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  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. Impaired visuomotor adaptation in adults with ADHD

    OpenAIRE

    Kurdziel, Laura B. F.; Dempsey, Katherine; Zahara, Mackenzie; Valera, Eve; Rebecca M.C. Spencer

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder in children that often continues into adulthood. It has been suggested that motor impairments in ADHD are associated with underlying cerebellar pathology. If such is the case, individuals with ADHD should be impaired on motor tasks requiring healthy cerebellar function. To test this, we compared performance of individuals with ADHD and ADHD-like symptoms with non-ADHD controls on a visuomotor adaptation task k...

  3. Effective Classroom Adaptations for Students with Visual Impairments.

    Science.gov (United States)

    Cox, Penny R.; Dykes, Mary K.

    2001-01-01

    This article discusses strategies for including students with visual impairments in general education settings. It explains categories of visual impairments and how students with visual impairments learn. Auditory learning and visual learning accommodations are addressed, and checklists for orientation and mobility adaptations, and for classroom…

  4. 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 peopl

  5. Spatial compression impairs prism-adaptation in healthy individuals

    OpenAIRE

    Roger Newport

    2013-01-01

    Neglect patients typically present with gross inattention to one side of space following damage to the contralateral hemisphere. While prism-adaptation is effective in ameliorating some neglect behaviours, the mechanisms involved and their relationship to neglect remain unclear. Recent studies have shown that conscious strategic control processes in prism-adaptation may be impaired in neglect patients, who are also reported to show extraordinarily long aftereffects compared to healthy partici...

  6. 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…

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

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    Yu-fei SHEN; Yu TANG; Xiao-jie ZHANG; Kai-xing HUANG; Wei-dong LE

    2013-01-01

    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.Methods:Human dopaminergic neuroblastoma SH-SY5Y cells were treated with the proteasome inhibitor lactacystin (5 pmol/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 pg) into the left hemisphere of C57BL/6 mice that were sacrificed 2 or 4weeks later.The midbrain tissues were dissected to assess alterations in autophagy using immunofluorescence,immunoblotting and electron microscopy assays.Results: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.Conclusion: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.

  8. Nitric oxide and coronary vascular endothelium adaptations in hypertension

    Directory of Open Access Journals (Sweden)

    Andrew S Levy

    2009-12-01

    Full Text Available Andrew S Levy*, Justin CS Chung*, Jeffrey T Kroetsch*, James WE RushDepartment of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada; *These authors contributed equally to this workAbstract: This review highlights a number of nitric oxide (NO-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been

  9. Oxidative Stress Adaptation with Acute, Chronic and Repeated Stress

    OpenAIRE

    Pickering, Andrew. M.; Vojtovich, Lesya; Tower, John; Davies, Kelvin J. A.

    2012-01-01

    Oxidative stress adaptation or hormesis is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells, and the fruit fly Drosophila melanogaster,...

  10. Adaptive Assessment of Young Children with Visual Impairment

    Science.gov (United States)

    Ruiter, Selma; Nakken, Han; Janssen, Marleen; Van Der Meulen, Bieuwe; Looijestijn, Paul

    2011-01-01

    The aim of this study was to assess the effect of adaptations for children with low vision of the Bayley Scales, a standardized developmental instrument widely used to assess development in young children. Low vision adaptations were made to the procedures, item instructions and play material of the Dutch version of the Bayley Scales of Infant…

  11. Nitric oxide and coronary vascular endothelium adaptations in hypertension.

    Science.gov (United States)

    Levy, Andrew S; Chung, Justin C S; Kroetsch, Jeffrey T; Rush, James W E

    2009-01-01

    This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS) to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca(2+) control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been studied extensively to establish mechanisms for sex differences in NO-dependent function. Genomic and nongenomic effects of estrogen on eNOS and direct and indirect antioxidant activities of estrogen are discussed as

  12. Increased oxidative stress and impaired antioxidant response in Lafora disease.

    Science.gov (United States)

    Romá-Mateo, Carlos; Aguado, Carmen; García-Giménez, José Luis; Ibáñez-Cabellos, José Santiago; Seco-Cervera, Marta; Pallardó, Federico V; Knecht, Erwin; Sanz, Pascual

    2014-10-01

    Lafora Disease (LD, OMIM 254780, ORPHA501) is a fatal neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in the vast majority of cases, by mutations in either EPM2A or EPM2B genes, encoding respectively laforin and malin. In the last years, several reports have revealed molecular details of these two proteins and have identified several processes affected in LD, but the pathophysiology of the disease still remains largely unknown. Since autophagy impairment has been reported as a characteristic treat in both Lafora disease cell and animal models, and as there is a link between autophagy and mitochondrial performance, we sought to determine if mitochondrial function could be altered in those models. Using fibroblasts from LD patients, deficient in laforin or malin, we found mitochondrial alterations, oxidative stress and a deficiency in antioxidant enzymes involved in the detoxification of reactive oxygen species (ROS). Similar results were obtained in brain tissue samples from transgenic mice deficient in either the EPM2A or EPM2B genes. Furthermore, in a proteomic analysis of brain tissue obtained from Epm2b-/- mice, we observed an increase in a modified form of peroxirredoxin-6, an antioxidant enzyme involved in other neurological pathologies, thus corroborating an alteration of the redox condition. These data support that oxidative stress produced by an increase in ROS production and an impairment of the antioxidant enzyme response to this stress play an important role in development of LD. PMID:26461389

  13. 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.

  14. [The role of preventing nitric oxide deficiency in the antihypertensive effect of adaptation to hypoxia].

    Science.gov (United States)

    Mashina, S Iu; Smirin, B V; Pokidyshev, D A; Malyshev, I Iu; Liamina, N P; Senchikin, V N; Markov, Kh M; Manukhin, E B

    2001-01-01

    Shortage of endothelial nitric oxide (NO) manifested as decreased daily urinary excretion of nitrate and nitrite as well as attenuated endothelium-dependent relaxation of conduit and resistance vessels progresses with age-related increase of blood pressure (BP) in stroke-prone spontaneously hypertensive rats (SHRSP). Simultaneous NO-dependent suppression of vascular contractions is, apparently, due to the inducible NO synthase activity in vascular smooth muscle specific for spontaneously hypertensive rat. Adaptation of rats to hypobaric hypoxia initiated at early hypertensive stage (at the age of 5-6 weeks) decelerates hypertension progress. The antihypertensive effect of the adaptation was accompanied by stimulation of endothelial NO synthesis and prevention of impaired NO-dependent response in isolated blood vessels. Nitric oxide stores were formed in the vascular wall of SHRSP and WKY rats at the same time. The obtained data indicate a significant role of correction of endothelial NO deficiency in the antihypertensive effect of adaptation to hypoxia. PMID:15926321

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

    Science.gov (United States)

    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…

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

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    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…

  17. The Development of Listener-Adapted Communication by Educable Mentally Impaired Children.

    Science.gov (United States)

    Bliss, Lynn S.

    1984-01-01

    The listener-adapted communication strategies of 40 educable mentally impaired and 40 nonmentally retarded children were investigated. The results revealed that age, listener, and group differences were evident as a function of the specific task the children were required to perform. (Author/CL)

  18. Humanin: a mitochondrial signaling peptide as a biomarker for impaired fasting glucose-related oxidative stress.

    Science.gov (United States)

    Voigt, Annet; Jelinek, Herbert F

    2016-05-01

    Mitochondrial RNR-2 (mt-RNR2, humanin) has been shown to play a role in protecting several types of cells and tissues from the effects of oxidative stress. Humanin (HN) functions through extracellular and intracellular pathways adjusting mitochondrial oxidative phosphorylation and ATP production. Addition of HN improved insulin sensitivity in animal models of diabetes mellitus but no clinical studies have been carried out to measure HN levels in humans associated with hyperglycemia. The plasma levels of HN in participants attending a diabetes complications screening clinic were measured. Clinical history and anthropometric data were obtained from all participants. Plasma levels of HN were measured by a commercial ELISA kit. All data were analyzed applying nonparametric statistics and general linear modeling to correct for age and gender. A significant decrease (P = 0.0001) in HN was observed in the impaired fasting glucose (IFG) group (n = 23; 204.84 ± 92.87 pg mL(-1)) compared to control (n = 58; 124.3 ± 83.91 pg mL(-1)) consistent with an adaptive cellular response by HN to a slight increase in BGL. PMID:27173674

  19. Oxidative Injury and Neuropathy in Diabetes and Impaired Glucose Tolerance

    OpenAIRE

    Russell, James W.; Berent-Spillson, Alison; Vincent, Andrea M.; Freimann, Catherine L.; Sullivan, Kelli A; Eva L Feldman

    2008-01-01

    Clinical studies suggest that impaired glucose tolerance (IGT) is associated with the development of neuropathy. The aim of the current study was to determine if neuropathy developed in the female Zucker Diabetic Fatty (ZDF) rat, an animal model of IGT and type 2 diabetes. The ZDF rat develops impaired glucose tolerance (IGT) when fed a control diet, and frank diabetes when fed a high fat diet. Following 10 weeks of hyperglycemia, sensory nerve action potentials (SNAP) and compound motor acti...

  20. The Muscle Oxidative Regulatory Response to Acute Exercise Is Not Impaired in Less Advanced COPD Despite a Decreased Oxidative Phenotype

    OpenAIRE

    Slot, Ilse G. M.; Bram van den Borst; Hellwig, Valéry A. C. V.; Esther Barreiro; Schols, Annemie M. W. J.; Gosker, Harry R.

    2014-01-01

    Already in an early disease stage, patients with chronic obstructive pulmonary disease (COPD) are confronted with impaired skeletal muscle function and physical performance due to a loss of oxidative type I muscle fibers and oxidative capacity (i.e. oxidative phenotype; Oxphen). Physical activity is a well-known stimulus of muscle Oxphen and crucial for its maintenance. We hypothesized that a blunted response of Oxphen genes to an acute bout of exercise could contribute to decreased Oxphen in...

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

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    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…

  2. Hereditary cerebellar ataxia progressively impairs force adaptation during goal-directed arm movements.

    Science.gov (United States)

    Maschke, Matthias; Gomez, Christopher M; Ebner, Timothy J; Konczak, Jürgen

    2004-01-01

    We investigated how humans with hereditary cerebellar degeneration [spinocerebellar ataxia (SCA) type 6 and 8, n = 9] and age- and sex-matched healthy controls (n = 9) adapted goal-directed arm movements to an unknown external force field. We tested whether learning could be generalized to untrained regions in the workspace, an aspect central to the idea of an internal model, and if any learning could be retained. After removal of the force field, SCA patients showed little or no learning-related aftereffects indicating that repeated force-field exposure never led to successful force compensation. In contrast, healthy control subjects quickly adapted their movements to the new force field. The difference in force adaptation was significant for movements to targets that required both the shoulder and elbow joint (P < 0.001). Moreover, the generalization of learned movements to targets outside the learned workspace was prevented by the cerebellar degeneration (P < 0.01). Retention of force adaptation was significantly lower in SCA patients (P = 0.003). The severity of ataxia in SCA patients correlated negatively with the extent of learning (r = -0.84, P = 0.004). Our findings imply that progressive loss of cerebellar function gradually impairs force adaptation. The failure to generalize learning suggests that cerebellar degeneration prevents the formation of an internal representation of the limb dynamics. PMID:13679403

  3. 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.

  4. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the effective preventive paradigm against mild cognitive impairment (MCI is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv. At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

  5. Thyroid disorders and nitric oxide in cardiovascular adaptation to hypovolemia.

    Science.gov (United States)

    Ogonowski, Natalia; Piro, Giselle; Pessah, Déborah; Arreche, Noelia; Puchulu, Bernardita; Balaszczuk, Ana M; Fellet, Andrea L

    2016-08-01

    This study aimed to investigate whether nitric oxide participates in the cardiovascular function and haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Sprague-Dawley rats aged 2months old treated with T3 (hyper, 20μg/100g body weight) or 0.02% methimazole (hypo, w/v) during 28days were pre-treated with N(G) nitro-l-arginine methyl ester (L-NAME) and submitted to 20% blood loss. Heart function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase activity and protein levels were performed. We found that hypo decreased fractional shortening and ejection fraction and increased left ventricle internal diameter. Hyper decreased ventricle diameter and no changes in cardiac contractility. Haemorrhage elicited a hypotension of similar magnitude within 10min. Then, this parameter was stabilized at about 30-40min and maintained until finalized, 120min. L-NAME rats showed that the immediate hypotension would be independent of nitric oxide. Nitric oxide synthase inhibition blunted the changes of heart rate induced by blood loss. Hyper and hypo had lower atrial enzyme activity associated with a decreased enzyme isoform in hypo. In ventricle, hyper and hypo had a higher enzyme activity, which was not correlated with changes in protein levels. Haemorrhage induced an increased heart nitric oxide production. We concluded that thyroid disorders were associated with hypertrophic remodelling which impacted differently on cardiac function and its adaptation to a hypovolemia. Hypovolemia triggered a nitric oxide synthase activation modulating the heart function to maintain haemodynamic homeostasis. This involvement depends on a specific enzyme isoform, cardiac chamber and thyroid state.

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

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    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.

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

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    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.

  8. Oxidative Stress Impairs Learning and Memory in apoE Knockout Mice

    OpenAIRE

    Evola, Marianne; Hall, Allyson; Wall, Trevor; Young, Alice; Grammas, Paula

    2010-01-01

    Cardiovascular risk factors, such as oxidative stress and elevated lipids, are linked to the development of cognitive impairment. A mediator common to both stressors is the apolipoprotein E (apoE). The objectives of this study are to determine the effects of apoE deficiency and diet-induced systemic oxidative stress in mice on vascular expression of inflammatory proteins and on cognitive function. Mice are placed on a diet enriched in homocysteine for fifteen weeks and then assessed for spati...

  9. 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.

  10. The nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness.

    Science.gov (United States)

    Dautov, R F; Ngo, D T M; Licari, G; Liu, S; Sverdlov, A L; Ritchie, R H; Kemp-Harper, B K; Horowitz, J D; Chirkov, Y Y

    2013-11-30

    Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10μM) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10μM) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200μM) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10μM) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator.

