditions, while the domestic load also behaves in a quite uncertain manner. In this scenario, to maintain the balance between generation and load, the development of an intelligent and adaptive control algorithm has preoccupied power engineers and researchers. This paper proposes a Hermite wavelet embedded NeuroFuzzy indirect adaptive MPPT (maximum power point tracking) control of photovoltaic (PV) systems to extract maximum power and a Hermite wavelet incorporated NeuroFuzzy indirect adaptive control of Solid Oxide Fuel Cells (SOFC) to obtain a swift response in a grid-connected hybrid power system. A comprehensive simulation testbed for a grid-connected hybrid power system (wind turbine, PV cells, SOFC, electrolyzer, battery storage system, supercapacitor (SC), micro-turbine (MT) and domestic load) is developed in Matlab/Simulink. The robustness and superiority of the proposed indirect adaptive control paradigm are evaluated through simulation results in a grid-connected hybrid power system testbed by comparison with a conventional PI (proportional and integral) control system. The simulation results verify the effectiveness of the proposed control paradigm.

  18. An eHealth Intervention to Promote Physical Activity and Social Network of Single, Chronically Impaired Older Adults: Adaptation of an Existing Intervention Using Intervention Mapping.

    Science.gov (United States)

    Boekhout, Janet M; Peels, Denise A; Berendsen, Brenda Aj; Bolman, Catherine Aw; Lechner, Lilian

    2017-11-23

    Especially for single older adults with chronic diseases, physical inactivity and a poor social network are regarded as serious threats to their health and independence. The Active Plus intervention is an automated computer-tailored eHealth intervention that has been proven effective to promote physical activity (PA) in the general population of adults older than 50 years. The aim of this study was to report on the methods and results of the systematic adaptation of Active Plus to the wishes and needs of the subgroup of single people older than 65 years who have one or more chronic diseases, as this specific target population may encounter specific challenges regarding PA and social network. The Intervention Mapping (IM) protocol was used to systematically adapt the existing intervention to optimally suit this specific target population. A literature study was performed, and quantitative as well as qualitative data were derived from health care professionals (by questionnaires, n=10) and the target population (by focus group interviews, n=14), which were then systematically integrated into the adapted intervention. As the health problems and the targeted behavior are largely the same in the original and adapted intervention, the outcome of the needs assessment was that the performance objectives remained the same. As found in the literature study and in data derived from health professionals and focus groups, the relative importance and operationalization of the relevant psychosocial determinants related to these objectives are different from the original intervention, resulting in a refinement of the change objectives to optimally fit the specific target population. This refinement also resulted in changes in the practical applications, program components, intervention materials, and the evaluation and implementation strategy for the subgroup of single, chronically impaired older adults. This study demonstrates that the adaptation of an existing intervention is an

  19. Swimming training induces liver adaptations to oxidative stress and insulin sensitivity in rats submitted to high-fat diet.

    Science.gov (United States)

    Zacarias, Aline Cruz; Barbosa, Maria Andrea; Guerra-Sá, Renata; De Castro, Uberdan Guilherme Mendes; Bezerra, Frank Silva; de Lima, Wanderson Geraldo; Cardoso, Leonardo M; Santos, Robson Augusto Souza Dos; Campagnole-Santos, Maria José; Alzamora, Andréia Carvalho

    2017-11-01

    Oxidative stress, physical inactivity and high-fat (FAT) diets are associated with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects of physical training (PT) were evaluated in rats with MS induced by FAT diet for 13 weeks, on oxidative stress and insulin signaling in the liver, during the last 6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine aminotransferase, glucose and insulin. Livers of FAT-SED rats increased superoxide dismutase activity, thiobarbituric acid-reactive substances, protein carbonyl and oxidized glutathione (GSSG); and decreased catalase activity, reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin, total cholesterol, MAP and HR; and their livers increased superoxide dismutase and catalase activities, the reduced glutathione/GSSG ratio and the expression of peroxisome proliferator-activated receptor gamma and insulin receptor compared to FAT-SED rats. These findings indicated adaptive responses to PT by restoring the oxidative balance and insulin signaling in the liver and certain biometric and biochemical parameters as well as MAP in MS rats.

  20. Aerobic and Anaerobic Thiosulfate Oxidation by a Cold-Adapted, Subglacial Chemoautotroph

    National Research Council Canada - National Science Library

    Harrold, Zoë R; Skidmore, Mark L; Hamilton, Trinity L; Desch, Libby; Amada, Kirina; van Gelder, Will; Glover, Kevin; Roden, Eric E; Boyd, Eric S

    2016-01-01

    Geochemical data indicate that protons released during pyrite (FeS2) oxidation are important drivers of mineral weathering in oxic and anoxic zones of many aquatic environments, including those beneath glaciers...

  1. Adaptive Responses to Oxidative Stress in the Filamentous Fungal Shiraia bambusicola

    Directory of Open Access Journals (Sweden)

    Huaxiang Deng

    2016-08-01

    Full Text Available Shiraia bambusicola can retain excellent physiological activity when challenged with maximal photo-activated hypocrellin, which causes cellular oxidative stress. The protective mechanism of this fungus against oxidative stress has not yet been reported. We evaluated the biomass and hypocrellin biosynthesis of Shiraia sp. SUPER-H168 when treated with high concentrations of H2O2. Hypocrellin production was improved by nearly 27% and 25% after 72 h incubation with 10 mM and 20 mM H2O2, respectively, while the inhibition ratios of exogenous 20 mM H2O2 on wild S. bambusicola and a hypocrellin-deficient strain were 20% and 33%, respectively. Under exogenous oxidative stress, the specific activities of catalase, glutathione reductase, and superoxide dismutase were significantly increased. These changes may allow Shiraia to maintain normal life activities under oxidative stress. Moreover, sufficient glutathione peroxidase was produced in the SUPER-H168 and hypocrellin-deficient strains, to further ensure that S. bambusicola has excellent protective abilities against oxidative stress. This study creates the possibility that the addition of high H2O2 concentrations can stimulate fungal secondary metabolism, and will lead to a comprehensive and coherent understanding of mechanisms against oxidative stresses from high hydrogen peroxide concentrations in the filamentous fungal Shiraia sp. SUPER-H168.

  2. Postsynaptic α1-Adrenergic Vasoconstriction Is Impaired in Young Patients With Vasovagal Syncope and Is Corrected by Nitric Oxide Synthase Inhibition.

    Science.gov (United States)

    Stewart, Julian M; Suggs, Melissa; Merchant, Sana; Sutton, Richard; Terilli, Courtney; Visintainer, Paul; Medow, Marvin S

    2016-08-01

    Syncope is a sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope (VVS). During VVS, gravitational pooling excessively reduces central blood volume and cardiac output. In VVS, as in hemorrhage, impaired adrenergic vasoconstriction and venoconstriction result in hypotension. We hypothesized that impaired adrenergic responsiveness because of excess nitric oxide can be reversed by reducing nitric oxide. We recorded cardiopulmonary dynamics in supine syncope patients and healthy volunteers (aged 15-27 years) challenged with a dose-response using the α1-agonist phenylephrine (PE), with and without the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine, monoacetate salt (L-NMMA). Systolic and diastolic pressures among control and VVS were the same, although they increased after L-NMMA and saline+PE (volume and pressor control for L-NMMA). Heart rate was significantly reduced by L-NMMA (Pnitric oxide synthase inhibition, demonstrated with our use of L-NMMA. © 2016 American Heart Association, Inc.

  3. Preliminary Data on the Interaction between Some Biometals and Oxidative Stress Status in Mild Cognitive Impairment and Alzheimer’s Disease Patients

    Directory of Open Access Journals (Sweden)

    Ioana-Miruna Balmuș

    2017-01-01

    Full Text Available Increased interest regarding the biometal mechanisms of action and the pathways in which they have regulatory roles was lately observed. Particularly, it was shown that biometal homeostasis dysregulation may lead to neurodegeneration including Alzheimer’s disease, Parkinson disease, or prion protein disease, since important molecular signaling mechanisms in brain functions implicate both oxidative stress and redox active biometals. Oxidative stress could be a result of a breakdown in metal-ion homeostasis which leads to abnormal metal protein chelation. In our previous work, we reported a strong correlation between Alzheimer’s disease and oxidative stress. Consequently, the aim of the present work was to evaluate some of the biometals’ levels (magnesium, manganese, and iron, the specific activity of some antioxidant enzymes (superoxide dismutase and glutathione peroxidase, and a common lipid peroxidation marker (malondialdehyde concentration, in mild cognitive impairment (n=15 and Alzheimer’s disease (n=15 patients, compared to age-matched healthy subjects (n=15. We found increased lipid peroxidation effects, low antioxidant defense, low magnesium and iron concentrations, and high manganese levels in mild cognitive impairment and Alzheimer’s disease patients, in a gradual manner. These data could be relevant for future association studies regarding the prediction of Alzheimer’s disease development risk or circling through stages by analyzing both active redox metals, oxidative stress markers, and the correlations in between.

  4. Technology-adaptable interventions for treating depression in adults with cognitive impairments: protocol for a systematic review.

    Science.gov (United States)

    Topolovec-Vranic, Jane; Mansoor, Yasmeen; Ennis, Naomi; Lightfoot, David

    2015-04-07

    Depression is a common comorbidity in individuals with cognitive impairment. Those with cognitive impairments face unique challenges in receiving the benefits of many conventional therapies for depression, and may have poorer outcomes in areas such as recovery and quality of life. However, the stigmatization of mental health disorders, cost barriers and physical disabilities may prevent these individuals from seeking mental health care. An online, self-help intervention specifically developed for adults with cognitive deficits and depression may be particularly beneficial to this population. We aim to inform the design of such an intervention through a systematic review by answering the following research question: among adults with cognitive impairment (including those with acquired brain injuries or neurodegenerative diseases), which technology-amenable interventions have been shown to effectively decrease symptoms of depression? Specifically, psychotherapeutic and/or behavioural interventions that could be delivered in a self-guided, online system will be included. Comprehensive electronic searches will be conducted in MEDLINE, EMBASE, PsycINFO and CINAHL. Additional studies will be obtained through manually searching the references of relevant systematic reviews, contacting primary authors of select articles and tracking conference proceedings and trial registries. Article titles and abstracts will be screened using predefined eligibility criteria, and then judged for their amenability to the proposed self-help, technology-based intervention. The full text of those articles with selected interventions will then be screened to determine final eligibility for inclusion. Included articles will be categorized by intervention type and assessed for risk of bias using the Cochrane Effective Practice and Organization of Care Risk of Bias tool for non-randomized trials, controlled before-after studies and interrupted time series. The primary outcome will be a change in

  5. Impact of exercise on diurnal and nocturnal markers of glycaemic variability and oxidative stress in obese individuals with type 2 diabetes or impaired glucose tolerance.

    Science.gov (United States)

    Farabi, Sarah S; Carley, David W; Smith, Donald; Quinn, Lauretta

    2015-09-01

    We measured the effects of a single bout of exercise on diurnal and nocturnal oxidative stress and glycaemic variability in obese subjects with type 2 diabetes mellitus or impaired glucose tolerance versus obese healthy controls. Subjects (in random order) performed either a single 30-min bout of moderate-intensity exercise or remained sedentary for 30 min at two separate visits. To quantify glycaemic variability, standard deviation of glucose (measured by continuous glucose monitoring system) and continuous overlapping net glycaemic action of 1-h intervals (CONGA-1) were calculated for three 12-h intervals during each visit. Oxidative stress was measured by 15-isoprostane F(2t) levels in urine collections for matching 12-h intervals. Exercise reduced daytime glycaemic variability (ΔCONGA-1 = -12.62 ± 5.31 mg/dL, p = 0.04) and urinary isoprostanes (ΔCONGA-1 = -0.26 ± 0.12 ng/mg, p = 0.04) in the type 2 diabetes mellitus/impaired glucose tolerance group. Daytime exercise-induced change in urinary 15-isoprostane F(2t) was significantly correlated with both daytime standard deviation (r = 0.68, p = 0.03) and with subsequent overnight standard deviation (r = 0.73, p = 0.027) in the type 2 diabetes mellitus/impaired glucose tolerance group. Exercise significantly impacts the relationship between diurnal oxidative stress and nocturnal glycaemic variability in individuals with type 2 diabetes mellitus/impaired glucose tolerance. © The Author(s) 2015.

  6. Adapted low intensity ergometer aerobic training for early and severely impaired stroke survivors: a pilot randomized controlled trial to explore its feasibility and efficacy.

    Science.gov (United States)

    Wang, Zun; Wang, Lei; Fan, Hongjuan; Jiang, Wenjun; Wang, Sheng; Gu, Zhaohua; Wang, Tong

    2014-09-01

    [Purpose] To evaluate the feasibility and efficacy of adapted low intensity ergometer aerobic training for early and severely impaired stroke survivors. [Subjects] The subjects were forty-eight early stroke survivors. [Methods] Eligible subjects were recruited and randomly assigned to an experimental group and a control group. Both groups participated in comprehensive rehabilitation training. Low intensity aerobic training was only performed by the experimental group. Outcome measures were the Fugl-Meyer motor score, Barthel index, exercise test time, peak heart rate, plasma glucose level and serum lipid profiles. [Results] Patients in the experimental group finished 88.6% of the total aerobic training sessions prescribed. In compliant participants (adherence≥80%), aerobic training significantly improved the Barthel index (from 40.1±21.1 to 79.2±14.2), Fugl-Meyer motor score (from 26.4±19.4 to 45.4±12.7), exercise test time (from 12.2±3.62 min to 13.9±3.6 min), 2-hour glucose level (from 9.22±1.16 mmol/L to 7.21±1.36 mmol/L) and homeostasis model of assessment for insulin resistence index (from 1.72±1.01 to 1.28±0.88). [Conclusion] Preliminary findings suggest that early and severely impaired stroke patients may benefit from low intensity ergometer aerobic training.

  7. Tong Luo Jiu Nao ameliorates Aβ1-40-induced cognitive impairment on adaptive behavior learning by modulating ERK/CaMKII/CREB signaling in the hippocampus.

    Science.gov (United States)

    Shi, Zhe; Lu, Cong; Sun, Xiuping; Wang, Qiong; Chen, Shanguang; Li, Yinghui; Qu, Lina; Chen, Lingling; Bu, Lanlan; Liao, Duanfang; Liu, Xinmin

    2015-03-11

    Tong Luo Jiu Nao (TLJN), a modern formula of Chinese medicine extracts on the basis of Traditional Chinese Medicine theory, has been used to treat dementia. The present study aimed to investigate its ameliorating effects on Aβ1-40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning (RDIL) tasks, and to determine its possible mechanism of action. Rats were pretreated with TLJN extract (0.9 and 1.8 g/kg, p.o.) for 10 daysbefore surgery, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aβ1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of biochemical parameters and molecules. Our findings first demonstrated that TLJN can improve Aβ1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should attribute to the modulation of ERK/CaMKII/CREB signaling in the hippocampus. TLJN can markedly enhance cognitions of Aβ1-40 microinjection animal model in adaptive behavioral tasks. It has the potential, possibly as complementary and alternative therapy, to prevent and/or delay the deterioration of cognitive impairment in AD.

  8. Nitric oxide and TNFα are critical regulators of reversible lymph node vascular remodeling and adaptive immune response.

    Directory of Open Access Journals (Sweden)

    Stephanie L Sellers

    Full Text Available Lymph node (LN vascular growth, at the level of the main arteriole, was recently characterized for the first time during infection. Arteriole diameter was shown to increase for at least seven days and to occur via a CD4(+ T cell dependent mechanism, with vascular expansion playing a critical role in regulating induction of adaptive immune response. Here, using intravital microscopy of the inguinal LN during herpes simplex type II (HSV-2 infection, the data provides the first studies that demonstrate arteriole expansion during infection is a reversible vascular event that occurs via eutrophic outward remodeling. Furthermore, using genetic ablation models, and pharmacological blockade, we reveal arteriole remodeling and LN hypertrophy to be dependent upon both endothelial nitric oxide synthase (eNOS and TNFα expression. Additionally, we reveal transient changes in nitric oxide (NO levels to be a notable feature of response to viral infection and LN vascular remodeling and provide evidence that mast cells are the critical source of TNFα required to drive arteriole remodeling. Overall, this study is the first to fully characterize LN arteriole vascular changes throughout the course of infection. It effectively reveals a novel role for NO and TNFα in LN cellularity and changes in LN vascularity, which represent key advances in understanding LN vascular physiology and adaptive immune response.

  9. Mitochondrial targeting of bilirubin regulatory enzymes: An adaptive response to oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Muhsain, Siti Nur Fadzilah, E-mail: sitinurfadzilah077@ppinang.uitm.edu.my [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Faculty of Pharmacy, University Teknologi Mara (Malaysia); Lang, Matti A., E-mail: m.lang@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia); Abu-Bakar, A' edah, E-mail: a.abubakar@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 4072 Brisbane, Queensland (Australia)

    2015-01-01

    The intracellular level of bilirubin (BR), an endogenous antioxidant that is cytotoxic at high concentrations, is tightly controlled within the optimal therapeutic range. We have recently described a concerted intracellular BR regulation by two microsomal enzymes: heme oxygenase 1 (HMOX1), essential for BR production and cytochrome P450 2A5 (CYP2A5), a BR oxidase. Herein, we describe targeting of these enzymes to hepatic mitochondria during oxidative stress. The kinetics of microsomal and mitochondrial BR oxidation were compared. Treatment of DBA/2J mice with 200 mg pyrazole/kg/day for 3 days increased hepatic intracellular protein carbonyl content and induced nucleo-translocation of Nrf2. HMOX1 and CYP2A5 proteins and activities were elevated in microsomes and mitoplasts but not the UGT1A1, a catalyst of BR glucuronidation. A CYP2A5 antibody inhibited 75% of microsomal BR oxidation. The inhibition was absent in control mitoplasts but elevated to 50% after treatment. An adrenodoxin reductase antibody did not inhibit microsomal BR oxidation but inhibited 50% of mitochondrial BR oxidation. Ascorbic acid inhibited 5% and 22% of the reaction in control and treated microsomes, respectively. In control mitoplasts the inhibition was 100%, which was reduced to 50% after treatment. Bilirubin affinity to mitochondrial and microsomal CYP2A5 enzyme is equally high. Lastly, the treatment neither released cytochrome c into cytoplasm nor dissipated membrane potential, indicating the absence of mitochondrial membrane damage. Collectively, the observations suggest that BR regulatory enzymes are recruited to mitochondria during oxidative stress and BR oxidation by mitochondrial CYP2A5 is supported by mitochondrial mono-oxygenase system. The induced recruitment potentially confers membrane protection. - Highlights: • Pyrazole induces oxidative stress in the mouse liver. • Pyrazole-induced oxidative stress induces mitochondrial targeting of key bilirubin regulatory enzymes, HMOX1

  10. Impairment of nitric oxide synthase but not heme oxygenase accounts for baroreflex dysfunction caused by chronic nicotine in female rats.

    Directory of Open Access Journals (Sweden)

    Mohamed A Fouda

    Full Text Available We recently reported that chronic nicotine impairs reflex chronotropic activity in female rats. Here, we sought evidence to implicate nitric oxide synthase (NOS and/or heme oxygenase (HO in the nicotine-baroreflex interaction. Baroreflex curves relating changes in heart rate to increases (phenylephrine or decreases (sodium nitroprusside in blood pressure were generated in conscious female rats treated with nicotine or saline in absence and presence of pharmacological modulators of NOS or HO activity. Compared with saline-treated rats, nicotine (2 mg/kg/day i.p., for 14 days significantly reduced the slopes of baroreflex curves, a measure of baroreflex sensitivity (BRS. Findings that favor the involvement of NOS inhibition in the nicotine effect were (i NOS inhibition (Nω-Nitro-L-arginine methyl ester, L-NAME reduced BRS in control rats but failed to do so in nicotine-treated rats, (ii L-arginine, NO donor, reversed the BRS inhibitory effect of nicotine. Alternatively, HO inhibition (zinc protoporphyrin IX, ZnPP had no effect on BRS in nicotine- or control rats and failed to reverse the beneficial effect of L-arginine on nicotine-BRS interaction. Similar to female rats, BRS was reduced by L-NAME, but not ZnPP, in male rats and the L-NAME effect was not accentuated after concomitant administration of nicotine. Baroreflex dysfunction caused by nicotine in female rats was blunted after supplementation with hemin (HO inducer but not tricarbonyldichlororuthenium(II dimer (CORM-2, a carbon monoxide (CO releasing molecule, or bilirubin, the breakdown product of heme catabolism. The facilitatory effect of hemin was abolished upon simultaneous treatment with L-NAME or 1H-[1], [2], [4] oxadiazolo[4,3-a] quinoxalin-1-one (inhibitor of soluble guanylate cyclase, sGC. The activities of HO and NOS in brainstem tissues were also significantly increased by hemin. Thus, the inhibition of NOS, but not HO, accounts for the baroreflex depressant of chronic nicotine

  11. The total triterpenoid saponins of Xanthoceras sorbifolia improve learning and memory impairments through against oxidative stress and synaptic damage.

    Science.gov (United States)

    Ji, Xue-Fei; Chi, Tian-Yan; Liu, Peng; Li, Lu-Yi; Xu, Ji-Kai; Xu, Qian; Zou, Li-Bo; Meng, Da-Li

    2017-02-15

    could significantly improve the impairments of learning and memory. The preliminary mechanism might associate with its protection effects against oxidative stress damage, cholinergic system deficiency and synaptic damage. TSX are perfectly suitable for AD patients as medicine or functional food, which would be a new candidate to treat AD. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Cross-cultural adaptation and validation of a Brazilian version of an instrument to assess impairments related to oral functioning of people with Down syndrome.

    Science.gov (United States)

    Bonanato, Karina; Pordeus, Isabela A; Compart, Thiago; Oliveira, Ana Cristina; Allison, Paul J; Paiva, Saul M

    2013-01-11

    An instrument was developed in Canada to assess impairments related to oral functioning of individuals with four years of age or older with Down syndrome (DS). The present study attempted to carry out the cross-cultural adaptation and validation of the instrument for the Brazilian Portuguese language and to test its reliability and validity. After translation and cross-cultural adaptation, the instrument was tested on caregivers of people with DS. Clinical examination for malocclusion was carried out in people with DS by two calibrated examiners. Inter and Intra examiner agreement was assessed by Intraclass Correlation Coefficient (ICC) and ranged from 0.92 to 0.97 respectively. Total of 157 people with DS and their caregivers were able to compose the sample. They were selected from eight institutions for people with DS in five cities of southeastern Brazil. The mean age of people with DS was 20.7 [±13.1] and for caregivers was 53.1 [±13.7]. The mean instrument score was 18.6 [±9.0]. Internal reliability ranged from 0.49 to 0.80 and external reliability ranged from 0.78 to 0.88. Construct validity was verified by significant correlations identified between malocclusion and the total instrument; and caregivers' educational level and the instrument (ppeople with DS and non-DS (ppeople with DS may be a valid instrument to this segment of the population in Brazil.

  13. The impact of visual and nonvisual factors on quality of life and adaptation in adults with visual impairment.

    Science.gov (United States)

    Hernandez Trillo, Ana; Dickinson, Christine M

    2012-06-28

    Quality of life (QoL) questionnaires have been suggested as the most appropriate way to measure the effectiveness of low vision rehabilitation. This study investigated the relative contribution of visual and psychosocial factors to different aspects of QoL in people with low vision. A total of 448 consecutive patients between the ages of 18 and 96 years, with best-corrected binocular visual acuity≤6/18 and attending a low vision clinic, were recruited. Telephone delivery of previously validated questionnaires was used. The Low Vision Quality of Life (LVQOL), the Adaptation to Age-Related Vision Loss (AVL)-12, and the Keele Participation Restriction Questionnaire (KAP) questionnaires were considered as outcome measures for functional vision, adaptation to vision loss, and participation restriction, respectively. Personality (BFI-10), religious beliefs (SBI-15), social support (MOS), the mental and physical components of general health (the MCS and PCS of SF-12), well-being (WHO-5), use of magnifiers (MLVQ), understanding of their eye condition and satisfaction with the eye clinic (MLVQ), level of education, and financial status were all considered as predictive of QoL. Regression analysis found the PCS and MCS from SF-12 to be major predictors of LVQOL, AVL-12, and KAP scores. Although distance visual acuity and contrast sensitivity were predictors of LVQOL scores, "use of magnifiers" did not contribute to any of the QoL measures. Nonvisual factors, such as physical and mental health, were found to be stronger predictors of QoL in people with low vision than visual factors such as contrast sensitivity and visual acuity, or the use of magnifiers. Researchers need to be aware when measuring QoL in a population with low vision that even vision-related QoL is strongly influenced by nonvisual variables.

  14. Gigaspora margarita with and without its endobacterium shows adaptive responses to oxidative stress.

    Science.gov (United States)

    Venice, Francesco; de Pinto, Maria Concetta; Novero, Mara; Ghignone, Stefano; Salvioli, Alessandra; Bonfante, Paola

    2017-11-01

    Arbuscular mycorrhizal (AM) fungi experience oxidative stress during the plant-fungal interaction, due to endogenous reactive oxygen species (ROS) produced by fungal metabolism and exogenous ROS produced by plant cells. Here, we examine the responses to H 2 O 2 in Gigaspora margarita, an AM fungus containing the endobacterial symbiont Candidatus Glomeribacter gigasporarum (CaGg). Previous studies revealed that G. margarita with its endobacterium produces more ATP and has higher respiratory activity than a cured line that lacks the endobacterium. This higher bioenergetic potential leads to higher production of ROS and to a higher ROS-detoxifying capacity, suggesting a direct or indirect role of the endobacterium in modulating fungal antioxidant responses. To test the hypothesis that the fungal-endobacterial symbiosis may enhance the fitness of the AM fungus in the presence of oxidative stress, we treated the fungus with a sublethal concentration of H 2 O 2 and performed RNA-seq analysis. Our results demonstrate that (i) irrespective of the endobacterium presence, G. margarita faces oxidative stress by activating multiple metabolic processes (methionine oxidation, sulfur uptake, the pentose phosphate pathway, activation of ROS-scavenger genes); (ii) in the presence of its endobacterium, G. margarita upregulates some metabolic pathways, like chromatin status modifications and iron metabolism; and (iii) contrary to our hypothesis, the cured line responds to H 2 O 2 by activating the transcription of specific ROS scavengers. We confirmed the RNA-seq findings by measuring the glutathione and ascorbate concentration, which was the same in both lines after H 2 O 2 treatment. We conclude that both fungal lines may face oxidative stress, but they activate alternative strategies.

  15. Impairment by hypoxia or hypoxia/reoxygenation of nitric oxide-mediated relaxation in isolated monkey coronary artery: the role of intracellular superoxide.

    Science.gov (United States)

    Tawa, Masashi; Yamamizu, Kohei; Geddawy, Ayman; Shimosato, Takashi; Imamura, Takeshi; Ayajiki, Kazuhide; Okamura, Tomio

    2011-01-01

    To investigate the effect of hypoxia or hypoxia/reoxygenation on vascular smooth muscle function, mechanical response of monkey coronary artery without endothelium was studied under normoxia, hypoxia, and hypoxia/reoxygenation. Hypoxia or hypoxia/reoxygenation impaired the relaxation by nitroglycerin or isosorbide dinitrate but not that by 8-bromoguanosine-3',5'-cyclic monophosphate or isoproterenol. Tempol restored the impaired relaxation by nitroglycerin or isosorbide dinitrate, but superoxide dismutase had no effect. Apocynin, an NADPH oxidase inhibitor, improved the nitroglycerin-induced relaxation under hypoxia, but not under reoxygenation. Under combined treatment of apocynin with oxypurinol (xanthine oxidase inhibitor), rotenone (mitochondria electron transport inhibitor), or both, hypoxic impairment of vasorelaxation was restored more effectively. Similarly, impairment of the nitroglycerin-induced vasorelaxation under hypoxia/reoxygenation was restored by combined treatment with three inhibitors, apocynin, oxypurinol, and rotenone. Increase in superoxide production under hypoxia tended to be inhibited by apocynin and that under hypoxia/reoxygenation was abolished by combined treatment with three inhibitors. These findings suggest that increased intracellular superoxide production under hypoxia or hypoxia/reoxygenation attenuates vasodilation mediated with a nitric oxide/soluble guanylyl cyclase, but not adenylyl cyclase, signaling pathway. The main source of superoxide production under hypoxia seems to be different from that under reoxygenation: superoxide is produced by NADPH oxidase during hypoxia, whereas it is produced by xanthine oxidase, mitochondria, or both during reoxygenation.[Supplementary Figure: available only at http://dx.doi.org/10.1254/jphs.11031FP].

  16. Omega-3 polyunsaturated fatty acids in large doses attenuate seizures, cognitive impairment, and hippocampal oxidative DNA damage in young kindled rats.

    Science.gov (United States)

    Abdel-Wahab, Basel A; Al-Qahtani, Jobran M; El-Safty, Samy A

    2015-01-01

    Omega-3 (OM3) dietary polyunsaturated fatty acids have promising seizure-protective effects, as well as enhancing effects of cognitive development and memory-related learning. This study aimed to explore the effect of large doses of OM3 on cognitive impairment and hippocampal oxidative DNA damage produced by seizures in epileptic children using a PTZ-kindled young rat model. Cognitive functions, biomarkers of oxidative stress, and DNA damage were assessed in PTZ-kindled young rats (30 mg/kg, i.p. once every other day for 13 injections) pretreated with OM3 (200-500 mg/kg, p.o.). Pretreatment with OM3 at the tested doses significantly attenuated PTZ-induced seizures and decreased cognitive impairment in both passive avoidance and elevated plus maze tests in the PTZ-kindled rats. Moreover, OM3 significantly attenuated the increase in hippocampal malondialdehyde and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, as well as the decrease in reduced glutathione (GSH) levels and GSH-peroxidase activity induced by PTZ kindling, in a dose-related manner. Relatively large dose levels of OM3 (200-500 mg/kg) effectively attenuated seizures and their associated cognitive deficits, and reduced oxidative stress and hippocampal DNA damage in PTZ-kindled young rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Cardiac Stim1 Silencing Impairs Adaptive Hypertrophy and Promotes Heart Failure Through Inactivation of mTORC2/Akt Signaling.

    Science.gov (United States)

    Bénard, Ludovic; Oh, Jae Gyun; Cacheux, Marine; Lee, Ahyoung; Nonnenmacher, Mathieu; Matasic, Daniel S; Kohlbrenner, Erik; Kho, Changwon; Pavoine, Catherine; Hajjar, Roger J; Hulot, Jean-Sébastien

    2016-04-12

    Stromal interaction molecule 1 (STIM1) is a dynamic calcium signal transducer implicated in hypertrophic growth of cardiomyocytes. STIM1 is thought to act as an initiator of cardiac hypertrophic response at the level of the sarcolemma, but the pathways underpinning this effect have not been examined. To determine the mechanistic role of STIM1 in cardiac hypertrophy and during the transition to heart failure, we manipulated STIM1 expression in mice cardiomyocytes by using in vivo gene delivery of specific short hairpin RNAs. In 3 different models, we found that Stim1 silencing prevents the development of pressure overload-induced hypertrophy but also reverses preestablished cardiac hypertrophy. Reduction in STIM1 expression promoted a rapid transition to heart failure. We further showed that Stim1 silencing resulted in enhanced activity of the antihypertrophic and proapoptotic GSK-3β molecule. Pharmacological inhibition of glycogen synthase kinase-3 was sufficient to reverse the cardiac phenotype observed after Stim1 silencing. At the level of ventricular myocytes, Stim1 silencing or inhibition abrogated the capacity for phosphorylation of Akt(S473), a hydrophobic motif of Akt that is directly phosphorylated by mTOR complex 2. We found that Stim1 silencing directly impaired mTOR complex 2 kinase activity, which was supported by a direct interaction between STIM1 and Rictor, a specific component of mTOR complex 2. These data support a model whereby STIM1 is critical to deactivate a key negative regulator of cardiac hypertrophy. In cardiomyocytes, STIM1 acts by tuning Akt kinase activity through activation of mTOR complex 2, which further results in repression of GSK-3β activity. © 2016 American Heart Association, Inc.

  18. Copper-induced adaptation, oxidative stress and its tolerance in Aspergillus niger UCP1261

    Directory of Open Access Journals (Sweden)

    Marcos A. Cavalcanti Luna

    2015-11-01

    Conclusions: The results indicate that the isolate was able to grow in high concentrations of copper, activates mechanisms for adaptation and tolerance in the presence of metal, and is highly efficient at removing the agent. Such data are fundamental if a better understanding is to be reached of the cellular and molecular abilities of native isolates, which can be used to develop bioprocesses in environmental and industrial areas.

  19. A Bacterial Receptor PcrK Senses the Plant Hormone Cytokinin to Promote Adaptation to Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Fang-Fang Wang

    2017-12-01

    Full Text Available Summary: Recognition of the host plant is a prerequisite for infection by pathogenic bacteria. However, how bacterial cells sense plant-derived stimuli, especially chemicals that function in regulating plant development, remains completely unknown. Here, we have identified a membrane-bound histidine kinase of the phytopathogenic bacterium Xanthomonas campestris, PcrK, as a bacterial receptor that specifically detects the plant cytokinin 2-isopentenyladenine (2iP. 2iP binds to the extracytoplasmic region of PcrK to decrease its autokinase activity. Through a four-step phosphorelay, 2iP stimulation decreased the phosphorylation level of PcrR, the cognate response regulator of PcrK, to activate the phosphodiesterase activity of PcrR in degrading the second messenger 3′,5′-cyclic diguanylic acid. 2iP perception by the PcrK-PcrR remarkably improves bacterial tolerance to oxidative stress by regulating the transcription of 56 genes, including the virulence-associated TonB-dependent receptor gene ctrA. Our results reveal an evolutionarily conserved, inter-kingdom signaling by which phytopathogenic bacteria intercept a plant hormone signal to promote adaptation to oxidative stress. : How pathogenic bacteria use receptors to recognize the signals of the host plant is unknown. Wang et al. have identified a bacterial receptor histidine kinase that specifically senses the plant hormone cytokinin. Through a four-step phosphorelay, cytokinin perception triggers degradation of a second messenger, c-di-GMP, to activate the bacterial response to oxidative stress. Keywords: histidine kinase, ligand, cytokinin, autokinase activity, phosphorelay, response regulator, two-component signal transduction system, Xanthomonas campestris pv. campestris, virulence, oxidative stress

  20. Impaired Prefrontal Cortical Function and Disrupted Adaptive Cognitive Control in Methamphetamine Abusers: An fMRI Study

    Science.gov (United States)

    Salo, Ruth; Ursu, Stefan; Buonocore, Michael H.; Leamon, Martin H; Carter, Cameron

    2009-01-01

    Background Methamphetamine (MA) abuse is associated with neurotoxicity to frontostriatal brain regions with concomitant deleterious effects on cognitive processes. Deficits in behavioral control are thought to be one contributing factor to the sustainment of addictive behaviors in chronic MA abuse. Methods In order to examine patterns of behavioral control relevant to addiction, we employed a fast-event related fMRI design to examine trial to trial reaction time (RT) adjustments in 12 chronic MA abusers who met DSM-IV criteria for MA dependence and 16 non-substance abusing controls. A variant of the Stroop task was employed to contrast the groups on error rates, RT Stroop conflict effect and the level of trial-to-trial adjustments seen after incongruent trials. Results The MA abusers exhibited reduced RT adjustments along with reduced activation in the right prefrontal cortex compared to controls on conditions that measured the ability to use exposure to conflict situations (i.e., conflict trials) to regulate behavior. MA abusers did not differ from controls on accuracy rates or within-trial Stroop conflict effects. Conclusions The observed deficits in trial to trial RT adjustments suggest that the ability to adapt a behavioral response based on prior experience may be compromised in MA abusers. Such adjustments are critical to everyday functioning and deficits in modifying behavior based on prior events may reflect a key deficit that contributes to maladaptive drug seeking behavior. PMID:19136097

  1. Impaired quality of life in growth hormone-deficient adults is independent of the altered skeletal muscle oxidative metabolism found in conditions with peripheral fatigue.

    Science.gov (United States)

    Sinha, Akash; Hollingsworth, Kieren G; Ball, Steve; Cheetham, Tim

    2014-01-01

    Growth hormone-deficient (GHD) adults often report impaired quality of life (QoL) - with fatigue, a key element. This deficit can improve following GH replacement. The basis of this response is unclear. Perturbations in skeletal muscle metabolism have been demonstrated in several conditions in which fatigue is a prominent symptom. We wished to define the role of skeletal muscle metabolism in the impaired QoL observed in patients with GHD. To compare in vivo skeletal muscle mitochondrial oxidative phosphorylation using phosphorus-31 magnetic resonance spectroscopy in matched untreated GHD adults, treated GHD adults and healthy volunteers. Twenty-two untreated GHD adults, 23 treated GHD adults and 20 healthy volunteers were recruited at a regional centre. All patients underwent assessment of muscle mitochondrial function (τ₁/₂ PCr) and proton handling using spectroscopy. Fasting biochemical analyses and anthropometric measurement were obtained. All patients completed the QoL-AGHDA and physical activity assessment (IPAQ) questionnaires. Untreated and treated GHD adults complained of significantly increased fatigue and an impaired QoL (P = 0·002) when compared to healthy controls. There was no difference in maximal mitochondrial function (P = 0·53) nor pH recovery (P = 0·38) of skeletal muscle between the three groups. Untreated GHD patients had significantly lower IGF-1 than both treated GHD and healthy volunteers (P muscle spectroscopic 'footprint' of altered mitochondrial oxidative function, anaerobic glycolysis or proton clearance that are a feature of several conditions in which fatigue is a prominent feature. These data suggest that the pathophysiology of fatigue and impaired QoL in GHD may have a significant central rather than peripheral (skeletal muscle) component. © 2013 John Wiley & Sons Ltd.

  2. A conserved role for the 20S proteasome and Nrf2 transcription factor in oxidative stress adaptation in mammals, Caenorhabditis elegans and Drosophila melanogaster.

    Science.gov (United States)

    Pickering, Andrew M; Staab, Trisha A; Tower, John; Sieburth, Derek; Davies, Kelvin J A

    2013-02-15

    In mammalian cells, hydrogen peroxide (H(2)O(2))-induced adaptation to oxidative stress is strongly dependent on an Nrf2 transcription factor-mediated increase in the 20S proteasome. Here, we report that both Caenorhabditis elegans nematode worms and Drosophila melanogaster fruit flies are also capable of adapting to oxidative stress with H(2)O(2) pre-treatment. As in mammalian cells, this adaptive response in worms and flies involves an increase in proteolytic activity and increased expression of the 20S proteasome, but not of the 26S proteasome. We also found that the increase in 20S proteasome expression in both worms and flies, as in mammalian cells, is important for the adaptive response, and that it is mediated by the SKN-1 and CNC-C orthologs of the mammalian Nrf2 transcription factor, respectively. These studies demonstrate that stress mechanisms operative in cell culture also apply in disparate intact organisms across a wide biological diversity.

  3. Neuronal Nitric-Oxide Synthase Deficiency Impairs the Long-Term Memory of Olfactory Fear Learning and Increases Odor Generalization

    Science.gov (United States)

    Pavesi, Eloisa; Heldt, Scott A.; Fletcher, Max L.

    2013-01-01

    Experience-induced changes associated with odor learning are mediated by a number of signaling molecules, including nitric oxide (NO), which is predominantly synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current study, we investigated the role of nNOS in the acquisition and retention of conditioned olfactory fear. Mice…

  4. Impaired inflammatory response and increased oxidative stress and neurodegeneration after brain injury in interleukin-6-deficient mice

    DEFF Research Database (Denmark)

    Penkowa, M; Giralt, M; Carrasco, J

    2000-01-01

    of the antioxidants Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-SOD, and catalase remained unaffected by the IL-6 deficiency. The lesioned mice showed increased oxidative stress, as judged by malondialdehyde (MDA) and nitrotyrosine (NITT) levels and by formation of inducible nitric oxide synthase (iNOS). IL-6KO mice...

  5. Impaired very long-chain acyl-CoA β-oxidation in human X-linked adrenoleukodystrophy fibroblasts is a direct consequence of ABCD1 transporter dysfunction.

    Science.gov (United States)

    Wiesinger, Christoph; Kunze, Markus; Regelsberger, Günther; Forss-Petter, Sonja; Berger, Johannes

    2013-06-28

    X-linked adrenoleukodystrophy (X-ALD), an inherited peroxisomal disorder, is caused by mutations in the ABCD1 gene encoding the peroxisomal ATP-binding cassette (ABC) transporter ABCD1 (adrenoleukodystrophy protein, ALDP). Biochemically, X-ALD is characterized by an accumulation of very long-chain fatty acids and partially impaired peroxisomal β-oxidation. In this study, we used primary human fibroblasts from X-ALD and Zellweger syndrome patients to investigate the peroxisomal β-oxidation defect. Our results show that the degradation of C26:0-CoA esters is as severely impaired as degradation of unesterified very long-chain fatty acids in X-ALD and is abolished in Zellweger syndrome. Interestingly, the β-oxidation rates for both C26:0-CoA and C22:0-CoA were similarly affected, although C22:0 does not accumulate in patient fibroblasts. Furthermore, we show that the β-oxidation defect in X-ALD is directly caused by ABCD1 dysfunction as blocking ABCD1 function with a specific antibody reduced β-oxidation to levels observed in X-ALD fibroblasts. By quantification of mRNA and protein levels of the peroxisomal ABC transporters and by blocking with specific antibodies, we found that residual β-oxidation activity toward C26:0-CoA in X-ALD fibroblasts is mediated by ABCD3, although the efficacy of ABCD3 appeared to be much lower than that of ABCD1. Finally, using isolated peroxisomes, we show that β-oxidation of C26:0-CoA is independent of additional CoA but requires a cytosolic factor of >10-kDa molecular mass that is resistant to N-ethylmaleimide and heat inactivation. In conclusion, our findings in human cells suggest that, in contrast to yeast cells, very long-chain acyl-CoA esters are transported into peroxisomes by ABCD1 independently of additional synthetase activity.

  6. Impaired Very Long-chain Acyl-CoA β-Oxidation in Human X-linked Adrenoleukodystrophy Fibroblasts Is a Direct Consequence of ABCD1 Transporter Dysfunction*

    Science.gov (United States)

    Wiesinger, Christoph; Kunze, Markus; Regelsberger, Günther; Forss-Petter, Sonja; Berger, Johannes

    2013-01-01

    X-linked adrenoleukodystrophy (X-ALD), an inherited peroxisomal disorder, is caused by mutations in the ABCD1 gene encoding the peroxisomal ATP-binding cassette (ABC) transporter ABCD1 (adrenoleukodystrophy protein, ALDP). Biochemically, X-ALD is characterized by an accumulation of very long-chain fatty acids and partially impaired peroxisomal β-oxidation. In this study, we used primary human fibroblasts from X-ALD and Zellweger syndrome patients to investigate the peroxisomal β-oxidation defect. Our results show that the degradation of C26:0-CoA esters is as severely impaired as degradation of unesterified very long-chain fatty acids in X-ALD and is abolished in Zellweger syndrome. Interestingly, the β-oxidation rates for both C26:0-CoA and C22:0-CoA were similarly affected, although C22:0 does not accumulate in patient fibroblasts. Furthermore, we show that the β-oxidation defect in X-ALD is directly caused by ABCD1 dysfunction as blocking ABCD1 function with a specific antibody reduced β-oxidation to levels observed in X-ALD fibroblasts. By quantification of mRNA and protein levels of the peroxisomal ABC transporters and by blocking with specific antibodies, we found that residual β-oxidation activity toward C26:0-CoA in X-ALD fibroblasts is mediated by ABCD3, although the efficacy of ABCD3 appeared to be much lower than that of ABCD1. Finally, using isolated peroxisomes, we show that β-oxidation of C26:0-CoA is independent of additional CoA but requires a cytosolic factor of >10-kDa molecular mass that is resistant to N-ethylmaleimide and heat inactivation. In conclusion, our findings in human cells suggest that, in contrast to yeast cells, very long-chain acyl-CoA esters are transported into peroxisomes by ABCD1 independently of additional synthetase activity. PMID:23671276

  7. Impairment of Several Immune Functions and Redox State in Blood Cells of Alzheimer’s Disease Patients. Relevant Role of Neutrophils in Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Carmen Vida

    2018-01-01

    Full Text Available Since aging is considered the most risk factor for sporadic Alzheimer’s Disease (AD, the age-related impairment of the immune system (immunosenescence, based on a chronic oxidative-inflammatory stress situation, could play a key role in the development and progression of AD. Although AD is accompanied by systemic disturbance, reflecting the damage in the brain, the changes in immune response and redox-state in different types of blood cells in AD patients have been scarcely studied. The aim was to analyze the variations in several immune functions and oxidative-inflammatory stress and damage parameters in both isolated peripheral neutrophils and mononuclear blood cells, as well as in whole blood cells, from patients diagnosed with mild (mAD and severe AD, and of age-matched controls (elderly healthy subjects as well as of adult controls. The cognitive decline of all subjects was determined by Mini-Mental State Examination (MMSE test (mAD stage was established at 20 ≤ MMSE ≤ 23 score; AD stage at <18 MMSE; elderly subjects >27 MMSE. The results showed an impairment of the immune functions of human peripheral blood neutrophils and mononuclear cells of mAD and AD patients in relation to healthy elderly subjects, who showed the typical immunosenescence in comparison with the adult individuals. However, several alterations were only observed in severe AD patients (lower chemotaxis, lipopolysaccharide lymphoproliferation, and interleukin (IL-10 release; higher basal proliferation, tumor necrosis factor (TNF-α release, and IL-10/TNF-α ratio, others only in mAD subjects (higher adherence, meanwhile others appeared in both mAD and AD patients (lower phytohemaglutinin lymphoproliferation and higher IL-6 release. This impairment of immune functions could be mediated by: (1 the higher oxidative stress and damage also observed in blood cells from mAD and AD patients and in isolated neutrophils [lower glutathione (GSH levels, high oxidized

  8. Impairment of Several Immune Functions and Redox State in Blood Cells of Alzheimer’s Disease Patients. Relevant Role of Neutrophils in Oxidative Stress

    Science.gov (United States)

    Vida, Carmen; Martinez de Toda, Irene; Garrido, Antonio; Carro, Eva; Molina, José Antonio; De la Fuente, Mónica

    2018-01-01

    Since aging is considered the most risk factor for sporadic Alzheimer’s Disease (AD), the age-related impairment of the immune system (immunosenescence), based on a chronic oxidative-inflammatory stress situation, could play a key role in the development and progression of AD. Although AD is accompanied by systemic disturbance, reflecting the damage in the brain, the changes in immune response and redox-state in different types of blood cells in AD patients have been scarcely studied. The aim was to analyze the variations in several immune functions and oxidative-inflammatory stress and damage parameters in both isolated peripheral neutrophils and mononuclear blood cells, as well as in whole blood cells, from patients diagnosed with mild (mAD) and severe AD, and of age-matched controls (elderly healthy subjects) as well as of adult controls. The cognitive decline of all subjects was determined by Mini-Mental State Examination (MMSE) test (mAD stage was established at 20 ≤ MMSE ≤ 23 score; AD stage at 27 MMSE). The results showed an impairment of the immune functions of human peripheral blood neutrophils and mononuclear cells of mAD and AD patients in relation to healthy elderly subjects, who showed the typical immunosenescence in comparison with the adult individuals. However, several alterations were only observed in severe AD patients (lower chemotaxis, lipopolysaccharide lymphoproliferation, and interleukin (IL)-10 release; higher basal proliferation, tumor necrosis factor (TNF)-α release, and IL-10/TNF-α ratio), others only in mAD subjects (higher adherence), meanwhile others appeared in both mAD and AD patients (lower phytohemaglutinin lymphoproliferation and higher IL-6 release). This impairment of immune functions could be mediated by: (1) the higher oxidative stress and damage also observed in blood cells from mAD and AD patients and in isolated neutrophils [lower glutathione (GSH) levels, high oxidized glutathione (GSSG)/GSH ratio, and GSSG

  9. A low-voltage complementary metal-oxide semiconductor adapter circuit suitable for input rail-to-rail operation

    Science.gov (United States)

    Tadić, Nikša; Zogović, Milena; Banjević, Mirjana; Zimmermann, Horst

    2010-11-01

    In this article, a low-voltage complementary metal-oxide semiconductor (CMOS) input signal adapter (ISA) suitable for input rail-to-rail operation of various types of analogue basic building blocks is presented. The adapter acts as a pre-stage with infinite input resistance and linear transfer characteristics. Its input signal is translated into the region fitting the operating range of the following stage. The generality of the proposed method is proven through the application of the ISA in different types of analogue basic building blocks designed in 0.5 μm CMOS technology. They are the following: below-negative-rail-to-above-positive-rail voltage-controlled transconductor, quasi rail-to-rail voltage-controlled resistor (VCR), rail-to-rail operational amplifier (OA) and quasi rail-to-rail second generation current conveyor. The proposed negative resistance quasi rail-to-rail VCR and rail-to-rail OA have been used in a Sallen and Key band-pass filter. All of these analogue basic building blocks and their applications in the form of the Sallen and Key band-pass filter operate from a single supply of 1.5 V. Simulation results confirm the predictions of the analysis performed.

  10. Old age and the associated impairment of bones' adaptation to loading are associated with transcriptomic changes in cellular metabolism, cell-matrix interactions and the cell cycle.

    Science.gov (United States)

    Galea, Gabriel L; Meakin, Lee B; Harris, Marie A; Delisser, Peter J; Lanyon, Lance E; Harris, Stephen E; Price, Joanna S

    2017-01-30

    In old animals, bone's ability to adapt its mass and architecture to functional load-bearing requirements is diminished, resulting in bone loss characteristic of osteoporosis. Here we investigate transcriptomic changes associated with this impaired adaptive response. Young adult (19-week-old) and aged (19-month-old) female mice were subjected to unilateral axial tibial loading and their cortical shells harvested for microarray analysis between 1h and 24h following loading (36 mice per age group, 6 mice per loading group at 6 time points). In non-loaded aged bones, down-regulated genes are enriched for MAPK, Wnt and cell cycle components, including E2F1. E2F1 is the transcription factor most closely associated with genes down-regulated by ageing and is down-regulated at the protein level in osteocytes. Genes up-regulated in aged bone are enriched for carbohydrate metabolism, TNFα and TGFβ superfamily components. Loading stimulates rapid and sustained transcriptional responses in both age groups. However, genes related to proliferation are predominantly up-regulated in the young and down-regulated in the aged following loading, whereas those implicated in bioenergetics are down-regulated in the young and up-regulated in the aged. Networks of inter-related transcription factors regulated by E2F1 are loading-responsive in both age groups. Loading regulates genes involved in similar signalling cascades in both age groups, but these responses are more sustained in the young than aged. From this we conclude that cells in aged bone retain the capability to sense and transduce loading-related stimuli, but their ability to translate acute responses into functionally relevant outcomes is diminished. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Antisense directed against PS-1 gene decreases brain oxidative markers in aged senescence accelerated mice (SAMP8) and reverses learning and memory impairment: a proteomics study

    Science.gov (United States)

    Fiorini, Ada; Sultana, Rukhsana; Förster, Sarah; Perluigi, Marzia; Cenini, Giovanna; Cini, Chiara; Cai, Jian; Klein, Jon B.; Farr, Susan A.; Niehoff, Michael L.; Morley, John E.; Kumar, Vijaya B.; Butterfield, D. Allan

    2013-01-01

    Amyloid β-peptide (Aβ) plays a central role in pathophysiology of Alzheimer’s disease (AD) through the induction of oxidative stress. This peptide is produced by proteolytic cleavage of amyloid precursor protein (APP) by the action of β- and γ-secretases. Previous studies demonstrated that reduction of Aβ, using an antisense oligonucleotide (AO) directed against the Aβ region of APP, reduced oxidative stress-mediated damage and prevented or reverted cognitive deficits in senescence-accelerated prone mice (SAMP8), a useful animal model to investigate the events related to Aβ pathology and possibly to the early phase of AD. In the current study, aged SAMP8 were treated by AO directed against PS-1, a component of the γ-secretase complex, and tested for learning and memory in T-maze foot shock avoidance and novel object recognition. Brain tissue was collected to identify the decrease of oxidative stress and to evaluate the proteins that are differently expressed and oxidized after the reduction in free radical levels induced by Aβ. We used both expression proteomics and redox proteomics approaches. In brain of AO-treated mice a decrease of oxidative stress markers was found, and the proteins identified by proteomics as expressed differently or nitrated are involved in processes known to be impaired in AD. Our results suggest that the treatment with AO directed against PS-1 in old SAMP8 mice reverses learning and memory deficits and reduces Aβ-mediated oxidative stress with restoration to the normal condition and identifies possible pharmacological targets to combat this devastating dementing disease. PMID:23777706

  12. Stress-Adaptive Response in Ovarian Cancer Drug Resistance: Role of TRAP1 in Oxidative Metabolism-Driven Inflammation.

    Science.gov (United States)

    Amoroso, Maria Rosaria; Matassa, Danilo Swann; Agliarulo, Ilenia; Avolio, Rosario; Maddalena, Francesca; Condelli, Valentina; Landriscina, Matteo; Esposito, Franca

    2017-01-01

    Metabolic reprogramming is one of the most frequent stress-adaptive response of cancer cells to survive environmental changes and meet increasing nutrient requirements during their growth. These modifications involve cellular bioenergetics and cross talk with surrounding microenvironment, in a dynamic network that connect different molecular processes, such as energy production, inflammatory response, and drug resistance. Even though the Warburg effect has long been considered the main metabolic feature of cancer cells, recent reports identify mitochondrial oxidative metabolism as a driving force for tumor growth in an increasing number of cellular contexts. In recent years, oxidative phosphorylation has been linked to a remodeling of inflammatory response due to autocrine or paracrine secretion of interleukines that, in turn, induces a regulation of gene expression involving, among others, molecules responsible for the onset of drug resistance. This process is especially relevant in ovarian cancer, characterized by low survival, high frequency of disease relapse and chemoresistance. Recently, the molecular chaperone TRAP1 (tumor necrosis factor-associated protein 1) has been identified as a key junction molecule in these processes in ovarian cancer: in fact, TRAP1 mediates a metabolic switch toward oxidative phosphorylation that, in turn, triggers cytokines secretion, with consequent gene expression remodeling, finally leading to cisplatin resistance and epithelial-to-mesenchymal transition in ovarian cancer models. This review summarizes how metabolism, chemoresistance, inflammation, and epithelial-to-mesenchymal transition are strictly interconnected, and how TRAP1 stays at the crossroads of these processes, thus shedding new lights on molecular networks at the basis of ovarian cancer. © 2017 Elsevier Inc. All rights reserved.

  13. In vivo oxidative stress alters thiol redox status of peroxiredoxin 1 and 6 and impairs rat sperm quality

    Directory of Open Access Journals (Sweden)

    Yannan Liu

    2017-01-01

    Full Text Available Oxidative stress, the imbalance between the production of reactive oxygen species (ROS and antioxidant activity is a major culprit of male infertility. Peroxiredoxins (PRDXs are major antioxidant enzymes of mammalian spermatozoa and are thiol oxidized and inactivated by ROS in a dose-dependent manner. Their deficiency and/or inactivation have been associated with men infertility. The aim of this study was to elucidate the impact of oxidative stress, generated by the in vivo tert-butyl hydroperoxide (tert-BHP treatment on rat epididymal spermatozoa during their maturation process. Adult Sprague-Dawley males were treated with 300 μmoles tert-BHP/kg or saline (control per day intraperitoneal for 15 days. Lipid peroxidation (2-thibarbituric acid reactive substances assay, total amount and thiol oxidation of PRDXs along with the total amount of superoxide dismutase (SOD, motility and DNA oxidation (8-hydroxy-deoxyguanosine were determined in epididymal spermatozoa. Total amount of PRDXs and catalase and thiol oxidation of PRDXs were determined in caput and cauda epididymis. While animals were not affected by treatment, their epididymal spermatozoa have decreased motility, increased levels of DNA oxidation and lipid peroxidation along with increased PRDXs (and not SOD amounts. Moreover, sperm PRDXs were highly thiol oxidized. There was a differential regulation in the expression of PRDX1 and PRDX6 in the epididymis that suggests a segment-specific role for PRDXs. In conclusion, PRDXs are increased in epididymal spermatozoa in an attempt to fight against the oxidative stress generated by tert-BHP in the epididymis. These findings highlight the role of PRDXs in the protection of sperm function and DNA integrity during epididymal maturation.

  14. In vivo oxidative stress alters thiol redox status of peroxiredoxin 1 and 6 and impairs rat sperm quality

    Science.gov (United States)

    Liu, Yannan; O’Flaherty, Cristian

    2017-01-01

    Oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and antioxidant activity is a major culprit of male infertility. Peroxiredoxins (PRDXs) are major antioxidant enzymes of mammalian spermatozoa and are thiol oxidized and inactivated by ROS in a dose-dependent manner. Their deficiency and/or inactivation have been associated with men infertility. The aim of this study was to elucidate the impact of oxidative stress, generated by the in vivo tert-butyl hydroperoxide (tert-BHP) treatment on rat epididymal spermatozoa during their maturation process. Adult Sprague-Dawley males were treated with μmoles tert-BHP/kg or saline (control) per day intraperitoneal for 15 days. Lipid peroxidation (2-thibarbituric acid reactive substances assay), total amount and thiol oxidation of PRDXs along with the total amount of superoxide dismutase (SOD), motility and DNA oxidation (8-hydroxy-deoxyguanosine) were determined in epididymal spermatozoa. Total amount of PRDXs and catalase and thiol oxidation of PRDXs were determined in caput and cauda epididymis. While animals were not affected by treatment, their epididymal spermatozoa have decreased motility, increased levels of DNA oxidation and lipid peroxidation along with increased PRDXs (and not SOD) amounts. Moreover, sperm PRDXs were highly thiol oxidized. There was a differential regulation in the expression of PRDX1 and PRDX6 in the epididymis that suggests a segment-specific role for PRDXs. In conclusion, PRDXs are increased in epididymal spermatozoa in an attempt to fight against the oxidative stress generated by tert-BHP in the epididymis. These findings highlight the role of PRDXs in the protection of sperm function and DNA integrity during epididymal maturation. PMID:26823067

  15. Protective effect of caffeine and a selective A2A receptor antagonist on impairment of memory and oxidative stress of aged rats.

    Science.gov (United States)

    Leite, Marlon Régis; Wilhelm, Ethel A; Jesse, Cristiano R; Brandão, Ricardo; Nogueira, Cristina Wayne

    2011-04-01

    In this study, the effects of caffeine (CAF) and SCH58261, a selective A(2A) receptor antagonist, on memory impairment and oxidative stress generated by aging in rats were investigated. Young and aged rats were treated daily per 10 days with CAF (30 mg/kg p.o.) or SCH58261 (0.5mg/kg, p.o.) or vehicle (1 ml/kg p.o.). Rats were trained and tested in a novel object recognition task. After the behavioral test, ascorbic acid and oxygen and nitrogen reactive species levels as well as Na(+)K(+) ATPase activity were determined in rat brain. The results demonstrated that the age-related memory deficit was reversed by treatment with CAF or SCH58261. Treatment with CAF or SCH58261 significantly normalized oxygen and nitrogen reactive species levels increased in brains of aged rats. Na(+)K(+) ATPase activity inhibited in brains of aged rats was also normalized by CAF or SCH58261 treatment. A decrease in basal ascorbic acid levels in brains of aged rats was not changed by CAF or SCH58261. These results demonstrated that CAF and SCH58261, modulators of adenosinergic receptors, were able to reverse age-associated memory impairment and to partially reduce oxidative stress. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

    Directory of Open Access Journals (Sweden)

    Qi Wang

    Full Text Available BACKGROUND: To investigate if microRNAs (miRNAs play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. METHODS: We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+ current. RESULTS: H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2, with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. CONCLUSIONS: Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

  17. Low-Dose Ionizing Radiation Affects Mesenchymal Stem Cells via Extracellular Oxidized Cell-Free DNA: A Possible Mediator of Bystander Effect and Adaptive Response

    Directory of Open Access Journals (Sweden)

    V. A. Sergeeva

    2017-01-01

    Full Text Available We have hypothesized that the adaptive response to low doses of ionizing radiation (IR is mediated by oxidized cell-free DNA (cfDNA fragments. Here, we summarize our experimental evidence for this model. Studies involving measurements of ROS, expression of the NOX (superoxide radical production, induction of apoptosis and DNA double-strand breaks, antiapoptotic gene expression and cell cycle inhibition confirm this hypothesis. We have demonstrated that treatment of mesenchymal stem cells (MSCs with low doses of IR (10 cGy leads to cell death of part of cell population and release of oxidized cfDNA. cfDNA has the ability to penetrate into the cytoplasm of other cells. Oxidized cfDNA, like low doses of IR, induces oxidative stress, ROS production, ROS-induced oxidative modifications of nuclear DNA, DNA breaks, arrest of the cell cycle, activation of DNA reparation and antioxidant response, and inhibition of apoptosis. The MSCs pretreated with low dose of irradiation or oxidized cfDNA were equally effective in induction of adaptive response to challenge further dose of radiation. Our studies suggest that oxidized cfDNA is a signaling molecule in the stress signaling that mediates radiation-induced bystander effects and that it is an important component of the development of radioadaptive responses to low doses of IR.

  18. Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle

    OpenAIRE

    Malkus, Kristen A; Tsika, Elpida; Ischiropoulos, Harry

    2009-01-01

    Abstract While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with o...

  19. Anesthetic ketamine impairs rats' recall of previous information: the nitric oxide synthase inhibitor N-nitro-L-arginine methylester antagonizes this ketamine-induced recognition memory deficit.

    Science.gov (United States)

    Boultadakis, Antonios; Pitsikas, Nikolaos

    2011-06-01

    There is poor experimental evidence concerning the effects of anesthetic doses of the noncompetitive N-methyl-D-aspartate receptor antagonist ketamine on rodents' memory abilities. The current study was designed (1) to investigate the consequences of posttraining administration of anesthetic ketamine (100 mg/kg intraperitoneally) on rats' recognition memory and (2) to evaluate the ability of the nitric oxide synthase inhibitor N-nitro-L-arginine methylester (L-NAME; 1, 3, and 10 mg/kg intraperitoneally) to counteract the expected behavioral deficits produced by anesthetic ketamine. Finally, in an attempt to clarify if the expected memory impairments produced by anesthetic ketamine were related to the anesthesia, we also tested the effects of a subanesthetic dose of it (3 mg/kg intraperitoneally) on rats' recognition memory. The novel object recognition test, a procedure assessing recognition memory in rats, was selected. Posttraining administration of anesthetic (but not of subanesthetic) ketamine disrupted rats' performance in the novel object recognition paradigm. The discrimination index (D) was decreased by ketamine from 0.415 (using saline) to 0.128, thus indicating that the anesthetic dose of ketamine impaired recognition memory. L-NAME (1-3, but not 10, mg/kg) reversed this memory deficit produced by ketamine; the D index of 0.128 using ketamine treatment was increased by 1 and 3 mg/kg L-NAME to 0.427 and 0.478, respectively. The current results indicate that anesthetic ketamine impaired rats' posttraining memory components (storage and/or retrieval of information) and that a nitric oxide component modulates its behavioral effects.

  20. Protective effect of taurine against potassium bromate-induced hemoglobin oxidation, oxidative stress, and impairment of antioxidant defense system in blood.

    Science.gov (United States)

    Ahmad, Mir Kaisar; Mahmood, Riaz

    2016-03-01

    Potassium bromate (KBrO3 ) is widely used as a food-additive and is a major water disinfection by-product. KBrO3 causes severe toxicity in humans and experimental animals. Bromate is considered a probable human carcinogen and a complete carcinogen in animals. We have investigated the potential role of taurine in protecting against KBrO3 -induced oxidative stress in rat blood. Animals were given taurine for 5 days prior to KBrO3 and then sacrificed. Blood was collected and used to prepare hemolysates and plasma, which were then used for the analysis of several biochemical parameters. Administration of single oral dose of KBrO3 alone induced hepato- and nephro-toxicity as evident by elevated marker levels in plasma. Lipid peroxidation and protein oxidation were increased both in plasma and erythrocytes, suggesting the induction of oxidative stress. KBrO3 increased methemoglobin, nitric oxide, and hydrogen peroxide levels. It also altered the activities of the major antioxidant enzymes and lowered the antioxidant power of blood. Administration of taurine, prior to treatment with KBrO3 , resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. These results show that taurine is effective in mitigating the oxidative insult induced in rat blood by KBrO3 . © 2014 Wiley Periodicals, Inc.

  1. Maternal docosahexaenoic acid feeding protects against impairment of learning and memory and oxidative stress in prenatally stressed rats: possible role of neuronal mitochondria metabolism.

    Science.gov (United States)

    Feng, Zhihui; Zou, Xuan; Jia, Haiqun; Li, Xuesen; Zhu, Zhongliang; Liu, Xuebo; Bucheli, Peter; Ballevre, Olivier; Hou, Yangfeng; Zhang, Weiguo; Wang, Junkaun; Chen, Yan; Liu, Jiankang

    2012-02-01

    Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, no study has been performed to investigate its preventive effect on prenatal stress-induced behavioral and molecular alterations in offspring. In the present study, rats were exposed to restraint stress on days 14-20 of pregnancy, three times a day, 2 hours each time; DHA was given at the doses of 100 and 300 mg/kg/day for two weeks. We showed that prenatal restraint stress caused (1) learning and memory impairment, (2) BDNF mRNA level decrease, (3) oxidative damage to proteins, (4) enhanced expression of nitric oxide synthase and apoptosis, and (5) abnormalities in mitochondrial metabolism that included changes in mitochondrial complexes I-V, and enhancement of expression of proteins involved in mitochondrial fusion/fission (Mfn-1, Mfn-2, Drp-1) and autophagy (Atg3, Atg7, Beclin-1, p-Akt, and p-mTOR) in the hippocampus of offspring. Besides the well-known role in child brain development, we reported the novel finding of DHA in protecting prenatal stress-induced cognitive dysfunction involving the modulation of mitochondrial function and dynamics. Maternal feeding of DHA significantly prevented prenatal stress-induced impairment of learning and memory and normalized the biomarkers of oxidative damage, apoptosis, and mitochondrial metabolism in the hippocampus of both male and female offspring. These results suggest that maternal feeding of DHA exerts preventive effects on prenatal stress-induced brain dysfunction and that modulation of mitochondrial metabolism may play critical role in DHA protection.

  2. Chronic nitric oxide deprivation induces an adaptive antioxidant status in human endothelial cells.

    Science.gov (United States)

    Cattaneo, Maria Grazia; Cappellini, Elisa; Ragni, Maurizio; Tacchini, Lorenza; Scaccabarozzi, Diletta; Nisoli, Enzo; Vicentini, Lucia Maria

    2013-11-01

    In a previous work, we showed an increased cell motility due to the accumulation and transcriptional activation of the Hypoxia Inducible Factor-1α (HIF-1α) and a reduced mitochondrial energy production in an in vitro model of endothelial dysfunction (ED) represented by human endothelial cells (ECs) chronically deprived of nitric oxide (NO) by L-NAME treatment. In the present study, in the attempt to unravel the pathway(s) linking NO deficiency to HIF-1α accumulation and activation, we focused our attention on Reactive Oxygen Species (ROS). We found that ROS were partially involved in HIF-1α stabilization, but not in the pro-migratory phenotype. Regarding mitochondrial dysfunction, it did not require neither ROS generation nor HIF-1α activity, and was not due to autophagy. Very interestingly, while acute treatment with L-NAME induced a transient increase in ROS formation, chronic NO deprivation by long term L-NAME exposure drastically reduced cellular ROS content giving rise to an antioxidant environment characterized by an increase in superoxide dismutase-2 (SOD-2) expression and activity, and by nuclear accumulation of the transcription factor NF-E2-related factor-2 (Nrf2). These results might have important implications for our understanding of the consequences of NO deprivation in endothelium behavior and in the onset of cardiovascular diseases. © 2013.

  3. Persisting in papyrus: size, oxidative stress, and fitness in freshwater organisms adapted to sustained hypoxia.

    Science.gov (United States)

    Joyner-Matos, Joanna; Chapman, Lauren J

    2013-08-01

    Aquatic hypoxia is generally viewed as stressful for aerobic organisms. However, hypoxia may also benefit organisms by decreasing cellular stress, particularly that related to free radicals. Thus, an ideal habitat may have the minimum O2 necessary to both sustain aerobic metabolism and reduce the need to scavenge free radicals and repair free radical damage. The ability of aquatic organisms to sustain aerobic metabolism relates in part to the ability to maximize gas diffusion, which can be facilitated by small body size when O2 uptake occurs across the body surface, by a large gill surface area, or by the ability to use atmospheric air. We use water-breathing organisms in chronically hypoxic papyrus (Cyperus papyrus) swamps of East Africa to test the hypothesis that cellular-level benefits of hypoxia may translate into increased fitness, especially for small organisms. A review of recent studies of fingernail clams (Sphaerium sp.) shows that clams living in sustained hypoxia have minimized oxidative stress and that these cellular-level benefits may lead to increased fitness. We suggest that organisms in the extreme conditions in the papyrus swamps provide a unique opportunity to challenge the conventional classification of hypoxic habitats as 'stressful' and normoxic habitats as 'optimal.' Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Vascular aging: chronic oxidative stress and impairment of redox signaling-consequences for vascular homeostasis and disease.

    Science.gov (United States)

    Bachschmid, Markus M; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A; Pimental, David; Loo, Bernd van der

    2013-02-01

    Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the 'free radical theory of aging' but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis.

  5. Increased Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Anna Lados-Krupa

    2015-01-01

    Full Text Available Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes. Methods. We assessed plasma fibrin clot permeation (Ks, a measure of the pore size in fibrin networks and clot lysis time induced by recombinant tissue plasminogen activator (CLT in 163 consecutive type 2 diabetic patients (92 men and 71 women aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE, 8-iso-prostaglandin F2α (8-iso-PGF2α, oxidized low-density lipoprotein (oxLDL, and advanced glycation end products (AGE. Results. There were inverse correlations between Ks and nitrotyrosine, sRAGE, 8-iso-PGF2α, and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant for Ks after adjustment for fibrinogen, disease duration, and HbA1c (all P<0.05, while oxLDL was the only independent predictor of CLT. Conclusions. Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control.

  6. Distinct transthyretin oxidation isoform profile in spinal fluid from patients with Alzheimer’s disease and mild cognitive impairment

    DEFF Research Database (Denmark)

    Poulsen, Keld; Bahl, Justyna Mc; Simonsen, Anja H

    2014-01-01

    such as Alzheimer's disease (AD) it is of interest to characterize CSF-TTR isoform distribution in AD patients and controls. Here, TTR isoforms are profiled directly from CSF by an optimized immunoaffinity-mass spectrometry method in 76 samples from patients with AD (n = 37), mild cognitive impairment (MCI, n = 17....... In addition to the diagnostic information the possibility of using TTR as a CSF oxymeter is of potential value in studies monitoring disease activity and developing new drugs for neurodegenerative diseases....