  11. Mammalian adaptation to extrauterine environment: mitochondrial functional impairment caused by prematurity.

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    Valcarce, C; Izquierdo, J M; Chamorro, M; Cuezva, J M

    1994-01-01

    In this paper we report that, compared with term rat neonates, both mitochondrial content and function are diminished in liver of preterm neonates (delivered 24 h before full term) compromising cellular energy provision in the postnatal period. In addition, there is a parallel reduction in the content of mRNAs encoding mitochondrial proteins in preterm rats. Also, efficient oxidative phosphorylation is not attained in these pups until 3 h after birth. Although isolated liver mitochondria from preterm neonates show a two-fold increase in F1-ATPase beta-subunit and cytochrome c oxidase activity 1 h after birth, the abnormal coupling efficiency between respiration and oxidative phosphorylation (ADP/O ratio) is due to maintenance of high H(+)-leakage values in the inner mitochondrial membrane. Postnatal reduction of the H+ leak occurs concomitantly with an increase in intra-mitochondrial adenine nucleotide concentration. Accumulation of adenine nucleotides in preterm and term liver mitochondria parallels the postnatal increase in total liver adenine nucleotides. Delayed postnatal induction of adenine biosynthesis most likely accounts for the lower adenine nucleotide pool in the liver of preterm neonates. The delayed postnatal accumulation of adenine nucleotides in mitochondria is thus responsible for the impairment in oxidative phosphorylation displayed by organelles of the preterm liver. Images Figure 1 PMID:7980455

  12. Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL

    Science.gov (United States)

    Favre, Dimitri; Ezanno, Hélène; Bonnefond, Amélie; Bonner, Caroline; Gmyr, Valéry; Kerr-Conte, Julie; Gauthier, Benoit R.; Widmann, Christian; Waeber, Gérard; Pattou, François; Froguel, Philippe; Abderrahmani, Amar

    2016-01-01

    Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment. PMID:27636901

  13. Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.

    Science.gov (United States)

    Plaisance, Valérie; Brajkovic, Saška; Tenenbaum, Mathie; Favre, Dimitri; Ezanno, Hélène; Bonnefond, Amélie; Bonner, Caroline; Gmyr, Valéry; Kerr-Conte, Julie; Gauthier, Benoit R; Widmann, Christian; Waeber, Gérard; Pattou, François; Froguel, Philippe; Abderrahmani, Amar

    2016-01-01

    Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment. PMID:27636901

  14. 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. PMID:27145241

  15. The muscle oxidative regulatory response to acute exercise is not impaired in less advanced COPD despite a decreased oxidative phenotype.

    Directory of Open Access Journals (Sweden)

    Ilse G M Slot

    Full Text Available Already in an early disease stage, patients with chronic obstructive pulmonary disease (COPD are confronted with impaired skeletal muscle function and physical performance due to a loss of oxidative type I muscle fibers and oxidative capacity (i.e. oxidative phenotype; Oxphen. Physical activity is a well-known stimulus of muscle Oxphen and crucial for its maintenance. We hypothesized that a blunted response of Oxphen genes to an acute bout of exercise could contribute to decreased Oxphen in COPD. For this, 28 patients with less advanced COPD (age 65 ± 7 yrs, FEV1 59 ± 16% predicted and 15 age- and gender-matched healthy controls performed an incremental cycle ergometry test. The Oxphen response to exercise was determined by the measurement of gene expression levels of Oxphen markers in pre and 4h-post exercise quadriceps biopsies. Because exercise-induced hypoxia and oxidative stress may interfere with Oxphen response, oxygen saturation and oxidative stress markers were assessed as well. Regardless of oxygen desaturation and absolute exercise intensities, the Oxphen regulatory response to exercise was comparable between COPD patients and controls with no evidence of increased oxidative stress. In conclusion, the muscle Oxphen regulatory response to acute exercise is not blunted in less advanced COPD, regardless of exercise-induced hypoxia. Hence, this study provides further rationale for incorporation of exercise training as integrated part of disease management to prevent or slow down loss of muscle Oxphen and related functional impairment in COPD.

  16. Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease.

    Science.gov (United States)

    Toda, Noboru; Okamura, Tomio

    2016-08-01

    Cerebral blood flow is mainly regulated by nitrergic (parasympathetic, postganglionic) nerves and nitric oxide (NO) liberated from endothelial cells in response to shear stress and stretch of vasculature, whereas sympathetic vasoconstrictor control is quite weak. On the other hand, peripheral vascular resistance and blood flow are mainly controlled by adrenergic vasoconstrictor nerves; endothelium-derived NO and nitrergic nerves play some roles as vasodilator factors. Cigarette smoking impairs NO synthesis in cerebral vascular endothelial cells and nitrergic nerves leading to interference with cerebral blood flow and glucose metabolism in the brain. Smoking-induced cerebral hypoperfusion is induced by impairment of synthesis and actions of NO via endothelial nitric oxide synthase (eNOS)/neuronal NOS (nNOS) inhibition and by increased production of oxygen radicals, resulting in decreased actions of NO on vascular smooth muscle. Nicotine acutely and chronically impairs the action of endothelial NO and also inhibits nitrergic nerve function in chronic use. Impaired cerebral blood supply promotes the synthesis of amyloid β that accelerates blood flow decrease. This vicious cycle is thought to be one of the important factors involving in Alzheimer's disease (AD). Quitting smoking is undoubtedly one of the important ways to prevent and delay the genesis or slow the progress of impaired cognitive function and AD. PMID:27530818

  17. 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…

  18. 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.

  19. 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.

  20. Cognitive impairment and Alzheimer’s disease: Links with oxidative stress and cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Alejandra Sekler

    2008-08-01

    Full Text Available Alejandra Sekler1,2, José M Jiménez2, Leonel Rojo2, Edgard Pastene3, Patricio Fuentes4, Andrea Slachevsky4, Ricardo B Maccioni1,21Center of Cognitive Neurosciences, International Center for Biomedicine (ICC, Santiago, Chile; 2Laboratory of Cellular, Molecular Biology and Neurosciences, Faculty of Sciences, Universidad de Chile, Santiago, Chile; 3Department of Pharmacy, Faculty of Pharmacy, University of Concepcion, Concepción, Chile; 4Unidad de Neurología Cognitiva y Demencias, Servicio de Neurología, Hospital del Salvador, Santiago, ChileAbstract: Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD, Parkinson’s disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP, plasma malondialdehyde and total antioxidative capacity (TAC, as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59 and a control group of neurologically normal subjects (n = 29, attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery, while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC of

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

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    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.

  2. Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.

    Science.gov (United States)

    Toda, Noboru; Okamura, Tomio

    2016-09-01

    Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures. PMID:27417104

  3. Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

    OpenAIRE

    Scazzocchio, Beatrice; Varì, Rosaria; D'Archivio, Massimo; Santangelo, Carmela; Filesi, Carmelina; Giovannini, Claudio; Masella, Roberta

    2009-01-01

    Oxidized LDL (oxLDL) increase in patients affected by type-2 diabetes, obesity, and metabolic syndrome. Likewise, insulin resistance, an impaired responsiveness of target tissues to insulin, is associated with those pathological conditions. To investigate a possible causal relationship between oxLDL and the onset of insulin resistance, we evaluated the response to insulin of 3T3-L1 adipocytes treated with oxLDL. We observed that oxLDL inhibited glucose uptake (−40%) through reduced glucose tr...

  4. Nitric oxide-induced oxidative stress impairs pacemaker function of murine interstitial cells of Cajal during inflammation.

    Science.gov (United States)

    Kaji, Noriyuki; Horiguchi, Kazuhide; Iino, Satoshi; Nakayama, Shinsuke; Ohwada, Tomohiko; Otani, Yuko; Firman; Murata, Takahisa; Sanders, Kenton M; Ozaki, Hiroshi; Hori, Masatoshi

    2016-09-01

    The pacemaker function of interstitial cells of Cajal (ICC) is impaired during intestinal inflammation. The aim of this study is to clarify the pathophysiological mechanisms of ICC dysfunction during inflammatory condition by using intestinal cell clusters. Cell clusters were prepared from smooth muscle layer of murine jejunum and treated with interferon-gamma and lipopolysaccharide (IFN-γ+LPS) for 24h to induce inflammation. Pacemaker function of ICC was monitored by measuring cytosolic Ca(2+) oscillation in the presence of nifedipine. Treatment with IFN-γ+LPS impaired the pacemaker activity of ICC with increasing mRNA level of interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6 in cell clusters; however, treatment with these cytokines individually had little effect on pacemaker activity of ICC. Treatment with IFN-γ+LPS also induced the expression of inducible nitric oxide synthase (iNOS) in smooth muscle cells and resident macrophages, but not in ICC. Pretreatment with NOS inhibitor, L-NAME or iNOS inhibitor, 1400W ameliorated IFN-γ+LPS-induced pacemaker dysfunction of ICC. Pretreatment with guanylate cyclase inhibitor, ODQ did not, but antioxidant, apocynin, to suppress NO-induced oxidative stress, significantly suppressed the impairment of ICC function induced by IFN-γ+LPS. Treatment with IFN-γ+LPS also decreased c-Kit-positive ICC, which was prevented by pretreatment with L-NAME. However, apoptotic ICC were not detected in IFN-γ+LPS-treated clusters, suggesting IFN-γ+LPS stimulation just changed the phenotype of ICC but not induced cell death. Moreover, ultrastructure of ICC was not disturbed by IFN-γ+LPS. In conclusion, ICC dysfunction during inflammation is induced by NO-induced oxidative stress rather than NO/cGMP signaling. NO-induced oxidative stress might be the main factor to induce phenotypic changes of ICC.

  5. Behavioral impairments and changes of nitric oxide and inducible nitric oxide synthase in the brains of molarless KM mice.

    Science.gov (United States)

    Pang, Qian; Hu, Xingxue; Li, Xinya; Zhang, Jianjun; Jiang, Qingsong

    2015-02-01

    More studies showed that as a common disorder in senior population, loss of teeth could adversely affect human cognitive function, and nitric oxide (NO) might play an important role in the cognitive function. However, the underlying mechanism has not yet been well-established. The objectives of this study are to evaluate behavior changes of KM mice after loss of molars, and levels of NO and inducible nitric oxide synthase (iNOS) in the brain in molarless condition. It is hypothesized that loss of molars of the mice tested results in the cognitive impairments and that the process is mediated by NO in the brain through the signaling pathways. Morris water maze is used to test the behavioral changes after 8 weeks of the surgery. The changes of NO and iNOS are evaluated by using Griess assay, western blot, and immunohistochemistry method. The results show that 8 weeks after loss of molars, the spatial learning and memory of KM mice impair and the levels of NO and iNOS in mice hippocampus increase. These findings suggest that molar extraction is associated with the behavioral impairment, and that the changes of NO and iNOS in the hippocampus may be involved in the behavioral changes in the molarless condition. PMID:25447296

  6. 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.

  7. The adaptation of nutrient oxidation to nutrient intake on a high-fat diet.

    NARCIS (Netherlands)

    Schrauwen, P.; van Marken Lichtenbelt, W.D.; Saris, W.H.M.; Westerterp, K.R.

    1997-01-01

    Department of Human Biology, Maastricht University, The Netherlands. Intervention studies have shown that the adaptation of fat oxidation to fat intake, when changing the dietary fat content, is not abrupt. This study was conducted to measure the time course of adaptation of oxidation rates to incre

  8. Hyperhomocysteinaemia in rats is associated with erectile dysfunction by impairing endothelial nitric oxide synthase activity.

    Science.gov (United States)

    Jiang, Weijun; Xiong, Lei; Bin Yang; Li, Weiwei; Zhang, Jing; Zhou, Qing; Wu, Qiuyue; Li, Tianfu; Zhang, Cui; Zhang, Mingchao; Xia, Xinyi

    2016-01-01

    To investigate the effect of hyperhomocysteinaemia (HHCy) on penile erectile function in a rat model, a methionine-rich diet was used in which erectile function, the reproductive system, and nitric oxide synthase were characterized. The intracavernous pressure, apomorphine experiments, measurement of oxidative stress, hematoxylin and eosin staining, immunohistochemistry analysis, reverse transcription-polymerase chain reactions and measurement of endothelial nitric oxide synthase activity were utilized. Our results showed that erections in the middle-dose, high-dose, and interference (INF) groups were significantly lower than the control (P < 0.05). INF group, being fed with vitamins B and folic acid, demonstrated markedly improved penile erections compared with the middle-dose group (P < 0.05). HHCy-induced eNOS and phospho-eNOS protein expression was reduced and the antioxidant effect was markedly impaired. The data of the present data provide evidence that HHCy is a vascular risk factor for erectile dysfunction by impairing cavernosa endothelial nitric oxide synthase activity. Intake of vitamins B can alleviate this abnormality. PMID:27221552

  9. Aldosterone increases oxidant stress to impair guanylyl cyclase activity by cysteinyl thiol oxidation in vascular smooth muscle cells.

    Science.gov (United States)

    Maron, Bradley A; Zhang, Ying-Yi; Handy, Diane E; Beuve, Annie; Tang, Shiow-Shih; Loscalzo, Joseph; Leopold, Jane A

    2009-03-20

    Hyperaldosteronism is associated with impaired endothelium-dependent vascular reactivity owing to increased reactive oxygen species and decreased bioavailable nitric oxide (NO(.)); however, the effects of aldosterone on vasodilatory signaling pathways in vascular smooth muscle cells (VSMC) remain unknown. Soluble guanylyl cyclase (GC) is a heterodimer that is activated by NO(.) to convert cytosolic GTP to cGMP, a second messenger required for normal VSMC relaxation. Here, we show that aldosterone (10(-9)-10(-7) mol/liter) diminishes GC activity by activating NADPH oxidase in bovine aortic VSMC to increase reactive oxygen species levels and induce oxidative posttranslational modification(s) of Cys-122, a beta(1)-subunit cysteinyl residue demonstrated previously to modulate NO(.) sensing by GC. In VSMC treated with aldosterone, Western immunoblotting detected evidence of GC beta(1)-subunit disulfide bonding, whereas mass spectrometry analysis of a homologous peptide containing the Cys-122-bearing sequence exposed to conditions of increased oxidant stress confirmed cysteinyl sulfinic acid (m/z 435), sulfonic acid (m/z 443), and disulfide (m/z 836) bond formation. The functional effect of these modifications was examined by transfecting COS-7 cells with wild-type GC or mutant GC containing an alanine substitution at Cys-122 (C122A). Exposure to aldosterone or hydrogen peroxide (H(2)O(2)) significantly decreased cGMP levels in cells expressing wild-type GC. In contrast, aldosterone or H(2)O(2) did not influence cGMP levels in cells expressing the mutant C122A GC, confirming that oxidative modification of Cys-122 specifically impairs GC activity. These findings demonstrate that pathophysiologically relevant concentrations of aldosterone increase oxidant stress to convert GC to an NO(.)-insensitive state, resulting in disruption of normal vasodilatory signaling pathways in VSMC.