  7. Adaptive cytoprotection through modulation of nitric oxide in ethanol-evoked gastritis.

    Science.gov (United States)

    Ko, Joshua Ka-Shun; Cho, Chi-Hin; Lam, Shiu-Kum

    2004-09-01

    To assess the mechanisms of protective action by different mild irritants through maintenance of gastric mucosal integrity and modulation of mucosal nitric oxide (NO) in experimental gastritis rats. Either 200 mL/L ethanol, 50 g/L NaCl or 0.3 mol/L HCl was pretreated to normal or 800 mL/L ethanol-induced acute gastritis Sprague-Dawley rats before a subsequent challenge with 500 mL/L ethanol. Both macroscopic lesion areas and histological damage scores were determined in the gastric mucosa of each group of animals. Besides, gastric mucosal activities of NO synthase isoforms and of superoxide dismutase, along with mucosal level of leukotriene (LT)C4 were measured. Macroscopic mucosal damages were protected by 200 mL/L ethanol and 50 g/L NaCl in gastritis rats. However, although 200 mL/L ethanol could protect the surface layers of mucosal cells in normal animals (protection attenuated by NG-nitro-L-arginine methyl ester), no cytoprotection against deeper histological damages was found in gastritis rats. Besides, inducible NO synthase activity was increased in the mucosa of gastritis animals and unaltered by mild irritants. Nevertheless, the elevation in mucosal LTC4 level following 500 mL/L ethanol administration and under gastritis condition was significantly reduced by pretreatment of all three mild irritants in both normal and gastritis animals. These findings suggest that the aggravated 500 mL/L ethanol-evoked mucosal damages under gastritis condition could be due to increased inducible NO and LTC4 production in the gastric mucosa. Only 200 mL/L ethanol is truly "cytoprotective" at the surface glandular level of non-gastritis mucosa. Furthermore, the macroscopic protection of the three mild irritants involves reduction of LTC4 level in both normal and gastritis mucosa, implicating preservation of the vasculature. Copyright 2004 The WJG Press ISSN

  8. Tiliacora triandra, an Anti-Intoxication Plant, Improves Memory Impairment, Neurodegeneration, Cholinergic Function, and Oxidative Stress in Hippocampus of Ethanol Dependence Rats

    Directory of Open Access Journals (Sweden)

    Nattaporn Phunchago

    2015-01-01

    Full Text Available Oxidative stress plays an important role in brain dysfunctions induced by alcohol. Since less therapeutic agent against cognitive deficit and brain damage induced by chronic alcohol consumption is less available, we aimed to assess the effect of Tiliacora triandra extract, a plant possessing antioxidant activity, on memory impairment, neuron density, cholinergic function, and oxidative stress in hippocampus of alcoholic rats. Male Wistar rats were induced ethanol dependence condition by semivoluntary intake of alcohol for 15 weeks. Alcoholic rats were orally given T. triandra at doses of 100, 200, and 400 mg·kg−1BW for 14 days. Memory assessment was performed every 7 days while neuron density, activities of AChE, SOD, CAT, and GSH-Px and, MDA level in hippocampus were assessed at the end of study. Interestingly, the extract mitigated the increased escape latency, AChE and MDA level. The extract also mitigated the decreased retention time, SOD, CAT, and GSH-Px activities, and neurons density in hippocampus induced by alcohol. These data suggested that the extract improved memory deficit in alcoholic rats partly via the decreased oxidative stress and the suppression of AChE. Therefore, T. triandra is the potential reagent for treating brain dysfunction induced by alcohol. However, further researches are necessary to understand the detail mechanism and possible active ingredient.

  9. Tiliacora triandra, an Anti-Intoxication Plant, Improves Memory Impairment, Neurodegeneration, Cholinergic Function, and Oxidative Stress in Hippocampus of Ethanol Dependence Rats.

    Science.gov (United States)

    Phunchago, Nattaporn; Wattanathorn, Jintanaporn; Chaisiwamongkol, Kowit

    2015-01-01

    Oxidative stress plays an important role in brain dysfunctions induced by alcohol. Since less therapeutic agent against cognitive deficit and brain damage induced by chronic alcohol consumption is less available, we aimed to assess the effect of Tiliacora triandra extract, a plant possessing antioxidant activity, on memory impairment, neuron density, cholinergic function, and oxidative stress in hippocampus of alcoholic rats. Male Wistar rats were induced ethanol dependence condition by semivoluntary intake of alcohol for 15 weeks. Alcoholic rats were orally given T. triandra at doses of 100, 200, and 400 mg·kg(-1)BW for 14 days. Memory assessment was performed every 7 days while neuron density, activities of AChE, SOD, CAT, and GSH-Px and, MDA level in hippocampus were assessed at the end of study. Interestingly, the extract mitigated the increased escape latency, AChE and MDA level. The extract also mitigated the decreased retention time, SOD, CAT, and GSH-Px activities, and neurons density in hippocampus induced by alcohol. These data suggested that the extract improved memory deficit in alcoholic rats partly via the decreased oxidative stress and the suppression of AChE. Therefore, T. triandra is the potential reagent for treating brain dysfunction induced by alcohol. However, further researches are necessary to understand the detail mechanism and possible active ingredient.

  10. Curcumin Reverses the Diazepam-Induced Cognitive Impairment by Modulation of Oxidative Stress and ERK 1/2/NF-κB Pathway in Brain

    Directory of Open Access Journals (Sweden)

    Alexandra C. Sevastre-Berghian

    2017-01-01

    Full Text Available Oxidative stress and inflammation can be involved in cognitive dysfunction associated with neurodegenerative disorders. Diazepam (DZP administration has been chosen to simulate the memory impairment. The aim of this study was to evaluate the effects of curcumin (CUR on spatial cognition, ambulatory activity, and blood and brain oxidative stress levels. The ERK/NF-κB signaling pathway and the histopathological changes in the hippocampus and frontal lobe, in diazepam-treated rats, were also analyzed. The animals were divided into 4 groups: control, carboxymethylcellulose (CMC + CUR, CMC + DZP, and CUR + CMC + DZP. CUR (150 mg/kg b.w. was orally administered for 28 days. DZP (2 mg/kg b.w. was intraperitoneally administered 20 minutes before the behavioral tests (open field test, Y-maze, and elevated plus maze. CUR improved the spontaneous alternation behavior, decreased the oxidative stress levels, both in the blood and in the hippocampus, and downregulated the extracellular signal-regulated kinase (ERK 1/2/nuclear transcription factor- (NF- κB/pNF-κB pathway in the hippocampus and the iNOS expression in the hippocampus and frontal lobe of the DZP-treated rats. Histopathologically, no microscopic changes were found. The immunohistochemical signal of iNOS decreased in the DZP and CUR-treated group. Thus, our findings suggest that curcumin administration may improve the cognitive performance and may also have an antioxidant effect.

  11. Enhanced Abscisic Acid-Mediated Responses in nia1nia2noa1-2 Triple Mutant Impaired in NIA/NR- and AtNOA1-Dependent Nitric Oxide Biosynthesis in Arabidopsis1[W

    Science.gov (United States)

    Lozano-Juste, Jorge; León, José

    2010-01-01

    Nitric oxide (NO) regulates a wide range of plant processes from development to environmental adaptation. Despite its reported regulatory functions, it remains unclear how NO is synthesized in plants. We have generated a triple nia1nia2noa1-2 mutant that is impaired in nitrate reductase (NIA/NR)- and Nitric Oxide-Associated1 (AtNOA1)-mediated NO biosynthetic pathways. NO content in roots of nia1nia2 and noa1-2 plants was lower than in wild-type plants and below the detection limit in nia1nia2noa1-2 plants. NIA/NR- and AtNOA1-mediated biosynthesis of NO were thus active and responsible for most of the NO production in Arabidopsis (Arabidopsis thaliana). The nia1nia2noa1-2 plants displayed reduced size, fertility, and seed germination potential but increased dormancy and resistance to water deficit. The increasing deficiency in NO of nia1nia2, noa1-2, and nia1nia2noa1-2 plants correlated with increased seed dormancy, hypersensitivity to abscisic acid (ABA) in seed germination and establishment, as well as dehydration resistance. In nia1nia2noa1-2 plants, enhanced drought tolerance was due to a very efficient stomata closure and inhibition of opening by ABA, thus uncoupling NO from ABA-triggered responses in NO-deficient guard cells. The NO-deficient mutants in NIA/NR- and AtNOA1-mediated pathways in combination with the triple mutant will be useful tools to functionally characterize the role of NO and the contribution of both biosynthetic pathways in regulating plant development and defense. PMID:20007448

  12. Enhanced abscisic acid-mediated responses in nia1nia2noa1-2 triple mutant impaired in NIA/NR- and AtNOA1-dependent nitric oxide biosynthesis in Arabidopsis.

    Science.gov (United States)

    Lozano-Juste, Jorge; León, José

    2010-02-01

    Nitric oxide (NO) regulates a wide range of plant processes from development to environmental adaptation. Despite its reported regulatory functions, it remains unclear how NO is synthesized in plants. We have generated a triple nia1nia2noa1-2 mutant that is impaired in nitrate reductase (NIA/NR)- and Nitric Oxide-Associated1 (AtNOA1)-mediated NO biosynthetic pathways. NO content in roots of nia1nia2 and noa1-2 plants was lower than in wild-type plants and below the detection limit in nia1nia2noa1-2 plants. NIA/NR- and AtNOA1-mediated biosynthesis of NO were thus active and responsible for most of the NO production in Arabidopsis (Arabidopsis thaliana). The nia1nia2noa1-2 plants displayed reduced size, fertility, and seed germination potential but increased dormancy and resistance to water deficit. The increasing deficiency in NO of nia1nia2, noa1-2, and nia1nia2noa1-2 plants correlated with increased seed dormancy, hypersensitivity to abscisic acid (ABA) in seed germination and establishment, as well as dehydration resistance. In nia1nia2noa1-2 plants, enhanced drought tolerance was due to a very efficient stomata closure and inhibition of opening by ABA, thus uncoupling NO from ABA-triggered responses in NO-deficient guard cells. The NO-deficient mutants in NIA/NR- and AtNOA1-mediated pathways in combination with the triple mutant will be useful tools to functionally characterize the role of NO and the contribution of both biosynthetic pathways in regulating plant development and defense.

  13. Part II. Initial molecular and cellular characterization of high nitric oxide-adapted human tongue squamous cell carcinoma cell lines.

    Science.gov (United States)

    Tarjan, Gabor; Haines, G Kenneth; Vesper, Benjamin J; Xue, Jiaping; Altman, Michael B; Yarmolyuk, Yaroslav R; Khurram, Huma; Elseth, Kim M; Roeske, John C; Aydogan, Bulent; Radosevich, James A

    2011-02-01

    It is not understood why some head and neck squamous cell carcinomas, despite having identical morphology, demonstrate different tumor aggressiveness, including radioresistance. High levels of the free radical nitric oxide (NO) and increased expression of the NO-producing enzyme nitric oxide synthase (NOS) have been implicated in tumor progression. We previously adapted three human tongue cancer cell lines to high NO (HNO) levels by gradually exposing them to increasing concentrations of an NO donor; the HNO cells grew faster than their corresponding untreated ("parent") cells, despite being morphologically identical. Herein we initially characterize the HNO cells and compare the biological properties of the HNO and parent cells. HNO/parent cell line pairs were analyzed for cell cycle distribution, DNA damage, X-ray and ultraviolet radiation response, and expression of key cellular enzymes, including NOS, p53, glutathione S-transferase-pi (GST-pi), apurinic/apyrimidinic endonuclease-1 (APE1), and checkpoint kinases (Chk1, Chk2). While some of these properties were cell line-specific, the HNO cells typically exhibited properties associated with a more aggressive behavior profile than the parent cells (greater S-phase percentage, radioresistance, and elevated expression of GST-pi/APE1/Chk1/Chk2). To correlate these findings with conditions in primary tumors, we examined the NOS, GST-pi, and APE1 expression in human tongue squamous cell carcinomas. A majority of the clinical samples exhibited elevated expression levels of these enzymes. Together, the results herein suggest cancer cells exposed to HNO levels can develop resistance to free radicals by upregulating protective mechanisms, such as GST-pi and APE1. These upregulated defense mechanisms may contribute to their aggressive expression profile.

  14. Diamond, graphite, and graphene oxide nanoparticles decrease migration and invasiveness in glioblastoma cell lines by impairing extracellular adhesion

    DEFF Research Database (Denmark)

    Wierzbicki, Mateusz; Jaworski, Slawomir; Kutwin, Marta

    2017-01-01

    The highly invasive nature of glioblastoma is one of the most significant problems regarding the treatment of this tumor. Diamond nanoparticles (ND), graphite nanoparticles (NG), and graphene oxide nanoplatelets (nGO) have been explored for their biomedical applications, especially for drug...

  15. Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation

    DEFF Research Database (Denmark)

    Wensaas, Andreas J; Rustan, Arild C; Just, Marlene

    2008-01-01

    Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence...... these processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA....... EPA markedly enhanced TAG accumulation in myotubes, more pronounced in T2D cells. TAG accumulation and fatty acid oxidation were inversely correlated only after EPA preincubation, and total level of acyl-CoA was reduced. Glucose oxidation (CO(2) formation) was enhanced and lactate production decreased...

  16. Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress.

    Science.gov (United States)

    Zanchi, Ana C T; Fagundes, Lucas S; Barbosa, Fernando; Bernardi, Rosane; Rhoden, Claudia Ramos; Saldiva, Paulo H N; do Valle, Angela Cristina

    2010-09-01

    The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary objectives, it was to evaluate if the change of filtered to nonfiltered environment could protect the cortex of rats against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into four groups (n = 12/group): pre and post-natal exposure until adulthood to filtered air (FA); pre-natal period to nonfiltered air (NFA-FA); until (21st post-natal day) and post-natal to filtered air until adulthood (PND21); pre-natal to filtered air until PND21 and post-natal to nonfiltered air until adulthood (FA-NFA); pre and post-natal to nonfiltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a significant increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730 +/- 0.217; NFA-FA: 1.101 +/- 0.217; FA-NFA: 1.014 +/- 0.300; NFA: 5.978 +/- 1.920 nmol MDA/mg total proteins; p = 0.007). NFA group presented a significant decrease in short-term discriminative (FA: 0.603 +/- 0.106; NFA-FA: 0.669 +/- 0.0666; FA-NFA: 0.374 +/- 0.178; NFA: -0.00631 +/- 0.106 sec; p = 0.006) and an improvement in habituation memories when compared to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative memory and cortical oxidative stress may mediate this process.

  17. Photo-Oxidative Stress-Driven Mutagenesis and Adaptive Evolution on the Marine Diatom Phaeodactylum tricornutum for Enhanced Carotenoid Accumulation

    Directory of Open Access Journals (Sweden)

    Zhiqian Yi

    2015-09-01

    Full Text Available Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve diatoms for value-added products. In this study, we utilized UVC radiation to induce mutations in the marine diatom Phaeodactylum tricornutum and screened strains with enhanced accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution (ALE was also used in parallel to develop altered phenotypic and biological functions in P. tricornutum and it was reported for the first time that ALE was successfully applied on diatoms for the enhancement of growth performance and productivity of value-added carotenoids to date. Liquid chromatography-mass spectrometry (LC-MS was utilized to study the composition of major pigments in the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains exhibited higher accumulation of fucoxanthin as well as neutral lipids compared to their wild type counterpart. In addition to UV mutagenesis, P. tricornutum strains developed by ALE also yielded enhanced biomass production and fucoxanthin accumulation under combined red and blue light. In short, both UV mutagenesis and ALE appeared as an effective approach to developing desired phenotypes in the marine diatoms via electromagnetic radiation-induced oxidative stress.

  18. Genome-guided analysis of physiological capacities of Tepidanaerobacter acetatoxydans provides insights into environmental adaptations and syntrophic acetate oxidation.

    Science.gov (United States)

    Müller, Bettina; Manzoor, Shahid; Niazi, Adnan; Bongcam-Rudloff, Erik; Schnürer, Anna

    2015-01-01

    This paper describes the genome-based analysis of Tepidanaerobacter acetatoxydans strain Re1, a syntrophic acetate-oxidising bacterium (SAOB). Principal issues such as environmental adaptations, metabolic capacities, and energy conserving systems have been investigated and the potential consequences for syntrophic acetate oxidation discussed. Briefly, in pure culture, T. acetatoxydans grows with different organic compounds and produces acetate as the main product. In a syntrophic consortium with a hydrogenotrophic methanogen, it can also reverse its metabolism and instead convert acetate to formate/H2 and CO2. It can only proceed if the product formed is continuously removed. This process generates a very small amount of energy that is scarcely enough for growth, which makes this particular syntrophy of special interest. As a crucial member of the biogas-producing community in ammonium-rich engineered AD processes, genomic features conferring ammonium resistance, bacterial defense, oxygen and temperature tolerance were found, as well as attributes related to biofilm formation and flocculation. It is likely that T. acetatoxydans can form an electrochemical gradient by putative electron-bifurcating Rnf complex and [Fe-Fe] hydrogenases, as observed in other acetogens. However, genomic deficiencies related to acetogenic metabolism and anaerobic respiration were discovered, such as the lack of formate dehydrogenase and F1F0 ATP synthase. This has potential consequences for the metabolic pathways used under SAO and non-SAO conditions. The two complete sets of bacteriophage genomes, which were found to be encoded in the genome, are also worthy of mention.

  19. Impaired translocation and activation of mitochondrial Akt1 mitigated mitochondrial oxidative phosphorylation Complex V activity in diabetic myocardium.

    Science.gov (United States)

    Yang, Jia-Ying; Deng, Wu; Chen, Yumay; Fan, Weiwei; Baldwin, Kenneth M; Jope, Richard S; Wallace, Douglas C; Wang, Ping H

    2013-06-01

    Insulin can translocate Akt to mitochondria in cardiac muscle. The goals of this study were to define sub-mitochondrial localization of the translocated Akt, to dissect the effects of insulin on Akt isoform translocation, and to determine the direct effect of mitochondrial Akt activation on Complex V activity in normal and diabetic myocardium. The translocated Akt sequentially localized to the mitochondrial intermembrane space, inner membrane, and matrix. To confirm Akt translocation, in vitro import assay showed rapid entry of Akt into mitochondria. Akt isoforms were differentially regulated by insulin stimulation, only Akt1 translocated into mitochondria. In the insulin-resistant Type 2 diabetes model, Akt1 translocation was blunted. Mitochondrial activation of Akt1 increased Complex V activity by 24% in normal myocardium in vivo and restored Complex V activity in diabetic myocardium. Basal mitochondrial Complex V activity was lower by 22% in the Akt1(-/-) myocardium. Insulin-stimulated Complex V activity was not impaired in the Akt1(-/-) myocardium, due to compensatory translocation of Akt2 to mitochondria. Akt1 is the primary isoform that relayed insulin signaling to mitochondria and modulated mitochondrial Complex V activity. Activation of mitochondrial Akt1 enhanced ATP production and increased phosphocreatine in cardiac muscle cells. Dysregulation of this signal pathway might impair mitochondrial bioenergetics in diabetic myocardium. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. The role of HYAL2 in LSS-induced glycocalyx impairment and the PKA-mediated decrease in eNOS-Ser-633 phosphorylation and nitric oxide production.

    Science.gov (United States)

    Kong, Xiangquan; Chen, Liang; Ye, Peng; Wang, Zhimei; Zhang, Junjie; Ye, Fei; Chen, Shaoliang

    2016-12-15

    Hyaluronan (HA) in the endothelial glycocalyx serves as a mechanotransducer for high-shear-stress-stimulated endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. Low shear stress (LSS) has been shown to contribute to endothelial inflammation and atherosclerosis by impairing the barrier and mechanotransduction properties of the glycocalyx. Here we focus on the possible role of hyaluronidase 2 (HYAL2) in LSS-induced glycocalyx impairment and the resulting alterations in eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVECs). We show that LSS strongly activates HYAL2 to degrade HA in the glycocalyx. The dephosphorylation of eNOS-Ser-633 under LSS was triggered after HA degradation by hyaluronidase and prevented by repairing the glycocalyx with high-molecular weight hyaluronan. Knocking down HYAL2 in HUVECs protected against HA degradation in the glycocalyx by inhibiting the expression and activity of HYAL2 and further blocked the dephosphorylation of eNOS-Ser-633 and the decrease in NO production in response to LSS. The LSS-induced dephosphorylation of PKA was completely abrogated in HYAL2 siRNA-transfected HUVECs. The LSS-induced dephosphorylation of eNOS-Ser-633 was also reversed by the PKA activator 8-Br-cAMP. We thus suggest that LSS inhibits eNOS-Ser-633 phosphorylation and, at least partially, NO production by activating HYAL2 to degrade HA in the glycocalyx. © 2016 Kong et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  1. Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice

    Energy Technology Data Exchange (ETDEWEB)

    Sadler, Natalie C.; Angel, Thomas E.; Lewis, Michael P.; Pederson, Leeanna M.; Chauvigne-Hines, Lacie M.; Wiedner, Susan D.; Zink, Erika M.; Smith, Richard D.; Wright, Aaron T.

    2012-10-24

    High-fat diet (HFD) induced obesity and concomitant development of insulin resistance (IR) and type 2 diabetes mellitus have been linked to mitochondrial dysfunction. However, it is not clear whether mitochondrial dysfunction is a direct effect of a HFD or if the mitochondrial function is reduced with increased HFD duration. We hypothesized that the function of mitochondrial oxidative and lipid metabolism functions in skeletal muscle mitochondria for HFD mice are similar or elevated relative to standard diet (SD) mice, thereby IR is neither cause nor consequence of mitochondrial dysfunction. We applied a chemical probe approach to identify functionally reactive ATPases and nucleotide-binding proteins in mitochondria isolated from skeletal muscle of C57Bl/6J mice fed HFD or SD chow for 2-, 8-, or 16-weeks; feeding time points known to induce IR. A total of 293 probe-labeled proteins were identified by mass spectrometry-based proteomics, of which 54 differed in abundance between HFD and SD mice. We found proteins associated with the TCA cycle, oxidative phosphorylation (OXPHOS), and lipid metabolism were altered in function when comparing SD to HFD fed mice at 2-weeks, however by 16-weeks HFD mice had TCA cycle, β-oxidation, and respiratory chain function at levels similar to or higher than SD mice.

  2. Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress.

    Directory of Open Access Journals (Sweden)

    Steven Frank Kemeny

    Full Text Available Uncontrolled blood glucose in people with diabetes correlates with endothelial cell dysfunction, which contributes to accelerated atherosclerosis and subsequent myocardial infarction, stroke, and peripheral vascular disease. In vitro, both low and high glucose induce endothelial cell dysfunction; however the effect of altered glucose on endothelial cell fluid flow response has not been studied. This is critical to understanding diabetic cardiovascular disease, since endothelial cell cytoskeletal alignment and nitric oxide release in response to shear stress from flowing blood are atheroprotective. In this study, porcine aortic endothelial cells were cultured in 1, 5.55, and 33 mM D-glucose medium (low, normal, and high glucose and exposed to 20 dynes/cm(2 shear stress for up to 24 hours in a parallel plate flow chamber. Actin alignment and endothelial nitric oxide synthase phosphorylation increased with shear stress for cells in normal glucose, but not cells in low and high glucose. Both low and high glucose elevated protein kinase C (PKC levels; however PKC blockade only restored actin alignment in high glucose cells. Cells in low glucose instead released vascular endothelial growth factor (VEGF, which translocated β-catenin away from the cell membrane and disabled the mechanosensory complex. Blocking VEGF in low glucose restored cell actin alignment in response to shear stress. These data suggest that low and high glucose alter endothelial cell alignment and nitric oxide production in response to shear stress through different mechanisms.

  3. Near infrared spectroscopy (NIRS as a new non-invasive tool to detect oxidative skeletal muscle impairment in children survived to acute lymphoblastic leukaemia.

    Directory of Open Access Journals (Sweden)

    Francesca Lanfranconi

    Full Text Available BACKGROUND: Separating out the effects of cancer and treatment between central and peripheral components of the O2 delivery chain should be of interest to clinicians for longitudinal evaluation of potential functional impairment in order to set appropriate individually tailored training/rehabilitation programmes. We propose a non-invasive method (NIRS, near infrared spectroscopy to be used in routine clinical practice to evaluate a potential impairment of skeletal muscle oxidative capacity during exercise in children previously diagnosed with acute lymphoblastic leukaemia (ALL. The purpose of this study was to evaluate the capacity of skeletal muscle to extract O2 in 10 children diagnosed with ALL, 1 year after the end of malignancy treatment, compared to a control group matched for gender and age (mean±SD = 7.8±1.5 and 7.3±1.4 years, respectively. METHODS AND FINDINGS: Participants underwent an incremental exercise test on a treadmill until exhaustion. Oxygen uptake ([Formula: see text], heart rate (HR, and tissue oxygenation status (Δ[HHb] of the vastus lateralis muscle evaluated by NIRS, were measured. The results showed that, in children with ALL, a significant linear regression was found by plotting [Formula: see text] vs Δ[HHb] both measured at peak of exercise. In children with ALL, the slope of the HR vs [Formula: see text] linear response (during sub-maximal and peak work rates was negatively correlated with the peak value of Δ[HHb]. CONCLUSIONS: The present study proves that the NIRS technique allows us to identify large inter-individual differences in levels of impairment in muscle O2 extraction in children with ALL. The outcome of these findings is variable and may reflect either muscle atrophy due to lack of use or, in the most severe cases, an undiagnosed myopathy.

  4. Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of D-galactose-induced aging mice.

    Science.gov (United States)

    Turgut, Nergiz Hacer; Mert, Derya Guliz; Kara, Haki; Egilmez, Hatice Reyhan; Arslanbas, Emre; Tepe, Bektas; Gungor, Huseyin; Yilmaz, Nese; Tuncel, Necati Baris

    2016-01-01

    Morus nigra L. (Moraceae) has various uses in traditional medicine. However, the effect of M. nigra on cognitive impairment has not been investigated yet. The objective of this study is to determine the phenolic acid content and DNA damage protection potential of M. nigra leaf extract and to investigate the extract effect on cognitive impairment and oxidative stress in aging mice. Phenolic acid content was determined by quantitative chromatographic analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. Thirty-two Balb-C mice were randomly divided into four groups (control, d-galactose, d-galactose + M. nigra 50, and d-galactose + M. nigra 100). Mice were administered d-galactose (100 mg/kg, subcutaneous) and M. nigra (50 or 100 mg/kg, orally) daily for 8 weeks. Behavioral responses were evaluated with Morris water maze. Activities of antioxidant enzymes and levels of malondialdehyde (MDA) were assayed in serum, brain, and liver. In extract, vanillic (632.093 μg/g) and chlorogenic acids (555.0 μg/g) were determined. The extract between 0.02 and 0.05 mg/mL effectively protected all DNA bands against the hazardous effect of UV and H2O2. Morus nigra significantly improved learning dysfunctions (p aging, partially due to its scavenging activity of free radicals and high antioxidant capacity.

  5. Comparison of adaptive neuro-fuzzy inference system and artificial neural networks for estimation of oxidation parameters of sunflower oil added with some natural byproduct extracts.

    Science.gov (United States)

    Karaman, Safa; Ozturk, Ismet; Yalcin, Hasan; Kayacier, Ahmed; Sagdic, Osman

    2012-01-15

    Apple pomace, orange peel and potato peel, which have important antioxidative compounds in their structures, are byproducts obtained from fruit or vegetable processing. Use of vegetable extracts is popular and a common technique in the preservation of vegetable oils. Utilization of apple pomace, orange peel and potato peel extracts as natural antioxidant agents in refined sunflower oil during storage in order to reduce or retard oxidation was investigated. All byproduct extracts were added at 3000 ppm to sunflower oil and different nonlinear models were constructed for the estimation of oxidation parameters. Peroxide values of sunflower oil samples containing different natural extracts were found to be lower compared to control sample. Adaptive neuro-fuzzy inference system (ANFIS) and artificial neural networks (ANN) were used for the construction of models that could predict the oxidation parameters and were compared to multiple linear regression (MLR) for the determination of the best model with high accuracy. It was shown that the ANFIS model with high coefficient of determination (R(2) = 0.999) performed better compared to ANN (R(2) = 0.899) and MLR (R(2) = 0.636) for the prediction of oxidation parameters Incorporation of different natural byproduct extracts into sunflower oil provided an important retardation in oxidation during storage. Effective predictive models were constructed for the estimation of oxidation parameters using ANFIS and ANN modeling techniques. These models can be used to predict oxidative parameter values. Copyright © 2011 Society of Chemical Industry.

  6. Subclinical mastitis in goats is associated with upregulation of nitric oxide-derived oxidative stress that causes reduction of milk antioxidative properties and impairment of its quality.

    Science.gov (United States)

    Silanikove, Nissim; Merin, Uzi; Shapiro, Fira; Leitner, Gabriel

    2014-01-01

    The aim of this study was to verify the existence of a nitric oxide (NO) cycle in goat milk and to study how changes in it affect milk composition during subclinical mastitis. Fifteen lactating dairy goats in which one udder-half was free from bacterial infection and the contra-lateral one was naturally infected with various species of coagulase-negative staphylococci were used. In comparison to uninfected glands, subclinical mastitis was associated with a decrease in milk yield, lactose concentration, and curd yield and an increase in nitrite and nitrate concentrations and with measurements reflecting increased formation of NO-derived free-radical nitrogen dioxide. The occurrence of NO cycling in goat milk was largely confirmed. The increase in the NO-derived stress during subclinical infection was not associated with significant increase in oxidatively modified substances, 3-nitrotyrosine, and carbonyls on proteins, but with increased levels of peroxides on fat. However, the relatively modest nitrosative stress in subclinically infected glands was associated with significant reduction in total antioxidant capacity and vitamin C levels in milk. We concluded that subclinical mastitis in goats caused by coagulase-negative staphylococci imposes negative changes in milk yield, milk quality for cheese production, and negatively affects the nutritional value of milk as food. Thus, subclinical mastitis in goats should be considered as a serious economic burden both by farmers and by the dairy industry. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat

    Directory of Open Access Journals (Sweden)

    Gao F

    2014-11-01

    hippocampal CA1 region. Our data suggest that Ber exerts anticonvulsant and neuroprotective effects on Pilo-induced epilepsy in rats. Simultaneously, Ber attenuates memory impairment. The beneficial effect may be partly due to mitigation of the oxidative stress burden. Keywords: status epilepticus, pilocarpine, memory impairment, oxidative stress, neuroprotection

  8. Jumping the gun: Smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Sobinoff, A.P.; Pye, V. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); Nixon, B.; Roman, S.D. [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Callaghan, NSW2308 (Australia); McLaughlin, E.A., E-mail: eileen.mclaughlin@newcastle.edu.au [Reproductive Science Group, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW2308 (Australia); ARC Centre of Excellence in Biotechnology and Development, University of Newcastle, Callaghan, NSW2308 (Australia)

    2012-04-01

    Benzo(a)pyrene (BaP) is an ovotoxic constituent of cigarette smoke associated with pre-mature ovarian failure and decreased rates of conception in IVF patients. Although the overall effect of BaP on female fertility has been documented, the exact molecular mechanisms behind its ovotoxicity remain elusive. In this study we examined the effects of BaP exposure on the ovarian transcriptome, and observed the effects of in vivo exposure on oocyte dysfunction. Microarray analysis of BaP cultured neonatal ovaries revealed a complex mechanism of ovotoxicity involving a small cohort of genes associated with follicular growth, cell cycle progression, and cell death. Histomorphological and immunohistochemical analysis supported these results, with BaP exposure causing increased primordial follicle activation and developing follicle atresia in vitro and in vivo. Functional analysis of oocytes obtained from adult Swiss mice treated neonatally revealed significantly increased levels of mitochondrial ROS/lipid peroxidation, and severely reduced sperm-egg binding and fusion in both low (1.5 mg/kg/daily) and high (3 mg/kg/daily) dose treatments. Our results reveal a complex mechanism of BaP induced ovotoxicity involving developing follicle atresia and accelerated primordial follicle activation, and suggest short term neonatal BaP exposure causes mitochondrial leakage resulting in reduced oolemma fluidity and impaired fertilisation in adulthood. This study highlights BaP as a key compound which may be partially responsible for the documented effects of cigarette smoke on follicular development and sub-fertility. -- Highlights: ► BaP exposure up-regulates canonical pathways linked with follicular growth/atresia. ► BaP causes primordial follicle activation and developing follicle atresia. ► BaP causes oocyte mitochondrial ROS and lipid peroxidation, impairing fertilisation. ► Short term neonatal BaP exposure compromises adult oocyte quality.

  9. Standardized extract of Withania somnifera (Ashwagandha) markedly offsets rotenone-induced locomotor deficits, oxidative impairments and neurotoxicity in Drosophila melanogaster.

    Science.gov (United States)

    Manjunath, M J; Muralidhara

    2015-04-01

    Withania somnifera (Ashwagandha, WS) or Indian ginseng possesses multiple pharmacological properties which are mainly attributed to the active constituents, withanolides. Despite its extensive usage as a memory enhancer and a nerve tonic, few attempts have been made to ascertain its usage in the management of Parkinson's disease. In the present study, we investigated the neuroameliorative effects of WS in a rotenone (ROT) model of Drosophila melanogaster (Oregon-K). Initially, we ascertained the ability of WS-enriched diet (0-0.05 %) to protect against ROT induced lethality and locomotor phenotype in adult male flies. Further, employing a co-exposure paradigm, we investigated the propensity of WS to offset ROT-induced oxidative stress, mitochondrial dysfunctions and neurotoxicity. WS conferred significant protection against ROT-induced lethality, while the survivor flies exhibited improved locomotor phenotype. Biochemical investigations revealed that ROT-induced oxidative stress was significantly diminished by WS enrichment. WS caused significant elevation in the levels of reduced GSH/non-protein thiols. Furthermore, the altered activity levels of succinate dehydrogenase, MTT, membrane bound enzymes viz., NADH-cytochrome-c reductase and succinate-cytochrome-c reductase were markedly restored to normalcy. Interestingly, ROT-induced perturbations in cholinergic function and depletion in dopamine levels were normalized by WS. Taken together these data suggests that the neuromodulatory effect of WS against ROT- induced neurotoxicity is probably mediated via suppression of oxidative stress and its potential to attenuate mitochondrial dysfunctions. Our further studies aim to understand the underlying neuroprotective mechanisms of WS and withanolides employing neuronal cell models.

  10. 60-Day chronic exposure to low concentrations of HgCl2 impairs sperm quality: hormonal imbalance and oxidative stress as potential routes for reproductive dysfunction in rats.

    Directory of Open Access Journals (Sweden)

    Caroline S Martinez

    Full Text Available Mercury is a toxic and bio-accumulative heavy metal of global concern. While good deals of research have been conducted on the toxic effects of mercury, little is known about the mechanisms involved in the pathogenesis of male reproductive dysfunction induced by mercury. Therefore, the purpose of this study was to assess the effects and underlying mechanisms of chronic mercury exposure at low levels on male reproductive system of rats. Three-month-old male Wistar rats were divided into two groups and treated for 60 days with saline (i.m., Control and HgCl2 (i.m. 1st dose: 4.6 µg/kg, subsequent doses 0.07 µg/kg/day. We analyzed sperm parameters, hormonal levels and biomarkers of oxidative stress in testis, epididymis, prostate and vas deferens. Mercury treatment decreased daily sperm production, count and motility and increased head and tail morphologic abnormalities. Moreover, mercury treatment decreased luteinizing hormone levels, increased lipid peroxidation on testis and decreased antioxidant enzymes activities (superoxide dismutase and catalase on reproductive organs. Our data demonstrate that 60-day chronic exposure to low concentrations of HgCl2 impairs sperm quality and promotes hormonal imbalance. The raised oxidative stress seems to be a potential mechanism involved on male reproductive toxicity by mercury.

  11. Pretreatment with Rhodiola rosea extract reduces cognitive impairment induced by intracerebroventricular streptozotocin in rats: implication of anti-oxidative and neuroprotective effects.

    Science.gov (United States)

    Qu, Ze-Qiang; Zhou, Yan; Zeng, Yuan-Shan; Li, Yan; Chung, Peter

    2009-08-01

    To investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer's disease (AD). Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons. The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg). R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.

  12. Insights into the Feelings, Thoughts, and Behaviors of Children with Visual Impairments: A Focus Group Study Prior to Adapting a Cognitive Behavior Therapy-Based Anxiety Intervention

    Science.gov (United States)

    Visagie, Lisa; Loxton, Helene; Stallard, Paul; Silverman, Wendy K.