  10. Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine.

    Science.gov (United States)

    Abdel-Salam, Omar M E; El-Sayed El-Shamarka, Marwa; Salem, Neveen A; El-Mosallamy, Aliaa E M K; Sleem, Amany A

    2012-01-01

    Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms and impaired memory, owing to blockade of striatal dopamine D2 receptors. Cinnarizine is a calcium channel blocker with D2 receptor blocking properties which is widely used in treatment of vertiginous disorders. The present study aimed to see whether cinnarizine would worsen the effect of haloperidol on memory function and on oxidative stress in mice brain. Cinnarizine (5, 10 or 20 mg/kg), haloperidol, or haloperidol combined with cinnarizine was administered daily via the subcutaneous route and mice were examined on weekly basis for their ability to locate a submerged plate in the water maze test. Mice were euthanized 30 days after starting drug injection. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) were determined in brain. Haloperidol substantially impaired water maze performance. The mean time taken to find the escape platform (latency) was significantly delayed by haloperidol (2 mg/kg, i.p.) on weeks 1-8 of the test, compared with saline control group. In contrast, those treated with haloperidol and cinnarizine showed significantly shorter latencies, which indicated that learning had occurred immediately. Haloperidol resulted in increased MDA in cortex, striatum, cerebellum and midbrain. GSH decreased in cortex, striatum and cerebellum and nitric oxide increased in cortex. Meanwhile, treatment with cinnarizine (20 mg/kg) and haloperidol resulted in significant decrease in MDA cortex, striatum, cerebellum and midbrain and an increase in GSH in cortex and striatum, compared with haloperidol group. These data suggest that cinnarizine improves the haloperidol induced brain oxidative stress and impairment of learning and memory in the water maze test in mice.

  11. Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine.

    Science.gov (United States)

    Abdel-Salam, Omar M E; El-Sayed El-Shamarka, Marwa; Salem, Neveen A; El-Mosallamy, Aliaa E M K; Sleem, Amany A

    2012-01-01

    Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms and impaired memory, owing to blockade of striatal dopamine D2 receptors. Cinnarizine is a calcium channel blocker with D2 receptor blocking properties which is widely used in treatment of vertiginous disorders. The present study aimed to see whether cinnarizine would worsen the effect of haloperidol on memory function and on oxidative stress in mice brain. Cinnarizine (5, 10 or 20 mg/kg), haloperidol, or haloperidol combined with cinnarizine was administered daily via the subcutaneous route and mice were examined on weekly basis for their ability to locate a submerged plate in the water maze test. Mice were euthanized 30 days after starting drug injection. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) were determined in brain. Haloperidol substantially impaired water maze performance. The mean time taken to find the escape platform (latency) was significantly delayed by haloperidol (2 mg/kg, i.p.) on weeks 1-8 of the test, compared with saline control group. In contrast, those treated with haloperidol and cinnarizine showed significantly shorter latencies, which indicated that learning had occurred immediately. Haloperidol resulted in increased MDA in cortex, striatum, cerebellum and midbrain. GSH decreased in cortex, striatum and cerebellum and nitric oxide increased in cortex. Meanwhile, treatment with cinnarizine (20 mg/kg) and haloperidol resulted in significant decrease in MDA cortex, striatum, cerebellum and midbrain and an increase in GSH in cortex and striatum, compared with haloperidol group. These data suggest that cinnarizine improves the haloperidol induced brain oxidative stress and impairment of learning and memory in the water maze test in mice. PMID:27540345

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Adapting Artworks for People Who Are Blind or Visually Impaired Using Raised Printing

    Science.gov (United States)

    Krivec, Tjaša; Muck, Tadeja; Germadnik, Rolanda Fugger; Majnaric, Igor; Golob, Gorazd

    2014-01-01

    Everyone has the right to freely participate in the cultural life of the community (United Nations, 2012). In Europe and around the globe, many efforts have been made in order to include people with visual impairments and blindness into the cultural life. The objects and artifacts exhibited in museums for people with visual impairments are…

  15. Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment

    Directory of Open Access Journals (Sweden)

    Qian Guo

    2015-01-01

    Full Text Available The clinical application of doxorubicin (DOX is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D is a steroid alkaloid extracted from a traditional Chinese medicine, Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH to oxidized glutathione (GSSG. Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α and nuclear respiratory factor 1 (NRF1, as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment.

  16. Impairment of extramitochondrial oxidative phosphorylation in mouse rod outer segments by blue light irradiation.

    Science.gov (United States)

    Calzia, Daniela; Panfoli, Isabella; Heinig, Nora; Schumann, Ulrike; Ader, Marius; Traverso, Carlo Enrico; Funk, Richard H W; Roehlecke, Cora

    2016-06-01

    Exposure to short wavelength light causes increased reactive oxygen intermediates production in the outer retina, particularly in the rod Outer Segments (OS). Consistently, the OS were shown to conduct aerobic ATP production through the ectopic expression of the electron transfer chain complexes I-IV and F1Fo-ATP synthase. These facts prompted us to verify if the oxidative phosphorylation in the OS is implied in the oxidative damage of the blue-light (BL) treated OS, in an organotypic model of mouse retina. Whole mouse eyeball cultures were treated with short wavelength BL (peak at 405 nm, output power 1 mW/cm(2)) for 6 h. Immunogold transmission electron microscopy confirmed the expression of Complex I and F1Fo-ATP synthase in the OS. In situ histochemical assays on unfixed sections showed impairment of respiratory Complexes I and II after BL exposure, both in the OS and IS, utilized as a control. Basal O2 consumption and ATP synthesis were impaired in the OS purified from blue-light irradiated eyeball cultures. Electron transfer capacity between Complex I and II as well as activity of Complexes I and II was decreased in blue-light irradiated purified OS. The severe malfunctioning of the OS aerobic respiratory capacity after 6 h BL treatment may be the consequence of a self-induced damage. BL exposure would cause an initial over-functioning of both the phototransduction and respiratory chain, with reactive oxygen species production. In a self-renewal vicious cycle, membrane and protein oxidative damage, proton leakage and uncoupling, would impair redox chains, perpetuating the damage and causing hypo-metabolism with eventual apoptosis of the rod. Data may shed new light on the rod-driven retinopathies such as Age Related Macular Degeneration, of which blue-light irradiated retina represents a model.

  17. KSR2 Mutations Are Associated with Obesity, Insulin Resistance, and Impaired Cellular Fuel Oxidation

    OpenAIRE

    Pearce, Laura R.; Atanassova, Neli; Banton, Matthew C.; Bottomley, Bill; van der Klaauw, Agatha A.; Revelli, Jean-Pierre; Hendricks, Audrey; Keogh, Julia M.; Henning, Elana; Doree, Deon; Jeter-Jones, Sabrina; Garg, Sumedha; Bochukova, Elena G.; Bounds, Rebecca; Ashford, Sofie

    2013-01-01

    Summary Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEK-ERK pathway and impair cellular fatty acid oxidation and glucose oxida...

  18. Oxidative stress and APO E polymorphisms in Alzheimer's disease and in mild cognitive impairment.

    Science.gov (United States)

    Chico, L; Simoncini, C; Lo Gerfo, A; Rocchi, A; Petrozzi, L; Carlesi, C; Volpi, L; Tognoni, G; Siciliano, G; Bonuccelli, U

    2013-08-01

    A number of evidences indicates oxidative stress as a relevant pathogenic factor in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Considering its recognized major genetic risk factors in AD, apolipoprotein (APO E) has been investigated in several experimental settings regarding its role in the process of reactive oxygen species (ROS) generation. The aim of this work has been to evaluate possible relationships between APO E genotype and plasma levels of selected oxidative stress markers in both AD and MCI patients. APO E genotypes were determined using restriction enzyme analysis. Plasma levels of oxidative markers, advanced oxidation protein products, iron-reducing ability of plasma and, in MCI, activity of superoxide dismutases were evaluated using spectrophotometric analysis. We found, compared to controls, increased levels of oxidized proteins and decreased values of plasma-reducing capacity in both AD patients (p < 0.0001) and MCI patients (p < 0.001); the difference between AD and MCI patients was significant only for plasma-reducing capacity (p < 0.0001), the former showing the lowest values. Superoxide dismutase activity was reduced, although not at statistical level, in MCI compared with that in controls. E4 allele was statistically associated (p < 0.05) with AD patients. When comparing different APO E genotype subgroups, no difference was present, as far as advanced oxidation protein products and iron-reducing ability of plasma levels were concerned, between E4 and non-E4 carriers, in both AD and MCI; on the contrary, E4 carriers MCI patients showed significantly decreased (p < 0.05) superoxide dismutase activity with respect to non-E4 carriers. This study, in confirming the occurrence of oxidative stress in AD and MCI patients, shows how it can be related, at least for superoxide dismutase activity in MCI, to APO E4 allele risk factor. PMID:23668794

  19. Beyond the redox imbalance: Oxidative stress contributes to an impaired GLUT3 modulation in Huntington's disease.

    Science.gov (United States)

    Covarrubias-Pinto, Adriana; Moll, Pablo; Solís-Maldonado, Macarena; Acuña, Aníbal I; Riveros, Andrea; Miró, María Paz; Papic, Eduardo; Beltrán, Felipe A; Cepeda, Carlos; Concha, Ilona I; Brauchi, Sebastián; Castro, Maite A

    2015-12-01

    Failure in energy metabolism and oxidative damage are associated with Huntington's disease (HD). Ascorbic acid released during synaptic activity inhibits use of neuronal glucose, favouring lactate uptake to sustain brain activity. Here, we observe a decreased expression of GLUT3 in STHdhQ111 cells (HD cells) and R6/2 mice (HD mice). Localisation of GLUT3 is decreased at the plasma membrane in HD cells affecting the modulation of glucose uptake by ascorbic acid. An ascorbic acid analogue without antioxidant activity is able to inhibit glucose uptake in HD cells. The impaired modulation of glucose uptake by ascorbic acid is directly related to ROS levels indicating that oxidative stress sequesters the ability of ascorbic acid to modulate glucose utilisation. Therefore, in HD, a decrease in GLUT3 localisation at the plasma membrane would contribute to an altered neuronal glucose uptake during resting periods while redox imbalance should contribute to metabolic failure during synaptic activity. PMID:26456058

  20. 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

    Accumulation of damaged macromolecules, including irreversibly oxidized proteins, is a hallmark of cellular and organismal ageing. Failure of protein homesotasis is a major contributor to the age-related accumulation of damaged proteins. In skeletal muscle, tissue maintenance and regeneration....... 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...... lipids for energy production. Such changes reflect alterations in membrane composition and dysregulation of sphingolipids signaling during senescence. This study establishes a new concept connecting oxidative protein modifications with the altered cellular metabolism associated with the senescent...

  1. The Role of Oxidative Stress in Etiopathogenesis of Chemotherapy Induced Cognitive Impairment (CICI)-"Chemobrain".

    Science.gov (United States)

    Gaman, Amelia Maria; Uzoni, Adriana; Popa-Wagner, Aurel; Andrei, Anghel; Petcu, Eugen-Bogdan

    2016-05-01

    Chemobrain or chemotherapy induced cognitive impairment (CICI) represents a new clinical syndrome characterised by memory, learning and motor function impairment. As numerous patients with cancer are long-term survivors, CICI represent a significant factor which may interfere with their quality of life. However, this entity CICI must be distinguished from other cognitive syndromes and addressed accordingly. At the present time, experimental and clinical research suggests that CICI could be induced by numerous factors including oxidative stress. This type of CNS injury has been previously described in cancer patients treated with common anti-neoplastic drugs such as doxorubicine, carmustine, methotrexate and cyclophosphamide. It seems that all these pharmacological factors promote neuronal death through a final common pathway represented by TNF alpha (tumour necrosis factor). However, as cancer in general is diagnosed more commonly in the aging population, the elderly oncological patient must be treated with great care since aging per se is also impacted by oxidative stress and potentiually by TNF alpha deleterious action on brain parenchyma. In this context, some patients may develop cognitive dysfunction well before the appearance of CICI. In addition, chemotherapy may worsen their cognitive function. Therefore, at the present time, there is an acute need for development of effective therapeutic methods to prevent CICI as well as new methods of early CICI diagnosis. PMID:27330845

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

    Directory of Open Access Journals (Sweden)

    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.

  3. A case of impairment of mitochondrial fatty acid beta-oxidation.

    Science.gov (United States)

    Hasegawa, Tomonobu; Hori, Naoaki; Du, Wenlin

    2002-06-01

    We describe a patient with impairment of mitochondrial fatty acid P-oxidation. A Japanese baby boy was delivered in the 38th week of gestation by emergency cesarean section due to fetal asphyxia. His birth weight was 1,985 g (head circumference 31.0 cm (10th percentile). His Apgar scores were 3 and 5 at 1 min and 5 min, respectively. Blood glucose was 12 mg/dl at 1 hour after birth, requiring glucose administration. On day 1 his serum CK was 20,780 IU/l, which was thought to be due to asphyxia. His serum CK levels gradually began to decrease. At 3 months of age, he sucked poorly, had poor body weight gain, and muscle hypotonia was observed. On day 117 his general condition was impaired, and marked hepatomegaly was observed. The blood glucose level was 43 mg/dl. The patient's urine was negative for ketone bodies. His serum triglyceride level was 3,670 mg/dl. Abdominal CT scan revealed a fatty liver. Serum levels of acyl carnitine from very-long chain fatty acid increased. On day 118 he died due to ventricular fibrillation. On necropsy, massive lipid deposition was observed in the liver, cardiac muscle, kidney, skeletal muscle, and intestinal mucosa. The ratio of very-long chain acyl-CoA dehydrogenase (VLCAD) activity for C16/C8 fatty acid was 0.50 (normal control 1.29), suggesting abnormal VLCAD. He was diagnosed as having impairment of mitochondrial fatty acid beta-oxidation, presumably due to the VLCAD deficiency. PMID:12125906

  4. Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases.