    2017-01-01

    Introduction: Anxiety is the most common psychological problem reported among children with visual impairments. Although cognitive behavior therapy interventions have proven successful in treating childhood anxiety, it is unclear whether they are suitable and accessible for children who have visual impairments. This study aimed to determine if and…

  13. Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver

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    Tao Zeng

    2018-04-01

    Full Text Available Protein kinase B (PKB/Akt plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD. Previous studies suggest that cytochrome P4502E1 (CYP2E1 plays causal roles in the pathogenesis of alcoholic fatty liver (AFL. We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver. Chronic ethanol exposure had no effects on the protein levels of phosphatidylinositol 3 kinase (PI3K and phosphatase and tensin homologue deleted on chromosome ten (PTEN, and led to a slight decrease of phosphoinositide-dependent protein kinase 1 (PDK-1 protein level. Ethanol exposure resulted in increased levels of malondialdehyde (MDA and 4-hydroxynonenal (4-HNE-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ, an efficient CYP2E1 inhibitor. Interestingly, N-acetyl-L-cysteine (NAC significantly attenuated chronic ethanol-induced hepatic fat accumulation and the decline of Akt phosphorylation at Thr308. In the in vitro studies, Akt phosphorylation was suppressed in CYP2E1-expressing HepG2 (CYP2E1-HepG2 cells compared with the negative control HepG2 (NC-HepG2 cells, and 4-HNE treatment led to significant decrease of Akt phosphorylation at Thr308 in wild type HepG2 cells. Lastly, pharmacological activation of Akt by insulin-like growth factor-1 (IGF-1 significantly alleviated chronic ethanol-induced fatty liver in mice. Collectively, these results indicate that CYP2E1-induced oxidative stress may be responsible for ethanol-induced suppression of Akt phosphorylation and pharmacological modulation of Akt in liver may be an effective strategy for the treatment of ethanol-induced fatty liver. Keywords

  14. Electroacupuncture ameliorates spatial learning and memory impairment via attenuating NOX2-related oxidative stress in a rat model of Alzheimer's disease induced by Aβ1-42.

    Science.gov (United States)

    Wu, G; Li, L; Li, H-M; Zeng, Y; Wu, W-C

    2017-04-29

    Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive deterioration of cognition and memory, in which oxidative stress has been played a crucial role in the pathology of AD. Electroacupuncture (EA) is a widely used therapy based on traditional acupuncture combined with modern electrotherapy in Asia. The present study aimed to determine the effects of EA treatment on spatial learning and memory impairment, and to elucidate the status of NOX2-related oxidative stress in a rat model of Alzheimer's disease induced by Beta-amyloid1-42 (Aβ1-42). Fifty-six adult female Sprague-Dawley (SD) rats were randomly divided into four groups: sham, sham+EA, AD and AD+EA. The rats in Sham+EA and AD+EA groups were respectively administrated EA treatment at Baihui and yongquan acupoints, once a day for 30 min, lasting for 28 days. The spatial learning and memory functions were assessed by Morris water maze (MWM) test. The activities of total antioxidant capacity (T-AOC), reactive oxygen species (ROS), malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) were evaluated. Moreover, the neuronal injury was detected by Nissl staining. Meanwhile, the NeuN expression was examined in the hippocampus, the expression levels of Nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase2(NOX2) was detected by immunofluorescence staining and western blot. The results showed that EA treatment significantly improved spatial learning and memory impairment in rats induced by Aβ1-42. Concomitantly, EA treatment markedly restored T-AOC and attenuated the abnormal increase in levels of ROS, MDA and 8-OH-dG in the hippocampus of the AD rats. More notably, EA treatment also effectively ameliorated neuronal injury and counteracted the aberrant increase of NOX2 levels in the hippocampus of AD rats. Our findings suggested that EA is a potential strategy for the treatment of AD, and the possible mechanism is associated with the alleviation of neuronal injury

  15. Grape Powder Supplementation Prevents Oxidative Stress–Induced Anxiety-Like Behavior, Memory Impairment, and High Blood Pressure in Rats123

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    Allam, Farida; Dao, An T.; Chugh, Gaurav; Bohat, Ritu; Jafri, Faizan; Patki, Gaurav; Mowrey, Christopher; Asghar, Mohammad; Alkadhi, Karim A.; Salim, Samina

    2013-01-01

    We examined whether or not grape powder treatment ameliorates oxidative stress–induced anxiety-like behavior, memory impairment, and hypertension in rats. Oxidative stress in Sprague-Dawley rats was produced by using l-buthionine-(S,R)-sulfoximine (BSO). Four groups of rats were used: 1) control (C; injected with vehicle and provided with tap water), 2) grape powder–treated (GP; injected with vehicle and provided for 3 wk with 15 g/L grape powder dissolved in tap water), 3) BSO-treated [injected with BSO (300 mg/kg body weight), i.p. for 7 d and provided with tap water], and 4) BSO plus grape powder–treated (GP+BSO; injected with BSO and provided with grape powder–treated tap water). Anxiety-like behavior was significantly greater in BSO rats compared with C or GP rats (P < 0.05). Grape powder attenuated BSO-induced anxiety-like behavior in GP+BSO rats. BSO rats made significantly more errors in both short- and long-term memory tests compared with C or GP rats (P < 0.05), which was prevented in GP+BSO rats. Systolic and diastolic blood pressure was significantly greater in BSO rats compared with C or GP rats (P < 0.05), whereas grape powder prevented high blood pressure in GP+BSO rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK-1/2) was activated (P < 0.05), whereas levels of glyoxalase-1 (GLO-1), glutathione reductase-1 (GSR-1), calcium/calmodulin-dependent protein kinase type IV (CAMK-IV), cAMP response element–binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were significantly less (P < 0.05) in BSO but not in GP+BSO rats compared with C or GP rats. We suggest that by regulating brain ERK-1/2, GLO-1, GSR-1, CAMK-IV, CREB, and BDNF levels, grape powder prevents oxidative stress–induced anxiety, memory impairment, and hypertension in rats. PMID:23596160

  16. Azadirachta indica mitigates behavioral impairments, oxidative damage, histological alterations and apoptosis in focal cerebral ischemia-reperfusion model of rats.

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    Vaibhav, Kumar; Shrivastava, Pallavi; Khan, Andleeb; Javed, Hayate; Tabassum, Rizwana; Ahmed, Md Ejaz; Khan, M Badruzzaman; Moshahid Khan, Mohd; Islam, Farah; Ahmad, Sayeed; Siddiqui, M Saeed; Safhi, Mohammed M; Islam, Fakhrul

    2013-08-01

    Azadirachta indica Linn. (Meliaceae) has been used from ancient times as a remedy for various ailments. The present study was designed to investigate the antioxidant and anti-apoptotic properties of A. indica seed extract (ASE) in transient middle cerebral artery occlusion (MCAO) rat model. Antioxidant potential of ASE was determined in vitro. Further, ASE was evaluated against neurological deficits, histological alterations (TTC, CV and H&E) and oxidative damage (TBARS, GSH and nitrite) in MCAO rats. Moreover, caspase-3 and -9 were analyzed to evaluate the anti-apoptotic activity of ASE. ASE has shown potent in vitro reducing power (126.2 mg AsAE/g extract) and free radical scavenging activities (DPPH 171.0 and NO 176.0 μg/ml). Furthermore, ASE inhibited oxidative stress and decreased the activities of caspase-3 (26.7 %, p < 0.05) and caspase-9 (31.2 %, p < 0.01) thus, reduced neuronal loss in MCAO rats. Our data revealed that ASE has potent antioxidant and anti-apoptotic properties, and may be explored for its active constituents against neurodegenerative diseases.

  17. Metabolite profiles reveal energy failure and impaired beta-oxidation in liver of mice with complex III deficiency due to a BCS1L mutation.

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    Heike Kotarsky

    Full Text Available BACKGROUND & AIMS: Liver is a target organ in many mitochondrial disorders, especially if the complex III assembly factor BCS1L is mutated. To reveal disease mechanism due to such mutations, we have produced a transgenic mouse model with c.232A>G mutation in Bcs1l, the causative mutation for GRACILE syndrome. The homozygous mice develop mitochondrial hepatopathy with steatosis and fibrosis after weaning. Our aim was to assess cellular mechanisms for disease onset and progression using metabolomics. METHODS: With mass spectrometry we analyzed metabolite patterns in liver samples obtained from homozygotes and littermate controls of three ages. As oxidative stress might be a mechanism for mitochondrial hepatopathy, we also assessed H(2O(2 production and expression of antioxidants. RESULTS: Homozygotes had a similar metabolic profile at 14 days of age as controls, with the exception of slightly decreased AMP. At 24 days, when hepatocytes display first histopathological signs, increases in succinate, fumarate and AMP were found associated with impaired glucose turnover and beta-oxidation. At end stage disease after 30 days, these changes were pronounced with decreased carbohydrates, high levels of acylcarnitines and amino acids, and elevated biogenic amines, especially putrescine. Signs of oxidative stress were present in end-stage disease. CONCLUSIONS: The findings suggest an early Krebs cycle defect with increases of its intermediates, which might play a role in disease onset. During disease progression, carbohydrate and fatty acid metabolism deteriorate leading to a starvation-like condition. The mouse model is valuable for further investigations on mechanisms in mitochondrial hepatopathy and for interventions.

  18. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice.

    Science.gov (United States)

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Jennifer Michelle; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-04-15

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways.

  19. Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats.

    Science.gov (United States)

    Ortiz-Avila, Omar; Gallegos-Corona, Marco Alonso; Sánchez-Briones, Luis Alberto; Calderón-Cortés, Elizabeth; Montoya-Pérez, Rocío; Rodriguez-Orozco, Alain R; Campos-García, Jesús; Saavedra-Molina, Alfredo; Mejía-Zepeda, Ricardo; Cortés-Rojo, Christian

    2015-08-01

    Electron transport chain (ETC) dysfunction, excessive ROS generation and lipid peroxidation are hallmarks of mitochondrial injury in the diabetic liver, with these alterations also playing a role in the development of non-alcoholic fatty liver disease (NAFLD). Enhanced mitochondrial sensitivity to lipid peroxidation during diabetes has been also associated to augmented content of C22:6 in membrane phospholipids. Thus, we aimed to test whether avocado oil, a rich source of C18:1 and antioxidants, attenuates the deleterious effects of diabetes on oxidative status of liver mitochondria by decreasing unsaturation of acyl chains of membrane lipids and/or by improving ETC functionality and decreasing ROS generation. Streptozocin-induced diabetes elicited a noticeable increase in the content of C22:6, leading to augmented mitochondrial peroxidizability index and higher levels of lipid peroxidation. Mitochondrial respiration and complex I activity were impaired in diabetic rats with a concomitant increase in ROS generation using a complex I substrate. This was associated to a more oxidized state of glutathione, All these alterations were prevented by avocado oil except by the changes in mitochondrial fatty acid composition. Avocado oil did not prevented hyperglycemia and polyphagia although did normalized hyperlipidemia. Neither diabetes nor avocado oil induced steatosis. These results suggest that avocado oil improves mitochondrial ETC function by attenuating the deleterious effects of oxidative stress in the liver of diabetic rats independently of a hypoglycemic effect or by modifying the fatty acid composition of mitochondrial membranes. These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis.

  20. Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin

    Science.gov (United States)

    Sambuceti, Gianmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augeri, Carla; Corselli, Mirko; Ghersi, Chiara; Chiavarina, Barbara; Rodella, Luigi F; L'Abbate, Antonio; Drummond, George; Abraham, Nader G; Frassoni, Francesco

    2009-01-01

    Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels. PMID:19038792

  1. Mitochondria-specific antioxidant supplementation does not influence endurance exercise training-induced adaptations in circulating angiogenic cells, skeletal muscle oxidative capacity or maximal oxygen uptake.

    Science.gov (United States)

    Shill, Daniel D; Southern, W Michael; Willingham, T Bradley; Lansford, Kasey A; McCully, Kevin K; Jenkins, Nathan T

    2016-12-01

    Reducing excessive oxidative stress, through chronic exercise or antioxidants, can decrease the negative effects induced by excessive amounts of oxidative stress. Transient increases in oxidative stress produced during acute exercise facilitate beneficial vascular training adaptations, but the effects of non-specific antioxidants on exercise training-induced vascular adaptations remain elusive. Circulating angiogenic cells (CACs) are an exercise-inducible subset of white blood cells that maintain vascular integrity. We investigated whether mitochondria-specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training in CACs, muscle mitochondrial capacity and maximal oxygen uptake in young healthy men. We show that endurance exercise training increases multiple CAC types, an adaptation that is not altered by MitoQ supplementation. Additionally, MitoQ does not affect skeletal muscle or whole-body aerobic adaptations to exercise training. These results indicate that MitoQ supplementation neither enhances nor attenuates endurance training adaptations in young healthy men. Antioxidants have been shown to improve endothelial function and cardiovascular outcomes. However, the effects of antioxidants on exercise training-induced vascular adaptations remain elusive. General acting antioxidants combined with exercise have not impacted circulating angiogenic cells (CACs). We investigated whether mitochondria-specific antioxidant (MitoQ) supplementation would affect the response to 3 weeks of endurance exercise training on CD3+ , CD3+ /CD31+ , CD14+ /CD31+ , CD31+ , CD34+ /VEGFR2+ and CD62E+ peripheral blood mononuclear cells (PBMCs), muscle mitochondrial capacity, and maximal oxygen uptake (VO2 max ) in healthy men aged 22.1 ± 0.7 years, with a body mass index of 26.9 ± 0.9 kg m-2 , and 24.8 ± 1.3% body fat. Analysis of main effects revealed that training induced 33, 105 and 285% increases in CD14+ /CD31+ , CD62E

  2. Acupuncture reduces memory impairment and oxidative stress and enhances cholinergic function in an animal model of alcoholism.

    Science.gov (United States)

    Phunchago, Nattaporn; Wattanathorn, Jintanaporn; Chaisiwamongkol, Kowit; Muchimapura, Supaporn; Thukham-Mee, Wipawee

    2015-02-01

    Currently, the therapeutic strategy against memory deficit induced by alcoholism is not satisfactory and is expensive. Therefore, an effective, low-cost strategy is required. On the basis of the memory-enhancing effect of stimulation of the HT7 acupoint, we aimed to determine whether acupuncture at the HT7 acupoint can reduce alcoholism-induced memory impairment. The possible underlying mechanism was also explored. Alcoholism was induced in male Wistar rats weighing 180-220 g. The alcoholic rats received either acupuncture at HT7 or sham acupuncture for 1 minute bilaterally once daily for 14 days. Their spatial memory was assessed after 1 day, 7 days, and 14 days of treatment. At the end of the study, the malondialdehyde level and the activities of catalase, superoxide dismutase, glutathione peroxidase, and acetylcholinesterase enzymes in the hippocampus were determined using colorimetric assays. The results showed that acupuncture at HT7 significantly decreased the acetylcholinesterase activity and the malondialdehyde level, but increased the activities of catalase, superoxide dismutase, and glutathione peroxidase in the hippocampus. These results suggest that acupuncture at HT7 can effectively reduce the alcoholism-induced memory deficit. However, further studies concerning the detailed relationships between the location of the HT7 acupoint and the changes in the observed parameters are required. Copyright © 2015. Published by Elsevier B.V.

  3. Decreased endothelial nitric oxide bioavailability, impaired microvascular function, and increased tissue oxygen consumption in children with falciparum malaria.

    Science.gov (United States)

    Yeo, Tsin W; Lampah, Daniel A; Kenangalem, Enny; Tjitra, Emiliana; Weinberg, J Brice; Granger, Donald L; Price, Ric N; Anstey, Nicholas M

    2014-11-15

    Endothelial nitric oxide (NO) bioavailability, microvascular function, and host oxygen consumption have not been assessed in pediatric malaria. We measured NO-dependent endothelial function by using peripheral artery tonometry to determine the reactive hyperemia index (RHI), and microvascular function and oxygen consumption (VO2) using near infrared resonance spectroscopy in 13 Indonesian children with severe falciparum malaria and 15 with moderately severe falciparum malaria. Compared with 19 controls, children with severe malaria and those with moderately severe malaria had lower RHIs (P = .03); 12% and 8% lower microvascular function, respectively (P = .03); and 29% and 25% higher VO2, respectively. RHIs correlated with microvascular function in all children with malaria (P function and increased oxygen consumption, likely contributing to the pathogenesis of the disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Acute but not chronic ethanol exposure impairs retinol oxidation in the small and large intestine of the rat

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Ellendt, K.; Lindros, K.

    2005-01-01

    BACKGROUND AND AIM: Ethanol has been shown to inhibit retinol oxidation at the level of alcohol dehydrogenase in liver and colon but not previously in the small intestine. In the present study we investigated how chronic alcohol feeding and acute ethanol exposure affects retinol dehydrogenase...... activity in the colon and small intestine of the rat. METHODS: Rats were fed ethanol in a liquid diet for six weeks. Control rats received a similar diet but with ethanol isocalorically replaced by carbohydrates. Retinol dehydrogenase was analyzed from cell cytosol samples from the small and the large...... higher, respectively). While chronic alcohol feeding did not affect these parameters, acute ethanol exposure reduced V(max) and V(max)/K(m) dose-dependently (p

  5. Impairment of the mitochondrial oxidative phosphorylation system and oxidative stress in liver of crucian carp (Carassius auratus L.) exposed to microcystins.

    Science.gov (United States)

    Zhao, Yanyan; Xie, Ping; Fan, Huihui; Zhao, Sujuan

    2014-01-01

    Hepatotoxic microcystins (MCs) are produced by cyanobacteria in diverse water bodies and the pathophysiology includes induction of reactive oxygen species and adenosine triphosphate (ATP) depletion in cells. In this study, we evaluated MCs induced changes in the oxidative phosphorylation (OXPHOS) system in mitochondria of crucian carp liver. Fish were subdivided into two groups that were intraperitoneally injected with two doses of MCs (50 and 200 MC-LReq μg/kg bw) and were sacrificed at 1, 3, 12, 24, and 48 h postinjection. The activities of five enzyme complexes of electron transport chain and mRNA expression of mitochondrial-encoded genes (cox1, cox2, cox3, and atp6) were significantly reduced in a time-dependent pattern after injection. There were also changes in mitochondrial ultrastructure, decreases in ATPase activities and reduction in antioxidant level after MCs exposure. Disorder in the OXPHOS system and decreased activities of antioxidative enzymes might contribute to bioenergy deficiency and consequent hepatocyte damage induced by MCs. Copyright © 2011 Wiley Periodicals, Inc.

  6. The Protective Role of Selenium on Scopolamine-Induced Memory Impairment, Oxidative Stress, and Apoptosis in Aged Rats: The Involvement of TRPM2 and TRPV1 Channels.

    Science.gov (United States)

    Balaban, Hasan; Nazıroğlu, Mustafa; Demirci, Kadir; Övey, İshak Suat

    2017-05-01

    Inhibition of Ca2+ entry into the hippocampus and dorsal root ganglion (DRG) through inhibition of N-methyl-D-aspartate (NMDA) receptor antagonist drugs is the current standard of care in neuronal diseases such as Alzheimer's disease, dementia, and peripheral pain. Oxidative stress activates Ca2+-permeable TRPM2 and TRPV1, and recent studies indicate that selenium (Se) is a potent TRPM2 and TRPV1 channel antagonist in the hippocampus and DRG. In this study, we investigated the neuroprotective properties of Se in primary hippocampal and DRG neuron cultures of aged rats when given alone or in combination with scopolamine (SCOP). Thirty-two aged (18-24 months old) rats were divided into four groups. The first and second groups received a placebo and SCOP (1 mg/kg/day), respectively. The third and fourth groups received intraperitoneal Se (1.5 mg/kg/ over day) and SCOP + Se, respectively. The hippocampal and DRG neurons also were stimulated in vitro with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel agonist (cumene hydroperoxide). We found that Se was fully effective in reversing SCOP-induced TRPM2 and TRPV1 current densities as well as errors in working memory and reference memory. In addition, Se completely reduced SCOP-induced oxidative toxicity by modulating lipid peroxidation, reducing glutathione and glutathione peroxidase. The Se and SCOP + Se treatments also decreased poly (ADP-ribose) polymerase activity, intracellular free Ca2+ concentrations, apoptosis, and caspase 3, caspase 9, and mitochondrial membrane depolarization values in the hippocampus. In conclusion, the current study reports on the cellular level for SCOP and Se on the different endocytotoxic cascades for the first time. Notably, the research indicates that Se can result in remarkable neuroprotective and memory impairment effects in the hippocampal neurons of rats. Graphical abstract Possible molecular pathways of involvement of selenium (Se) in scopolamine (SCOP) induced

  7. An additive factor analysis of the effect of sub-anaesthetic doses of nitrous oxide on information processing: evidence for an impairment of the motor adjustment stage.

    Science.gov (United States)

    Courtière, Alain; Hardouin, Jeannine; Vidal, Franck; Possamaï, Camille-Aimé; Hasbroucq, Thierry

    2003-02-01

    Nitrous oxide (N(2)O) inhalation, at subanaesthetic concentrations, impairs choice reaction time (RT). However, the functional locus of this effect remains to be ascertained. In the present study, this issue was investigated by applying the additive factor logic to the RTs of rats performing a visuo-motor task. The task consisted of either a left-side or a right-side body displacement to a visual stimulus displayed in either the left or right hemispace. The experimental design involved the manipulation of two task factors (stimulus luminance and foreperiod duration) the effects of which are additive on RT. Inhaled N(2)O (from 0% to 60%) was varied as the third factor of the design. N(2)O prolonged RT in a dose-dependent manner and this effect was additive with that of stimulus luminance, whilst it interacted with that of foreperiod duration. Moreover, at low concentrations (10-20%), N(2)O abolished the effect of foreperiod, possibly through a disturbance of time estimation processes, whereas at higher concentrations (30-40%) N(2)O enhanced the effect of foreperiod, probably by slowing down motor processes. Movement time (MT) was decreased by N(2)O at 20-40%. The present data provide evidence that N(2)O impairs information processing by altering at least the stage of motor adjustment. In addition, N(2)O spares the sensory processes implemented during the stimulus preprocessing stage. A subsidiary result is that at some concentrations, N(2)O displays opposite effects on reaction time and movement time. These results demonstrate that the additive factor method constitutes a powerful new tool for studying the pharmacology of information processing in animal models.

  8. Sulforaphane improves oxidative status without attenuating the inflammatory response or cardiac impairment induced by ischemia-reperfusion in rats.

    Science.gov (United States)

    Bonetto, Jéssica Hellen Poletto; Fernandes, Rafael Oliveira; Seolin, Bruna Gazzi de Lima; Müller, Dalvana Daneliza; Teixeira, Rayane Brinck; Araujo, Alex Sander; Vassallo, Dalton; Schenkel, Paulo Cavalheiro; Belló-Klein, Adriane

    2016-05-01

    Sulforaphane, a natural isothiocyanate, demonstrates cardioprotection associated with its capacity to stimulate endogenous antioxidants and to inhibit inflammation. The aim of this study was to investigate whether sulforaphane is capable of attenuating oxidative stress and inflammatory responses through the TLR4/MyD88/NFκB pathway, and thereby could modulate post-ischemic ventricular function in isolated rat hearts submitted to ischemia and reperfusion. Male Wistar rats received sulforaphane (10 mg·kg(-1)·day(-1)) or vehicle i.p. for 3 days. Global ischemia was performed using isolated hearts, 24 h after the last injection, by interruption of the perfusion flow. The protocol included a 20 min pre-ischemic period followed by 20 min of ischemia and a 20 min reperfusion. Although no changes in mechanical function were observed, sulforaphane induced a significant increase in superoxide dismutase and heme oxygenase-1 expression (both 66%) and significantly reduced reactive oxygen species levels (7%). No differences were observed for catalase and glutathione peroxidase expression or their activities, nor for thioredoxin reductase, glutaredoxin reductase and glutathione-S-transferase. No differences were found in lipid peroxidation or TLR4, MyD88, and NF-κB expression. In conclusion, although sulforaphane was able to stimulate endogenous antioxidants modestly, this result did not impact inflammatory signaling or cardiac function of hearts submitted to ischemia and reperfusion.

  9. Single-walled carbon nanotubes and graphene oxides induce autophagosome accumulation and lysosome impairment in primarily cultured murine peritoneal macrophages.

    Science.gov (United States)

    Wan, Bin; Wang, Zi-Xia; Lv, Qi-Yan; Dong, Ping-Xuan; Zhao, Li-Xia; Yang, Yu; Guo, Liang-Hong

    2013-08-14

    The wide application of carbon nanomaterials in various fields urges in-depth understanding of the toxic effects and underlying mechanisms of these materials on biological systems. Cell autophagy was recently recognized as an important lysosome-based pathway of cell death, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles, but the underlying mechanisms are still uncertain due to the fact that autophagosome accumulation can result from autophagy induction and/or autophagy blockade. In this study, we first evaluated the toxicity of acid-functionalized single-walled carbon nanotubes and graphene oxides, and found that both carbon nanomaterials induced adverse effects in murine peritoneal macrophages, and GOs were more potent than AF-SWCNTs. Both carbon nanomaterials induced autophagosome accumulation and the conversion of LC3-I to LC3-II. However, degradation of the autophagic substrate p62 protein was also inhibited by both nanomaterials. Further analyses on lysosomes revealed that both carbon nanomaterials accumulated in macrophage lysosomes, leading to lysosome membrane destabilization, which indicates reduced autophagic degradation. The effects of AF-SWCNTs and GOs on cell autophagy revealed by this study may shed light on the potential toxic mechanism and suggest caution on their utilization. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Interaction between Maternal and Offspring Diet to Impair Vascular Function and Oxidative Balance in High Fat Fed Male Mice

    Science.gov (United States)

    Torrens, Christopher; Ethirajan, Priya; Bruce, Kimberley D.; Cagampang, Felino R. A.; Siow, Richard C. M.; Hanson, Mark A.; Byrne, Christopher D.; Mann, Giovanni E.; Clough, Geraldine F.

    2012-01-01

    Aims To determine the impact of maternal and post-weaning consumption of a high fat diet on endothelium-dependent vasorelaxation and redox regulation in adult male mouse offspring. Methods Female C57BL6J mice were fed an obesogenic high fat diet (HF, 45% kcal fat) or standard chow (C, 21% kcal fat) pre-conception and throughout pregnancy and lactation. Post-weaning, male offspring were continued on the same diet as their mothers or placed on the alternative diet to give 4 dietary groups (C/C, HF/C, C/HF and HF/HF) which were studied at 15 or 30 weeks of age. Results There were significant effects of maternal diet on offspring body weight (pmaternal diet there was also an effect of offspring post-weaning dietary fat to increase systolic blood pressure (pMaternal consumption of a HF diet is associated with changes in vascular function and oxidative balance in the offspring of similar magnitude to those seen with consumption of a high fat diet post-weaning. Further, this disadvantageous vascular phenotype is exacerbated by age to influence the risk of developing obesity, raised blood pressure and endothelial dysfunction in adult life. PMID:23227196

  11. Subtle reproductive impairment through nitric oxide-mediated mechanisms in sea urchins from an area affected by harmful algal blooms

    Science.gov (United States)

    Migliaccio, Oriana; Castellano, Immacolata; di Cioccio, Davide; Tedeschi, Gabriella; Negri, Armando; Cirino, Paola; Romano, Giovanna; Zingone, Adriana; Palumbo, Anna

    2016-05-01

    The health of the sea urchin Paracentrotus lividus, a key species in the Mediterranean Sea, is menaced by several pressures in coastal environments. Here, we aimed at assessing the reproductive ability of apparently healthy P. lividus population in a marine protected area affected by toxic blooms of Ostreospsis cf. ovata. Wide-ranging analyses were performed in animals collected prior to and during the bloom, as well as at several times thereafter, during the reproductive season. Adults showed a low fertilization rate, along with high nitric oxide (NO) levels in the gonads and the nitration of the major yolk protein toposome, which is an important player in sea urchin development. Serious developmental anomalies were observed in the progeny, which persist several months after the bloom. NO levels were high in the different developmental stages, which also showed variations in the transcription of several genes that were found to be directly or indirectly modulated by NO. These results highlight subtle but important reproductive flaws transmitted from the female gonads to the offspring with the NO involvement. Despite a recovery along time after the bloom, insidious damages can be envisaged in the local sea urchin population, with possible reverberation on the whole benthic system.

  12. Impaired Pulmonary Arterial Vasoconstriction and Nitric Oxide-Mediated Relaxation Underlie Severe Pulmonary Hypertension in Sugen-Hypoxia Rat Model.

    Science.gov (United States)

    Christou, Helen; Hudalla, Hannes; Michael, Zoe; Filatava, Evgenia; Li, Jun; Zhu, Minglin; Possomato-Vieira, Jose; Dias-Junior, Carlos; Kourembanas, Stella; Khalil, Raouf A

    2017-12-06

    Pulmonary vasoreactivity could determine the responsiveness to vasodilators and in turn the prognosis of pulmonary hypertension (PH). We hypothesized that pulmonary vasoreactivity is impaired, and examined the underlying mechanisms, in the sugen-hypoxia rat model of severe PH. Male Sprague-Dawley rats were injected with sugen (20 mg/kg sc) and exposed to hypoxia (9% O2) for 3 weeks followed by 4 weeks in normoxia (Su/Hx), or treated with sugen alone (Su) or hypoxia alone (Hx) or neither (Nx). After hemodynamic measurements, the heart was assessed for right ventricular hypertrophy (Fulton's Index), the pulmonary artery, aorta and mesenteric arteries were isolated for vascular function studies, and contractile markers were measured in pulmonary artery using quantitative PCR. Other rats were used for morphometric analysis of pulmonary vascular remodeling. Right ventricular systolic pressure and Fulton's Index were higher in Su/Hx vs Su, Hx and Nx rats. Pulmonary vascular remodeling was more prominent in Su/Hx vs Nx rats. In pulmonary artery rings, contraction to high KCl (96 mM) was less in Su/Hx vs Nx and Su, and phenylephrine-induced contraction was reduced in Su/Hx vs Nx, Hx and Su. Acetylcholine (ACh)-induced relaxation was less in Su/Hx vs Nx and Hx, suggesting reduced endothelium-dependent vasodilation. ACh relaxation was inhibited by NOS and guanylate cyclase blockade in all groups, suggesting a role of the NO-cGMP pathway. Nitrate/nitrite production in response to ACh was less in Su/Hx vs Nx, supporting reduced endothelial NO production. Sodium nitroprusside (10-8 M) caused less relaxation in Su/Hx vs Nx, Hx and Su, suggesting decreased responsiveness of vascular smooth muscle (VSM) to vasodilators. Neither contraction nor relaxation differed in the aorta or mesenteric arteries of all groups. PCR analysis showed decreased expression of contractile markers in pulmonary artery of Su/Hx vs Nx. The reduced responsiveness to vasoconstrictors and NO

  13. Reduction of death rate due to acute myocardial infarction in subjects with cancers through systemic restoration of impaired nitric oxide.

    Directory of Open Access Journals (Sweden)

    Rajeshwary Ghosh

    Full Text Available INTRODUCTION: Excessive aggregation of platelets at the site of plaque rupture on the coronary artery led to the formation of thrombus which is reported to precipitate acute myocardial infarction (AMI. Nitric oxide (NO has been reported to inhibit platelet aggregation and induce thrombolysis through the in situ formation of plasmin. As the plasma NO level in AMI patients from two different ethnic groups was reduced to 0 µM (median compared to 4.0 µM (median in normal controls, the effect of restoration of the NO level to normal ranges on the rate of death due to AMI was determined. METHODS AND RESULTS: The restoration of plasma NO level was achieved by a sticking small cotton pad (10×25 mm containing 0.28 mmol sodium nitroprusside (SNP in 0.9% NaCl to the abdominal skin of the participants using non-toxic adhesive tape which was reported to normalize the plasma NO level. The participants (8,283 were volunteers in an independent study who had different kinds of cancers and did not wish to use any conventional therapy for their condition but opted to receive SNP "pad" for their condition for 3 years. The use of SNP "pad" which normalized (≈4.0 µM the plasma NO level that in consequence reduced the death rate due to AMI, among the participants, was found to be significantly reduced compared to the death due to AMI in normal population. CONCLUSION: Our data suggested that the use of SNP "pad" significantly reduced the death due to AMI. TRIAL REGISTRATION: www.ctri.nic.in CTRI/2013/12/004236.

  14. Bioaccumulation, stress, and swimming impairment in Daphnia magna exposed to multiwalled carbon nanotubes, graphene, and graphene oxide.

    Science.gov (United States)

    Cano, Amanda M; Maul, Jonathan D; Saed, Mohammad; Shah, Smit A; Green, Micah J; Cañas-Carrell, Jaclyn E

    2017-08-01

    The use of carbon-based nanomaterials (CNMs) such as multiwalled carbon nanotubes (MWCNTs), graphene, and graphene oxide (GO) is increasing across many applications because of their unique and versatile properties. These CNMs may enter the aquatic environment through many pathways, creating the potential for organism exposure. The present study addresses the bioaccumulation and toxicity seen in Daphnia magna exposed to CNMs dispersed in sodium dodecyl benzene sulfonate (SDBS). In study I, D. magna were exposed to varying outer diameters of MWCNTs for 24 h in moderately hard or hard freshwater. Bioaccumulation of MWCNT was found in all treatments, with the highest concentrations (0.53 ± 0.27 μg/g) in D. magna exposed in hard freshwater (p < 0.005). The median lethal concentration (LC50) was determined for D. magna exposed to CNMs in moderately hard and hard freshwater. In study II, D. magna were exposed to CNMs for 72 h in moderately hard freshwater to assess swimming velocity and generation of reactive oxygen species (ROS) detected by dichlorofluorescein fluorescence. An overall decrease was seen in D. magna swimming velocity after exposure to CNMs. The generation of ROS was significantly higher (1.54 ± 0.38 dichlorofluorescein mM/mg dry wt) in D. magna exposed to MWCNTs of smaller outer diameters than in controls after 72 h (p < 0.05). These results suggest that further investigation of CNM toxicity and behavior in the aquatic environment is needed. Environ Toxicol Chem 2017;36:2199-2204. © 2017 SETAC. © 2017 SETAC.

  15. Reduction of brain mitochondrial β-oxidation impairs complex I and V in chronic alcohol intake: the underlying mechanism for neurodegeneration.

    Directory of Open Access Journals (Sweden)

    James Haorah

    Full Text Available Neuropathy and neurocognitive deficits are common among chronic alcohol users, which are believed to be associated with mitochondrial dysfunction in the brain. The specific type of brain mitochondrial respiratory chain complexes (mRCC that are adversely affected by alcohol abuse has not been studied. Thus, we examined the alterations of mRCC in freshly isolated mitochondria from mice brain that were pair-fed the ethanol (4% v/v and control liquid diets for 7-8 weeks. We observed that alcohol intake severely reduced the levels of complex I and V. A reduction in complex I was associated with a decrease in carnitine palmitoyltransferase 1 (cPT1 and cPT2 levels. The mitochondrial outer (cPT1 and inner (cPT2 membrane transporter enzymes are specialized in acylation of fatty acid from outer to inner membrane of mitochondria for ATP production. Thus, our results showed that alterations of cPT1 and cPT2 paralleled a decrease β-oxidation of palmitate and ATP production, suggesting that impairment of substrate entry step (complex I function can cause a negative impact on ATP production (complex V function. Disruption of cPT1/cPT2 was accompanied by an increase in cytochrome C leakage, while reduction of complex I and V paralleled a decrease in depolarization of mitochondrial membrane potential (ΔΨ, monitored by JC-1 fluorescence and ATP production in alcohol intake. We noted that acetyl-L-carnitine (ALC, a cofactor of cPT1 and cPT2 prevented the adverse effects of alcohol while coenzyme Q10 (CoQ10 was not very effective against alcohol insults. These results suggest that understanding the molecular, biochemical, and signaling mechanisms of the CNS mitochondrial β-oxidation such as ALC can mitigate alcohol related neurological disorders.

  16. 2-(2-benzofuranyl)-2-imidazoline (2-BFI) improved the impairments in AD rat models by inhibiting oxidative stress, inflammation and apoptosis.