    Science.gov (United States)

    Scazzocchio, Beatrice; Varì, Rosaria; D'Archivio, Massimo; Santangelo, Carmela; Filesi, Carmelina; Giovannini, Claudio; Masella, Roberta

    2009-05-01

    Oxidized LDL (oxLDL) increase in patients affected by type-2 diabetes, obesity, and metabolic syndrome. Likewise, insulin resistance, an impaired responsiveness of target tissues to insulin, is associated with those pathological conditions. To investigate a possible causal relationship between oxLDL and the onset of insulin resistance, we evaluated the response to insulin of 3T3-L1 adipocytes treated with oxLDL. We observed that oxLDL inhibited glucose uptake (-40%) through reduced glucose transporter 4 (GLUT4) recruitment to the plasma membrane (-70%), without affecting GLUT4 gene expression. These findings were associated to the impairment of insulin signaling. Specifically, in oxLDL-treated cells insulin receptor (IR) substrate-1 (IRS-1) was highly degraded likely because of the enhanced Ser(307)phosphorylation. This process was largely mediated by the activation of the inhibitor of kappaB-kinase beta (IKKbeta) and the c-Jun NH(2)-terminal kinase (JNK). Moreover, the activation of IKKbeta positively regulated the nuclear content of nuclear factor kappaB (NF-kappaB), by inactivating the inhibitor of NF-kappaB (IkappaBalpha). The activated NF-kappaB further impaired per se GLUT4 functionality. Specific inhibitors of IKKbeta, JNK, and NF-kappaB restored insulin sensitivity in adipocytes treated with oxLDL. These data provide the first evidence that oxLDL, by activating serine/threonine kinases, impaired adipocyte response to insulin affecting pathways involved in the recruitment of GLUT4 to plasma membranes (PM). This suggests that oxLDL might participate in the development of insulin resistance. PMID:19136667

  5. Nitric oxide-mediated endothlium-dependent vasodilation is impaired with borderline high-LDL cholesterol.

    Science.gov (United States)

    Diehl, Kyle J; Stauffer, Brian L; Greiner, Jared J; Weil, Brian R; DeSouza, Christopher A

    2012-02-01

    The experimental aims of this study were to determine: (1) whether nitric oxide-mediated endothelium-dependent vasodilation is blunted in adult humans with borderline high plasma low-density lipoprotein (LDL)-cholesterol compared with adults with optimal/near optimal LDL-cholesterol levels; and, if so: (2) whether the magnitude of impairment in adults with borderline high LDL-cholesterol is similar to adults with high LDL-cholesterol. Forearm blood flow responses to intraarterial infusions of acetylcholine and sodium nitroprusside were measured in 50 middle-aged (43-64 year) adults: 20 in the optimal/near optimal LDL-cholesterol range (<130 mg/dL); 20 with borderline high LDL-cholesterol (130-159 mg/dL); and 10 with high LDL-cholesterol ($160 mg/dL). In addition, blood flow responses to acetylcholine were determined in the absence and presence of the endothelial nitric oxide synthase inhibitor N(G) -monomethyl-L-arginine (L-NMMA). Vasodilation to acetylcholine was ~20% lower (p < 0.05) in the borderline high (from 4.3 ± 0.2 to 12.3 ± 0.8 mL/100 mL tissue/min) and high (from 4.3 ± 0.3 to 12.0 ± 0.5 mL/100 mL tissue/min) LDL-cholesterol groups compared with the optimal/near optimal (from 4.4 ± 0.2 to 14.5 ± 0.5 mL/100 mL tissue/min) LDL-cholesterol group. L-NMMA significantly reduced (~30%) the vasodilator response to acetylcholine in the optimal/near optimal LDL-cholesterol group but not the borderline high or high LDL-cholesterol groups. Borderline high LDL-cholesterol is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation.

  6. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    Science.gov (United States)

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  7. Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide

    Science.gov (United States)

    Nyhan, Daniel; Kim, Soonyul; Dunbar, Stacey; Li, Dechun; Shoukas, Artin; Berkowitz, Dan E.

    2002-01-01

    Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N(G)-nitro-L-arginine methyl ester (10(-5) M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

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

    Directory of Open Access Journals (Sweden)

    Masaaki Adachi

    Full Text Available BACKGROUND: 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. PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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.

  9. A review of adaptive mechanisms in cell responses towards oxidative stress caused by dental resin monomers.

    Science.gov (United States)

    Krifka, Stephanie; Spagnuolo, Gianrico; Schmalz, Gottfried; Schweikl, Helmut

    2013-06-01

    Dental composite resins are biomaterials commonly used to aesthetically restore the structure and function of teeth impaired by caries, erosion, or fracture. Residual monomers released from resin restorations as a result of incomplete polymerization processes interact with living oral tissues. Monomers like triethylene glycol dimethacrylate (TEGDMA) or 2-hydroxylethyl methacrylate (HEMA) are cytotoxic via apoptosis, induce genotoxic effects, and delay the cell cycle. Monomers also influence the response of cells of the innate immune system, inhibit specific odontoblast cell functions, or delay the odontogenic differentiation and mineralization processes in pulp-derived cells including stem cells. These observations indicate that resin monomers act as environmental stressors which inevitably disturb regulatory cellular networks through interference with signal transduction pathways. We hypothesize that an understanding of the cellular mechanisms underlying these phenomena will provide a better estimation of the consequences associated with dental therapy using composite materials, and lead to innovative therapeutic strategies and improved materials being used at tissue interfaces within the oral cavity. Current findings strongly suggest that monomers enhance the formation of reactive oxygen species (ROS), which is most likely the cause of biological reactions activated by dental composites and resin monomers. The aim of the present review manuscript is to discuss adaptive cell responses to oxidative stress caused by monomers. The particular significance of a tightly controlled network of non-enzymatic as well as enzymatic antioxidants for the regulation of cellular redox homeostasis and antioxidant defense in monomer-exposed cells will be addressed. The expression of ROS-metabolizing antioxidant enzymes like superoxide dismutase (SOD1), glutathione peroxidase (GPx1/2), and catalase in cells exposed to monomers will be discussed with particular emphasis on the role

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. Age-associated memory impairment. Assessing the role of nitric oxide.

    Science.gov (United States)

    Meyer, R C; Spangler, E L; Kametani, H; Ingram, D K

    1998-11-20

    Several neurotransmitter systems have been investigated to assess hypothesized mechanisms underlying the decline in recent memory abilities in normal aging and in Alzheimer's disease. Examining the performance of F344 rats in a 14-unit T-maze (Stone maze), we have focused on the muscarinic cholinergic (mACh) and the N-methyl-D-aspartate (NMDA) glutamate (Glu) systems and their interactions. Maze learning is impaired by antagonists to mACh or NMDA receptors. We have also shown that stimulation of mACh receptors can overcome a maze learning deficit induced by NMDA blockade, and stimulation of the NMDA receptor can overcome a similar blockade of mACh receptors. No consistent evidence in rats has been produced from our laboratory to reveal significant age-related declines in mACh or NMDA receptor binding in the hippocampus (HC), a brain region that is greatly involved in processing of recent memory. Thus, we have directed attention to the possibility of a common signal transduction pathway, the nitric oxide (NO) system. Activated by calcium influx through the NMDA receptor, NO is hypothesized to be a retrograde messenger that enhances presynaptic Glu release. Maze learning can be impaired by inhibiting the synthetic enzyme for NO, nitric oxide synthase (NOS), or enhanced by stimulating NO release. However, we have found no age-related loss of NOS-containing HC neurons or fibers in rats. Additionally, other laboratories have reported no evidence of an age-related loss of HC NOS activity. In a microdialysis study we have found preliminary evidence of reduced NO production following NMDA stimulation. We are currently working to identify the parameters of this phenomenon as well as testing various strategies for safely stimulating the NO system to improve memory function in aged rats. PMID:9928439

  13. Normal adaptations to exercise despite protection against oxidative stress

    OpenAIRE

    Higashida, Kazuhiko; Kim, Sang Hyun; Higuchi, Mitsuru; Holloszy, John O.; Han, Dong-Ho

    2011-01-01

    It has been reported that supplementation with the antioxidant vitamins C and E prevents the adaptive increases in mitochondrial biogenesis and GLUT4 expression induced by endurance exercise. We reevaluated the effects of these antioxidants on the adaptive responses of rat skeletal muscle to swimming in a short-term study consisting of 9 days of vitamins C and E with exercise during the last 3 days and a longer-term study consisting of 8 wk of antioxidant vitamins with exercise during the las...

  14. Neutrophilic iron oxidizers adapted to highly oxic environments

    DEFF Research Database (Denmark)

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

    Rapid sand filtration is an economical way to treat anoxic groundwaters and involves aeration followed by particulate and soluble substrate removal via deep bed filtration. The anoxic source groundwater can contain several potential electron donors (CH4, Fe2+, Mn2+, NH4+ and assimilable organic...... indicate that neutrophilic iron oxidizers in highly oxic environments like drinking water treatment systems can be abundant (5 E+04 to 7 E+05 cells per gram of wet sand material). It was furthermore observed that the diversity of the cultivated dominant iron oxidizers differs substantially from those...

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

    DEFF Research Database (Denmark)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner;

    2016-01-01

    OBJECTIVE: 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. METHODS: To identify pathways related t...... 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....... methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. RESULTS: 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. CONCLUSIONS: Our data indicate that impaired muscle BCAA...

  16. 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

    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...

  17. Perindopril Attenuates Lipopolysaccharide-Induced Amyloidogenesis and Memory Impairment by Suppression of Oxidative Stress and RAGE Activation.

    Science.gov (United States)

    Goel, Ruby; Bhat, Shahnawaz Ali; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2016-02-17

    Clinical and preclinical studies account hypertension as a risk factor for dementia. We reported earlier that angiotensin-converting enzyme (ACE) inhibition attenuated the increased vulnerability to neurodegeneration in hypertension and prevented lipopolysaccharide (LPS)-induced memory impairment in normotensive wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Recently, a receptor for advanced glycation end products (RAGE) has been reported to induce amyloid beta (Aβ1-42) deposition and memory impairment in hypertensive animals. However, the involvement of ACE in RAGE activation and amyloidogenesis in the hypertensive state is still unexplored. Therefore, in this study, we investigated the role of ACE on RAGE activation and amyloidogenesis in memory-impaired NWRs and SHRs. Memory impairment was induced by repeated (on days 1, 4, 7, and 10) intracerebroventricular (ICV) injections of LPS in SHRs (25 μg) and NWRs (50 μg). Our data showed that SHRs exhibited increased oxidative stress (increased gp91-phox/NOX-2 expression and ROS generation), RAGE, and β-secretase (BACE) expression without Aβ1-42 deposition. LPS (25 μg, ICV) further amplified oxidative stress, RAGE, and BACE activation, culminating in Aβ1-42 deposition and memory impairment in SHRs. Similar changes were observed at the higher dose of LPS (50 μg, ICV) in NWRs. Further, LPS-induced oxidative stress was associated with endothelial dysfunction and reduction in cerebral blood flow (CBF), more prominently in SHRs than in NWRs. Finally, we showed that perindopril (0.1 mg/kg, 15 days) prevented memory impairment by reducing oxidative stress, RAGE activation, amyloidogenesis, and improved CBF in both SHRs and NWRs. These findings suggest that perindopril might be used as a therapeutic strategy for the early stage of dementia. PMID:26689453

  18. 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.

  19. Nitric oxide and coronary vascular endothelium adaptations in hypertension

    OpenAIRE

    Levy, Andrew S.; Justin CS Chung; Kroetsch, Jeffrey T; et al.,

    2009-01-01

    Andrew S Levy*, Justin CS Chung*, Jeffrey T Kroetsch*, James WE RushDepartment of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada; *These authors contributed equally to this workAbstract: This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary compl...

  20. Ammonia-oxidizing archaea have better adaptability in oxygenated/hypoxic alternant conditions compared to ammonia-oxidizing bacteria.

    Science.gov (United States)

    Liu, Shuai; Hu, Baolan; He, Zhanfei; Zhang, Bin; Tian, Guangming; Zheng, Ping; Fang, Fang

    2015-10-01

    Ammonia oxidation is performed by both ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Few studies compared the adaptability of AOA and AOB for oxygenated/hypoxic alternant conditions in water-level-fluctuating zones. Here, using qPCR and 454 high-throughput sequencing of functional amoA genes of AOA and AOB, we examined the changes of abundances, diversities, and community structures of AOA and AOB in periodically flooded soils compared to the non-flooded soils in Three Gorges Reservoir. The increased AOA operational taxonomic unit (OTU) numbers and the higher ratios of abundance (AOA:AOB) in the periodically flooded soils suggested AOA have better adaptability for oxygenated/hypoxic alternant conditions in the water-level-fluctuating zones in the Three Gorges Reservoir and probably responsible for the ammonia oxidation there. Canonical correspondence analysis (CCA) showed that oxidation-reduction potential (ORP) had the most significant effect on the community distribution of AOA (p ammonia-oxidizing microbes. ORP was significantly negatively correlated with AOA OTU numbers (p < 0.05), ratio of OTU numbers (AOA:AOB) (p < 0.01), and ratio of amoA gene abundances (AOA:AOB) (p < 0.05). ORP was also significantly positively correlated with AOB abundance (p < 0.05).