    Science.gov (United States)

    Tian, Ji-Sha; Zhai, Qi-Jin; Zhao, Ying; Chen, Rui; Zhao, Lian-Dong

    2017-01-01

    Alzheimer's Disease (AD) is one of the commonest neural degeneration in aging population, and has become a global health challenge. 2-(2-benzofuranyl)-2-imidazoline (2-BFI) was reported to effectively improved the damage of patients with neuropathological disorders. In the present study, we investigated the effect of 2-BFI on the improvement of antioxidative, inflammation, and apoptosis in AD rats. Sprague-Dawley rats (2 months old, n=40) were used in this study and after injection of Aβ1-42 into hippocampal CA1 (Cornu Ammonis) region, the rats were given high, moderate and low dose of 2-BFI though intraperitoneal (i.p.) injection. Then spatial memory and navigation ability were analyzed by Morrize Water Maze. For the molecular testing, chemical colorimetry, ELISA and immunoblotting were performed to measure the activities of antioxidative enzymes, the abundance of immune cytokines and expression of apoptotic proteins, respectively. Hematoxylin and Eosin staining was used to analyze the pathological changes. We observed that 2-BFI significantly ameliorated the learning and memory abilities in rat models with AD by dosage treatment, as demonstrated by the shorten learning latency and greater times of travel across the platform quadrant. Additionally, reactive oxygen species (ROS) and malondialdehyde (MDA), were decreased after treatment of 2-BFI with dosage dependency, while the activities of superoxidase dismutase (SOD) and (GPX) Glutathione peroxidase were in turn enhanced, suggesting that 2-BFI could protect the antioxidative enzymes and reduce the oxidative stress in the hippocampus. Moreover, the expression of inflammatory factors including TNF-a and IL-1β were decreased after 2-BFI treatment. Additionally, the neuronal apoptosis was also attenuated, as shown by Western blot results. Taken together, the cognitive impairment in AD rats could be significantly improved by 2-BFI in a dose-dependent manner through suppressing oxidants accumulation, inhibiting of

  17. Visual Impairment

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Visual Impairment KidsHealth / For Teens / Visual Impairment What's in ... with the brain, making vision impossible. What Is Visual Impairment? Many people have some type of visual ...

  18. Experimental Research on Therapeutic Efficacy of Traditional Chinese Medicine Shengjing Capsule Extracts in Treating Spermatogenesis Impairment Induced by Oxidative Stress.

    Science.gov (United States)

    Zhou, Shaohu; Wen, Zhiwei; Liang, Aijun; Zhang, Shuting

    2016-01-05

    To investigate antioxidant effects of traditional Chinese Shengjing capsule extracts (sperm-producing capsule, with functions of tonifying kidney and invigorating kidney essence) on testes, epididymides, and sperms of rats. We randomly divided 50 rats into 5 groups. G1: normal control group (treated with saline); G2: cadmium chloride group; G3: cadmium chloride+ low doses of drugs; G4: cadmium chloride + medium doses of drugs; and G5: cadmium chloride + high doses of drugs (equivalent dose: 0.45 g/kg). In addition to the normal control group, the other 4 groups started receiving intraperitoneal injection of cadmium chloride (1 mg/kg, i.p.). Testicular glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and malondialdehyde aldehyde (MDA) were measured by ELISA; epididymis histopathological examination was performed; testis serum testosterone (T) was measured; specimens of the epididymal semen were analyzed for sperm concentration, morphology, vitality, and DNA fragmentation rate. Sperm count and activity of rats in the model control group decreased significantly; their MDA concentration of testicular and epididymal homogenates increased greatly; while the vitality of SOD and GSH-Px dropped sharply. All indexes mentioned above were significantly different from those of the blank control group (P<0.05); the sperm count and activity of rats treated with Shengjing capsule (sperm-producing capsule) decreased, but were still significantly higher than those of the model group (P<0.05). MDA level of rats treated with Shengjing capsule were significantly lower than that of the model group (P<0.05), while their SOD and GSH-Px activity were significantly higher than the model group (P<0.05). The normal morphology rate and DNA integrity rate of groups treated with Shengjing capsule were significantly higher than those of the model group (P<0.05). Shengjing can enhance the activity of antioxidant enzymes and inhibit oxidative stress. It can also repair testicular and

  19. Gamma rays induce DNA damage and oxidative stress associated with impaired growth and reproduction in the copepod Tigriopus japonicus

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jeonghoon; Won, Eun-Ji; Lee, Bo-Young [Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Hwang, Un-Ki [Marine Ecological Risk Assessment Center, West Sea Fisheries Research Institute, National Fisheries Research and Development Institute, Incheon 400-420 (Korea, Republic of); Kim, Il-Chan; Yim, Joung Han [Division of Life Sciences, Korea Polar Research Institute, Incheon 406-840 (Korea, Republic of); Leung, Kenneth Mei Yee [School of Biological Sciences and the Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong (China); Lee, Yong Sung [Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Lee, Jae-Seong, E-mail: jslee2@skku.edu [Department of Biological Sciences, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

    2014-07-01

    irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50–200 Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase the expression of antioxidant enzymes and proteins with chaperone-related functions, thereby significantly affecting life history parameters such as fecundity and molting in the copepod T. japonicus.

  20. Gamma rays induce DNA damage and oxidative stress associated with impaired growth and reproduction in the copepod Tigriopus japonicus.

    Science.gov (United States)

    Han, Jeonghoon; Won, Eun-Ji; Lee, Bo-Young; Hwang, Un-Ki; Kim, Il-Chan; Yim, Joung Han; Leung, Kenneth Mei Yee; Lee, Yong Sung; Lee, Jae-Seong

    2014-07-01

    Nuclear radioisotope accidents are potentially ecologically devastating due to their impact on marine organisms. To examine the effects of exposure of a marine organism to radioisotopes, we irradiated the intertidal copepod Tigriopus japonicus with several doses of gamma radiation and analyzed the effects on mortality, fecundity, and molting by assessing antioxidant enzyme activities and gene expression patterns. No mortality was observed at 96h, even in response to exposure to a high dose (800Gy) of radiation, but mortality rate was significantly increased 120h (5 days) after exposure to 600 or 800Gy gamma ray radiation. We observed a dose-dependent reduction in fecundity of ovigerous females; even the group irradiated with 50Gy showed a significant reduction in fecundity, suggesting that gamma rays are likely to have a population level effect. In addition, we observed growth retardation, particularly at the nauplius stage, in individuals after gamma irradiation. In fact, nauplii irradiated with more than 200Gy, though able to molt to copepodite stage 1, did not develop into adults. Upon gamma radiation, T. japonicus showed a dose-dependent increase in reactive oxygen species (ROS) levels, the activities of several antioxidant enzymes, and expression of double-stranded DNA break damage genes (e.g. DNA-PK, Ku70, Ku80). At a low level (sub-lethal dose) of gamma irradiation, we found dose-dependent upregulation of p53, implying cellular damage in T. japonicus in response to sub-lethal doses of gamma irradiation, suggesting that T. japonicus is not susceptible to sub-lethal doses of gamma irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50-200Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase

  1. Methanolic extract of Piper nigrum fruits improves memory impairment by decreasing brain oxidative stress in amyloid beta(1-42) rat model of Alzheimer's disease.

    Science.gov (United States)

    Hritcu, Lucian; Noumedem, Jaurès A; Cioanca, Oana; Hancianu, Monica; Kuete, Victor; Mihasan, Marius

    2014-04-01

    The present study analyzed the possible memory-enhancing and antioxidant proprieties of the methanolic extract of Piper nigrum L. fruits (50 and 100 mg/kg, orally, for 21 days) in amyloid beta(1-42) rat model of Alzheimer's disease. The memory-enhancing effects of the plant extract were studied by means of in vivo (Y-maze and radial arm-maze tasks) approaches. Also, the antioxidant activity in the hippocampus was assessed using superoxide dismutase-, catalase-, glutathione peroxidase-specific activities and the total content of reduced glutathione, malondialdehyde, and protein carbonyl levels. The amyloid beta(1-42)-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory and reference memory errors within radial arm-maze task. Administration of the plant extract significantly improved memory performance and exhibited antioxidant potential. Our results suggest that the plant extract ameliorates amyloid beta(1-42)-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.

  2. Complete genome sequence of Nitrosomonas sp. Is79, an ammonia oxidizing bacterium adapted to low ammonium concentrations

    NARCIS (Netherlands)

    Bollmann, A.; Sedlacek, C.J.; Norton, J.; Laanbroek, H.J.; Suwa, Y.; Stein, L.Y.; Klotz, M.G.; Arp, D.; Sayavedra-Soto, L.; Lu, M.; Bruce, D.; Detter, C.; Tapia, R.; Han, J.; Woyke, T.; Lucas, S.; Pitluck, S.; Pennacchio, L.; Nolan, M.; Land, M.L.; Huntemann, M.; Deshpande, S.; Han, C.; Chen, A.; Kyrpides, N.; Mavromatis, K.; Markowitz, V.; Szeto, E.; Ivanova, N.; Mikhailova, N.; Pagani, I.; Pati, A.; Peters, L.; Ovchinnikova, G.; Goodwin, L.

    2013-01-01

    Nitrosomonas sp. Is79 is a chemolithoautotrophic ammonia-oxidizing bacterium that belongs to the family Nitrosomonadaceae within the phylum Proteobacteria. Ammonia oxidation is the first step of nitrification, an important process in the global nitrogen cycle ultimately resulting in the production

  3. A Systematic Review of the Literature on Parenting of Young Children with Visual Impairments and the Adaptions for Video-Feedback Intervention to Promote Positive Parenting (VIPP)

    NARCIS (Netherlands)

    van den Broek, Ellen G. C.; van Eijden, Ans J P M; Overbeek, Mathilde M.; Kef, Sabina; Sterkenburg, Paula S.; Schuengel, Carlo

    Secure parent-child attachment may help children to overcome the challenges of growing up with a visual or visual-and-intellectual impairment. A large literature exists that provides a blueprint for interventions that promote parental sensitivity and secure attachment. The Video-feedback

  4. Progesterone impairs cell respiration and suppresses a compensatory increase in glucose transport in isolated rat skeletal muscle: a non-genomic mechanism contributing to metabolic adaptation to late pregnancy?

    Science.gov (United States)

    Gras, F; Brunmair, B; Quarré, L; Szöcs, Z; Waldhäusl, W; Fürnsinn, C

    2007-12-01

    The aim of the study was to gain better insight into the mechanisms responsible for impaired glucose metabolism during late pregnancy. We explored the direct effects of progesterone on glucose metabolism of skeletal muscle. Specimens of skeletal muscle from untreated rats were incubated with progesterone and rates of substrate fluxes through the various pathways of glucose metabolism were analysed. Progesterone dose-dependently reduced the rates of glucose and pyruvate oxidation (insulin-stimulated rates after 5 h of exposure to 1 and 10 mumol/l progesterone: glucose oxidation, -6 +/- 4%, NS, and -39 +/- 4%, p glucose transport, but this response was blunted in the case of progesterone (change of glucose transport in response to 10 mumol/l progesterone vs 60 nmol/l rotenone, both causing a reduction in glucose oxidation by -39%: progesterone, +14 +/- 8% vs rotenone, +84 +/- 23%, p glucose oxidation after 30 min: -29 +/- 7%, p glucose transport, causing cellular carbohydrate deficiency in isolated rat skeletal muscle. This effect is mediated by a direct, rapid and non-genomic mechanism and could contribute to pregnancy-associated changes in glucose homeostasis.

  5. Fus1 KO mouse as a model of oxidative stress-mediated sporadic Alzheimer’s disease: circadian disruption and long-term spatial and olfactory memory impairments.

    Directory of Open Access Journals (Sweden)

    Guillermo Coronas-Samano

    2016-11-01

    Full Text Available Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4-5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1, disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK, autophagy (decreased levels of LC3-II, PKC (decreased levels of RACK1 and calcium signaling (decreased levels of Calb2 in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus, in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term, olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie, spatial memory (learning impairments on finding the platform in the Morris water maze and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation, association memory (passive avoidance or in species-typical behavior (nest building and no increased anxiety (open field, light-dark box or depression/anhedonia (sucrose preference at this relatively young age. These

  6. Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model.

    Science.gov (United States)

    Hu, Y; Niu, X; Wang, G; Huang, J; Liu, M; Peng, B

    2016-11-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF-α, IL-1β, and IL-6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS-induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were

  7. WISC-IV Profile in High-Functioning Autism Spectrum Disorders: Impaired Processing Speed Is Associated with Increased Autism Communication Symptoms and Decreased Adaptive Communication Abilities

    Science.gov (United States)

    Oliveras-Rentas, Rafael E.; Kenworthy, Lauren; Roberson, Richard B.; Martin, Alex; Wallace, Gregory L.

    2012-01-01

    Changes in the Wechsler Intelligence Scales for Children-IV (WISC-IV) may affect the IQ profile characteristic of autism spectrum disorders (ASD). Moreover, the association of particular component cognitive abilities (unlike overall IQ) with symptomatology and adaptive functioning in ASD remains unclear. This archival study characterizes the…

  8. Postprandial oxidative losses of free and protein-bound amino acids in the diet: interactions and adaptation

    NARCIS (Netherlands)

    Nolles, J.A.; Verreijen, A.M.; Koopmanschap, R.E.; Verstegen, M.W.A.; Schreurs, V.V.A.M.

    2009-01-01

    Postprandial oxidation of dietary free amino acids or egg white protein was studied using the [13CO2] breath test in rats, as well as in humans. Thirty-eight male rats were assigned to four dietary test groups. Two diets only differed in their protein fraction. Diet I contained 21% egg white

  9. Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo

    Directory of Open Access Journals (Sweden)

    Thorsten Peters

    2012-01-01

    Full Text Available Absence of β2 integrins (CD11/CD18 leads to leukocyte-adhesion deficiency-1 (LAD1, a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−. CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT. In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl21 acetyl chicken γ globulin (NP21-CG, even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1.

  10. Loss of the Arabidopsis thaliana P4-ATPase ALA3 Reduces Adaptability to Temperature Stresses and Impairs Vegetative, Pollen, and Ovule Development

    DEFF Research Database (Denmark)

    McDowell, Stephen C.; Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager

    2013-01-01

    ) to less than 0.2% (stressed). Together, these results support a model in which ALA3 functions to modify endomembranes in multiple cell types, enabling structural changes, or signaling functions that are critical in plants for normal development and adaptation to varied growth environments....... upon both temperature and soil, and varied between 40% and 80% that of wild-type under different conditions. We also demonstrate that ala3 mutants have reduced fecundity resulting from a combination of decreased ovule production and pollen tube growth defects. In-vitro pollen tube growth assays showed...

  11. Gold Nanoparticles Promote Oxidant-Mediated Activation of NF-κB and 53BP1 Recruitment-Based Adaptive Response in Human Astrocytes.

    Science.gov (United States)

    Mytych, Jennifer; Lewinska, Anna; Zebrowski, Jacek; Wnuk, Maciej

    2015-01-01

    Nanogold-based materials are promising candidate tools for nanobased medicine. Nevertheless, no conclusive information on their cytotoxicity is available. In the present study, we investigated the effects of gold nanoparticles (AuNPs) on human astrocytes in vitro. Nanogold treatment in a wide range of concentrations did not result in cytotoxicity. In contrast, nanogold provoked changes in the astrocyte cell cycle and induced senescence-associated β-galactosidase activity. AuNPs promoted oxidative stress and caused activation of NF-κB pathway. After nanogold treatment, an inverse correlation between the formation of 53BP1 foci and micronuclei generation was observed. The robust 53BP1 recruitment resulted in reduced micronuclei production. Thus, nanogold treatment stimulated an adaptive response in a human astrocyte cell.

  12. Candida albicans response regulator gene SSK1 regulates a subset of genes whose functions are associated with cell wall biosynthesis and adaptation to oxidative stress.

    Science.gov (United States)

    Chauhan, Neeraj; Inglis, Diane; Roman, Elvira; Pla, Jesus; Li, Dongmei; Calera, Jose A; Calderone, Richard

    2003-10-01

    Ssk1p of Candida albicans is a putative response regulator protein of the Hog1 two-component signal transduction system. In Saccharomyces cerevisiae, the phosphorylation state of Ssk1p determines whether genes that promote the adaptation of cells to osmotic stress are activated. We have previously shown that C. albicans SSK1 does not complement the ssk1 mutant of S. cerevisiae and that the ssk1 mutant of C. albicans is not sensitive to sorbitol. In this study, we show that the C. albicans ssk1 mutant is sensitive to several oxidants, including hydrogen peroxide, t-butyl hydroperoxide, menadione, and potassium superoxide when each is incorporated in yeast extract-peptone-dextrose (YPD) agar medium. We used DNA microarrays to identify genes whose regulation is affected by the ssk1 mutation. RNA from mutant cells (strain CSSK21) grown in YPD medium for 3 h at 30 degrees C was reverse transcribed and then compared with similarly prepared RNA from wild-type cells (CAF2). We observed seven genes from mutant cells that were consistently up regulated (three-fold or greater compared to CAF2). In S. cerevisiae, three (AHP1, HSP12, and PYC2) of the seven genes that were up regulated provide cells with an adaptation function in response to oxidative stress; another gene (GPH1) is regulated under stress conditions by Hog1p. Three other genes that are up regulated encode a cell surface protein (FLO1), a mannosyl transferase (MNN4-4), and a putative two-component histidine kinase (CHK1) that regulates cell wall biosynthesis in C. albicans. Of the down-regulated genes, ALS1 is a known cell adhesin in C. albicans. Verification of the microarray data was obtained by reverse transcription-PCR for HSP12, AHP1, CHK1, PYC2, GPH1, ALS1, MNN4-4, and FLO1. To further determine the function of Ssk1p in the Hog1p signal transduction pathway in C. albicans, we used Western blot analysis to measure phosphorylation of Hog1p in the ssk1 mutant of C. albicans when grown under either osmotic or

  13. Visual impairment workshop for sighted students

    OpenAIRE

    Habjan, Iva

    2015-01-01

    The education process based on the inclusion concept enables primary school education close to home to children with visual impairment. Before admission of visual impairment pupil, the school environment and didactic materials are adapted and teachers are provided with additional training. The preparation of sighted peers is often ignored, who form erroneous ideas through observing the adaptations and activities of a visual impairment peer, or adopt prejudices and stereotypical beliefs from ...

  14. Adaptation and Impairment of DNA Repair Function in Pollen of Betula verrucosa and Seeds of Oenothera biennis from Differently Radionuclide-contaminated Sites of Chernobyl

    Science.gov (United States)

    Boubriak, I. I.; Grodzinsky, D. M.; Polischuk, V. P.; Naumenko, V. D.; Gushcha, N. P.; Micheev, A. N.; McCready, S. J.; Osborne, D. J.

    2008-01-01

    Background and Aims The plants that have remained in the contaminated areas around Chernobyl since 1986 encapsulate the effects of radiation. Such plants are chronically exposed to radionuclides that they have accumulated internally as well as to α-, β- and γ-emitting radionuclides from external sources and from the soil. This radiation leads to genetic damage that can be countered by DNA repair systems. The objective of this study is to follow DNA repair and adaptation in haploid cells (birch pollen) and diploid cells (seed embryos of the evening primrose) from plants that have been growing in situ in different radionuclide fall-out sites in monitored regions surrounding the Chernobyl explosion of 1986. Methods Radionuclide levels in soil were detected using gamma-spectroscopy and radiochemistry. DNA repair assays included measurement of unscheduled DNA synthesis, electrophoretic determination of single-strand DNA breaks and image analysis of rDNA repeats after repair intervals. Nucleosome levels were established using an ELISA kit. Key Results Birch pollen collected in 1987 failed to perform unscheduled DNA synthesis, but pollen at γ/β-emitter sites has now recovered this ability. At a site with high levels of combined α- and γ/β-emitters, pollen still exhibits hidden damage, as shown by reduced unscheduled DNA synthesis and failure to repair lesions in rDNA repeats properly. Evening primrose seed embryos generated on plants at the same γ/β-emitter sites now show an improved DNA repair capacity and ability to germinate under abiotic stresses (salinity and accelerated ageing). Again those from combined α- and γ/β-contaminated site do not show this improvement. Conclusions Chronic irradiation at γ/β-emitter sites has provided opportunities for plant cells (both pollen and embryo cells) to adapt to ionizing irradiation and other environmental stresses. This may be explained by facilitation of DNA repair function. PMID:17981881

  15. C-Phycocyanin protects SH-SY5Y cells from oxidative injury, rat retina from transient ischemia and rat brain mitochondria from Ca2+/phosphate-induced impairment.

    Science.gov (United States)

    Marín-Prida, Javier; Pentón-Rol, Giselle; Rodrigues, Fernando Postalli; Alberici, Luciane Carla; Stringhetta, Karina; Leopoldino, Andréia Machado; Naal, Zeki; Polizello, Ana Cristina Morseli; Llópiz-Arzuaga, Alexey; Rosa, Marcela Nunes; Liberato, José Luiz; Santos, Wagner Ferreira Dos; Uyemura, Sergio Akira; Pentón-Arias, Eduardo; Curti, Carlos; Pardo-Andreu, Gilberto L

    2012-12-01

    Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat brain mitochondria (RBM). In SH-SY5Y cells, t-BOOH induced a significant reduction of cell viability as assessed by an MTT assay, and the reduction was effectively prevented by treatment with C-PC in the low micromolar concentration range. Transient ischemia in rat retinas was induced by increasing the intraocular pressure to 120mmHg for 45min, which was followed by 15min of reperfusion. This event resulted in a cell density reduction to lower than 50% in the inner nuclear layer (INL), which was significantly prevented by the intraocular pre-treatment with C-PC for 15min. In the RBM exposed to 3mM phosphate and/or 100μM Ca(2+), C-PC prevented in the low micromolar concentration range, the mitochondrial permeability transition as assessed by mitochondrial swelling, the membrane potential dissipation, the increase of reactive oxygen species levels and the release of the pro-apoptotic cytochrome c. In addition, C-PC displayed a strong inhibitory effect against an electrochemically-generated Fenton reaction. Therefore, C-PC is a potential neuroprotective agent against ischemic stroke, resulting in reduced neuronal oxidative injury and the protection of mitochondria from impairment. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Diabetic beta-cells can achieve self-protection against oxidative stress through an adaptive up-regulation of their antioxidant defenses.

    Directory of Open Access Journals (Sweden)

    Grégory Lacraz

    Full Text Available BACKGROUND: Oxidative stress (OS, through excessive and/or chronic reactive oxygen species (ROS, is a mediator of diabetes-related damages in various tissues including pancreatic beta-cells. Here, we have evaluated islet OS status and beta-cell response to ROS using the GK/Par rat as a model of type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: Localization of OS markers was performed on whole pancreases. Using islets isolated from 7-day-old or 2.5-month-old male GK/Par and Wistar control rats, 1 gene expression was analyzed by qRT-PCR; 2 insulin secretion rate was measured; 3 ROS accumulation and mitochondrial polarization were assessed by fluorescence methods; 4 antioxidant contents were quantified by HPLC. After diabetes onset, OS markers targeted mostly peri-islet vascular and inflammatory areas, and not islet cells. GK/Par islets revealed in fact protected against OS, because they maintained basal ROS accumulation similar or even lower than Wistar islets. Remarkably, GK/Par insulin secretion also exhibited strong resistance to the toxic effect of exogenous H(2O(2 or endogenous ROS exposure. Such adaptation was associated to both high glutathione content and overexpression (mRNA and/or protein levels of a large set of genes encoding antioxidant proteins as well as UCP2. Finally, we showed that such a phenotype was not innate but spontaneously acquired after diabetes onset, as the result of an adaptive response to the diabetic environment. CONCLUSIONS: The GK/Par model illustrates the effectiveness of adaptive response to OS by beta-cells to achieve self-tolerance. It remains to be determined to what extend such islet antioxidant defenses upregulation might contribute to GK/Par beta-cell secretory dysfunction.

  17. Integrating nitric oxide, nitrite and hydrogen sulfide signaling in the physiological adaptations to hypoxia: A comparative approach

    DEFF Research Database (Denmark)

    Fago, Angela; Jensen, Frank Bo; Tota, Bruno

    2012-01-01

    Hydrogen sulfide (H2S), nitric oxide (NO) and nitrite (NO2-) are formed in vivo and are of crucial importance in the tissue response to hypoxia, particularly in the cardiovascular system, where these signaling molecules are involved in a multitude of processes including the regulation of vascular...... tone, cellular metabolic function and cytoprotection. This report summarizes current advances on the mechanisms by which these signaling pathways act and may have evolved in animals with different tolerance to hypoxia, as presented and discussed during the scientific sessions of the annual meeting...... of the Society for Experimental Biology in 2011 in Glasgow. It also highlights the need and potential for a comparative approach of study and collaborative effort to identify potential link(s) between the signaling pathways involving NO, nitrite and H2S in the whole-body responses to hypoxia....

  18. Integrating nitric oxide, nitrite and hydrogen sulfide signaling in the physiological adaptations to hypoxia: A comparative approach.

    Science.gov (United States)

    Fago, Angela; Jensen, Frank B; Tota, Bruno; Feelisch, Martin; Olson, Kenneth R; Helbo, Signe; Lefevre, Sjannie; Mancardi, Daniele; Palumbo, Anna; Sandvik, Guro K; Skovgaard, Nini

    2012-05-01

    Hydrogen sulfide (H(2)S), nitric oxide (NO) and nitrite (NO(2)(-)) are formed in vivo and are of crucial importance in the tissue response to hypoxia, particularly in the cardiovascular system, where these signaling molecules are involved in a multitude of processes including the regulation of vascular tone, cellular metabolic function and cytoprotection. This report summarizes current advances on the mechanisms by which these signaling pathways act and may have evolved in animals with different tolerance to hypoxia, as presented and discussed during the scientific sessions of the annual meeting of the Society for Experimental Biology in 2011 in Glasgow. It also highlights the need and potential for a comparative approach of study and collaborative effort to identify potential link(s) between the signaling pathways involving NO, nitrite and H(2)S in the whole-body responses to hypoxia. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. The 2013 SFRBM discovery award: selected discoveries from the butterfield laboratory of oxidative stress and its sequela in brain in cognitive disorders exemplified by Alzheimer disease and chemotherapy induced cognitive impairment.

    Science.gov (United States)

    Butterfield, D Allan

    2014-09-01

    This retrospective review on discoveries of the roles of oxidative stress in brain of subjects with Alzheimer disease (AD) and animal models thereof as well as brain from animal models of chemotherapy-induced cognitive impairment (CICI) results from the author receiving the 2013 Discovery Award from the Society for Free Radical Biology and Medicine. The paper reviews our laboratory's discovery of protein oxidation and lipid peroxidation in AD brain regions rich in amyloid β-peptide (Aβ) but not in Aβ-poor cerebellum; redox proteomics as a means to identify oxidatively modified brain proteins in AD and its earlier forms that are consistent with the pathology, biochemistry, and clinical presentation of these disorders; how Aβ in in vivo, ex vivo, and in vitro studies can lead to oxidative modification of key proteins that also are oxidatively modified in AD brain; the role of the single methionine residue of Aβ(1-42) in these processes; and some of the potential mechanisms in the pathogenesis and progression of AD. CICI affects a significant fraction of the 14 million American cancer survivors, and due to diminished cognitive function, reduced quality of life of the persons with CICI (called "chemobrain" by patients) often results. A proposed mechanism for CICI employed the prototypical ROS-generating and non-blood brain barrier (BBB)-penetrating chemotherapeutic agent doxorubicin (Dox, also called adriamycin, ADR). Because of the quinone moiety within the structure of Dox, this agent undergoes redox cycling to produce superoxide free radical peripherally. This, in turn, leads to oxidative modification of the key plasma protein, apolipoprotein A1 (ApoA1). Oxidized ApoA1 leads to elevated peripheral TNFα, a proinflammatory cytokine that crosses the BBB to induce oxidative stress in brain parenchyma that affects negatively brain mitochondria. This subsequently leads to apoptotic cell death resulting in CICI. This review outlines aspects of CICI consistent with

  20. The 2013 Discovery Award from the Society for Free Radical Biology and Medicine: Selected Discoveries from the Butterfield Laboratory of Oxidative Stress and Its Sequelae in Brain in Cognitive Disorders Exemplified by Alzheimer Disease and Chemotherapy Induced Cognitive Impairment

    Science.gov (United States)

    Butterfield, D. Allan

    2014-01-01

    This retrospective review on discoveries of the roles of oxidative stress in brain of subjects with Alzheimer disease (AD) and animal models thereof as well as brain from animal models of chemotherapy induced cognitive impairment (CICI) results from the author receiving the 2013 Discovery Award from the Society for Free Radical Biology and Medicine. The paper reviews our laboratory's discovery of: protein oxidation and lipid peroxidation in AD brain regions rich in amyloid β-peptide (Aβ) but not in Aβ-poor cerebellum; redox proteomics as a means to identify oxidatively modified brain proteins in AD and its earlier forms that are consistent with the pathology, biochemistry, and clinical presentation of these disorders; how Aβ in in vivo, ex vivo, and in vitro studies can lead to oxidative modification of key proteins that also are oxidatively modified in AD brain; the role of the single methionine residue of Aβ(1-42) in these processes; and some of the potential mechanisms in the pathogenesis and progression of AD. CICI affects a significant fraction of the 14 million American cancer survivors, and due to diminished cognitive function, reduced quality of life of the persons with CICI (called “chemobrain” by patients) often results. A proposed mechanism for CICI employed the prototypical ROS-generating and non-blood brain barrier (BBB)-penetrating chemotherapeutic agent doxorubicin (Dox, also called adriamycin, ADR). Because of the quinone moiety within the structure of Dox, this agent undergoes redox cycling to produce superoxide free radical peripherally. This, in turn, leads to oxidative modification of the key plasma protein, Apolipoprotein A1 (ApoA1). Oxidized ApoA1 leads to elevated peripheral TNFα, a pro-inflammatory cytokine that crosses the BBB to induce oxidative stress in brain parenchyma that affects negatively brain mitochondria. This subsequently leads to apoptotic cell death resulting in CICI. This review outlines aspects of CICI consistent

  1. Loss of the Arabidopsis thaliana P₄-ATPase ALA3 reduces adaptability to temperature stresses and impairs vegetative, pollen, and ovule development.

    Directory of Open Access Journals (Sweden)

    Stephen C McDowell

    Full Text Available Members of the P4 subfamily of P-type ATPases are thought to help create asymmetry in lipid bilayers by flipping specific lipids between the leaflets of a membrane. This asymmetry is believed to be central to the formation of vesicles in the secretory and endocytic pathways. In Arabidopsis thaliana, a P4-ATPase associated with the trans-Golgi network (ALA3 was previously reported to be important for vegetative growth and reproductive success. Here we show that multiple phenotypes for ala3 knockouts are sensitive to growth conditions. For example, ala3 rosette size was observed to be dependent upon both temperature and soil, and varied between 40% and 80% that of wild-type under different conditions. We also demonstrate that ala3 mutants have reduced fecundity resulting from a combination of decreased ovule production and pollen tube growth defects. In-vitro pollen tube growth assays showed that ala3 pollen germinated ∼2 h slower than wild-type and had approximately 2-fold reductions in both maximal growth rate and overall length. In genetic crosses under conditions of hot days and cold nights, pollen fitness was reduced by at least 90-fold; from ∼18% transmission efficiency (unstressed to less than 0.2% (stressed. Together, these results support a model in which ALA3 functions to modify endomembranes in multiple cell types, enabling structural changes, or signaling functions that are critical in plants for normal development and adaptation to varied growth environments.

  2. The impact of robot-mediated adaptive I-TRAVLE training on impaired upper limb function in chronic stroke and multiple sclerosis.

    Science.gov (United States)

    Maris, Anneleen; Coninx, Karin; Seelen, Henk; Truyens, Veronik; De Weyer, Tom; Geers, Richard; Lemmens, Mieke; Coolen, Jolijn; Stupar, Sandra; Lamers, Ilse; Feys, Peter

    2018-01-01

    The current study aimed to investigate proof-of-concept efficacy of an individualized, robot-mediated training regime for people with MS (pwMS) and stroke patients. Thirteen pwMS and 14 chronic stroke patients performed 36 (stroke) or 40 (pwMS) training sessions with the I-TRAVLE system. Evaluation of upper limb function was performed at baseline, after training and at 3 months follow-up. Clinical outcome measures consisted of active range of motion (ROM), Motricity Index, Jamar handgrip strength, perceived fatigue and strength, Wolf Motor Function Test (WFMT) and ABILHAND. Robot-generated outcome measures consisted of movement velocity, ROM and actual covered distance compared to straight-line distance. In pwMS, significant improvements were found after training in active shoulder ROM, handgrip strength, perceived strength and WMFT activities. No significant change in clinical outcome was found in stroke patients, except for perceived strength. Significant improvement in speed and movement duration was found after training in both groups. At follow-up, clinical outcome deteriorated in pwMS and was maintained in stroke patients. Robot-mediated training resulted in improved movement coordination in both groups, as well as clinical improvement in pwMS. Absence of functional improvements in stroke patients may relate to severe upper limb dysfunction at baseline. Implications for Rehabilitation Robot-mediated training improved strength, active range of motion and upper limb capacity in pwMS. Robot-mediated therapy allows for adapted training difficulty.

  3. Impaired Driving

    Science.gov (United States)

    Impaired driving is dangerous. It's the cause of more than half of all car crashes. It means operating ... texting Having a medical condition which affects your driving For your safety and the safety of others, do not drive while impaired. Have someone else drive you or take public ...

  4. The response regulator BcSkn7 is required for vegetative differentiation and adaptation to oxidative and osmotic stresses in Botrytis cinerea.

    Science.gov (United States)

    Yang, Qianqian; Yin, Dafang; Yin, Yanni; Cao, Yi; Ma, Zhonghua

    2015-04-01

    The high-osmolarity glycerol pathway plays an important role in the responses of fungi to various environmental stresses. Saccharomyces cerevisiae Skn7 is a response regulator in the high-osmolarity glycerol pathway, which regulates the oxidative stress response, cell cycle and cell wall biosynthesis. In this study, we characterized an Skn7 orthologue BcSkn7 in Botrytis cinerea. BcSKN7 can partly restore the growth defects of S. cerevisiae SKN7 mutant and vice versa. The BcSKN7 mutant (ΔBcSkn7-1) revealed increased sensitivity to ionic osmotic and oxidative stresses and to ergosterol biosynthesis inhibitors. In addition, ΔBcSkn7-1 was also impaired dramatically in conidiation and sclerotial formation. Western blot analysis showed that BcSkn7 positively regulated the phosphorylation of BcSak1 (the orthologue of S. cerevisiae Hog1) under osmotic stress, indicating that BcSkn7 is associated with the high-osmolarity glycerol pathway in B. cinerea. In contrast with BcSak1, BcSkn7 is not involved in the regulation of B. cinerea virulence. All of the phenotypic defects of ΔBcSkn7-1 are restored by genetic complementation of the mutant with the wild-type BcSKN7. The results of this study indicate that BcSkn7 plays an important role in the regulation of vegetative differentiation and in the response to various stresses in B. cinerea. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  5. Adaptação de escalas de silhuetas bidimensionais e tridimensionais para o deficiente visual Adaptation of two and three dimensional silhouette scales for the visually impaired

    Directory of Open Access Journals (Sweden)

    Fabiane Frota da Rocha Morgado

    2011-04-01

    Full Text Available O objetivo deste estudo foi descrever o processo de adaptação da Escala de Silhuetas Bidimensionais (ESB e de criação da Escala de Silhuetas Tridimensionais (EST. Para isso uma pesquisa de cunho qualitativo realizado em três etapas: na primeira, foi solicitada a autorização do prof. Stunkard para a utilização de seu instrumento como parâmetro para a confecção das Escalas. Na segunda, foi confeccionada a ESB e na terceira, a EST. Estas Escalas foram elaboradas considerando os critérios técnicos da Divisão de Pesquisa e Produção de Material Especializado do Instituto Benjamin Constant - RJ. Os resultados indicaram que a ESB foi confeccionada em linguagem grafo-tátil em alto relevo e é composta por nove bonecos masculinos e nove femininos, com diferentes formas corporais, texturizados com lixa de parede e linha. Os bonecos possuem 8,5 cm de altura. A EST foi composta por nove bonecos masculinos e nove femininos, com diferentes pesos e formas corporais. Os modelos foram confeccionados através de processo artesanal e constituídos de gesso pedra. Os bonecos do gênero masculino possuem altura de 15,5 cm e os do gênero feminino, 13,5 cm. Conclui-se que as informações contidas na descrição detalhada dos processos de confecção da ESB e EST podem ser um referencial para adaptações futuras e melhoradas de outras Escalas de figuras humanas, desenvolvidas a partir deste primeiro referencial.The objective of this study was to describe the process of adaptation of the Two Dimencional Silhouette Scale (2DSS and the development of a Three Dimensional Silhouette Scale (3DSS. To that end, a qualitative study was conducted in three stages: In the first one, the creator of the tool, Mr. Stunkard was contacted for permission to use his instrument as a parameter for the development of the scales. In the second and third ones, the 2DSS and the 3DSS were developed, respectively. These scales were developed considering the technical criteria

  6. Monitoring antioxidant defenses and free radical production in space-flight, aviation and railway engine operators, for the prevention and treatment of oxidative stress, immunological impairment, and pre-mature cell aging.

    Science.gov (United States)

    De Luca, C; Deeva, I; Mariani, S; Maiani, G; Stancato, A; Korkina, L

    2009-01-01

    Degenerative diseases, immune impairment, and premature ageing commonly affect professional categories exposed to severe environmental and psychological stress. Among these, cosmonauts routinely experience extreme conditions due to microgravity, space radiation, altered oxygen supply, physical and mental fatigue during training, spaceflight, and post-flight. Long route aviation pilots display elevated oncogenic risk, connected with cosmic radiation overexposure, and high mortality rates for cardiovascular causes. Engine drivers, like pilots, are affected by health consequences of psycho-emotional stress, and burnout syndrome. The free radical (FR)/antioxidant (AO) imbalance is a common feature in all these pathological conditions. To assess the effective relevance of oxidative stress, we analyzed blood and urine reliable markers of FR production and AO defenses in 12 Russian cosmonauts, 55 airline pilots, 63 train engine drivers, and 50 age-matched controls by measuring the following: (a) lipophilic/hydrophilic low-molecular weight AO and AO enzyme activities, (b) nitric oxide, superoxide anion, hydroperoxide production, and (c) urinary catecholamine/serotonine metabolites and lipoperoxidation markers. Cosmonauts showed elevated granulocyte superoxide and nitric oxide production, increased erythrocyte superoxide dismutase activity and glutathione oxidation, and drastically decreased plasma/leucocyte lipophilic AO levels (P pilots, like train drivers, displayed a mild but constant oxidative stress, more pronounced in intercontinental routes pilots, and consistent with lymphocyte chromosomal alterations, DNA oxidation, and cardiovascular malfunction. Results obtained on these selected professionals operating under wearing conditions offer a solid molecular basis for advising the regular monitoring of clinical biochemistry laboratory markers of AO/FR status, to tailor individually specific AO supplementation and diet regimen, and monitor treatment outcomes.

  7. Cafeteria diet overfeeding in young male rats impairs the adaptive response to fed/fasted conditions and increases adiposity independent of body weight.

    Science.gov (United States)

    Castro, H; Pomar, C A; Picó, C; Sánchez, J; Palou, A

    2015-03-01

    We analyzed the effects of a short exposure to a cafeteria diet during early infancy in rats on their metabolic response to fed/fasting conditions in key tissues involved in energy homeostasis. Ten-day-old male pups were fed a control or a cafeteria diet for 12 days and then killed under ad libitum feeding conditions or 12 h fasting. The expression of key genes related to energy metabolism in liver, retroperitoneal white adipose tissue (WAT) and hypothalamus were analyzed. Despite no differences in body weight, cafeteria-fed animals had almost double the fat mass of control rats. They also showed higher food intake, higher leptinemia and altered hypothalamic expression of Neuropetide Y, suggesting a dysfunction in the control of food intake. Unlike controls, cafeteria-fed animals did not decrease WAT expression of Pparg, sterol regulatory element binding transcription factor 1 or Cidea under fasting conditions, and displayed lower Pnpla2 expression than controls. In liver, compared with controls, cafeteria animals presented: (i) lower expression of genes related with fatty acid uptake and lipogenesis under ad libitum-fed conditions; (ii) higher expression of fatty acid oxidation-related genes and glucokinase under fasting conditions; (iii) greater expression of leptin and insulin receptors; and higher protein levels of insulin receptor and the pAMPK/AMPK ratio. A short period of exposure to a cafeteria diet in early infancy in rat pups is enough to disturb the metabolic response to fed/fasting conditions in key tissues involved in energy homeostasis, particularly in WAT, and hence induces an exacerbated body fat accumulation and increased metabolic risk, with no apparent effects on body weight.

  8. Simvastatin ameliorates cognitive impairments via inhibition of oxidative stress‑induced apoptosis of hippocampal cells through the ERK/AKT signaling pathway in a rat model of senile dementia.

    Science.gov (United States)

    Liu, Wenting; Zhao, Yan; Zhang, Xinyu; Ji, Jiangang

    2018-01-01

    Senile dementia is a degenerative disease of the nervous system associated with cognitive impairments, memory disorders, executive dysfunctions, cognitive decline and dementia. Previous reports suggested that simvastatin presents ameliorative effects in the progression of senile dementia. However, the mechanism underlying simvastatin‑mediated improvements of cognitive competence during the progression of senile dementia remains to be elucidated. In the present study, a potential mechanism underlying simvastatin activity in hippocampal cells, was investigated. Results of the present study demonstrated that simvastatin significantly improved cognitive impairments, memory competence, amyloid plaques, loss of neurons and synapses, neurofibrillary tangles and oxidative damage in experimental rats. Results of the present study demonstrated that administration of simvastatin regulates superoxide dismutase, reactive oxygen species, catalase and glutathione in oxidative stress processes in hippocampal cells. Apoptosis of hippocampal cells was suppressed by simvastatin treatment in rats with senile dementia. Notably, the administration of simvastatin inhibited activating transcription factor‑6‑mediated extracellular signal‑regulated kinase/AKT serine/threonine kinase (ERK/AKT) signaling pathway in hippocampal cells. Taken together, the preclinical results of the present study indicate that simvastatin is efficient in preventing memory lapse and inhibiting apoptosis of hippocampal cells via the ERK/AKT signaling pathway, which may in the future improve cognitive decline and dementia in patients.

  9. Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia.

    Science.gov (United States)

    Tsui, Albert K Y; Marsden, Philip A; Mazer, C David; Adamson, S Lee; Henkelman, R Mark; Ho, J J David; Wilson, David F; Heximer, Scott P; Connelly, Kim A; Bolz, Steffen-Sebastian; Lidington, Darcy; El-Beheiry, Mostafa H; Dattani, Neil D; Chen, Kevin M; Hare, Gregory M T

    2011-10-18

    Cells sense and respond to changes in oxygen concentration through gene regulatory processes that are fundamental to survival. Surprisingly, little is known about how anemia affects hypoxia signaling. Because nitric oxide synthases (NOSs) figure prominently in the cellular responses to acute hypoxia, we defined the effects of NOS deficiency in acute anemia. In contrast to endothelial NOS or inducible NOS deficiency, neuronal NOS (nNOS)(-/-) mice demonstrated increased mortality during anemia. Unlike wild-type (WT) animals, anemia did not increase cardiac output (CO) or reduce systemic vascular resistance (SVR) in nNOS(-/-) mice. At the cellular level, anemia increased expression of HIF-1α protein and HIF-responsive mRNA levels (EPO, VEGF, GLUT1, PDK1) in the brain of WT, but not nNOS(-/-) mice, despite comparable reductions in tissue PO(2). Paradoxically, nNOS(-/-) mice survived longer during hypoxia, retained the ability to regulate CO and SVR, and increased brain HIF-α protein levels and HIF-responsive mRNA transcripts. Real-time imaging of transgenic animals expressing a reporter HIF-α(ODD)-luciferase chimeric protein confirmed that nNOS was essential for anemia-mediated increases in HIF-α protein stability in vivo. S-nitrosylation effects the functional interaction between HIF and pVHL. We found that anemia led to nNOS-dependent S-nitrosylation of pVHL in vivo and, of interest, led to decreased expression of GSNO reductase. These findings identify nNOS effects on the HIF/pVHL signaling pathway as critically important in the physiological responses to anemia in vivo and provide essential mechanistic insight into the differences between anemia and hypoxia.

  10. Antioxidant enzymes and oxidative stress adaptation to exercise training: Comparison of endurance, resistance, and concurrent training in untrained males

    Directory of Open Access Journals (Sweden)

    Kamal Azizbeigi

    2014-06-01

    Full Text Available The aim of this study was to compare the effect of endurance training (ET, resistance training (RT, and concurrent training (CT on circulating antioxidant capacity and oxidative stress. For this purpose, 30 men aged 21.7 ± 2.4 years were assigned to the following three training groups: ET, which included continuous running with incremental intensity that was increased up to 80% of maximal heart rate (n = 10; RT, which included a beginning load of 50% of one repetition maximum (1RM that was increased up to 80% of 1RM (n = 10; and CT, which included ET and RT programs every other day during the week (n = 10. Activities of superoxide dismutase (SOD and glutathione peroxidase (GPx in erythrocytes and total antioxidant capacity (TAC and malondialdehyde (MDA level in plasma were measured. The results showed that SOD significantly increased by 21.85% (p = 0.020, 9.54% (p = 0.032, and 14.55% (p = 0.038 in the ET, RT, and CT groups, respectively. Furthermore, the activity of erythrocyte GPx significantly increased in the ET (p = 0.018 and CT (p = 0.042 groups. The TAC increased significantly in the ET (p = 0.040 and CT (p = 0.049 groups compared with the pretest values. The MDA level significantly decreased in the ET group by 32.7% (p = 0.028, by 32% in the RT group (p = 0.025, and by 29.1% (p = 0.047 in the CT group. However, there was no significant difference in the interaction of time and group between variables of SOD and GPx enzymes and TAC of plasma and MDA in the ET, RT, and CT groups (p < 0.05. It can be concluded that all three training types induced the same changes in redox state (increased SOD activity and reduction in MDA levels, but at different rates.

  11. Prediction of effect of natural antioxidant compounds on hazelnut oil oxidation by adaptive neuro-fuzzy inference system and artificial neural network.

    Science.gov (United States)

    Yalcin, Hasan; Ozturk, Ismet; Karaman, Safa; Kisi, Ozgur; Sagdic, Osman; Kayacier, Ahmed

    2011-05-01

    In this study, natural compounds including gallic acid, ellagic acid, quercetin, β-carotene, and retinol were used as antioxidant agents in order to prevent and decrease oxidation in hazelnut oil. Quercetin showed the strongest antioxidative effect among the antioxidative agents, during storage. The accuracy of adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network (ANN) models was studied to estimate the oil samples' peroxide value (PV), free fatty acid (FFA), and iodine values (IV). The root mean square error (RMSE), mean absolute error (MAE), and determination coefficient (R(2)) statistics were used to evaluate the models' accuracy. Comparison of the models showed that the ANFIS model performed better than the ANN and multiple linear regressions (MLR) models for estimating the PV, FFA, and IV. The values of R(2) and RMSE were found to be 0.9966 and 2.51, 0.6269 and 88.55, 0.5120 and 101.8 for the ANFIS, ANN, and MLR models for PV in testing period, respectively. The MLR was found to be insufficient for estimating various properties of the oil samples. © 2011 Institute of Food Technologists®

  12. Cell Death and Learning Impairment in Mice Caused by in Vitro Modified Pro-NGF Can Be Related to Its Increased Oxidative Modifications in Alzheimer Disease

    Science.gov (United States)

    Kichev, Anton; Ilieva, Ekaterina V.; Piñol-Ripoll, Gerard; Podlesniy, Petar; Ferrer, Isidro; Portero-Otín, Manuel; Pamplona, Reinald; Espinet, Carme

    2009-01-01

    Pro-nerve growth factor (pro-NGF) is expressed at increased levels in Alzheimer’s disease (AD)-affected brains and is able to induce cell death in cultures; however, the reasons for these phenomena remain elusive. Here we show that pro-NGF in human AD-affected hippocampus and entorhinal cortex is modified by advanced glycation and lipoxidation end-products in a stage-dependent manner. These modifications block pro-NGF processing to mature NGF, thus making the proneurotrophin especially effective in inducing apoptosis of PC12 cells in culture through the p75 neurotrophin receptor. The processing of advanced glycation and lipoxidation end-products in vitro modified recombinant human pro-NGF is severely impaired, as evidenced by Western blot and by examining its physiological functionality in cell cultures. We also report that modified recombinant human pro-NGF, as well as pro-NGF isolated from human brain affected by AD, cause impairment of learning tasks when administered intracerebroventricularly in mice, which correlates with AD-associated learning impairment. Taken together, the data we present here offer a novel pathway of ethiopathogenesis in AD caused by advanced glycation and lipoxidation end-products modification of pro-NGF. PMID:19893045

  13. Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats

    Science.gov (United States)

    Sun, Wenyan; Yan, Chunhong; Frost, Bess; Wang, Xin; Hou, Chen; Zeng, Mengqi; Gao, Hongli; Kang, Yuming; Liu, Jiankang

    2016-01-01

    High blood pressure, or “hypertension,” is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension. PMID:27713551

  14. Physical Impairment

    Science.gov (United States)

    Trewin, Shari

    Many health conditions can lead to physical impairments that impact computer and Web access. Musculoskeletal conditions such as arthritis and cumulative trauma disorders can make movement stiff and painful. Movement disorders such as tremor, Parkinsonism and dystonia affect the ability to control movement, or to prevent unwanted movements. Often, the same underlying health condition also has sensory or cognitive effects. People with dexterity impairments may use a standard keyboard and mouse, or any of a wide range of alternative input mechanisms. Examples are given of the diverse ways that specific dexterity impairments and input mechanisms affect the fundamental actions of Web browsing. As the Web becomes increasingly sophisticated, and physically demanding, new access features at the Web browser and page level will be necessary.

  15. Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB.

    Science.gov (United States)

    Kim, Young Eun; Hwang, Chul Ju; Lee, Hee Pom; Kim, Chun Sik; Son, Dong Ju; Ham, Young Wan; Hellström, Mats; Han, Sang-Bae; Kim, Hee Sik; Park, Eun Kyung; Hong, Jin Tae

    2017-05-01

    Neuroinflammation is significant in the pathogenesis and development of Alzheimer's disease (AD). Previously, we showed lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairment. We investigated the possible preventive effects of punicalagin (PUN), a component of pomegranate, on memory deficiency caused by LPS, along with the fundamental mechanisms. LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory effects of PUN. PUN (1.5 mg/kg) ameliorates LPS (250 μg/kg daily 7 times)-induced memory impairment as well as prevents the LPS-induced expression of inflammatory proteins. In in vitro study, we also found that PUN (1 μg/ml) inhibited the LPS-(10, 20 and 50 μM) induced expression of iNOS and Cox-2 as well as the production of ROS, NO, TNF-α and IL-1β. PUN also suppress activation of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into the nucleus in LPS treated mouse brain and cultured astrocytes and microglial BV-2 cells. Consistent with the inhibitory effect on neuro inflammation, PUN inhibited LPS-induced Aβ 1-42 generation through down-regulation of APP and BACE1 expression in in vivo and in vitro study. Moreover, PUN directly binds to NF-κB subunit p50 evidenced by a docking model and pull down assay. These results suggest that PUN inhibits LPS-induced memory impairment via anti-inflammatory and anti-amylogenic mechanisms through inhibition of NF-κB activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Hearing Impairments

    Science.gov (United States)

    Cavender, Anna; Ladner, Richard E.

    For many people with hearing impairments, the degree of hearing loss is only a small aspect of their disability and does not necessarily determine the types of accessibility solutions or accommodations that may be required. For some people, the ability to adjust the audio volume may be sufficient. For others, translation to a signed language may be more appropriate. For still others, access to text alternatives may be the best solution. Because of these differences, it is important for researchers in Web accessibility to understand that people with hearing impairments may have very different cultural-linguistic traditions and personal backgrounds.

  17. All Vision Impairment

    Science.gov (United States)

    ... Statistics and Data > All Vision Impairment All Vision Impairment Vision Impairment Defined Vision impairment is defined as the best- ... 2010 U.S. Age-Specific Prevalence Rates for Vision Impairment by Age and Race/Ethnicity Table for 2010 ...

  18. Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β-Cells Function.

    Science.gov (United States)

    Carrasco-Pozo, Catalina; Tan, Kah Ni; Gotteland, Martin; Borges, Karin

    2017-01-01

    Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve β-cell function and eventually control hyperglycemia.

  19. Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β-Cells Function

    Directory of Open Access Journals (Sweden)

    Catalina Carrasco-Pozo

    2017-01-01

    Full Text Available Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve β-cell function and eventually control hyperglycemia.

  20. Assessment of thyroid endocrine system impairment and oxidative stress mediated by cobalt ferrite (CoFe2O4) nanoparticles in zebrafish larvae.

    Science.gov (United States)

    Ahmad, Farooq; Liu, Xiaoyi; Zhou, Ying; Yao, Hongzhou; Zhao, Fangfang; Ling, Zhaoxing; Xu, Chao

    2016-12-01

    Fascinating super paramagnetic uniqueness of iron oxide particles at nano-scale level make them extremely useful in the state of the art therapies, equipments, and techniques. Cobalt ferrite (CoFe 2 O 4 ) magnetic nanoparticles (MNPs) are extensively used in nano-based medicine and electronics, results in extensive discharge and accumulation into the environment. However, very limited information is available for their endocrine disrupting potential in aquatic organisms. In this study, the thyroid endocrine disrupting ability of CoFe 2 O 4 NPs in Zebrafish larvae for 168-h post fertilization (hpf) was evaluated. The results showed the elevated amounts of T4 and T3 hormones by malformation of hypothalamus pituitary axis in zebrafish larvae. These elevated levels of whole body THs leads to delayed hatching, head and eye malformation, arrested development, and alterations in metabolism. The influence of THs disruption on ROS production and change in activities of catalase (CAT), mu-glutathione s-transferase (mu-GST), and acid phosphatase (AP) were also studied. The production of significantly higher amounts of in vivo generation of ROS leads to membrane damage and oxidative stress. Presences of NPs and NPs agglomerates/aggregates were also the contributing factors in mechanical damaging the membranes and physiological structure of thyroid axis. The increased activities of CAT, mu-GST, and AP confirmed the increased oxidative stress, possible DNA, and metabolic alterations, respectively. The excessive production of in vivo ROS leads to severe apoptosis in head, eye, and heart region confirming that malformation leads to malfunctioning of hypothalamus pituitary axis. ROS-induced oxidative DNA damage by formation of 8-OHdG DNA adducts elaborates the genotoxicity potential of CoFe 2 O 4 NPs. This study will help us to better understand the risk and assessment of endocrine disrupting potential of nanoparticles. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2068

  1. Roles of Amyloid β-Peptide-Associated Oxidative Stress and Brain Protein Modifications in the Pathogenesis of Alzheimer's Disease and Mild Cognitive Impairment

    OpenAIRE

    Butterfield, D. Allan; Reed, Tanea; Newman, Shelley F.; Sultana, Rukhsana

    2007-01-01

    Oxidative stress has been implicated to play a crucial role in the pathogenesis of a number of diseases, including neurodegenerative disorders, cancer, and ischemia just to name a few. Alzheimer's disease (AD) is an age-related neurodegenerative disorder that is recognized as the most common form of dementia. AD is histopathologically characterized by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles, the presence of oligomers of amyloid β-peptide (Aβ), and ...

  2. Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model.

    Directory of Open Access Journals (Sweden)

    Yun-Ching Huang

    Full Text Available Cigarette use is an independent risk factor for the development of erectile dysfunction (ED. While the association between chronic smoking and ED is well established, the fundamental mechanism(s of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS for 4 weeks (n = 10, 12 weeks (n = 10, and 24 weeks (n = 10. At the 24-week time point all rats were assessed with intracavernous pressure (ICP during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS. Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED.

  3. Ginsenosides Rd and Re co-treatments improve rotenone-induced oxidative stress and mitochondrial impairment in SH-SY5Y neuroblastoma cells.

    Science.gov (United States)

    González-Burgos, E; Fernández-Moriano, Carlos; Lozano, R; Iglesias, I; Gómez-Serranillos, M P

    2017-11-01

    Oxidative stress and mitochondrial dysfunction play key roles in Parkinson's disease (PD) initiation and progression. Ginsenosides are major compounds of Ginseng species and they are responsible for pharmacological activity. The aim of this study was to investigate the potential neuroprotective effects and mechanism of the major ginsenosides Rd and Re in rotenone-induced oxidative stress model in human neuroblastoma SH-SY5Y cells. Co-treatments with both ginsenosides inhibited the increased intracellular ROS production and by-products lipid peroxidation accumulation caused by rotenone. Moreover, these ginsenosides upregulated SOD and aconitase enzymes activities, and glutathione system; these antioxidant properties are related to Nrf2 induction and radical scavenger effect. Additionally, the results showed that both Rd and Re attenuated the extent of depolarization of mitochondrial membrane potential and restored calcium levels. Furthermore, these compounds prevented apoptosis by modulating Bax and Bcl-2 proteins and inhibiting cytochrome c release and caspase-3 activation. The ginsenoside Rd resulted to be more active than ginsenoside Re. These findings highlighted the efficacy of these compounds as neuroprotectant compounds for PD prevention and treatment through reducing oxidative stress, improving mitochondrial integrity and functions, and inhibiting apoptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

    Directory of Open Access Journals (Sweden)

    Petra Maria Hermann

    2014-12-01

    Full Text Available TThe aging brain can undergo a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (peroxidation of membrane lipids and activation of phospholipase A2 (PLA2 enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the Biology of cognitive aging we (1 portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and (2 recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

  5. Staphylococcus aureus Adapts to Oxidative Stress by Producing H2O2-Resistant Small-Colony Variants via the SOS Response

    Science.gov (United States)

    Painter, Kimberley L.; Strange, Elizabeth; Bamford, Kathleen B.; Armstrong-James, Darius

    2015-01-01

    The development of chronic and recurrent Staphylococcus aureus infections is associated with the emergence of slow-growing mutants known as small-colony variants (SCVs), which are highly tolerant of antibiotics and can survive inside host cells. However, the host and bacterial factors which underpin SCV emergence during infection are poorly understood. Here, we demonstrate that exposure of S. aureus to sublethal concentrations of H2O2 leads to a specific, dose-dependent increase in the population frequency of gentamicin-resistant SCVs. Time course analyses revealed that H2O2 exposure caused bacteriostasis in wild-type cells during which time SCVs appeared spontaneously within the S. aureus population. This occurred via a mutagenic DNA repair pathway that included DNA double-strand break repair proteins RexAB, recombinase A, and polymerase V. In addition to triggering SCV emergence by increasing the mutation rate, H2O2 also selected for the SCV phenotype, leading to increased phenotypic stability and further enhancing the size of the SCV subpopulation by reducing the rate of SCV reversion to the wild type. Subsequent analyses revealed that SCVs were significantly more resistant to the toxic effects of H2O2 than wild-type bacteria. With the exception of heme auxotrophs, gentamicin-resistant SCVs displayed greater catalase activity than wild-type bacteria, which contributed to their resistance to H2O2. Taken together, these data reveal a mechanism by which S. aureus adapts to oxidative stress via the production of a subpopulation of H2O2-resistant SCVs with enhanced catalase production. PMID:25690100

  6. Human adaptation to smog

    Energy Technology Data Exchange (ETDEWEB)

    Evans, G.W. (Univ. of California, Irvine) Jacobs, S.V.; Frager, N.B.

    1982-10-01

    This study examined the health effects of human adaptation to photochemical smog. A group of recent arrivals to the Los Angeles air basin were compared to long-term residents of the basin. Evidence for adaptation included greater irritation and respiratory problems among the recent arrivals and desensitization among the long-term residents in their judgments of the severity of the smog problem to their health. There was no evidence for biochemical adaptation as measured by hemoglobin response to oxidant challenge. The results were discussed in terms of psychological adaption to chronic environmental stressors.

  7. Chronic exposure to a high-fat diet induces hepatic steatosis, impairs nitric oxide bioavailability, and modifies the mitochondrial proteome in mice.

    Science.gov (United States)

    Eccleston, Heather B; Andringa, Kelly K; Betancourt, Angela M; King, Adrienne L; Mantena, Sudheer K; Swain, Telisha M; Tinsley, Heather N; Nolte, Ryan N; Nagy, Tim R; Abrams, Gary A; Bailey, Shannon M

    2011-07-15

    Obesity-related pathologies, such as nonalcoholic fatty liver disease, are linked to mitochondrial dysfunction and nitric oxide (NO) deficiency. Herein, we tested the hypothesis that a high-fat diet (HFD) modifies the liver mitochondrial proteome and alters proteins involved in NO metabolism, namely arginase 1 and endothelial NO synthase. Male C57BL/6 mice were fed a control or HFD and liver mitochondria were isolated for proteomics and reactive oxygen species measurements. Steatosis and hepatocyte ballooning were present in livers of HFD mice, with no pathology observed in the controls. HFD mice had increased serum glucose and decreased adiponectin. Mitochondrial reactive oxygen species was increased after 8 weeks in the HFD mice, but decreased at 16 weeks compared with the control, which was accompanied by increased uncoupling protein 2. Using proteomics, 22 proteins were altered as a consequence of the HFD. This cohort consists of oxidative phosphorylation, lipid metabolism, sulfur amino acid metabolism, and chaperone proteins. We observed a HFD-dependent increase in arginase 1 and decrease in activated endothelial NO synthase. Serum and liver nitrate + nitrite were decreased by HFD. In summary, these data demonstrate that a HFD causes steatosis, alters NO metabolism, and modifies the liver mitochondrial proteome; thus, NO may play an important role in the processes responsible for nonalcoholic fatty liver disease.

  8. Hydroxyl radical scavenger ameliorates cisplatin-induced nephrotoxicity by preventing oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria.

    Science.gov (United States)

    Santos, N A G; Bezerra, C S Catão; Martins, N M; Curti, C; Bianchi, M L P; Santos, A C

    2008-01-01

    Nephrotoxicity is the major dose-limiting factor of cisplatin chemotherapy. Reactive oxygen species generated in mitochondria are thought to be the main cause of cellular damage in such injury. The present study examined, in vivo, the protective potential of the hydroxyl radical scavenger dimethylthiourea (DMTU) against cisplatin-induced effects on renal mitochondrial bioenergetics, redox state and oxidative stress. Adult male Wistar rats (200 to 220 g) were divided into four groups of eight animals each. The control group was treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml/100 g body weight). The second group was given only DMTU (500 mg/kg body weight, i.p, followed by 125 mg/Kg, i.p., twice a day until they were killed). The third group was given a single injection of cisplatin (10 mg/kg body weight, i.p.). The fourth group was given DMTU (500 mg/kg body weight, i.p.), just before the cisplatin injection (10 mg/kg body weight, i.p.), followed by injections of DMTU (125 mg/kg body weight, i.p.) twice a day until they were killed. Animals were killed 72 h after the treatment. Besides not presenting any direct effect on mitochondria, DMTU substantially inhibited cisplatin-induced mitochondrial injury and cellular death by apoptosis, suppressing the occurrence of acute renal failure. All the following cisplatin-induced effects were prevented by DMTU: (1) increased plasmatic levels of creatinine and blood urea nitrogen (BUN); (2) decreased ATP content, calcium uptake and electrochemical potential; (3) oxidation of lipids, including cardiolipin; and oxidation of proteins, including sulfhydryl, and aconitase enzyme, as well as accumulation of carbonyl proteins; (4) depletion of the antioxidant defense (NADPH and GSH) and (5) increased activity of the apoptosis executioner caspase-3. Our findings show the important role played by mitochondria and hydroxyl radicals in cisplatin-induced nephrotoxicity, as well as the effectiveness of DMTU in

  9. Protection against brain tissues oxidative damage as a possible mechanism for the beneficial effects of Rosa damascena hydroalcoholic extract on scopolamine induced memory impairment in rats.

    Science.gov (United States)

    Mohammadpour, Toktam; Hosseini, Mahmoud; Naderi, Asieh; Karami, Reza; Sadeghnia, Hamid Reza; Soukhtanloo, Mohammad; Vafaee, Farzaneh

    2015-10-01

    Hypnotic, analgesic, anticonvulsant, and antioxidant effects of Rosa damascena have been reported. This study, investigated the effect of R. damascena hydroalcoholic extract on memory performance in a scopolamine-induced memory impairment model. The rats were divided into control group received just saline; scopolamine group was treated by saline for 2 weeks, but was injected by scopolamine 30 minutes before each trial in Morris water maze test; treatment groups (scopolamine + extract 50; Sco + Ext 50) and (scopolamine + extract 250; Sco + Ext 250) were daily treated by 50 and 250 mg/kg of R. damascena extract (2 weeks) and were finally injected by scopolamine before each trial in Morris water maze. The brains were removed for biochemical measurements. Time latency and path length in the scopolamine group were higher than control (P < 0.01 to <0.001). Both treatment groups showed shorter traveled distance and time latency compared with scopolamine group (P < 0.05 to <0.001). Time spent in target quadrant by scopolamine group was lower than control (P < 0.05), while Sco + Ext 250 group spent longer time in target quadrant than scopolamine group (P < 0.05). Malondialdehyde concentrations in hippocampal and cortical tissues of scopolamine group were higher, while thiol concentrations were lower than control ones (P < 0.001). Treatment by both doses of the extract decreased the malondialdehyde concentration, while increased the thiol concentration (P < 0.05 to <0.001). The results of this study showed that the hydroalcoholic extract of R. damascena prevents scopolamine-induced memory deficits. This finding suggests that memory improvement may be in part due to the antioxidant effects.

  10. In vitro hepatotoxicity of 'Legal X': the combination of 1-benzylpiperazine (BZP) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) triggers oxidative stress, mitochondrial impairment and apoptosis.

    Science.gov (United States)

    Dias da Silva, Diana; Silva, Maria João; Moreira, Patrícia; Martins, Maria João; Valente, Maria João; Carvalho, Félix; Bastos, Maria de Lourdes; Carmo, Helena

    2017-03-01

    N-Benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) are two synthetic phenylpiperazine analogues that have been frequently commercialized in combination as an alternative to ecstasy ('Legal X'). Despite reports of several clinical complications following the use of these drugs in association, few studies have been conducted so far to elucidate their combined toxicity. The present study was aimed at clarifying the cytotoxic effects of mixtures of BZP and TFMPP in vitro. Human-derived HepaRG cells and primary rat hepatocytes were exposed to the drugs, individually or combined at different mixture ratios, and cytotoxicity was assessed by the MTT assay. Mixture additivity expectations were calculated by the independent action and the concentration addition (CA) models and compared with the experimental outcomes. To delineate the mechanisms underlying the elicited effects, a range of stress endpoints was evaluated, including oxidative stress, energetic imbalance, and metabolic interactions. It was observed that primary rat hepatocytes are more sensitive than HepaRG cells to the toxicity of BZP (EC50 2.20 and 6.60 mM, respectively) and TFMPP (EC50 0.14 and 0.45 mM, respectively). For all BZP-TFMPP combinations tested, CA was the most appropriate model to predict the mixture effects. TFMPP proved to act additively with BZP to produce significant hepatotoxicity (p < 0.01). Remarkably, substantial mixture effects were observed even when each drug was present at concentrations that were harmless individually. In primary hepatocytes, a small deviation from additivity (antagonism) was observed toward the upper range of the concentration-response curve. GC/MS data suggest that a metabolic interaction may be at a play, as the mixture favors the metabolism of both substances, to a significant extent in the case of BZP (p < 0.05). Also, our results demonstrate the influence of oxidative stress and energetic imbalance on these effects (increase in RNS

  11. Acompanhamento da adaptação de próteses auditivas em crianças surdas Evaluating the adaptation of hearing aids for hearing impaired children

    Directory of Open Access Journals (Sweden)

    Bianca Pinheiro Lanzetta

    2010-06-01

    Full Text Available OBJETIVOS: descrever as características audiológicas e sociais de crianças surdas e avaliar a incidência de retornos para acompanhamento no Programa de Saúde Auditiva. MÉTODOS: foram analisados os prontuários de crianças que receberam as próteses auditivas pelo Programa de Saúde Auditiva, em Vila Velha - Espírito Santo. A população estudada foi constituída por 50 crianças, na faixa etária de zero a oito anos, de ambos os sexos, com diagnóstico de perda auditiva sensorioneural de grau leve a profundo. O protocolo de pesquisa foi preenchido a partir dos dados de prontuários para a obtenção das informações desejadas. RESULTADOS: a solicitação de retorno pelo Serviço Social propiciou o comparecimento de quase da metade da população (44%; os demais achados foram indicativos da associação entre o retorno para acompanhamento e a rotina escolar. CONCLUSÕES: o referido programa atinge predominantemente famílias com rendimento mensal entre um e dois salários mínimos; o diagnóstico da surdez ocorre entre dois e três anos de idade cronológica neste estudo; a época da primeira adaptação de próteses auditivas, aos seis anos de idade, é bastante tardia; o contato com os pais, por meio do Serviço Social, viabiliza o acompanhamento proposto, influenciado positivamente também pela rotina escolar.PURPOSE: to describe the compliance and attitudes of hearing-impaired children towards the treatment and support offered by the Hearing Health Program, a public health endeavor, and assessing patients’ returns for follow-ups. METHODS: participants consisted of fifty children aged from 0 to 8 years, with a diagnosis of mild to severe sensorineural hearing loss. The children received the hearing aids from the Hearing Health Program, in Vila Velha, in the state of Espírito Santo, Brazil. The research protocol was completed using both medical records and a socio-economical profile survey of the affected children, including the

  12. Enhanced role of elaidic acid on acrylamide-induced oxidative stress in epididymis and epididymal sperm that contributed to the impairment of spermatogenesis in mice.

    Science.gov (United States)

    Zhang, Jian-xin; Yue, W B; Ren, Y S; Zhang, C X

    2010-09-01

    Acrylamide (ACR) and trans fatty acids (TFA) could be found co-existent in many foods processed by high temperature. Our study investigated effect of elaidic acid (ELA), the predominant TFA, on deficits of spermatogenesis induced by ACR. Results showed that ELA enhanced the decreases of spermatogonia along with mature sperms after treatment of ACR, and that spermatozoa quality was significantly reduced by addition of ELA to mice treated with ACR. Moreover, ELA play an enhancing role in ACR-induced up-regulating of malondialdehyde (MDA) level in epididymal sperm and cauda epididymides, also up-regulating of protein carbonyls (PCOs) level in cauda epididymides. Meanwhile, ELA play an enhancing role in ACR-induced reducing of activity of superoxide dismutases (SOD) in epididymal sperm, corpus and cauda epididymides, also the reducing of activity of glutathione peroxidase (GPx) in cauda epididymides. These data suggest that ELA enhances ACR-induced oxidative stress in the epididymis and epididymal sperm of mice and has subsequent effect on spermatogenesis in mice testis.

  13. Triclosan (TCS) and Triclocarban (TCC) cause lifespan reduction and reproductive impairment through oxidative stress-mediated expression of the defensome in the monogonont rotifer (Brachionus koreanus).

    Science.gov (United States)

    Han, Jeonghoon; Won, Eun-Ji; Hwang, Un-Ki; Kim, Il-Chan; Yim, Joung Han; Lee, Jae-Seong

    2016-01-01

    Triclosan (TCS) and Triclocarban (TCC) are used as antimicrobial agents and have been widely dispersed and detected in the marine environment. However, the toxicities of TCS and TCC have been poorly investigated in marine invertebrates. In this study, the effects of TCS and TCC on mortality, population growth, lifespan, and fecundity were examined in the monogonont rotifer (Brachionus koreanus) using cellular ROS levels, GST enzymatic activity, and gene expression of defensomes. The median lethal concentration (LC50) of TCS (393.1μg/L) and TCC (388.1μg/L) was also determined in the same species. In TCS- and TCC-exposed B. koreanus, growth retardation and reduced fecundity were observed and were shown to have a potentially deleterious effect on the life cycle of B. koreanus. In addition, time-dependent increases in ROS content (%) and GST enzymatic activity were shown in response to TCS and TCC exposure. Additionally, transcript levels of detoxification proteins (e.g., CYPs), antioxidant proteins (e.g., GST-sigma, Cu/ZnSOD, CAT), and heat shock proteins (Hsps) were modulated in response to TCS and TCC exposure over a 24h period. Our results indicate that TCS and TCC induce oxidative stress and transcriptional regulation of detoxification, antioxidant, and heat shock proteins, resulting in changes in lifespan and fecundity. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Amelioration of Aspirin Induced Oxidative Impairment and Apoptotic Cell Death by a Novel Antioxidant Protein Molecule Isolated from the Herb Phyllanthus niruri

    Science.gov (United States)

    Bhattacharyya, Sudip; Ghosh, Shatadal; Sil, Parames C.