  1. The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses.

    Science.gov (United States)

    Anz, D; Kruger, S; Haubner, S; Rapp, M; Bourquin, C; Endres, S

    2014-06-01

    Inhibitors of dipeptidylpeptidase IV (DPP-IV) represent a novel class of frequently used anti-diabetic drugs. In addition to its function in metabolic regulation, DPP-IV also plays a role in the immune system. Whether the DPP-IV inhibitors sitagliptin, vildagliptin or saxagliptin impair immune responses is, however, currently unknown. Here, we investigated the effect of these agents on both innate and adaptive immunity. We found that the DPP-IV inhibitors did not affect the innate immune response induced by Toll-like receptor (TLR) ligands, as cytokine secretion and induction of co-stimulatory molecules by human blood mononuclear cells was not impaired. Furthermore, proliferation of T cells and suppressive function of regulatory T cells was preserved. Mice treated with vildagliptin showed normal cytokine production, immune cell activation and lymphocyte trafficking upon TLR activation. Thus, crucial immunological parameters remain unaffected upon treatment with DPP-IV inhibitors, a fact that is reassuring with respect to safety of these drugs. PMID:24320733

  2. 5-Lipoxygenase Deficiency Impairs Innate and Adaptive Immune Responses during Fungal Infection

    OpenAIRE

    Adriana Secatto; Lilian Cataldi Rodrigues; Carlos Henrique Serezani; Simone Gusmão Ramos; Marcelo Dias-Baruffi; Lúcia Helena Faccioli; Medeiros, Alexandra I.

    2012-01-01

    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 in...

  3. Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice.

    Science.gov (United States)

    Zhao, Ran-Ran; Xu, Xiao-Chen; Xu, Fei; Zhang, Wei-Li; Zhang, Wen-Lin; Liu, Liang-Min; Wang, Wei-Ping

    2014-06-13

    Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL/6 mice were administered with subconvulsive dose of pentylenetetrazole (37 mg/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures.

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

    OpenAIRE

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

    2013-01-01

    Abstract Background 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. Findings After translation and cross-cultural adaptation, the instrument was tested on caregivers of people with DS. Clinical examina...

  5. Ammonia-oxidizing archaea have better adaptability in oxygenated/hypoxic alternant conditions compared to ammonia-oxidizing bacteria.

    Science.gov (United States)

    Liu, Shuai; Hu, Baolan; He, Zhanfei; Zhang, Bin; Tian, Guangming; Zheng, Ping; Fang, Fang

    2015-10-01

    Ammonia oxidation is performed by both ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Few studies compared the adaptability of AOA and AOB for oxygenated/hypoxic alternant conditions in water-level-fluctuating zones. Here, using qPCR and 454 high-throughput sequencing of functional amoA genes of AOA and AOB, we examined the changes of abundances, diversities, and community structures of AOA and AOB in periodically flooded soils compared to the non-flooded soils in Three Gorges Reservoir. The increased AOA operational taxonomic unit (OTU) numbers and the higher ratios of abundance (AOA:AOB) in the periodically flooded soils suggested AOA have better adaptability for oxygenated/hypoxic alternant conditions in the water-level-fluctuating zones in the Three Gorges Reservoir and probably responsible for the ammonia oxidation there. Canonical correspondence analysis (CCA) showed that oxidation-reduction potential (ORP) had the most significant effect on the community distribution of AOA (p amoA gene abundances (AOA:AOB) (p < 0.05). ORP was also significantly positively correlated with AOB abundance (p < 0.05). PMID:26099334

  6. 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.

  7. An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in C. elegans

    Science.gov (United States)

    Kato, Masaomi; Kashem, Mohammed Abul; Cheng, Chao

    2016-01-01

    Adaptation to an environmental or metabolic perturbation is a feature of the evolutionary process. Recent insights into microRNA function suggest that microRNAs serve as key players in a robust adaptive response against stress in animals through their capacity to fine-tune gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene, mir-60, in the nematode C. elegans promotes an adaptive response to chronic – a mild and long-term – oxidative stress exposure. The pathway involved appears to be unique since the canonical stress-responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in xenobiotic metabolism and pathogen defense responses are up-regulated by the loss of mir-60. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis. PMID:27623524

  8. Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress

    DEFF Research Database (Denmark)

    Brouwers, O; Niessen, P M; Haenen, G;

    2010-01-01

    AIMS/HYPOTHESIS: Impaired nitric oxide (NO)-dependent vasorelaxation plays a key role in the development of diabetic vascular complications. We investigated the effect of hyperglycaemia on impaired vasoreactivity and a putative role therein of the AGE precursor methylglyoxal. METHODS: The effects......-induced impairment of vasoreactivity. CONCLUSIONS/INTERPRETATION: These data show that hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation is mediated by increased intracellular methylglyoxal levels in a pathway dependent on oxidative stress....... for AGE ligand S100b did (p stress marker nitrotyrosine. Antioxidant pre-incubation prevented methylglyoxal...

  9. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates

    Energy Technology Data Exchange (ETDEWEB)

    van der Westhuyzen, J.; Fernandes-Costa, F.; Metz, J.

    1982-11-01

    Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment--the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Isolation and characterization of Caulobacter mutants impaired in adaptation to stationary phase

    Directory of Open Access Journals (Sweden)

    Italiani Valéria C. S.

    2003-01-01

    Full Text Available The entry into stationary phase causes a change in the pattern of gene expression of bacteria, when the cells must express a whole set of genes involved mainly with resistance to starvation and to environmental stresses. As an attempt to identify genes important for the survival of Caulobacter crescentus in stationary phase, we have screened a library of 5,000 clones generated by random transposon mutagenesis for mutants that showed reduced viability after prolonged growth. Four clones were selected, which displayed either lower viability or a longer time of recovery from stationary phase. The genes disrupted were identified, and the gene products were found to be mainly involved with amino acid metabolism (glutamate N-acetyltransferase, 4-hydroxyphenylpyruvate dioxygenase and L-aspartate oxidase or with recombination (exonuclease RecJ. Each mutant was tested for resistance to stresses, such as oxidative, saline, acidic, heat and UV exposure, showing different responses. Although the mutations obtained were not in genes involved specifically in stationary phase, our results suggest that amino acids metabolism may play an important role in keeping viability during this growth phase.

  13. Cytokine-induced impairment of short-chain fatty acid oxidation and viability in human colonic epithelial cells

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Horn, T;

    2000-01-01

    Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate...... oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage...

  14. Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells

    OpenAIRE

    Aragonès Gemma; Saavedra Paula; Heras Mercedes; Cabré Anna; Girona Josefa; Masana Lluís

    2012-01-01

    Abstract Background Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production by endothelial cells in vitro. Methods In human umbilical vascular endothelial cells (HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS) expression and activation a...

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

    Directory of Open Access Journals (Sweden)

    Jiayong Zhong

    2015-06-01

    Full Text Available 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.

  16. 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.

  17. Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation.

    Science.gov (United States)

    El-Hattab, Ayman W; Hsu, Jean W; Emrick, Lisa T; Wong, Lee-Jun C; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

    2012-04-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism.

  18. The novel adaptive rotating beam test unmasks sensorimotor impairments in a transgenic mouse model of Parkinson's disease.

    Science.gov (United States)

    Gerstenberger, Julia; Bauer, Anne; Helmschrodt, Christin; Richter, Angelika; Richter, Franziska

    2016-05-01

    Development of disease modifying therapeutics for Parkinson's disease (PD), the second most common neurodegenerative disorder, relies on availability of animal models which recapitulate the disease hallmarks. Only few transgenic mouse models, which mimic overexpression of alpha-synuclein, show dopamine loss, behavioral impairments and protein aggregation. Mice overexpressing human wildtype alpha-synuclein under the Thy-1 promotor (Thy1-aSyn) replicate these features. However, female mice do not exhibit a phenotype. This was attributed to a potentially lower transgene expression located on the X chromosome. Here we support that female mice overexpress human wildtype alpha-synuclein only about 1.5 fold in the substantia nigra, compared to about 3 fold in male mice. Since female Thy1-aSyn mice were shown previously to exhibit differences in corticostriatal communication and synaptic plasticity similar to their male counterparts we hypothesized that female mice use compensatory mechanisms and strategies to not show overt motor deficits despite an underlying endophenotype. In order to unmask these deficits we translated recent findings in PD patients that sensory abnormalities can enhance motor dysfunction into a novel behavioral test, the adaptive rotating beam test. We found that under changing sensory input female Thy1-aSyn mice showed an overt phenotype. Our data supports that the integration of sensorimotor information is likely a major contributor to symptoms of movement disorders and that even low levels of overexpression of human wildtype alpha-synuclein has the potential to disrupt processing of these information. The here described adaptive rotating beam test represents a sensitive behavioral test to detect moderate sensorimotor alterations in mouse models. PMID:26880341

  19. The novel adaptive rotating beam test unmasks sensorimotor impairments in a transgenic mouse model of Parkinson's disease.

    Science.gov (United States)

    Gerstenberger, Julia; Bauer, Anne; Helmschrodt, Christin; Richter, Angelika; Richter, Franziska

    2016-05-01

    Development of disease modifying therapeutics for Parkinson's disease (PD), the second most common neurodegenerative disorder, relies on availability of animal models which recapitulate the disease hallmarks. Only few transgenic mouse models, which mimic overexpression of alpha-synuclein, show dopamine loss, behavioral impairments and protein aggregation. Mice overexpressing human wildtype alpha-synuclein under the Thy-1 promotor (Thy1-aSyn) replicate these features. However, female mice do not exhibit a phenotype. This was attributed to a potentially lower transgene expression located on the X chromosome. Here we support that female mice overexpress human wildtype alpha-synuclein only about 1.5 fold in the substantia nigra, compared to about 3 fold in male mice. Since female Thy1-aSyn mice were shown previously to exhibit differences in corticostriatal communication and synaptic plasticity similar to their male counterparts we hypothesized that female mice use compensatory mechanisms and strategies to not show overt motor deficits despite an underlying endophenotype. In order to unmask these deficits we translated recent findings in PD patients that sensory abnormalities can enhance motor dysfunction into a novel behavioral test, the adaptive rotating beam test. We found that under changing sensory input female Thy1-aSyn mice showed an overt phenotype. Our data supports that the integration of sensorimotor information is likely a major contributor to symptoms of movement disorders and that even low levels of overexpression of human wildtype alpha-synuclein has the potential to disrupt processing of these information. The here described adaptive rotating beam test represents a sensitive behavioral test to detect moderate sensorimotor alterations in mouse models.

  20. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway.

    Science.gov (United States)

    Sebastián, David; Sorianello, Eleonora; Segalés, Jessica; Irazoki, Andrea; Ruiz-Bonilla, Vanessa; Sala, David; Planet, Evarist; Berenguer-Llergo, Antoni; Muñoz, Juan Pablo; Sánchez-Feutrie, Manuela; Plana, Natàlia; Hernández-Álvarez, María Isabel; Serrano, Antonio L; Palacín, Manuel; Zorzano, Antonio

    2016-08-01

    Mitochondrial dysfunction and accumulation of damaged mitochondria are considered major contributors to aging. However, the molecular mechanisms responsible for these mitochondrial alterations remain unknown. Here, we demonstrate that mitofusin 2 (Mfn2) plays a key role in the control of muscle mitochondrial damage. We show that aging is characterized by a progressive reduction in Mfn2 in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, analysis of muscle Mfn2-deficient mice revealed that aging-induced Mfn2 decrease underlies the age-related alterations in metabolic homeostasis and sarcopenia. Mfn2 deficiency reduced autophagy and impaired mitochondrial quality, which contributed to an exacerbated age-related mitochondrial dysfunction. Interestingly, aging-induced Mfn2 deficiency triggers a ROS-dependent adaptive signaling pathway through induction of HIF1α transcription factor and BNIP3. This pathway compensates for the loss of mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that Mfn2 repression in muscle during aging is a determinant for the inhibition of mitophagy and accumulation of damaged mitochondria and triggers the induction of a mitochondrial quality control pathway. PMID:27334614

  1. 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. PMID:27038927

  2. 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.

  3. Estimation of Kinetic Parameters for Autocatalytic Oxidation of Cyclohexane Based on a Modified Adaptive Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    刘平乐; 邹丽珊; 罗和安; 王良芥; 郑金华

    2004-01-01

    A modified genetic algorithm of multiple selection strategies, crossover strategies and adaptive operator is constructed, and it is used to estimate the kinetic parameters in autocatalytic oxidation of cyclohexane. The influences of selection strategy, crossover strategy and mutation strategy on algorithm performance are discussed. This algorithm with a specially designed adaptive operator avoids the problem of local optimum usually associated with using standard genetic algorithm and simplex method. The kinetic parameters obtained from the modified genetic algorithm are credible and the calculation results using these parameters agree well with experimental data. Furthermore, a new kinetic model of cyclohexane autocatalytic oxidation is established and the kinetic parameters are estimated by using the modified genetic algorithm.

  4. Coenzyme Q10 supplementation reverses age-related impairments in spatial learning and lowers protein oxidation

    OpenAIRE

    Shetty, Ritu A.; Forster, Michael J.; Sumien, Nathalie

    2012-01-01

    Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. S...

  5. Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

    Directory of Open Access Journals (Sweden)

    Arya A

    2016-03-01

    Full Text Available Aditya Arya,1 Anamika Gangwar,1 Sushil Kumar Singh,2 Manas Roy,3,4 Mainak Das,3 Niroj Kumar Sethy,1 Kalpana Bhargava1 1Peptide and Proteomics Division, Defense Institute of Physiology and Allied Sciences, 2Functional Materials Division, Solid State Physics Laboratory, Defense Research and Development Organization, Timarpur, Delhi, 3Biological Science and Bioengineering, Indian Institute of Technology, Kanpur, 4Department of Chemistry, Indian Institute of Engineering Science and Technology, Howrah, India Abstract: Structural and functional integrity of the brain is adversely affected by reduced oxygen saturation, especially during chronic hypoxia exposure and often encountered by altitude travelers or dwellers. Hypoxia-induced generation of reactive nitrogen and oxygen species reportedly affects the cortex and hippocampus regions of the brain, promoting memory impairment and cognitive dysfunction. Cerium oxide nanoparticles (CNPs, also known as nanoceria, switch between +3 and +4 oxidation states and reportedly scavenge superoxide anions, hydrogen peroxide, and peroxynitrite in vivo. In the present study, we evaluated the neuroprotective as well as the cognition-enhancing activities of nanoceria during hypobaric hypoxia. Using polyethylene glycol-coated 3 nm nanoceria (PEG-CNPs, we have demonstrated efficient localization of PEG-CNPs in rodent brain. This resulted in significant reduction of oxidative stress and associated damage during hypoxia exposure. Morris water maze-based memory function tests revealed that PEG-CNPs ameliorated hypoxia-induced memory impairment. Using microscopic, flow cytometric, and histological studies, we also provide evidences that PEG-CNPs augmented hippocampus neuronal survival and promoted neurogenesis. Molecular studies revealed that PEG-CNPs promoted neurogenesis through the 5'-adenine monophosphate-activated protein kinase–protein kinase C–cyclic adenosine monophosphate response element-binding protein

  6. The Use of Complex Assessment of Morphofunctional State of Pancreatic Microvasculature to Study the Adaptation of the Body to Motor Activity in Impaired Glucose Tolerance

    Directory of Open Access Journals (Sweden)

    Nikonova L.G.