    2014-01-01

    Aspirin has been used for a long time as an analgesic and anti-pyretic drug. Limitations of its use, however, remain for the gastro-intestinal side effects and erosions. Although the role of aspirin on gastro-intestinal injury has been extensively studied, the molecular mechanisms underlying aspirin-induced liver and spleen pathophysiology are poorly defined. The present study has been conducted to investigate whether phyllanthus niruri protein (PNP) possesses any protective role against aspirin mediated liver and spleen tissue toxicity, and if so, what signaling pathways it utilizes to convey its protective action. Aspirin administration in mice enhanced serum marker (ALP) levels, reactive oxygen species (ROS) generation, reduced antioxidant power and altered oxidative stress related biochemical parameters in liver and spleen tissues. Moreover, we observed that aspirin intoxication activated both the extrinsic and intrinsic apoptotic pathways, as well as down regulated NF-κB activation and the phosphorylation of p38 and JNK MAPKs. Histological assessments and TUNEL assay also supported that aspirin induced tissue damages are apoptotic in nature. PNP treatment after aspirin exposure effectively neutralizes all these abnormalities via the activation of survival PI3k/Akt pathways. Combining all results suggest that PNP could be a potential protective agent to protect liver and spleen from the detrimental effects of aspirin. PMID:24586486

  15. Biphasic regulation of lysosomal exocytosis by oxidative stress.

    Science.gov (United States)

    Ravi, Sreeram; Peña, Karina A; Chu, Charleen T; Kiselyov, Kirill

    2016-11-01

    Oxidative stress drives cell death in a number of diseases including ischemic stroke and neurodegenerative diseases. A better understanding of how cells recover from oxidative stress is likely to lead to better treatments for stroke and other diseases. The recent evidence obtained in several models ties the process of lysosomal exocytosis to the clearance of protein aggregates and toxic metals. The mechanisms that regulate lysosomal exocytosis, under normal or pathological conditions, are only beginning to emerge. Here we provide evidence for the biphasic effect of oxidative stress on lysosomal exocytosis. Lysosomal exocytosis was measured using the extracellular levels of the lysosomal enzyme beta-hexosaminidase (ß-hex). Low levels or oxidative stress stimulated lysosomal exocytosis, but inhibited it at high levels. Deletion of the lysosomal ion channel TRPML1 eliminated the stimulatory effect of low levels of oxidative stress. The inhibitory effects of oxidative stress appear to target the component of lysosomal exocytosis that is driven by extracellular Ca 2+ . We propose that while moderate oxidative stress promotes cellular repair by stimulating lysosomal exocytosis, at high levels oxidative stress has a dual pathological effect: it directly causes cell damage and impairs damage repair by inhibiting lysosomal exocytosis. Harnessing these adaptive mechanisms may point to pharmacological interventions for diseases involving oxidative proteotoxicity or metal toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Involvement of interleukin-6-regulated nitric oxide synthase in hemorrhagic cystitis and impaired bladder contractions in young rats induced by acrolein, a urinary metabolite of cyclophosphamide.

    Science.gov (United States)

    Wang, Ching-Chia; Weng, Te-I; Wu, En-Ting; Wu, Mei-Hwan; Yang, Rong-Sen; Liu, Shing-Hwa

    2013-01-01

    Hemorrhagic cystitis is a common complication in children receiving cyclophosphamide, a chemotherapeutic alkylating agent. Acrolein is a urinary metabolite from cyclophosphamide and can induce hemorrhagic cystitis. Here, we investigated the effects and mechanisms of acrolein by intravesical instillation on urinary bladder muscle contractions and pathological alterations in rats. Acrolein instillation significantly increased the muscle contractions of rat bladder detrusor after 1 and 6 h but markedly decreased detrusor contractions after 24 h. Acrolein increased phosphorylated protein kinase C (pan-PKC) expressions in bladders after 1 and 6 h but inhibited it after 24 h. Inducible nitric oxide (NO) synthase (iNOS) protein expressions were markedly induced in bladders 24 h after acrolein treatment. Twenty-four-hour acrolein instillation increased the levels of nitrite/nitrate and interleukin-6 (IL-6) in the urinary bladder. The iNOS inhibitors significantly inhibited the acrolein-increased nitrite/nitrate levels, but not IL-6 levels. IL-6-neutralizing antibodies effectively inhibited the acrolein-increased NOx levels. The increased detrusor contractions by 1-h acrolein treatment were significantly reversed by the PKC inhibitor RO32-0432, and the decreased detrusor contractions by 24-h acrolein treatment were significantly reversed by the iNOS inhibitor and IL-6-neutralizing antibody. Both the iNOS inhibitor and IL-6-neutralizing antibody effectively reversed the increased iNOS expression, decreased PKC phosphorylation, increased bladder weight, and hemorrhagic cystitis in rats 24 h after acrolein treatment. Taken together, these results suggest that an IL-6-regulated iNOS/NO signaling pathway participates in the acrolein-triggered detrusor contraction inhibition and hemorrhagic cystitis. These findings may help us to find a new strategy to treat cyclophosphamide-induced hemorrhagic cystitis.

  17. [Impaired consciousness].

    Science.gov (United States)

    Sugino, Tatsuya

    2013-06-01

    Consciousness disorder is one of the common signs that clinicians treat every day. It is further more frequently found in elderly patients, but it is often difficult to make an exact diagnosis and to give a suitable treatment for each case. There are many kinds of diseases or systemic disorders which impair consciousness, and moreover, various backgrounds (e.g. their lifestyle, mental problems, etc.) characteristic for aged people often make the diagnosis unclear. Therefore, it is very important for every physician assigned to emergency room to have broad viewpoint and to make careful examinations approaching such patients. Needless to say, if the patient is facing crisis, more priority should be given to emergency treatment than to precise diagnosis.

  18. Visual impairment in the hearing impaired students

    OpenAIRE

    Gogate Parikshit; Rishikeshi Nikhil; Mehata Reshma; Ranade Satish; Kharat Jitesh; Deshpande Madan

    2009-01-01

    Background : Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. Aim : To detect and treat visual impairment, if any, in hearing-impaired children. Setting and Design : Observational, clinical case series of hearing-impaired children in schools providing special education. Materials and Methods : Hearing-impaired children in selected schools underwent detailed vis...

  19. Physiological adaptations to reproduction. I. Experimentally increasing litter size enhances aspects of antioxidant defence but does not cause oxidative damage in mice.

    Science.gov (United States)

    Garratt, Michael; Pichaud, Nicolas; King, Edith D Aloise; Brooks, Robert C

    2013-08-01

    Life history theory suggests that investment in reproduction can trade off against growth, longevity and both reproduction and performance later in life. One possible reason for this trade-off is that reproduction directly causes somatic damage. Oxidative stress, an overproduction of reactive oxygen species in relation to cellular defences, can correlate with reproductive investment and has been implicated as a pathway leading to senescence. This has led to the suggestion that this aspect of physiology could be an important mechanism underlying the trade-off between reproduction and lifespan. We manipulated female reproductive investment to test whether oxidative stress increases with reproduction in mice. Each female's pups were cross-fostered to produce litters of either two or eight, representing low and high levels of reproductive investment for wild mice. No differences were observed between reproductive groups at peak lactation for several markers of oxidative stress in the heart and gastrocnemius muscle. Surprisingly, oxidative damage to proteins was lower in the livers of females with a litter size of eight than in females with two pups or non-reproductive control females. While protein oxidation decreased, activity levels of the antioxidant enzyme superoxide dismutase increased in the liver, suggesting this may be one pathway used to protect against oxidative stress. Our results highlight the need for caution when interpreting correlative relationships and suggest that oxidative stress does not increase with enhanced reproductive effort during lactation.

  20. Dysfunction of Rapid Neural Adaptation in Dyslexia.

    Science.gov (United States)

    Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

    2016-12-21

    Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Prediction of oxidation parameters of purified Kilka fish oil including gallic acid and methyl gallate by adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network.

    Science.gov (United States)

    Asnaashari, Maryam; Farhoosh, Reza; Farahmandfar, Reza

    2016-10-01

    As a result of concerns regarding possible health hazards of synthetic antioxidants, gallic acid and methyl gallate may be introduced as natural antioxidants to improve oxidative stability of marine oil. Since conventional modelling could not predict the oxidative parameters precisely, artificial neural network (ANN) and neuro-fuzzy inference system (ANFIS) modelling with three inputs, including type of antioxidant (gallic acid and methyl gallate), temperature (35, 45 and 55 °C) and concentration (0, 200, 400, 800 and 1600 mg L(-1) ) and four outputs containing induction period (IP), slope of initial stage of oxidation curve (k1 ) and slope of propagation stage of oxidation curve (k2 ) and peroxide value at the IP (PVIP ) were performed to predict the oxidation parameters of Kilka oil triacylglycerols and were compared to multiple linear regression (MLR). The results showed ANFIS was the best model with high coefficient of determination (R(2)  = 0.99, 0.99, 0.92 and 0.77 for IP, k1 , k2 and PVIP , respectively). So, the RMSE and MAE values for IP were 7.49 and 4.92 in ANFIS model. However, they were to be 15.95 and 10.88 and 34.14 and 3.60 for the best MLP structure and MLR, respectively. So, MLR showed the minimum accuracy among the constructed models. Sensitivity analysis based on the ANFIS model suggested a high sensitivity of oxidation parameters, particularly the induction period on concentrations of gallic acid and methyl gallate due to their high antioxidant activity to retard oil oxidation and enhanced Kilka oil shelf life. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  2. Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Impagnatiello Francesco

    2010-11-01

    Full Text Available Abstract Background Current evidence suggests a role of neuroinflammation in the pathogenesis of Parkinson's disease (PD and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP model of basal ganglia injury. Reportedly, nonsteroidal anti-inflammatory drugs (NSAIDs mitigate DAergic neurotoxicity in rodent models of PD. Consistent with these findings, epidemiological analysis indicated that certain NSAIDs may prevent or delay the progression of PD. However, a serious impediment of chronic NSAID therapy, particularly in the elderly, is gastric, renal and cardiac toxicity. Nitric oxide (NO-donating NSAIDs, have a safer profile while maintaining anti-inflammatory activity of parent compounds. We have investigated the oral activity of the NO-donating derivative of flurbiprofen, [2-fluoro-α-methyl (1,1'-biphenyl-4-acetic-4-(nitrooxybutyl ester], HCT1026 (30 mg kg-1 daily in rodent chow in mice exposed to the parkinsonian neurotoxin MPTP. Methods Ageing mice were fed with a control, flurbiprofen, or HCT1026 diet starting ten days before MPTP administration and continuing for all the experimental period. Striatal high affinity synaptosomial dopamine up-take, motor coordination assessed with the rotarod, tyrosine hydroxylase (TH- and dopamine transporter (DAT fiber staining, stereological cell counts, immunoblotting and gene expression analyses were used to assess MPTP-induced nigrostriatal DAergic toxicity and glial activation 1-40 days post-MPTP. Results HCT1026 was well tolerated and did not cause any measurable toxic effect, whereas flurbiprofen fed mice showed severe gastrointestinal side-effects. HCT1026 efficiently counteracted motor impairment and reversed MPTP-induced decreased synaptosomal [3H]dopamine uptake, TH- and DAT-stained fibers in striatum and TH+ neuron loss in subtantia nigra pars compacta (SNpc, as opposed to age-matched mice fed with a control diet. These effects were associated to a significant decrease in reactive

  3. Synthesis and Application of an Environmentally Insensitive Cy3-Based Arsenical Fluorescent Probe to Identify Adaptive Microbial Responses Involving Proximal Dithiol Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Na; Su, Dian; Cort, John R.; Chen, Baowei; Xiong, Yijia; Qian, Weijun; Konopka, Allan; Bigelow, Diana J.; Squier, Thomas C.

    2013-03-06

    Reversible disulfide oxidation between proximal cysteines in proteins represents a common regulatory control mechanism to modulate flux through metabolic pathways in response to changing environmental conditions. To enable in vivo measurements of cellular redox changes linked to disulfide bond formation, we have synthesized a cell-permeable monosubstituted cyanine dye derivatized with arsenic (i.e., TRAP_Cy3) to trap and visualize dithiols in cytosolic proteins. Alkylation of reactive thiols prior to displacement of the bound TRAP-Cy3 by ethanedithiol permits facile protein capture and mass spectrometric identification of proximal reduced dithiols to the exclusion of individual cysteines. Applying TRAP_Cy3 to evaluate cellular responses to increases in oxygen and light levels in the photosynthetic microbe Synechococcus sp. PCC 7002, we observe large decreases in the abundance of reduced dithiols in cellular proteins, which suggest redox-dependent mechanisms involving the oxidation of proximal disulfides. Under these same growth conditions that result in the oxidation of proximal thiols, there is a reduction in the abundance of post-translational oxidative modifications involving nitrotyrosine and methionine sulfoxide formation. These results suggest that the redox status of proximal cysteines respond to environmental conditions, acting to regulate metabolic flux and minimize the formation of reactive oxygen species to decrease oxidative protein damage.

  4. Upregulation of the mitochondrial Lon Protease allows adaptation to acute oxidative stress but dysregulation is associated with chronic stress, disease, and aging

    Directory of Open Access Journals (Sweden)

    Jenny K. Ngo

    2013-01-01

    Full Text Available The elimination of oxidatively modified proteins is a crucial process in maintaining cellular homeostasis, especially during stress. Mitochondria are protein-dense, high traffic compartments, whose polypeptides are constantly exposed to superoxide, hydrogen peroxide, and other reactive species, generated by ‘electron leakage’ from the respiratory chain. The level of oxidative stress to mitochondrial proteins is not constant, but instead varies greatly with numerous metabolic and environmental factors. Oxidized mitochondrial proteins must be removed rapidly (by proteolytic degradation or they will aggregate, cross-link, and cause toxicity. The Lon Protease is a key enzyme in the degradation of oxidized proteins within the mitochondrial matrix. Under conditions of acute stress Lon is highly inducible, possibly with the oxidant acting as the signal inducer, thereby providing increased protection. It seems that under chronic stress conditions, however, Lon levels actually decline. Lon levels also decline with age and with senescence, and senescent cells even lose the ability to induce Lon during acute stress. We propose that the regulation of Lon is biphasic, in that it is up-regulated during transient stress and down-regulated during chronic stress and aging, and we suggest that the loss of Lon responsiveness may be a significant factor in aging, and in age-related diseases.

  5. Upregulation of the mitochondrial Lon Protease allows adaptation to acute oxidative stress but dysregulation is associated with chronic stress, disease, and aging.

    Science.gov (United States)

    Ngo, Jenny K; Pomatto, Laura C D; Davies, Kelvin J A

    2013-02-09

    The elimination of oxidatively modified proteins is a crucial process in maintaining cellular homeostasis, especially during stress. Mitochondria are protein-dense, high traffic compartments, whose polypeptides are constantly exposed to superoxide, hydrogen peroxide, and other reactive species, generated by 'electron leakage' from the respiratory chain. The level of oxidative stress to mitochondrial proteins is not constant, but instead varies greatly with numerous metabolic and environmental factors. Oxidized mitochondrial proteins must be removed rapidly (by proteolytic degradation) or they will aggregate, cross-link, and cause toxicity. The Lon Protease is a key enzyme in the degradation of oxidized proteins within the mitochondrial matrix. Under conditions of acute stress Lon is highly inducible, possibly with the oxidant acting as the signal inducer, thereby providing increased protection. It seems that under chronic stress conditions, however, Lon levels actually decline. Lon levels also decline with age and with senescence, and senescent cells even lose the ability to induce Lon during acute stress. We propose that the regulation of Lon is biphasic, in that it is up-regulated during transient stress and down-regulated during chronic stress and aging, and we suggest that the loss of Lon responsiveness may be a significant factor in aging, and in age-related diseases.

  6. Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

    Directory of Open Access Journals (Sweden)

    D. T. Yates

    2012-01-01

    Full Text Available Fetal adaptations to placental insufficiency alter postnatal metabolic homeostasis in skeletal muscle by reducing glucose oxidation rates, impairing insulin action, and lowering the proportion of oxidative fibers. In animal models of intrauterine growth restriction (IUGR, skeletal muscle fibers have less myonuclei at birth. This means that myoblasts, the sole source for myonuclei accumulation in fibers, are compromised. Fetal hypoglycemia and hypoxemia are complications that result from placental insufficiency. Hypoxemia elevates circulating catecholamines, and chronic hypercatecholaminemia has been shown to reduce fetal muscle development and growth. We have found evidence for adaptations in adrenergic receptor expression profiles in myoblasts and skeletal muscle of IUGR sheep fetuses with placental insufficiency. The relationship of β-adrenergic receptors shifts in IUGR fetuses because Adrβ2 expression levels decline and Adrβ1 expression levels are unaffected in myofibers and increased in myoblasts. This adaptive response would suppress insulin signaling, myoblast incorporation, fiber hypertrophy, and glucose oxidation. Furthermore, this β-adrenergic receptor expression profile persists for at least the first month in IUGR lambs and lowers their fatty acid mobilization. Developmental programming of skeletal muscle adrenergic receptors partially explains metabolic and endocrine differences in IUGR offspring, and the impact on metabolism may result in differential nutrient utilization.

  7. Cortical Visual Impairment

    Science.gov (United States)

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Cortical Visual Impairment En Español Read in Chinese What is cortical visual impairment? Cortical visual impairment (CVI) is a decreased ...

  8. Speech impairment (adult)

    Science.gov (United States)

    Language impairment; Impairment of speech; Inability to speak; Aphasia; Dysarthria; Slurred speech; Dysphonia voice disorders ... but anyone can develop a speech and language impairment suddenly, usually in a trauma. APHASIA Alzheimer disease ...

  9. Specific Language Impairment

    Science.gov (United States)

    ... Home » Health Info » Voice, Speech, and Language Specific Language Impairment On this page: What is specific language ... percent of children in kindergarten. What is specific language impairment? Specific language impairment (SLI) is a language ...

  10. Oxidative stress response and Nrf2 signaling in aging.

    Science.gov (United States)

    Zhang, Hongqiao; Davies, Kelvin J A; Forman, Henry Jay

    2015-11-01

    Increasing oxidative stress, a major characteristic of aging, has been implicated in a variety of age-related pathologies. In aging, oxidant production from several sources is increased, whereas antioxidant enzymes, the primary lines of defense, are decreased. Repair systems, including the proteasomal degradation of damaged proteins, also decline. Importantly, the adaptive response to oxidative stress declines with aging. Nrf2/EpRE signaling regulates the basal and inducible expression of many antioxidant enzymes and the proteasome. Nrf2/EpRE activity is regulated at several levels, including transcription, posttranslation, and interactions with other proteins. This review summarizes current studies on age-related impairment of Nrf2/EpRE function and discusses the changes in Nrf2 regulatory mechanisms with aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Oxidative stress response and Nrf2 signaling in aging

    Science.gov (United States)

    Zhang, Hongqiao; Davies, Kelvin J. A.; Forman, Henry Jay

    2015-01-01

    Increasing oxidative stress, a major characteristic of aging, has been implicated in variety of age-related pathologies. In aging, oxidant production from several sources is increased while antioxidant enzymes, the primary lines of defense, are decreased. Repair systems, including the proteasomal degradation of damaged proteins also declines. Importantly, the adaptive response to oxidative stress declines with aging. Nrf2/EpRE signaling regulates the basal and inducible expression of many antioxidant enzymes and the proteasome. Nrf2/EpRE activity is regulated at several levels including transcription, post-translation, and interaction with other proteins. This review summarizes current studies on age-related impairment of Nrf2/EpRE function and discusses the change of Nrf2 regulatory mechanisms with aging. PMID:26066302

  12. Naringenin ameliorates streptozotocin-induced diabetic rat renal impairment by downregulation of TGF-β1 and IL-1 via modulation of oxidative stress correlates with decreased apoptotic events.

    Science.gov (United States)

    Roy, Souvik; Ahmed, Faiqa; Banerjee, Sritama; Saha, Urmi

    2016-09-01

    Naringenin, a flavonone and a nutritive antioxidant which is mostly obtained from grapefruit, orange or tomato skin, has been extensively studied due to its radical scavenging activity. The present study investigates the protective effect of naringenin on rat kidney after streptozotocin-induced diabetes. Sixty male Wistar rats were divided into six groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg) in groups II, III and IV. Naringenin 5 mg/kg body weight was given to groups III and V, but 10 mg/kg was given to groups IV and VI, orally once a day for 10 weeks. After which all animals were sacrificed, and the biochemical, histopathological, immunohistochemical and apoptotic assays were conducted. Naringenin treatment with 5 and 10 mg/kg significantly decreased (p < 0.05) the serum biochemical parameters, elevated tissue malondialdehyde levels and increased (p < 0.01) the reduced superoxide dismutase, catalase and reduced glutathione enzyme activities in the diabetic kidney. Diabetes-induced naringenin-treated groups showed an improved histology and revealed a significant reduction in apoptosis activity (7.2 ± 0.01 and 1.8 ± 0.05) and in expression of TGF-β1 (18.9 ± 3.4 and 10.2 ± 2.1) at a dose of 5 and 10 mg/kg, respectively. Similarly, in contrast to the diabetic group, a significant difference was observed in the IL-1 expression (15.68 ± 4.3) in 5 mg/kg and (9.85 ± 2.1) in 10 mg/kg naringenin-treated groups. Naringenin acts as a protective agent in diabetic renal impairment by altering oxidative stress, modulation of cytokines expression and apoptotic events.

  13. Dynamics of nitrification and denitrification in root- oxygenated sediments and adaptation of ammonia-oxidizing bacteria to low-oxygen or anoxic habitats

    NARCIS (Netherlands)

    Bodelier, P.L.E.; Libochant, J.A.; Blom, C.W.P.M.; Laanbroek, H.J.

    1996-01-01

    Oxygen-releasing plants may provide aerobic niches in anoxic sediments and soils for ammonia-oxidizing bacteria, The oxygen- releasing, aerenchymatous emergent macrophyte Glycerin maxima had a strong positive effect on numbers and activities of the nitrifying bacteria in its root zone in spring and

  14. Adapted ECMO criteria for newborns with persistent pulmonary hypertension after inhaled nitric oxide and/or high-frequency oscillatory ventilation.

    NARCIS (Netherlands)

    Berkel, S. van; Binkhorst, M.; Heijst, A.F.J. van; Wijnen, M.H.W.A.; Liem, K.D.

    2013-01-01

    PURPOSE: Early prediction of extracorporeal membrane oxygenation (ECMO) requirement in term newborns with persistent pulmonary hypertension (PPHN), partially responding to inhaled nitric oxide (iNO) and/or high-frequency oscillatory ventilation (HFOV), based on oxygenation parameters. METHODS: This

  15. Cortical visual impairment

    OpenAIRE

    Koželj, Urša

    2013-01-01

    In this thesis we discuss cortical visual impairment, diagnosis that is in the developed world in first place, since 20 percent of children with blindness or low vision are diagnosed with it. The objectives of the thesis are to define cortical visual impairment and the definition of characters suggestive of the cortical visual impairment as well as to search for causes that affect the growing diagnosis of cortical visual impairment. There are a lot of signs of cortical visual impairment. ...

  16. Characteristics and adaptability of iron- and sulfur-oxidizing microorganisms used for the recovery of metals from minerals and their concentrates

    Directory of Open Access Journals (Sweden)

    Rawlings Douglas E

    2005-05-01

    Full Text Available Abstract Microorganisms are used in large-scale heap or tank aeration processes for the commercial extraction of a variety of metals from their ores or concentrates. These include copper, cobalt, gold and, in the past, uranium. The metal solubilization processes are considered to be largely chemical with the microorganisms providing the chemicals and the space (exopolysaccharide layer where the mineral dissolution reactions occur. Temperatures at which these processes are carried out can vary from ambient to 80°C and the types of organisms present depends to a large extent on the process temperature used. Irrespective of the operation temperature, biomining microbes have several characteristics in common. One shared characteristic is their ability to produce the ferric iron and sulfuric acid required to degrade the mineral and facilitate metal recovery. Other characteristics are their ability to grow autotrophically, their acid-tolerance and their inherent metal resistance or ability to acquire metal resistance. Although the microorganisms that drive the process have the above properties in common, biomining microbes usually occur in consortia in which cross-feeding may occur such that a combination of microbes including some with heterotrophic tendencies may contribute to the efficiency of the process. The remarkable adaptability of these organisms is assisted by several of the processes being continuous-flow systems that enable the continual selection of microorganisms that are more efficient at mineral degradation. Adaptability is also assisted by the processes being open and non-sterile thereby permitting new organisms to enter. This openness allows for the possibility of new genes that improve cell fitness to be selected from the horizontal gene pool. Characteristics that biomining microorganisms have in common and examples of their remarkable adaptability are described.

  17. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    Directory of Open Access Journals (Sweden)

    Samuel Rommelaere

    Full Text Available Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

  18. Image Enhancement For The Visually Impaired

    Science.gov (United States)

    Peli, Eli; Peli, Tamar

    1984-02-01

    Application of image processing for the visually impaired is discussed. Image degradation in the low vision patient's visual system can be specified as a transfer function obtained by measurements of contrast sensitivity. The effectiveness of adaptive image enhancement for printed pictures is demonstrated using an optically simulated cataractous lens.

  19. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial lighting ceases......Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...

  20. Visual impairment in the hearing impaired students.

    Science.gov (United States)

    Gogate, Parikshit; Rishikeshi, Nikhil; Mehata, Reshma; Ranade, Satish; Kharat, Jitesh; Deshpande, Madan

    2009-01-01

    Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. To detect and treat visual impairment, if any, in hearing-impaired children. Observational, clinical case series of hearing-impaired children in schools providing special education. Hearing-impaired children in selected schools underwent detailed visual acuity testing, refraction, external ocular examination and fundoscopy. Ocular motility testing was also performed. Teachers were sensitized and trained to help in the assessment of visual acuity using Snellen's E charts. Refractive errors and squint were treated as per standard practice. Excel software was used for data entry and SSPS for analysis. The study involved 901 hearing-impaired students between four and 21 years of age, from 14 special education schools. A quarter of them (216/901, 24%) had ocular problems. Refractive errors were the most common morbidity 167(18.5%), but only 10 children were using appropriate spectacle correction at presentation. Fifty children had visual acuity less than 20/80 at presentation; after providing refractive correction, this number reduced to three children, all of whom were provided low-vision aids. Other common conditions included strabismus in 12 (1.3%) children, and retinal pigmentary dystrophy in five (0.6%) children. Ocular problems are common in hearing-impaired children. Screening for ocular problems should be made mandatory in hearing-impaired children, as they use their visual sense to compensate for the poor auditory sense.

  1. Classification and adaptive behavior prediction of children with autism spectrum disorder based upon multivariate data analysis of markers of oxidative stress and DNA methylation.

    Science.gov (United States)

    Howsmon, Daniel P; Kruger, Uwe; Melnyk, Stepan; James, S Jill; Hahn, Juergen

    2017-03-01

    The number of diagnosed cases of Autism Spectrum Disorders (ASD) has increased dramatically over the last four decades; however, there is still considerable debate regarding the underlying pathophysiology of ASD. This lack of biological knowledge restricts diagnoses to be made based on behavioral observations and psychometric tools. However, physiological measurements should support these behavioral diagnoses in the future in order to enable earlier and more accurate diagnoses. Stepping towards this goal of incorporating biochemical data into ASD diagnosis, this paper analyzes measurements of metabolite concentrations of the folate-dependent one-carbon metabolism and transulfuration pathways taken from blood samples of 83 participants with ASD and 76 age-matched neurotypical peers. Fisher Discriminant Analysis enables multivariate classification of the participants as on the spectrum or neurotypical which results in 96.1% of all neurotypical participants being correctly identified as such while still correctly identifying 97.6% of the ASD cohort. Furthermore, kernel partial least squares is used to predict adaptive behavior, as measured by the Vineland Adaptive Behavior Composite score, where measurement of five metabolites of the pathways was sufficient to predict the Vineland score with an R2 of 0.45 after cross-validation. This level of accuracy for classification as well as severity prediction far exceeds any other approach in this field and is a strong indicator that the metabolites under consideration are strongly correlated with an ASD diagnosis but also that the statistical analysis used here offers tremendous potential for extracting important information from complex biochemical data sets.

  2. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.

    Science.gov (United States)

    Vasconcelos, Andrea R; Yshii, Lidia M; Viel, Tania A; Buck, Hudson S; Mattson, Mark P; Scavone, Cristoforo; Kawamoto, Elisa M

    2014-05-06

    Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels. Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

  3. Visual Impairment, Including Blindness

    Science.gov (United States)

    ... Who Knows What? (log-in required) Select Page Visual Impairment, Including Blindness Mar 31, 2017 Links updated, ... doesn’t wear his glasses. Back to top Visual Impairments in Children Vision is one of our ...

  4. Mild Cognitive Impairment (MCI)

    Science.gov (United States)

    Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It can involve ...

  5. Kids' Quest: Vision Impairment

    Science.gov (United States)

    ... Fact Check Up Tourette Questions I Have Vision Impairment Quest Vision Fact Check Up Vision Questions I ... Tweet Share Compartir What should you know? Vision impairment means that a person’s eyesight cannot be corrected ...

  6. Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans

    NARCIS (Netherlands)

    Wanders, Ronald J. A.; Komen, Jasper; Kemp, Stephan

    2011-01-01

    Fatty acids (FAs) can be degraded via different mechanisms including alpha-, beta- and omega-oxidation. In humans, a range of different genetic diseases has been identified in which either mitochondrial FA beta-oxidation, peroxisomal FA beta-oxidation or FA alpha-oxidation is impaired. Treatment

  7. ADAPT Dataset

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Diagnostics and Prognostics Testbed (ADAPT) Project Lead: Scott Poll Subject Fault diagnosis in electrical power systems Description The Advanced...

  8. Adaptive skills

    Directory of Open Access Journals (Sweden)

    Staša Stropnik

    2013-02-01

    Full Text Available Adaptive skills are defined as a collection of conceptual, social and practical skills that are learned by people in order to function in their everyday lives. They include an individual's ability to adapt to and manage her or his surroundings to effectively function and meet social or community expectations. Good adaptive skills promote individual's independence in different environments, whereas poorly developed adaptive skills are connected to individual's dependency and with greater need for control and help with everyday tasks. Assessment of adaptive skills is often connected to assessment of intellectual disability, due to the reason that the diagnosis of intellectual disability includes lower levels of achievements on standardized tests of intellectual abilities as well as important deficits in adaptive skills. Assessment of adaptive behavior is a part of standard assessment battery with children and adults with different problems, disorders or disabilities that affect their everyday functioning. This contribution also presents psychometric tools most regularly used for assessment of adaptive skills and characteristics of adaptive skills with individual clinical groups.

  9. Through the Spattered Windshield: A Visually Impaired Teacher's Internship.

    Science.gov (United States)

    Smith, Douglas James

    2000-01-01

    A visually impaired student teacher, her cooperating teachers, and college supervisor cooperated to make her internship successful. Adaptations included making early contact to enable adaptation of resources, focusing on capabilities rather than limitations of challenged interns, empowering interns to determine their own solutions to problems,…

  10. Adaptive alterations in the fatty acids composition under induced oxidative stress in heavy metal-tolerant filamentous fungus Paecilomyces marquandii cultured in ascorbic acid presence.

    Science.gov (United States)

    Słaba, Mirosława; Gajewska, Ewa; Bernat, Przemysław; Fornalska, Magdalena; Długoński, Jerzy

    2013-05-01

    The ability of the heavy metal-tolerant fungus Paecilomyces marquandii to modulate whole cells fatty acid composition and saturation in response to IC50 of Cd, Pb, Zn, Ni, and Cu was studied. Cadmium and nickel caused the most significant growth reduction. In the mycelia cultured with all tested metals, with the exception of nickel, a rise in the fatty acid unsaturation was noted. The fungus exposure to Pb, Cu, and Ni led to significantly higher lipid peroxidation. P. marquandii incubated in the presence of the tested metals responded with an increase in the level of linoleic acid and escalation of electrolyte leakage. The highest efflux of electrolytes was caused by lead. In these conditions, the fungus was able to bind up to 100 mg g(-1) of lead, whereas the content of the other metals in the mycelium was significantly lower and reached from 3.18 mg g(-1) (Cu) to 15.21 mg g(-1) (Zn). Additionally, it was shown that ascorbic acid at the concentration of 1 mM protected fungal growth and prevented the changes in the fatty acid composition and saturation but did not alleviate lipid peroxidation or affect the increased permeability of membranes after lead exposure. Pro-oxidant properties of ascorbic acid in the copper-stressed cells manifested strong growth inhibition and enhanced metal accumulation as a result of membrane damage. Toxic metals action caused cellular modulations, which might contributed to P. marquandii tolerance to the studied metals. Moreover, these changes can enhance metal removal from contaminated environment.

  11. Visual impairment in the hearing impaired students

    Directory of Open Access Journals (Sweden)

    Gogate Parikshit

    2009-01-01

    Full Text Available Background : Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. Aim : To detect and treat visual impairment, if any, in hearing-impaired children. Setting and Design : Observational, clinical case series of hearing-impaired children in schools providing special education. Materials and Methods : Hearing-impaired children in selected schools underwent detailed visual acuity testing, refraction, external ocular examination and fundoscopy. Ocular motility testing was also performed. Teachers were sensitized and trained to help in the assessment of visual acuity using Snellen′s E charts. Refractive errors and squint were treated as per standard practice. Statistical Analysis : Excel software was used for data entry and SSPS for analysis. Results : The study involved 901 hearing-impaired students between four and 21 years of age, from 14 special education schools. A quarter of them (216/901, 24% had ocular problems. Refractive errors were the most common morbidity 167(18.5%, but only 10 children were using appropriate spectacle correction at presentation. Fifty children had visual acuity less than 20/80 at presentation; after providing refractive correction, this number reduced to three children, all of whom were provided low-vision aids. Other common conditions included strabismus in 12 (1.3% children, and retinal pigmentary dystrophy in five (0.6% children. Conclusion : Ocular problems are common in hearing-impaired children. Screening for ocular problems should be made mandatory in hearing-impaired children, as they use their visual sense to compensate for the poor auditory sense.

  12. Memory Impairment in Children with Language Impairment

    Science.gov (United States)

    Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily

    2010-01-01

    Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…

  13. [Inflammation and oxidation: predictive and/or causative factors].

    Science.gov (United States)

    Fernández-Viadero, Carlos; Jiménez-Sanz, Magdalena; Fernández-Pérez, Anzu; Verduga Vélez, Rosario; Crespo Santiago, Dámaso

    2016-06-01

    Brain ageing leads to a series of changes that reduce the processes of adaptation and response. These transformations can end in cognitive impairment and/or dementia. Although the cause of these changes is diverse, inflammation and oxidative stress explain some of the pathophysiological mechanisms of these anomalies of brain functioning. Neuroinflammation triggers neuronal injury through the presence of inflammatory cytokines and the activation of microglia through membrane receptors and nuclear activation factors. This neuroinflammatory phenomenon also affects neuron plasticity, altering the genesis and maintenance of long-term potentiation, leading to impairment of hippocampus-dependent memory. Oxidative stress and the production of free oxygen radicals also cause toxic effects in aged brains, largely due to lipid peroxidation and DNA damage. The identification of the molecular mechanisms involved in the pathogenesis of these events could shed new light on possible therapeutic targets and offer strategies for the prevention of diseases related to brain ageing, cognitive impairment and dementia. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Unripe Musa paradisiacal fruit diet ameliorates impaired glucose ...

    African Journals Online (AJOL)

    Excess iron impairs glucose regulatory mechanisms through an increase in oxidative stress. Unripe Musa paradisiaca fruit (UMP) diets have been reported to alleviate diabetes and exert antioxidant effects. In this study, some glucose regulatory indices were investigated in Wistar rats with iron-induced oxidative stress and ...