    2012-03-01

    Full Text Available The aim of the investigation is to consider the possibility of using the assessment data of microvasculature to study morphofunctional state of terminal vessels of exocrine and endocrine parts of pancreas in dogs with impaired glucose tolerance after physical exertion. Materials and methods. 30 mature male dogs with impaired glucose tolerance were studied: the 1st group — with no physical exertion, the 2nd — with short-term physical exertion and the 3rd — with extreme physical exertion. Morphological changes of the microvasculature components of pancreatic exocrine and endocrine parts were studied after the single motor load actions on the organism using histological, histochemical, electron-microscopical and morphometric methods. Results. Complex assessment enabled to reveal various adaptive changes of pancreatic microvasculature in animals with impaired glucose tolerance when exposed to optimal and maximum physical exertion. The exposure to short-term load results in developing compensatory adaptive transformations in the terminal part of vasculature of the both parts of the pancreas. Extreme loads along with reactive changes caused by single physical exercise lead to destructive alterations of microvasculature elements of primarily exocrine part. The information can be taken into consideration when studying impairment mechanisms in physical exertion environment and when developing regimens of motor activity in prediabetic persons.

  7. Impaired learning in rats in a 14-unit T-maze by 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, is attenuated by the nitric oxide donor, molsidomine.

    Science.gov (United States)

    Meyer, R C; Spangler, E L; Patel, N; London, E D; Ingram, D K

    1998-01-01

    In previous experiments, it was demonstrated that systemic or central administration of the nitric oxide synthase (NO synthase) inhibitor, NG-nitro-L-arginine (N-Arg), produced dose-dependent learning impairments in rats in a 14-unit T-maze; and that sodium nitroprusside, a NO donor, could attenuate the impairment. Since N-Arg is not specific for neuronal NO synthase and produces hypertension, it is possible that effects on the cardiovasculature may have contributed to the impaired maze performance. In the present experiment, we have investigated the maze performance of 3-4 months old male Fischer-344 rats following treatment with 7-nitroindazole, a NO synthase inhibitor that is selective for neuronal NO synthase and does not produce hypertension. In addition, we examined the effects of the NO donor, molsidomine, which is much longer acting than sodium nitroprusside. Rats were pretrained to avoid footshock in a straight runway and received training in a 14-unit T-maze 24 h later. In an initial dose-response study, rats received intraperitoneal (i.p.) injections of either 7-nitroindazole (25, 50, or 65 mg/kg) or peanut oil 30 min prior to maze training. 7-nitroindazole produced significant, dose-dependent maze acquisition deficits, with 65 mg/kg producing the greatest learning impairment. This dose of 7-nitroindazole had no significant effect on systolic blood pressure. Following the dose-response study, rats were given i.p. injections of either 7-nitroindazole (70 mg/kg) plus saline, 7-nitroindazole (70 mg/kg) plus the NO donor, molsidomine (2 or 4 mg/kg), or peanut oil plus saline as controls. Both doses of molsidomine significantly attenuated the learning deficit induced by 7-nitroindazole relative to controls. These findings represent the first evidence that impaired learning produced by inhibition of neuronal NO synthase can be overcome by systemic administration of a NO donor. PMID:9489851

  8. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows.

    Directory of Open Access Journals (Sweden)

    Ole Lamp

    Full Text Available High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS and one pair-fed (PF at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1, cows were challenged for 6 days (P2 by heat stress (temperature humidity index (THI = 76 or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows.

  9. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows

    Science.gov (United States)

    Derno, Michael; Otten, Winfried; Mielenz, Manfred; Nürnberg, Gerd

    2015-01-01

    High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS) and one pair-fed (PF) at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1), cows were challenged for 6 days (P2) by heat stress (temperature humidity index (THI) = 76) or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows. PMID:25938406

  10. Impaired suppressive activities of human MUTYH variant proteins against oxidative mutagenesis

    Institute of Scientific and Technical Information of China (English)

    Kazuya Shinmura; Masanori Goto; Hong Tao; Shun Matsuura; Tomonari Matsuda; Haruhiko Sugimura

    2012-01-01

    AIM:To investigate the suppressive activity of MUTYH variant proteins against mutations caused by oxidative lesion,8-hydroxyguanine (8OHG),in human cells.METHODS:p.R154H,p.M255V,p.L360P,and p.P377L MUTYH variants,which were previously found in patients with colorectal polyposis and cancer,were selected for use in this study.Human H1299 cancer cell lines inducibly expressing wild-type (WT) MUTYH (type 2) or one of the 4 above-mentioned MUTYH variants were established using the piggyBac transposon vector system,enabling the genomic integration of the transposon sequence for MUTYH expression.MUTYH expression was examined after cumate induction using Western blotting analysis and immunofiuorescence analysis.The intracellular localization of MUTYH variants tagged with FLAG was also immunofluorescently examined.Next,the mutation frequency in the supF of the shuttle plasmid pMY189 containing a single 8OHG residue at position 159 of the supFwas compared between empty vector cells and cells expressing WT MUTYH or one of the 4 MUTYH variants using a supF forward mutation assay.RESULTS:The successful establishment of human cell lines inducibly expressing WT MUTYH or one of the 4 MUTYH variants was concluded based on the detection of MUTYH expression in these cell lines after treatment with cumate.All of the MUTYH variants and WT MUTYH were localized in the nucleus,and nuclear localization was also observed for FLAG-tagged MUTYH.The mutation frequency ofsupFwas 2.2 x 102in the 8OHG-containing pMY189 plasmid and 2.5× 10-4 in WT pMY189 in empty vector cells,which was an 86-fold increase with the introduction of 8OHG.The mutation frequency (4.7 × 10-3) of supF in the 8OHG-containing pMY189 plasmid in cells overexpressing WT MUTYH was significantly lower than in the empty vector cells (P < 0.01).However,the mutation frequencies of the supF in the 8OHG-containing pMY189 plasmid in cells overexpressing the p.R154H,p.M255V,p.L360P,or p.P377L MUTYH variant were 1.84 × 10-2,1.55

  11. Effect of protein oxidation on the impaired quality of dry-cured loins produced from frozen pork meat.

    Science.gov (United States)

    Lorido, Laura; Ventanas, Sonia; Akcan, Tolga; Estévez, Mario

    2016-04-01

    Dry-cured loins elaborated from frozen (-20 °C/20 weeks)/thawed longissimus dorsi muscles (F) were compared with counterparts elaborated from fresh (unfrozen) muscles (UF) for the extent of protein oxidation (carbonylation and Schiff base formation) and their sensory profile (quantitative-descriptive analysis). All samples had similar moisture, fat and protein contents (p>0.05). In accordance with previous studies, freezing meat prior to processing affected the oxidative stability of meat proteins. This chemical change occurred concomitantly with modifications of the sensory profile of the loins as F-samples received significantly (p<0.05) higher scores for rancid and salty flavor, hardness and fibrousness than UF-counterparts. The formation of cross-links (assessed as Schiff bases) during freezing and the subsequent processing may have contributed to strengthening the meat structure and hence, impairing the texture properties of dry-cured loins.

  12. 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.

  13. Impaired training-induced adaptation of blood pressure in COPD patients: implication of the muscle capillary bed

    Directory of Open Access Journals (Sweden)

    Gouzi F

    2016-09-01

    exercise BP was reduced in CSs (DP: 89±10 mmHg vs 85±9 mmHg; P<0.001/SP: 204±25 mmHg vs 196±27 mmHg; P<0.05, it did not change in COPD patients (DP: 94±14 mmHg vs 97±16 mmHg; P=0.46/SP: 202±27 mmHg vs 208±24 mmHg; P=0.13. The change in muscle C/F ratio was negatively correlated with maximal exercise SP in CSs and COPD patients (r=-0.41; P=0.02. Conclusion: COPD patients showed impaired training-induced BP adaptation related to a change in muscle capillarization, suggesting the possibility of blunted angiogenesis. Keywords: angiogenesis, hypertension, pulmonary rehabilitation

  14. 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 sodium...

  15. Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

    Science.gov (United States)

    Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

    2016-04-01

    Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD. PMID:26638718

  16. Mechanisms of endothelial dysfunction after ionized radiation: selective impairment of the nitric oxide component of endothelium-dependent vasodilation.

    Science.gov (United States)

    Soloviev, Anatoly I; Tishkin, Sergey M; Parshikov, Alexander V; Ivanova, Irina V; Goncharov, Eugene V; Gurney, Alison M

    2003-03-01

    (1) Gamma radiation impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about radiation effects on other endothelial mediators. (2) This study investigated the mechanisms of endothelial dysfunction in rabbits subjected to whole-body irradiation from a cobalt(60) source. (3) The endothelium-dependent relaxation of rabbit aorta evoked by acetylcholine (ACh) or A23187 was impaired in a dose-dependent manner by irradiation at 2 Gy or above. Inhibition was evident 9 days post-irradiation and persisted over the 30 day experimental period. (4) Endothelium-independent responses to glyceryl trinitrate (GTN), sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1) were suppressed over a similar dose range at 7-9 days post-irradiation, but recovered fully by 30 days post-irradiation. (5) In healthy vessels, ACh-induced relaxation was inhibited by L-N(omega)-nitroarginine (L-NA; 3 x 10(-4) M) and charybdotoxin (10(-8) M) plus apamin (10(-6) M) but resistant to indomethacin, indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). Supporting this, ACh caused smooth muscle hyperpolarization that was reduced by L-NA and charybdotoxin plus apamin. (6) In irradiated vessels, responses to ACh were insensitive to L-NA but abolished by charybdotoxin plus apamin, indicating selective loss of NO-mediated relaxation. (7) In animals treated shortly after irradiation with the antioxidant, alpha-tocopherol acetate, the NO-dependent relaxation was restored without effect on the EDHF-dependent component. (8) The results imply that radiation selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level. PMID:12642385

  17. Adaptation of the theory of superconductivity to the behavior of oxides

    Energy Technology Data Exchange (ETDEWEB)

    Teller, E.

    1989-07-01

    An adaptation of the conventional theory to high-temperature superconductors is proposed. Excitation of electrons from below the Fermi surface to above the Fermi surface (according to Bardeen, Copper and Schrieffer) is replaced by excitation from a filled energy band into an empty one. The energy bands are constructed from two-dimensional Bloch functions in neighboring layers of the oxide lattices. Strong coupling with lattice displacements is due to the removal of the topmost electrons from the O/sup 2/minus// ions in the perovskite planes. The main methods of the BCS theory are retained. The formation and observability of a super-lattice is discussed.

  18. 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.

  19. Ectomycorrhizal fungi decompose soil organic matter using oxidative mechanisms adapted from saprotrophic ancestors.

    Science.gov (United States)

    Shah, Firoz; Nicolás, César; Bentzer, Johan; Ellström, Magnus; Smits, Mark; Rineau, Francois; Canbäck, Björn; Floudas, Dimitrios; Carleer, Robert; Lackner, Gerald; Braesel, Jana; Hoffmeister, Dirk; Henrissat, Bernard; Ahrén, Dag; Johansson, Tomas; Hibbett, David S; Martin, Francis; Persson, Per; Tunlid, Anders

    2016-03-01

    Ectomycorrhizal fungi are thought to have a key role in mobilizing organic nitrogen that is trapped in soil organic matter (SOM). However, the extent to which ectomycorrhizal fungi decompose SOM and the mechanism by which they do so remain unclear, considering that they have lost many genes encoding lignocellulose-degrading enzymes that are present in their saprotrophic ancestors. Spectroscopic analyses and transcriptome profiling were used to examine the mechanisms by which five species of ectomycorrhizal fungi, representing at least four origins of symbiosis, decompose SOM extracted from forest soils. In the presence of glucose and when acquiring nitrogen, all species converted the organic matter in the SOM extract using oxidative mechanisms. The transcriptome expressed during oxidative decomposition has diverged over evolutionary time. Each species expressed a different set of transcripts encoding proteins associated with oxidation of lignocellulose by saprotrophic fungi. The decomposition 'toolbox' has diverged through differences in the regulation of orthologous genes, the formation of new genes by gene duplications, and the recruitment of genes from diverse but functionally similar enzyme families. The capacity to oxidize SOM appears to be common among ectomycorrhizal fungi. We propose that the ancestral decay mechanisms used primarily to obtain carbon have been adapted in symbiosis to scavenge nutrients instead. PMID:26527297

  20. 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.

  1. Coenzyme Q10 enhances the anticonvulsant effect of phenytoin in pilocarpine-induced seizures in rats and ameliorates phenytoin-induced cognitive impairment and oxidative stress.

    Science.gov (United States)

    Tawfik, Mona K

    2011-12-01

    Conventional antiepileptic drugs fail to adequately control seizures and predispose to cognitive impairment and oxidative stress with chronic usage in a significant proportion of patients with epilepsy. Coenzyme Q10 (CoQ10), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. To evaluate the neuroprotective effects of CoQ10 in rats against the observed oxidative stress during seizures induced by pilocarpine, and to study its interactions with the conventional antiepileptic drug phenytoin, two experiments were performed. Experiment 1 was conducted to test the effect of phenytoin, CoQ10, or both on seizure severity and oxidative markers in the pilocarpine model of epilepsy. Experiment 2 was conducted to test the effect of 2 weeks of chronic treatment with phenytoin, CoQ10, or both on oxidative markers and behavioral tests in rats. Overall, CoQ10 reduced the severity of pilocarpine-induced seizures and the severity of oxidative stress. Moreover, it potentiated the antiepileptic effects afforded by phenytoin treatment, with the potential safety and efficacy in ameliorating oxidative stress and cognitive impairment caused by chronic phenytoin therapy. Our findings strongly suggest that CoQ10 can be considered a safe and effective adjuvant to phenytoin therapy in epilepsy both to ameliorate seizure severity and to protect against seizure-induced oxidative damage by reducing the cognitive impairment and oxidative stress associated with chronic use of phenytoin.