  15. Personality Testing with Visually Impaired Adults in Applied Occupational Settings: A Review of the Literature.

    Science.gov (United States)

    Reid, Juliet

    2000-01-01

    This article describes controversies over the use of personality tests with adults with visual impairments in applied occupational testing. It reviews studies of personality profiles of sighted individuals and individuals with visual impairments and studies in which the content of items has been adapted for adults who are visually impaired.…

  16. Redox homeostasis, oxidative stress and disuse muscle atrophy

    Science.gov (United States)

    Pellegrino, Maria Antonietta; Desaphy, Jean-François; Brocca, Lorenza; Pierno, Sabata; Camerino, Diana Conte; Bottinelli, Roberto

    2011-01-01

    Abstract A pivotal role has been ascribed to oxidative stress in determining the imbalance between protein synthesis and degradation leading to muscle atrophy in many pathological conditions and in disuse. However, a large variability in disuse-induced alteration of redox homeostasis through muscles, models and species emerges from the literature. Whereas the causal role of oxidative stress appears well established in the mechanical ventilation model, findings are less compelling in the hindlimb unloaded mice and very limited in humans. The mere coexistence of muscle atrophy, indirect indexes of increased reactive oxygen species (ROS) production and impairment of antioxidant defence systems, in fact, does not unequivocally support a causal role of oxidative stress in the phenomenon. We hypothesise that in some muscles, models and species only, due to a large redox imbalance, the leading phenomena are activation of proteolysis and massive oxidation of proteins, which would become more susceptible to degradation. In other conditions, due to a lower extent and variable time course of ROS production, different ROS-dependent, but also -independent intracellular pathways might dominate determining the variable extent of atrophy and even dispensable protein oxidation. The ROS production and removal are complex and finely tuned phenomena. They are indeed important intracellular signals and redox balance maintains normal muscle homeostasis and can underlie either positive or negative adaptations to exercise. A precise approach to determine the levels of ROS in living cells in various conditions appears to be of paramount importance to define and support such hypotheses. PMID:21320887

  17. Depression in cognitive impairment.

    Science.gov (United States)

    Pellegrino, Laurel D; Peters, Matthew E; Lyketsos, Constantine G; Marano, Christopher M

    2013-09-01

    Depression and cognitive disorders, including dementia and mild cognitive impairment, are common in the elderly. Depression is also a common feature of cognitive impairment although the symptoms of depression in cognitive impairment differ from depression without cognitive impairment. Pre-morbid depression approximately doubles the risk of subsequent dementia. There are two predominant, though not mutually exclusive, constructs linking pre-morbid depression to subsequent cognitive impairment: Alzheimer's pathology and the vascular depression hypothesis. When evaluating a patient with depression and cognitive impairment, it is important to obtain caregiver input and to evaluate for alternative etiologies for depressive symptoms such as delirium. We recommend a sequential approach to the treatment of depression in dementia patients: (1) a period of watchful waiting for milder symptoms, (2) psychosocial treatment program, (3) a medication trial for more severe symptoms or failure of psychosocial interventions, and (4) possible ECT for refractory symptoms.

  18. Hypertension and cognitive impairment

    Directory of Open Access Journals (Sweden)

    Su-hang SHANG

    2015-08-01

    Full Text Available As a leading risk factor for stroke, hypertension is also an important risk factor for cognitive impairment. Midlife hypertension doubles the risk of dementia later in life and accelerates the progression of dementia, but the correlation between late-life blood pressure and cognitive impairment is still unclear. Beside blood pressure, the effect of pulse pressure, blood pressure variability and circadian rhythm of blood pressure on cognition is currently attracting more and more attention. Hypertension induces alterations in cerebrovascular structure and functions, which lead to brain lesions including cerebral atrophy, stroke, lacunar infarcts, diffuse white matter damage, microinfarct and microhemorrhage, resuling in cognitive impairment. Hypertension also impairs the metabolism and transfer of amyloid-β protein (Aβ, thus accelerates cognitive impairment. Individualized therapy, focusing on characteristics of hypertensive patients, may be a good choice for prevention and treatment of cognitive impairment. DOI: 10.3969/j.issn.1672-6731.2015.08.004

  19. Ambiguous Adaptation

    DEFF Research Database (Denmark)

    Møller Larsen, Marcus; Lyngsie, Jacob

    We investigate why some exchange relationships terminate prematurely. We argue that investments in informal governance structures induce premature termination in relationships already governed by formal contracts. The formalized adaptive behavior of formal governance structures and the flexible...... and reciprocal adaptation of informal governance structure create ambiguity in situations of contingencies, which, subsequently, increases the likelihood of premature relationship termination. Using a large sample of exchange relationships in the global service provider industry, we find support for a hypothesis...

  20. Lithium and Renal Impairment

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Kessing, Lars Vedel; Nolen, Willem A

    2018-01-01

    INTRODUCTION: Lithium is established as an effective treatment of mania, of depression in bipolar and unipolar disorder, and in maintenance treatment of these disorders. However, due to the necessity of monitoring and concerns about irreversible adverse effects, in particular renal impairment......, after long-term use, lithium might be underutilized. METHODS: This study reviewed 6 large observational studies addressing the risk of impaired renal function associated with lithium treatment and methodological issues impacting interpretation of results. RESULTS: An increased risk of renal impairment...

  1. Phospholipase A2 – nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment

    OpenAIRE

    Petra Maria Hermann; Shawn Nathan Watson; Willem Carel Wildering

    2014-01-01

    TThe aging brain can undergo a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative disea...

  2. Criteria for driver impairment

    NARCIS (Netherlands)

    Brookhuis, K.A.; De Waard, D.; Fairclough, S.H

    2003-01-01

    Most traffic accidents can be attributed to driver impairment, e.g. inattention, fatigue, intoxication, etc. It is now technically feasible to monitor and diagnose driver behaviour with respect to impairment with the aid of a limited number of in-vehicle sensors. However, a valid framework for the

  3. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Kongshaug, Jesper; Søndergaard, Karin

    2015-01-01

    offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial lighting ceases...... to be static, and no longer acts as a kind of spatial constancy maintaining stability and order? Moreover, what new potentials open in lighting design? This book is one of four books that is published in connection with the research project entitled LED Lighting; Interdisciplinary LED Lighting Research...

  4. Selection of metastatic breast cancer cells based on adaptability of their metabolic state.

    Directory of Open Access Journals (Sweden)

    Balraj Singh

    Full Text Available A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis

  5. Adaptive test

    DEFF Research Database (Denmark)

    Kjeldsen, Lars Peter; Eriksen, Mette Rose

    2010-01-01

    Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale.......Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale....

  6. Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers.

    Science.gov (United States)

    Burke, Louise M; Ross, Megan L; Garvican-Lewis, Laura A; Welvaert, Marijke; Heikura, Ida A; Forbes, Sara G; Mirtschin, Joanne G; Cato, Louise E; Strobel, Nicki; Sharma, Avish P; Hawley, John A

    2017-05-01

    Three weeks of intensified training and mild energy deficit in elite race walkers increases peak aerobic capacity independent of dietary support. Adaptation to a ketogenic low carbohydrate, high fat (LCHF) diet markedly increases rates of whole-body fat oxidation during exercise in race walkers over a range of exercise intensities. The increased rates of fat oxidation result in reduced economy (increased oxygen demand for a given speed) at velocities that translate to real-life race performance in elite race walkers. In contrast to training with diets providing chronic or periodised high carbohydrate availability, adaptation to an LCHF diet impairs performance in elite endurance athletes despite a significant improvement in peak aerobic capacity. We investigated the effects of adaptation to a ketogenic low carbohydrate (CHO), high fat diet (LCHF) during 3 weeks of intensified training on metabolism and performance of world-class endurance athletes. We controlled three isoenergetic diets in elite race walkers: high CHO availability (g kg -1  day -1 : 8.6 CHO, 2.1 protein, 1.2 fat) consumed before, during and after training (HCHO, n = 9); identical macronutrient intake, periodised within or between days to alternate between low and high CHO availability (PCHO, n = 10); LCHF (economy. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  7. Adaptation Insights

    International Development Research Centre (IDRC) Digital Library (Canada)

    be given greater access to relevant information to help them adapt their farming practices and socio- economic strategies to climate change? To address this challenge, the project “InfoClim,” led by Senegal's. Ecological Monitoring Centre. (CSE) with support from the. CCAA program, aims at improving the access of farmers ...

  8. Adaptation Insights

    International Development Research Centre (IDRC) Digital Library (Canada)

    and local adaptive capacity. During a monitoring and evaluation session, farmers indicated that the downscaled climate outlook has helped them to make more appropriate on-farm decisions. Figure 2 illustrates the effects of seasonal forecasts on the decisions farmers made in regards to the type/ variety of seeds to plant.

  9. Adaptive ethnography

    DEFF Research Database (Denmark)

    Berth, Mette

    2005-01-01

    This paper focuses on the use of an adaptive ethnography when studying such phenomena as young people's use of mobile media in a learning perspective. Mobile media such as PDAs and mobile phones have a number of affordances which make them potential tools for learning. However, before we begin...

  10. Impairment in Non-Word Repetition: A Marker for Language Impairment or Reading Impairment?

    Science.gov (United States)

    Baird, Gillian; Slonims, Vicky; Simonoff, Emily; Dworzynski, Katharina

    2011-01-01

    Aim: A deficit in non-word repetition (NWR), a measure of short-term phonological memory proposed as a marker for language impairment, is found not only in language impairment but also in reading impairment. We evaluated the strength of association between language impairment and reading impairment in children with current, past, and no language…

  11. Staged membrane oxidation reactor system

    Science.gov (United States)

    Repasky, John Michael; Carolan, Michael Francis; Stein, VanEric Edward; Chen, Christopher Ming-Poh

    2013-04-16

    Ion transport membrane oxidation system comprising (a) two or more membrane oxidation stages, each stage comprising a reactant zone, an oxidant zone, one or more ion transport membranes separating the reactant zone from the oxidant zone, a reactant gas inlet region, a reactant gas outlet region, an oxidant gas inlet region, and an oxidant gas outlet region; (b) an interstage reactant gas flow path disposed between each pair of membrane oxidation stages and adapted to place the reactant gas outlet region of a first stage of the pair in flow communication with the reactant gas inlet region of a second stage of the pair; and (c) one or more reactant interstage feed gas lines, each line being in flow communication with any interstage reactant gas flow path or with the reactant zone of any membrane oxidation stage receiving interstage reactant gas.

  12. Carbohydrate intake and glycemic index affect substrate oxidation during a controlled weight cycle in healthy men.

    Science.gov (United States)

    Kahlhöfer, J; Lagerpusch, M; Enderle, J; Eggeling, B; Braun, W; Pape, D; Müller, M J; Bosy-Westphal, A

    2014-09-01

    Because both, glycemic index (GI) and carbohydrate content of the diet increase insulin levels and could thus impair fat oxidation, we hypothesized that refeeding a low GI, moderate-carbohydrate diet facilitates weight maintenance. Healthy men (n=32, age 26.0±3.9 years; BMI 23.4±2.0 kg/m(2)) followed 1 week of controlled overfeeding, 3 weeks of caloric restriction and 2 weeks of hypercaloric refeeding (+50, -50 and +50% energy requirement) with low vs high GI (41 vs 74) and moderate vs high CHO intake (50% vs 65% energy). We measured adaptation of fasting macronutrient oxidation and the capacity to supress fat oxidation during an oral glucose tolerance test. Changes in fat mass were measured by quantitative magnetic resonance. During overfeeding, participants gained 1.9±1.2 kg body weight, followed by a weight loss of -6.3±0.6 kg and weight regain of 2.8±1.0 kg. Subjects with 65% CHO gained more body weight compared with 50% CHO diet (Pmetabolic flexibility was unaffected by refeeding at 50% CHO but clearly impaired by 65% CHO diet (Pcarbohydrate content affect substrate oxidation and thus the regain in body weight in healthy men. These results argue in favor of a lower glycemic load diet for weight maintenance after weight loss.

  13. Impairments to Vision

    Science.gov (United States)

    ... an external Non-Government web site. Impairments to Vision Normal Vision Diabetic Retinopathy Age-related Macular Degeneration In this ... pictures, fixate on the nose to simulate the vision loss. In diabetic retinopathy, the blood vessels in ...

  14. The visually impaired patient

    National Research Council Canada - National Science Library

    Rosenberg, EA

    2008-01-01

    ... and independent living for the visually impaired patient. In the United States, the four most prevalent etiologies of vision loss in persons 40 years and older are age-related macular degeneration, cataracts, glaucoma, and diabetic retinopathy...

  15. Aids for visual impairment.

    OpenAIRE

    Dudley, N. J.

    1990-01-01

    This article provides only a flavour of the type and range of aids available to the visually impaired person. Many other aids for leisure, learning, and daily living are illustrated in the RNIB equipment and games catalogue.

  16. Speech and Language Impairments

    Science.gov (United States)

    ... What? (log-in required) Select Page Speech and Language Impairments Jun 16, 2010 A legacy disability fact ... 11] Back to top Development of Speech and Language Skills in Childhood Speech and language skills develop ...

  17. Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses

    Science.gov (United States)

    Nawrocka, Daria; Kornicka, Katarzyna; Śmieszek, Agnieszka

    2017-01-01

    Equine Metabolic Syndrome (EMS) is a steadily growing life-threatening endocrine disorder linked to insulin resistance, oxidative stress, and systemic inflammation. Inflammatory microenvironment of adipose tissue constitutes the direct tissue milieu for various cell populations, including adipose-derived mesenchymal stromal cells (ASCs), widely considered as a potential therapeutic cell source in the course of the treatment of metabolic disorders. Moreover, elevated oxidative stress induces inflammation in intestinal epithelial cells (IECs)—the first-line cells exposed to dietary compounds. In the conducted research, we showed that in vitro application of Spirulina platensis contributes to the restoration of ASCs’ and IECs’ morphology and function through the reduction of cellular oxidative stress and inflammation. Enhanced viability, suppressed senescence, and improved proliferation of ASCs and IECs isolated from metabolic syndrome-affected individuals were evident following exposition to Spirulina. A protective effect of the investigated extract against mitochondrial dysfunction and degeneration was also observed. Moreover, our data demonstrate that Spirulina extract effectively suppressed LPS-induced inflammatory responses in macrophages. In vivo studies showed that horses fed with a diet based on Spirulina platensis supplementation lost weight and their insulin sensitivity improved. Thus, our results indicate the engagement of Spirulina platensis nourishing as an interesting alternative approach for supporting the conventional treatment of equine metabolic syndrome. PMID:28771165

  18. Adaptation Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Huq, Saleemul

    2011-11-15

    Efforts to help the world's poor will face crises in coming decades as climate change radically alters conditions. Action Research for Community Adapation in Bangladesh (ARCAB) is an action-research programme on responding to climate change impacts through community-based adaptation. Set in Bangladesh at 20 sites that are vulnerable to floods, droughts, cyclones and sea level rise, ARCAB will follow impacts and adaptation as they evolve over half a century or more. National and international 'research partners', collaborating with ten NGO 'action partners' with global reach, seek knowledge and solutions applicable worldwide. After a year setting up ARCAB, we share lessons on the programme's design and move into our first research cycle.

  19. Hedonic "adaptation"

    Directory of Open Access Journals (Sweden)

    Paul Rozin

    2008-02-01

    Full Text Available People live in a world in which they are surrounded by potential disgust elicitors such as ``used'' chairs, air, silverware, and money as well as excretory activities. People function in this world by ignoring most of these, by active avoidance, reframing, or adaptation. The issue is particularly striking for professions, such as morticians, surgeons, or sanitation workers, in which there is frequent contact with major disgust elicitors. In this study, we study the ``adaptation'' process to dead bodies as disgust elicitors, by measuring specific types of disgust sensitivity in medical students before and after they have spent a few months dissecting a cadaver. Using the Disgust Scale, we find a significant reduction in disgust responses to death and body envelope violation elicitors, but no significant change in any other specific type of disgust. There is a clear reduction in discomfort at touching a cold dead body, but not in touching a human body which is still warm after death.

  20. Adaptive VFH

    Science.gov (United States)

    Odriozola, Iñigo; Lazkano, Elena; Sierra, Basi

    2011-10-01

    This paper investigates the improvement of the Vector Field Histogram (VFH) local planning algorithm for mobile robot systems. The Adaptive Vector Field Histogram (AVFH) algorithm has been developed to improve the effectiveness of the traditional VFH path planning algorithm overcoming the side effects of using static parameters. This new algorithm permits the adaptation of planning parameters for the different type of areas in an environment. Genetic Algorithms are used to fit the best VFH parameters to each type of sector and, afterwards, every section in the map is labelled with the sector-type which best represents it. The Player/Stage simulation platform has been chosen for making all sort of tests and to prove the new algorithm's adequateness. Even though there is still much work to be carried out, the developed algorithm showed good navigation properties and turned out to be softer and more effective than the traditional VFH algorithm.

  1. Adaptive ethnography

    DEFF Research Database (Denmark)

    Berth, Mette

    2005-01-01

    This paper focuses on the use of an adaptive ethnography when studying such phenomena as young people's use of mobile media in a learning perspective. Mobile media such as PDAs and mobile phones have a number of affordances which make them potential tools for learning. However, before we begin...... formal and informal learning contexts. The paper also proposes several adaptive methodological techniques for studying young people's interaction with mobiles....... to design and develop educational materials for mobile media platforms we must first understand everyday use and behaviour with a medium such as a mobile phone. The paper outlines the research design for a PhD project on mobile learning which focuses on mobile phones as a way to bridge the gap between...

  2. Strategic Adaptation

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    2015-01-01

    This article provides an overview of theoretical contributions that have influenced the discourse around strategic adaptation including contingency perspectives, strategic fit reasoning, decision structure, information processing, corporate entrepreneurship, and strategy process. The related conc....... This model incorporates elements of central strategizing, autonomous entrepreneurial behavior, interactive information processing, and open communication systems that enhance the organization's ability to observe exogenous changes and respond effectively to them....

  3. ADAPTATION EVALUATION

    Directory of Open Access Journals (Sweden)

    Björn PETERS, M.Sc.

    2001-01-01

    Full Text Available Twenty subjects with lower limb disabilities participated in a simulator study. The purpose of the study was to investigate how an Adaptive Cruise Control (ACC system together with two different hand controls for accelerator and brake influenced workload, comfort and driving behaviour and to further develop a method to evaluate vehicle adaptations for drivers with disabilities. The installed ACC system could maintain a constant speed selected and set by the driver and it also adapted speed in order to keep a safe distance to a leading vehicle. Furthermore, it included a stop-and-go function. Two common types of hand controls for accelerator and brake were used. The hand controls were different both with respect to function, single or dual levers, and position, on the steering column or between the front seats. The subjects were all experienced drivers of adapted cars equipped with hand controls. All subjects drove 100km at two occasions, with and without the ACC system available but with the same hand control. Subjective workload was found to be significantly lower and performance better for the ACC condition. The difference in speed variation between manual and ACC supported driving increased with the distance driven which seems to support the previous finding. The subjects thought they could control both speed and distance to leading vehicles better while the ACC was available. ACC driving did not influence reaction time, speed level, lateral position or variation in lateral position. Headway during car following situations was shorter for the ACC condition compared to manual driving. The ACC was well received, trusted and wanted. It was concluded that the ACC system substantially decreased workload, increased comfort and did not influence safety negatively. The only difference found between the two types of hand controls was that drivers using the dual lever system had less variation in lateral position. The applied evaluation method proved

  4. Impaired but undiagnosed.

    Science.gov (United States)

    Angold, A; Costello, E J; Farmer, E M; Burns, B J; Erkanli, A

    1999-02-01

    To investigate the prevalence and outcomes of individuals with psychosocial impairment not meeting DSM-III-R criteria for any of 29 well-defined disorders and to suggest operational definitions for not otherwise specified (NOS) diagnoses and V codes. Two-stage general population sampling resulted in 1,015 youths aged 9, 11, and 13 years being interviewed in the first wave of the Great Smoky Mountains Study. They were reinterviewed 1 year later using the Child and Adolescent Psychiatric Assessment. The weighted prevalence of sibling relational problems was found to be 1.4%. That of parent-child relational problems was 3.6% and that of relational problems NOS was 0.6%. The overall rate of symptomatic impairment was 9.4%. Across a variety of "caseness measures," those with symptomatic impairment proved to be more disturbed than those without either a diagnosis or impairment, and as disturbed as those with a diagnosis but without impairment. Children and adolescents who do not meet DSM-III-R criteria for any well-defined disorder but who have symptoms associated with psychosocial impairment should be regarded as suffering from a psychiatric disorder. It is suggested that researchers adopt this definition for the many NOS diagnoses included in the DSM nosology and implement it in their research diagnostic algorithms.

  5. Revisiting nicotine's role in the ageing brain and cognitive impairment

    DEFF Research Database (Denmark)

    Majdi, Alireza; Kamari, Farzin; Vafaee, Manouchehr Seyedi

    2017-01-01

    Brain ageing is a complex process which in its pathologic form is associated with learning and memory dysfunction or cognitive impairment. During ageing, changes in cholinergic innervations and reduced acetylcholinergic tonus may trigger a series of molecular pathways participating in oxidative...... in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment....

  6. Impairment in non‐word repetition: a marker for language impairment or reading impairment?

    National Research Council Canada - National Science Library

    BAIRD, GILLIAN; SLONIMS, VICKY; SIMONOFF, EMILY; DWORZYNSKI, KATHARINA

    2011-01-01

    Aim  A deficit in non‐word repetition (NWR), a measure of short‐term phonological memory proposed as a marker for language impairment, is found not only in language impairment but also in reading impairment...

  7. Coordinated balancing of muscle oxidative metabolism through PGC-1{alpha} increases metabolic flexibility and preserves insulin sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Summermatter, Serge [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Troxler, Heinz [Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University Children' s Hospital, University of Zurich, Steinwiesstrasse 75, CH-8032 Zurich (Switzerland); Santos, Gesa [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Handschin, Christoph, E-mail: christoph.handschin@unibas.ch [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland)

    2011-04-29

    Highlights: {yields} PGC-1{alpha} enhances muscle oxidative capacity. {yields} PGC-1{alpha} promotes concomitantly positive and negative regulators of lipid oxidation. {yields} Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. {yields} Balanced oxidation prevents detrimental acylcarnitine and ROS generation. {yields} Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1{alpha} on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1{alpha} in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1{alpha} induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1{alpha} enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1{alpha} boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1{alpha} coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1{alpha} does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1{alpha} mimic the beneficial effects of endurance training

  8. Nitric oxide and superoxide: interference with hypoxic signaling.

    Science.gov (United States)

    Brüne, Bernhard; Zhou, Jie

    2007-07-15

    Sensing and responding to changes in oxygen partial pressure assures that the cellular oxygen supply is tightly controlled in order to balance the risks of oxidative damage vs. oxygen deficiency. The hypoxia inducible factor (HIF) regulatory system is controlled by prolyl hydroxylases (PHDs), the von Hippel Lindau protein (pVHL), and the 26S proteasome and transduces changes in oxygenation to adequate intracellular adaptive responses. A functional HIF response requires stabilization of the alpha-subunit, e.g. HIF-1alpha, during hypoxia and dimerization with HIF-1beta, to drive target gene activation. Intriguingly, high concentrations of nitric oxide (NO) stabilize HIF-1alpha and thus mimic a hypoxic response under normoxia. Mechanistically, NO blocks PHD activity and attenuates proline hydroxylation of HIF-1alpha. This causes dissociation of pVHL from HIF-1alpha and, consequently, HIF-1alpha accumulates because proteasomal destruction is impaired. However, during hypoxia low concentrations of NO facilitate destruction of HIF-1alpha and thus reverse HIF signaling. Under these conditions, NO impairs respiration and avoids oxygen gradients that limit PHD activity. An additional layer of complexity comprises the interaction of NO with O(2)(-). Signaling qualities attributed to NO are antagonized by compensatory flux rates of O(2)(-) and vice versa to adjust levels of HIF-1alpha under normoxia and hypoxia. The liaison of NO and hypoxia is versatile and ranges from courting to matrimony and divorce.

  9. Visually impaired caregivers: perspectives from patient focus groups.

    Science.gov (United States)

    Martinez, Bethany S; Williams, Michael; Fuhr, Patti

    2009-01-01

    With the aging of the population, more persons who are severely visually impaired are now caring for a spouse or significant other. The purpose of this qualitative study is to learn more about this previously unreported, yet vulnerable, population of visually impaired caregivers. Focus groups and 1-on-1 interviews were conducted with legally blind U.S. English-speaking adults who served as informal caregivers of adults. Visually impaired caregivers discussed the challenges of caregiving and how their visual impairment affected their caregiving responsibilities. Interview transcripts were analyzed using grounded theory. Standardized questionnaires captured demographic and social characteristics. Fourteen adults participated. Seven major themes emerged from the interviews: (1) impact of lack of transportation, (2) concern over care recipient's quality of life, (3) utilization of support, (4) all encompassing demand, (5) cyclical adaptations, (6) anxieties of the caregivers, and (7) positive aspects of caregiving. Although visually impaired caregivers experience challenges similar to other caregivers, they differ in their report of added burden because of visual impairment, with extraordinary difficulty in transportation issues and the necessity of cyclical adaptations as their vision worsens. This is, to our knowledge, the first qualitative study of visually impaired caregivers and brings to light the unique problems faced by this special cohort of caregivers.

  10. Adaptive Memory: Animacy Enhances Free Recall but Impairs Cued Recall

    Science.gov (United States)

    Popp, Earl Y.; Serra, Michael J.

    2016-01-01

    Recent research suggests that human memory systems evolved to remember animate things better than inanimate things. In the present experiments, we examined whether these effects occur for both free recall and cued recall. In Experiment 1, we directly compared the effect of animacy on free recall and cued recall. Participants studied lists of…

  11. Yoga-teaching protocol adapted for children with visual impairment

    Directory of Open Access Journals (Sweden)

    Soubhagyalaxmi Mohanty

    2016-01-01

    Conclusions: Specially designed protocol may pave the way to impart yoga in an exciting and comfortable way to children with VI. More studies are needed to further investigate the effectiveness of this new yoga protocol in similar settings.

  12. Trainable Mentally Impaired/Severely Multiply Impaired/Autistic Impaired/Severely Mentally Impaired. Product Evaluation Report 1989-1990.

    Science.gov (United States)

    Claus, Richard N.; And Others

    The evaluation report describes special education services provided to trainable mentally impaired (TMI), autistic impaired (AI), severely multiply impaired (SXI), and severely mentally impaired (SMI) students at and through the Melvin G. Millet Learning Center (Bridgeport, Michigan). The eight program components are described individually and…

  13. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2011-04-08

    Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

  14. Type 2 diabetes is associated with impaired endothelium-dependent, flow-mediated dilation, but impaired glucose metabolism is not - The Hoorn study

    NARCIS (Netherlands)

    Henry, R.M.A.; Ferreira, I.; Kostense, P.J.; Dekker, J.M.; Nijpels, G.; Heine, R.J.; Kamp, O.; Bouter, L.M.; Stehouwer, C.D.A.

    2004-01-01

    Background: Type 2 diabetes (DM2) and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease risk. Impaired endothelial synthesis of nitric oxide (NO) is an important feature of atherothrombosis and can be estimated from endothelium-dependent flow-mediated dilation

  15. Impaired visuomotor generalization by inconsistent attentional contexts.

    Science.gov (United States)

    Wang, Tony S L; Song, Joo-Hyun

    2017-09-01

    In daily life, people are constantly presented with situations in which they have to learn and acquire new motor skills in complex environments, where attention is often distracted by other events. Being able to generalize and perform the acquired motor action in different environments is a crucial part of visuomotor learning. The current study examined whether attentional distraction impairs generalization of visuomotor adaptation or whether consistent distraction can operate as an internal cue to facilitate generalization. Using a dual-task paradigm combining visuomotor rotational adaptation and an attention-demanding secondary task, we showed that switching the attentional context from training (dual-task) to generalization (single-task) reduced the range of transfer of visuomotor adaptation to untrained directions. However, when consistent distraction was present throughout training and generalization, visuomotor generalization was equivalent to without distractions at all. Furthermore, this attentional context-dependent generalization was evident even when sensory modality of distractions differed between training and generalization. Therefore, the general nature of the dual tasks, rather than the specific stimuli, is associated with visuomotor memory and serves as a critical cue for generalization. Taken together, we demonstrated that attention plays a critical role during sensorimotor adaptation in selecting and associating multisensory signals with motor memory. This finding provides insight into developing learning programs that are generalizable in complex daily environments.NEW & NOTEWORTHY Learning novel motor actions in complex environments with attentional distraction is a critical function. Successful motor learning involves the ability to transfer the acquired skill from the trained to novel environments. Here, we demonstrate attentional distraction does not impair visuomotor adaptation. Rather, consistency in the attentional context from training

  16. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-01-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  17. Dopamine Oxidation and Autophagy

    Directory of Open Access Journals (Sweden)

    Patricia Muñoz

    2012-01-01

    Full Text Available The molecular mechanisms involved in the neurodegenerative process of Parkinson's disease remain unclear. Currently, there is a general agreement that mitochondrial dysfunction, α-synuclein aggregation, oxidative stress, neuroinflammation, and impaired protein degradation are involved in the neurodegeneration of dopaminergic neurons containing neuromelanin in Parkinson's disease. Aminochrome has been proposed to play an essential role in the degeneration of dopaminergic neurons containing neuromelanin by inducing mitochondrial dysfunction, oxidative stress, the formation of neurotoxic α-synuclein protofibrils, and impaired protein degradation. Here, we discuss the relationship between the oxidation of dopamine to aminochrome, the precursor of neuromelanin, autophagy dysfunction in dopaminergic neurons containing neuromelanin, and the role of dopamine oxidation to aminochrome in autophagy dysfunction in dopaminergic neurons. Aminochrome induces the following: (i the formation of α-synuclein protofibrils that inactivate chaperone-mediated autophagy; (ii the formation of adducts with α- and β-tubulin, which induce the aggregation of the microtubules required for the fusion of autophagy vacuoles and lysosomes.

  18. Increasing dietary fat elicits similar changes in fat oxidation and markers of muscle oxidative capacity in lean and obese humans.

    Directory of Open Access Journals (Sweden)

    Audrey Bergouignan

    Full Text Available In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN and obese (OB adults exposed to a 2-day high-fat (HF diet. Ten LN (BMI = 22.5±2.5 kg/m², age = 30±8 yrs and nine OB (BMI = 35.9±4.93 kg/m², 38±5 yrs, Mean±SD were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy and HF (50% of energy diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01 during LF, and similarly decreased during HF in LN (0.86±0.01 and OB (0.85±0.01. The expression of pyruvate dehydrogenase kinase 4 (PDK4 and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity.

  19. Social communication impairments: pragmatics.

    Science.gov (United States)

    Russell, Robert L

    2007-06-01

    Social communication or pragmatic impairments are characterized and illustrated as involving inappropriate or ineffective use of language and gesture in social contexts. Three clinical vignettes illustrate different pragmatic impairments and the wealth of diagnostic information that can be garnered from observation of a child's social communication behavior. Definitions of, and developmental milestones in, domains of pragmatic competence are provided. Several screening instruments are suggested for use in assessing pragmatic competence within the time-frame of a pediatric examination. Frequent comorbid psychiatric conditions are described and a sample of current neurobiologic research is briefly summarized.

  20. Adaptive and Intellectual Functioning in Autistic and Nonautistic Retarded Children.

    Science.gov (United States)

    Carpentieri, Sarah; Morgan, Sam B.

    1996-01-01

    This study examined the relationship between adaptive functioning and intellectual functioning in 18 children with autism and mental retardation and 20 children with mental retardation. The children with autism showed significantly more impairment in adaptive behavior composite scores, verbal reasoning abilities, socialization skills, and…

  1. 2.45 GHz Microwave Radiation Impairs Learning and Spatial Memory via Oxidative/Nitrosative Stress Induced p53-Dependent/Independent Hippocampal Apoptosis: Molecular Basis and Underlying Mechanism.

    Science.gov (United States)

    Shahin, Saba; Banerjee, Somanshu; Singh, Surya Pal; Chaturvedi, Chandra Mohini

    2015-12-01

    A close association between microwave (MW) radiation exposure and neurobehavioral disorders has been postulated but the direct effects of MW radiation on central nervous system still remains contradictory. This study was performed to understand the effect of short (15 days) and long-term (30 and 60 days) low-level MW radiation exposure on hippocampus with special reference to spatial learning and memory and its underlying mechanism in Swiss strain male mice, Mus musculus. Twelve-weeks old mice were exposed to 2.45 GHz MW radiation (continuous-wave [CW] with overall average power density of 0.0248 mW/cm(2) and overall average whole body specific absorption rate value of 0.0146 W/Kg) for 2 h/day over a period of 15, 30, and 60 days). Spatial learning and memory was monitored by Morris Water Maze. We have checked the alterations in hippocampal oxidative/nitrosative stress, neuronal morphology, and expression of pro-apoptotic proteins (p53 and Bax), inactive executioner Caspase- (pro-Caspase-3), and uncleaved Poly (ADP-ribose) polymerase-1 in the hippocampal subfield neuronal and nonneuronal cells (DG, CA1, CA2, and CA3). We observed that, short-term as well as long-term 2.45 GHz MW radiation exposure increases the oxidative/nitrosative stress leading to enhanced apoptosis in hippocampal subfield neuronal and nonneuronal cells. Present findings also suggest that learning and spatial memory deficit which increases with the increased duration of MW exposure (15 stress induced p53-dependent/independent activation of hippocampal neuronal and nonneuronal apoptosis associated with spatial memory loss. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Deoxynivalenol impairs hepatic and intestinal gene expression of selected oxidative stress, tight junction and inflammation proteins in broiler chickens, but addition of an adsorbing agent shifts the effects to the distal parts of the small intestine.

    Science.gov (United States)

    Osselaere, Ann; Santos, Regiane; Hautekiet, Veerle; De Backer, Patrick; Chiers, Koen; Ducatelle, Richard; Croubels, Siska

    2013-01-01

    Broiler chickens are rather resistant to deoxynivalenol and thus, clinical signs are rarely seen. However, effects of subclinical concentrations of deoxynivalenol on both the intestine and the liver are less frequently studied at the molecular level. During our study, we investigated the effects of three weeks of feeding deoxynivalenol on the gut wall morphology, intestinal barrier function and inflammation in broiler chickens. In addition, oxidative stress was evaluated in both the liver and intestine. Besides, the effect of a clay-based mycotoxin adsorbing agent on these different aspects was also studied. Our results show that feeding deoxynivalenol affects the gut wall morphology both in duodenum and jejenum of broiler chickens. A qRT-PCR analysis revealed that deoxynivalenol acts in a very specific way on the intestinal barrier, since only an up-regulation in mRNA expression of claudin 5 in jejunum was observed, while no effects were seen on claudin 1, zona occludens 1 and 2. Addition of an adsorbing agent resulted in an up-regulation of all the investigated genes coding for the intestinal barrier in the ileum. Up-regulation of Toll-like receptor 4 and two markers of oxidative stress (heme-oxigenase or HMOX and xanthine oxidoreductase or XOR) were mainly seen in the jejunum and to a lesser extent in the ileum in response to deoxynivalenol, while in combination with an adsorbing agent main effect was seen in the ileum. These results suggest that an adsorbing agent may lead to higher concentrations of deoxynivalenol in the more distal parts of the small intestine. In the liver, XOR was up-regulated due to DON exposure. HMOX and HIF-1α (hypoxia-inducible factor 1α) were down-regulated due to feeding DON but also due to feeding the adsorbing agent alone or in combination with DON.

  3. Deoxynivalenol impairs hepatic and intestinal gene expression of selected oxidative stress, tight junction and inflammation proteins in broiler chickens, but addition of an adsorbing agent shifts the effects to the distal parts of the small intestine.

    Directory of Open Access Journals (Sweden)

    Ann Osselaere

    Full Text Available Broiler chickens are rather resistant to deoxynivalenol and thus, clinical signs are rarely seen. However, effects of subclinical concentrations of deoxynivalenol on both the intestine and the liver are less frequently studied at the molecular level. During our study, we investigated the effects of three weeks of feeding deoxynivalenol on the gut wall morphology, intestinal barrier function and inflammation in broiler chickens. In addition, oxidative stress was evaluated in both the liver and intestine. Besides, the effect of a clay-based mycotoxin adsorbing agent on these different aspects was also studied. Our results show that feeding deoxynivalenol affects the gut wall morphology both in duodenum and jejenum of broiler chickens. A qRT-PCR analysis revealed that deoxynivalenol acts in a very specific way on the intestinal barrier, since only an up-regulation in mRNA expression of claudin 5 in jejunum was observed, while no effects were seen on claudin 1, zona occludens 1 and 2. Addition of an adsorbing agent resulted in an up-regulation of all the investigated genes coding for the intestinal barrier in the ileum. Up-regulation of Toll-like receptor 4 and two markers of oxidative stress (heme-oxigenase or HMOX and xanthine oxidoreductase