  2. Adapt

    Science.gov (United States)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  3. The swan-neck lesion: proximal tubular adaptation to oxidative stress in nephropathic cystinosis.

    Science.gov (United States)

    Galarreta, Carolina I; Forbes, Michael S; Thornhill, Barbara A; Antignac, Corinne; Gubler, Marie-Claire; Nevo, Nathalie; Murphy, Michael P; Chevalier, Robert L

    2015-05-15

    Cystinosis is an inherited disorder resulting from a mutation in the CTNS gene, causing progressive proximal tubular cell flattening, the so-called swan-neck lesion (SNL), and eventual renal failure. To determine the role of oxidative stress in cystinosis, histologic sections of kidneys from C57BL/6 Ctns(-/-) and wild-type mice were examined by immunohistochemistry and morphometry from 1 wk to 20 mo of age. Additional mice were treated from 1 to 6 mo with vehicle or mitoquinone (MitoQ), an antioxidant targeted to mitochondria. The leading edge of the SNL lost mitochondria and superoxide production, and became surrounded by a thickened tubular basement membrane. Progression of the SNL as determined by staining with lectin from Lotus tetragonolobus accelerated after 3 mo, but was delayed by treatment with MitoQ (38 ± 4% vs. 28 ± 1%, P injury molecule-1 (KIM-1) nor cell death was observed. After 9 mo, clusters of proximal tubules exhibited localized oxidative stress (4-hydroxynonenal binding), expressed KIM-1, and underwent apoptosis, leading to the formation of atubular glomeruli and accumulation of interstitial collagen. We conclude that nephron integrity is initially maintained in the Ctns(-/-) mouse by adaptive flattening of cells of the SNL through loss of mitochondria, upregulation of transgelin, and thickened basement membrane. This adaptation ultimately fails in adulthood, with proximal tubular disruption, formation of atubular glomeruli, and renal failure. Antioxidant treatment targeted to mitochondria delays initiation of the SNL, and may provide therapeutic benefit in children with cystinosis. PMID:25694483

  4. EFFECTS OF ADDROGRAPHIS PANICULATA (NEES. ON ARSENIC- INDUCED ALTERED GLUCOSE HOMEOSTASIS AND OXIDATIVE IMPAIRMENT IN PANCREAS OF SWISS MICE

    Directory of Open Access Journals (Sweden)

    MANDAVA V. RAO

    2007-01-01

    Full Text Available The effect of Andrographis paniculata (Nees. on arsenic-induced changes in biochemical and cellular antioxident sytem was studies in adult female mice. Daily oral administration of arsenic trioxide (0.5 and 1.0mg/kg b.w for 30days induced a significant increase in blood glucose level which was associated with impaired glucose tolrence. Arsenic treatment also resulted in elevated level panreatic tissue specific makers such as activities of amylase and lipase in serum indicating pancreatic dysfunction. Interestingly, this biochemical dysfuntion was accompanied by a marked dose related enchancement of lipid peroxidation indicating significant induction of oxidative damage. Additional evidence such as deletion in reduced gluatathione levels and alterations in enzymic antioxidant defences like superoxide dismutase, catalase and glutathione peroxidase in pancreas suggested induction of oxidative stress. Concomitant administration of Adrographis paniculata (50 mg/kg b.w. with arsenic significant restored all these parameters. These results suggest that Adrographis paniculata is capable to reducing arsenic-induce cellular oxidative and inflammatory changes in pancreas.

  5. 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. PMID:25935538

  6. Lipid mobilisation and oxidative stress as metabolic adaptation processes in dairy heifers during transition period.

    Science.gov (United States)

    Turk, R; Podpečan, O; Mrkun, J; Kosec, M; Flegar-Meštrić, Z; Perkov, S; Starič, J; Robić, M; Belić, M; Zrimšek, P

    2013-10-01

    The objective of this study was to evaluate metabolic disorders and oxidative stress in dairy heifers during the transition period. Possible relationships between lipid mobilisation indicators and oxidative stress markers were investigated as well. Nineteen dairy heifers were included in the study. Blood samples were collected at the time of estrus synchronisation in heifers, at insemination, three weeks after insemination, one week before calving, at calving and 1, 2, 4 and 8 weeks postpartum. Common metabolic parameters, beta-hydroxybutyrate (BHB), free fatty acids (FFA), paraoxonase-1 (PON1) activity and total antioxidative status (TAS) were analysed. Around insemination, no significant difference was observed in the majority of tested parameters (P>0.05). However, the transition period markedly affected the concentration of triglycerides, total cholesterol, HDL-C, BHB, FFA, TAS and PON1activity. Positive correlations between PON1 activity and total cholesterol, HDL-C and triglycerides were noted but inverse correlations with FFA, BHB and bilirubin were found indicating that PON1 activity changed with lipid metabolism and was influenced by negative energy balance. These findings suggest that lipid mobilisation and oxidative stress are part of a complex metabolic adaptation to low energy balance which reaches equilibrium later in advanced lactation.

  7. 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...

  8. Protective effect of melatonin on propoxur-induced impairment of memory and oxidative stress in rats.

    Science.gov (United States)

    Mehta, Kapil D; Mehta, Ashish K; Halder, Sumita; Khanna, Naresh; Tripathi, Ashok K; Sharma, Krishna K

    2014-06-01

    Propoxur (a carbamate pesticide) has been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of propoxur over cognitive function by melatonin (MEL). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus, and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT) activity. A significant reduction in SDL and prolongation of TL was observed for the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 when compared with control. One week treatment with MEL (50 mg/kg/d; i.p.) antagonized the effect of propoxur on SDL, as well as TL. Propoxur produced a statistically significant increase in the brain MDA levels and decrease in the brain GSH levels and CAT activity. Treatment with MEL attenuated the effect of propoxur on oxidative stress. The results of the present study thus show that MEL has the potential to attenuate cognitive dysfunction and oxidative stress induced by toxicants like propoxur in the brain.

  9. 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.

  10. 听觉障碍学生学习适应性的调查研究%An Investigation on the Learning Adaptability of Students with Hearing Impairments

    Institute of Scientific and Technical Information of China (English)

    杨福义; 谭和平; 陈进; 李方璐

    2012-01-01

    Abstract: With subjects of 242 students with hearing impairments from grade 7 to grade 12, this study investigated hearing im-paired students' learning adaptability. The results indicated that : ( 1 ) The global learning adaptability of hearing impaired students was universally medium or under medium level. Quite a few students with hearing impairments were diversely maladaptive in the domain of learning attitude, learning technology, learning environment and mental and physical health. ;(2)There existed significant grade differ- ence in hearing impaired students' learning adaptability. Their learning adaptability put up the trend to recede first and then rise with the increasing of grade. ; ( 3 ) There also existed significant gender difference in learning adaptability of students with hearing impair- ments. Females' global and four individual levels of learning adaptability were significantly higher than those of males ; (4) Hearing im- paired students' cognitive style model were mostly impulsive model. Their memory model were mostly visual model or in - between model; ( 5 ) More than half students with hearing impairments attributed their academic achievements to inner - directed reason. More than one third students with hearing impairments attributed their academic achievements to outer - directed reason; ( 6 ) Hearing im-paired students' learning time at home was less than that of normal students. Practitioners should take into account hearing impaired students' learning adaptability characteristics while giving instructions to this kind of students.%本研究采用《学习适应性测验》对242名初一——高三年级听觉障碍学生的学习适应性进行调查研究。结果表明:(1)听障学生的总体学习适应性普遍处于中等或中等以下水平,在学习态度、学习技术、学习环境和心身健康四个方面都有相当比例的学生表现出不同程

  11. eNOS activation and NO function: pregnancy adaptive programming of capacitative entry responses alters nitric oxide (NO) output in vascular endothelium--new insights into eNOS regulation through adaptive cell signaling.

    Science.gov (United States)

    Boeldt, D S; Yi, F X; Bird, I M

    2011-09-01

    In pregnancy, vascular nitric oxide (NO) production is increased in the systemic and more so in the uterine vasculature, thereby supporting maximal perfusion of the uterus. This high level of functionality is matched in the umbilical vein, and in corresponding disease states such as pre-eclampsia, reduced vascular responses are seen in both uterine artery and umbilical vein. In any endothelial cell, NO actually produced by endothelial NO synthase (eNOS) is determined by the maximum capacity of the cell (eNOS expression levels), eNOS phosphorylation state, and the intracellular [Ca(2+)](i) concentration in response to circulating hormones or physical forces. Herein, we discuss how pregnancy-specific reprogramming of NO output is determined as much by pregnancy adaptation of [Ca(2+)](i) signaling responses as it is by eNOS expression and phosphorylation. By examining the changes in [Ca(2+)](i) signaling responses from human hand vein endothelial cells, uterine artery endothelial cells, and human umbilical vein endothelial cells in (where appropriate) nonpregnant, normal pregnant, and pathological pregnant (pre-eclamptic) state, it is clear that pregnancy adaptation of NO output occurs at the level of sustained phase 'capacitative entry' [Ca(2+)](i) response, and the adapted response is lacking in pre-eclamptic pregnancies. Moreover, gap junction function is an essential permissive regulator of the capacitative response and impairment of NO output results from any inhibitor of gap junction function, or capacitative entry using TRPC channels. Identifying these [Ca(2+)](i) signaling mechanisms underlying normal pregnancy adaptation of NO output not only provides novel targets for future treatment of diseases of pregnancy but may also apply to other common forms of hypertension. PMID:21555345

  12. Methodological Adaptations for Investigating the Perceptions of Language-Impaired Adolescents Regarding the Relative Importance of Selected Communication Skills

    Science.gov (United States)

    Reed, Vicki A.; Brammall, Helen

    2006-01-01

    This article describes the systematic and detailed processes undertaken to modify a research methodology for use with language-impaired adolescents. The original methodology had been used previously with normally achieving adolescents and speech pathologists to obtain their opinions about the relative importance of selected communication skills…

  13. Protection from Palmitate-Induced Mitochondrial DNA Damage Prevents from Mitochondrial Oxidative Stress, Mitochondrial Dysfunction, Apoptosis, and Impaired Insulin Signaling in Rat L6 Skeletal Muscle Cells

    OpenAIRE

    Yuzefovych, Larysa V.; Solodushko, Viktoriya A.; Wilson, Glenn L.; Rachek, Lyudmila I.

    2011-01-01

    Saturated free fatty acids have been implicated in the increase of oxidative stress, mitochondrial dysfunction, apoptosis, and insulin resistance seen in type 2 diabetes. The purpose of this study was to determine whether palmitate-induced mitochondrial DNA (mtDNA) damage contributed to increased oxidative stress, mitochondrial dysfunction, apoptosis, impaired insulin signaling, and reduced glucose uptake in skeletal muscle cells. Adenoviral vectors were used to deliver the DNA repair enzyme ...

  14. Reversal of propoxur-induced impairment of memory and oxidative stress by 4'-chlorodiazepam in rats.

    Science.gov (United States)

    Mehta, Kapil Dev; Garg, Gobind Rai; Mehta, Ashish K; Arora, Tarun; Sharma, Amit K; Khanna, Naresh; Tripathi, Ashok K; Sharma, Krishna K

    2010-01-01

    Carbamate pesticides like propoxur have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was designed to explore the modulation of the effects of propoxur over cognitive function by progesterone (PROG) and 4'-chlorodiazepam (4CD). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus, transfer latency (TL) on a plus maze and spatial navigation test on Morris water maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT) activity. A significant reduction in SDL and prolongation of TL and spatial navigation test was found for the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 as compared with control. One-week treatment with 4CD (0.5 mg/kg/d; i.p.) antagonized the effect of propoxur on SDL, spatial navigation test as well as TL; whereas, PROG failed to modulate this effect at a dose of 15 mg/kg/d, i.p. Propoxur produced a statistically significant increase in the brain MDA levels and decrease in the brain GSH levels and CAT activity. Treatment with 4CD at the above dose attenuated the effect of propoxur on oxidative stress whereas PROG (15 mg/kg/d; i.p.) failed to influence the same. The results of the present study thus show that 4-CD has the potential to attenuate cognitive dysfunction and oxidative stress induced by toxicants like propoxur in the brain.

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

    OpenAIRE

    Marcella Mauro; Matteo Crosera; Marco Pelin; Chiara Florio; Francesca Bellomo; Gianpiero Adami; Piero Apostoli; Giuseppe Palma; Massimo Bovenzi; Marco Campanini; Francesca Larese Filon

    2015-01-01

    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 huma...

  16. Distinct Phenotypes Caused by Mutation of MSH2 in Trypanosome Insect and Mammalian Life Cycle Forms Are Associated with Parasite Adaptation to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Viviane Grazielle-Silva

    2015-06-01

    Full Text Available DNA repair mechanisms are crucial for maintenance of the genome in all organisms, including parasites where successful infection is dependent both on genomic stability and sequence variation. MSH2 is an early acting, central component of the Mismatch Repair (MMR pathway, which is responsible for the recognition and correction of base mismatches that occur during DNA replication and recombination. In addition, recent evidence suggests that MSH2 might also play an important, but poorly understood, role in responding to oxidative damage in both African and American trypanosomes.To investigate the involvement of MMR in the oxidative stress response, null mutants of MSH2 were generated in Trypanosoma brucei procyclic forms and in Trypanosoma cruzi epimastigote forms. Unexpectedly, the MSH2 null mutants showed increased resistance to H2O2 exposure when compared with wild type cells, a phenotype distinct from the previously observed increased sensitivity of T. brucei bloodstream forms MSH2 mutants. Complementation studies indicated that the increased oxidative resistance of procyclic T. brucei was due to adaptation to MSH2 loss. In both parasites, loss of MSH2 was shown to result in increased tolerance to alkylation by MNNG and increased accumulation of 8-oxo-guanine in the nuclear and mitochondrial genomes, indicating impaired MMR. In T. cruzi, loss of MSH2 also increases the parasite capacity to survive within host macrophages.Taken together, these results indicate MSH2 displays conserved, dual roles in MMR and in the response to oxidative stress. Loss of the latter function results in life cycle dependent differences in phenotypic outcomes in T. brucei MSH2 mutants, most likely because of the greater burden of oxidative stress in the insect stage of the parasite.

  17. Impairment of Hepatic and Renal Functions by 2,5-Hexanedione Is Accompanied by Oxidative Stress in Rats

    Directory of Open Access Journals (Sweden)

    Isaac A. Adedara

    2014-01-01

    Full Text Available 2,5-Hexanedione (2,5-HD is the toxic metabolite of n-hexane which is widely used as solvent in numerous industries. The present study elucidated the precise mechanism of 2,5-HD in hepatorenal toxicity by determining the involvement of oxidative stress in rats. Adult male Wistar rats were exposed to 0, 0.25, 0.5, and 1% 2,5-HD in drinking water for 21 days. Exposure to 2,5-HD caused liver and kidney atrophy evidenced by significant elevation in serum aminotransferases, alkaline phosphatase, albumin, bilirubin, urea, creatinine, and electrolytes levels compared with control. The marked dose-dependent increase in total cholesterol (TC, triglyceride (TG, and low-density lipoprotein (LDL was accompanied with significant decrease in high-density lipoprotein (HDL levels in 2,5-HD-exposed animals when compared with the control. Administration of 2,5-HD significantly diminished glutathione (GSH level but increased the activities of superoxide dismutase (SOD, catalase, glutathione peroxidase (GPx, and glutathione-S-transferase (GST concomitantly with marked elevation in hydrogen peroxide (H2O2 and malondialdehyde (MDA levels in liver and kidney of the treated groups compared with control. These findings suggest that undue exposure to 2,5-HD at environmentally relevant levels may impair liver and kidney functions through induction of oxidative stress.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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....

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

    OpenAIRE

    Tatiana Barichello; Santos, Ana Lucia B.; Cintia Silvestre; Generoso, Jaqueline S.; Cipriano, Andreza L.; Fabricia Petronilho; Felipe Dal-Pizzol; Comim, Clarissa M.; João Quevedo

    2011-01-01

    Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10  μ L 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 corte...

  1. Self-Adaptive Spike-Time-Dependent Plasticity of Metal-Oxide Memristors

    Science.gov (United States)

    Prezioso, M.; Merrikh Bayat, F.; Hoskins, B.; Likharev, K.; Strukov, D.

    2016-02-01

    Metal-oxide memristors have emerged as promising candidates for hardware implementation of artificial synapses - the key components of high-performance, analog neuromorphic networks - due to their excellent scaling prospects. Since some advanced cognitive tasks require spiking neuromorphic networks, which explicitly model individual neural pulses (“spikes”) in biological neural systems, it is crucial for memristive synapses to support the spike-time-dependent plasticity (STDP). A major challenge for the STDP implementation is that, in contrast to some simplistic models of the plasticity, the elementary change of a synaptic weight in an artificial hardware synapse depends not only on the pre-synaptic and post-synaptic signals, but also on the initial weight (memristor’s conductance) value. Here we experimentally demonstrate, for the first time, an STDP behavior that ensures self-adaptation of the average memristor conductance, making the plasticity stable, i.e. insensitive to the initial state of the devices. The experiments have been carried out with 200-nm Al2O3/TiO2-x memristors integrated into 12 × 12 crossbars. The experimentally observed self-adaptive STDP behavior has been complemented with numerical modeling of weight dynamics in a simple system with a leaky-integrate-and-fire neuron with a random spike-train input, using a compact model of memristor plasticity, fitted for quantitatively correct description of our memristors.

  2. Speech communication strategies in older children: acoustic-phonetic and linguistic adaptations to a hearing-impaired peer

    OpenAIRE

    Granlund, S. C.

    2015-01-01

    This thesis examines the communication strategies used by both hearing (NH) and hearing-impaired (HI) children when interacting with a peer with hearing loss, focusing on the acoustic-phonetic and linguistic properties of their speech. To elicit frequent repetitions of segmental contrasts in HI children’s spontaneous speech in interaction, a new task was developed using minimal pair keywords in a communicative game context. In addition, another referential communication task, the ‘spot the di...

  3. Oxidative Stress Impairs Cell Death by Repressing the Nuclease Activity of Mitochondrial Endonuclease G

    Directory of Open Access Journals (Sweden)

    Jason L.J. Lin

    2016-07-01

    Full Text Available Endonuclease G (EndoG is a mitochondrial protein that is released from mitochondria and relocated into the nucleus to promote chromosomal DNA fragmentation during apoptosis. Here, we show that oxidative stress causes cell-death defects in C. elegans through an EndoG-mediated cell-death pathway. In response to high reactive oxygen species (ROS levels, homodimeric CPS-6—the C. elegans homolog of EndoG—is dissociated into monomers with diminished nuclease activity. Conversely, the nuclease activity of CPS-6 is enhanced, and its dimeric structure is stabilized by its interaction with the worm AIF homolog, WAH-1, which shifts to disulfide cross-linked dimers under high ROS levels. CPS-6 thus acts as a ROS sensor to regulate the life and death of cells. Modulation of the EndoG dimer conformation could present an avenue for prevention and treatment of diseases resulting from oxidative stress.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Androgen Induces Adaptation to Oxidative Stress in Prostate Cancer: Implications for Treatment with Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Jehonathan H. Pinthus

    2007-01-01

    Full Text Available Radiation therapy is a standard treatment for prostate cancer (PC. The postulated mechanism of action for radiation therapy is the generation of reactive oxygen species (ROS. Adjuvant androgen deprivation (AD therapy has been shown to confer a survival advantage over radiation alone in high-risk localized PC. However, the mechanism of this interaction is unclear. We hypothesize that androgens modify the radioresponsiveness of PC through the regulation of cellular oxidative homeostasis. Using androgen receptor (AR+ 22rv1 and AR− PC3 human PC cell lines, we demonstrated that testosterone increased basal reactive oxygen species (bROS levels, resulting in dose-dependent activation of phospho-p38 and pAKT, increased expression of clusterin, catalase, manganese superoxide dismutase. Similar data were obtained in three human PC xenografts; WISH-PC14, WISH-PC23, CWR22, growing in testosterone-supplemented or castrated SCID mice. These effects were reversible through AD or through incubation with a reducing agent. Moreover, testosterone increased the activity of catalase, superoxide dismutases, glutathione reductase. Consequently, AD significantly facilitated the response of AR+ cells to oxidative stress challenge. Thus, testosterone induces a preset cellular adaptation to radiation through the generation of elevated bROS, which is modified by AD. These findings provide a rational for combined hormonal and radiation therapy for localized PC.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation.

    Science.gov (United States)

    El-Hattab, Ayman W; Emrick, Lisa T; Hsu, Jean W; Chanprasert, Sirisak; Almannai, Mohammed; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

    2016-04-01

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS syndrome. When compared to control subjects, children with MELAS syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS syndrome. Thus, the initiation of treatment with NO precursors may be

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

    Energy Technology Data Exchange (ETDEWEB)

    Bollmann, Annette [Miami University, Oxford, OH; Sedlacek, Christopher J [Miami University, Oxford, OH; Laanbroek, Hendrikus J [Netherlands Institute of Ecology (NIOO-KNAW); Suwa, Yuichi [Chuo University, Tokyo, Japan; Stein, Lisa Y [University of California, Riverside; Klotz, Martin G [University of Louisville, Louisville; Arp, D J [Oregon State University; Sayavedra-Soto, LA [Oregon State University; Lu, Megan [Los Alamos National Laboratory (LANL); Bruce, David [Los Alamos National Laboratory (LANL); Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Tapia, Roxanne [Los Alamos National Laboratory (LANL); Han, James [U.S. Department of Energy, Joint Genome Institute; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Pennacchio, Len [U.S. Department of Energy, Joint Genome Institute; Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Huntemann, Marcel [U.S. Department of Energy, Joint Genome Institute; Deshpande, Shweta [U.S. Department of Energy, Joint Genome Institute; Han, Cliff [Los Alamos National Laboratory (LANL); Chen, Amy [U.S. Department of Energy, Joint Genome Institute; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Markowitz, Victor [U.S. Department of Energy, Joint Genome Institute; Szeto, Ernest [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Pagani, Ioanna [U.S. Department of Energy, Joint Genome Institute; Pati, Amrita [U.S. Department of Energy, Joint Genome Institute; Peters, Lin [U.S. Department of Energy, Joint Genome Institute; Ovchinnikova, Galina [U.S. Department of Energy, Joint Genome Institute; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL)

    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 chromosome with a total of 3,553 protein coding genes and 44 RNA genes was sequenced by the DOE-Joint Genome Institute Program CSP 2006.

  9. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity.

    Science.gov (United States)

    Gil-Ortega, Marta; Stucchi, Paula; Guzmán-Ruiz, Rocío; Cano, Victoria; Arribas, Silvia; González, M Carmen; Ruiz-Gayo, Mariano; Fernández-Alfonso, Maria S; Somoza, Beatriz

    2010-07-01

    Perivascular adipose tissue (PVAT) plays a paracrine role in regulating vascular tone. We hypothesize that PVAT undergoes adaptative mechanisms during initial steps of diet-induced obesity (DIO) which contribute to preserve vascular function. Four-week-old male C57BL/6J mice were assigned either to a control [low-fat (LF); 10% kcal from fat] or to a high-fat diet (HF; 45% kcal from fat). After 8 wk of dietary treatment vascular function was analyzed in the whole perfused mesenteric bed (MB) and in isolated mesenteric arteries cleaned of PVAT. Relaxant responses to acetylcholine (10(-9)-10(-4) m) and sodium nitroprusside (10(-12)-10(-5) m) were significantly ameliorated in the whole MB from HF animals. However, there was no difference between HF and LF groups in isolated mesenteric arteries devoid of PVAT. The enhancement of relaxant responses detected in HF mice was not attributable to an increased release of nitric oxide (NO) from the endothelium nor to an increased sensitivity and/or activity of muscular guanilylcyclase. Mesenteric PVAT of HF animals showed an increased bioavailability of NO, detected by 4,5-diaminofluorescein diacetate (DAF2-DA) staining, which positively correlated with plasma leptin levels. DAF-2DA staining was absent in PVAT from ob/ob mice but was detected in these animals after 4-wk leptin replacement. The main finding in this study is that adaptative NO overproduction occurs in PVAT during early DIO which might be aimed at preserving vascular function. PMID:20410199

  10. PEGylated Carbon Nanotubes Impair Retrieval of Contextual Fear Memory and Alter Oxidative Stress Parameters in the Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Lidiane Dal Bosco

    2015-01-01

    Full Text Available Carbon nanotubes (CNT are promising materials for biomedical applications, especially in the field of neuroscience; therefore, it is essential to evaluate the neurotoxicity of these nanomaterials. The present work assessed the effects of single-walled CNT functionalized with polyethylene glycol (SWCNT-PEG on the consolidation and retrieval of contextual fear memory in rats and on oxidative stress parameters in the hippocampus. SWCNT-PEG were dispersed in water at concentrations of 0.5, 1.0, and 2.1 mg/mL and infused into the rat hippocampus. The infusion was completed immediately after training and 30 min before testing of a contextual fear conditioning task, resulting in exposure times of 24 h and 30 min, respectively. The results showed that a short exposure to SWCNT-PEG impaired fear memory retrieval and caused lipid peroxidation in the hippocampus. This response was transient and overcome by the mobilization of antioxidant defenses at 24 h. These effects occurred at low and intermediate but not high concentration of SWCNT-PEG, suggesting that the observed biological response may be related to the concentration-dependent increase in particle size in SWCNT-PEG dispersions.

  11. 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.

  12. Deletion of the von Hippel-Lindau gene causes sympathoadrenal cell death and impairs chemoreceptor-mediated adaptation to hypoxia.

    Science.gov (United States)

    Macías, David; Fernández-Agüera, Mary Carmen; Bonilla-Henao, Victoria; López-Barneo, José

    2014-12-01

    Mutations of the von Hippel-Lindau (VHL) gene are associated with pheochromocytomas and paragangliomas, but the role of VHL in sympathoadrenal homeostasis is unknown. We generated mice lacking Vhl in catecholaminergic cells. They exhibited atrophy of the carotid body (CB), adrenal medulla, and sympathetic ganglia. Vhl-null animals had an increased number of adult CB stem cells, although the survival of newly generated neuron-like glomus cells was severely compromised. The effects of Vhl deficiency were neither prevented by pharmacological inhibition of prolyl hydroxylases or selective genetic down-regulation of prolyl hydroxylase-3, nor phenocopied by hypoxia inducible factor overexpression. Vhl-deficient animals appeared normal in normoxia but survived for only a few days in hypoxia, presenting with pronounced erythrocytosis, pulmonary edema, and right cardiac hypertrophy. Therefore, in the normal sympathoadrenal setting, Vhl deletion does not give rise to tumors but impairs development and plasticity of the peripheral O₂-sensing system required for survival in hypoxic conditions.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Mauro, Marcella; Crosera, Matteo; Pelin, Marco; Florio, Chiara; Bellomo, Francesca; Adami, Gianpiero; Apostoli, Piero; De Palma, Giuseppe; Bovenzi, Massimo; Campanini, Marco; Filon, Francesca Larese

    2015-07-01

    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.

  15. 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...

  16. Effects of a lyophilized aqueous extract of Feretia apodanthera Del. (Rubiaceae) on pentylenetetrazole-induced kindling, oxidative stress, and cognitive impairment in mice.

    Science.gov (United States)

    Taiwe, G S; Moto, F C O; Ayissi, E R M; Ngoupaye, G T; Njapdounke, J S K; Nkantchoua, G C N; Kouemou, N; Omam, J P O; Kandeda, A K; Pale, S; Pahaye, D; Ngo Bum, E

    2015-02-01

    Feretia apodanthera Del. (Rubiaceae) is extensively used in ethnomedicine in Cameroon and Nigeria for epilepsy, febrile convulsions, and rheumatic pains and for enhancing cognitive performance. The aim of the present study was to examine the effects of a lyophilized aqueous extract of F. apodanthera on the course of kindling development, kindling-induced learning deficit, oxidative stress markers, and cholinesterase activity in pentylenetetrazole (PTZ)-kindled mice. Pentylenetetrazole, 30mg/kg, induced kindling in mice after 30.00±1.67days. The aqueous extract of F. apodanthera showed dose-dependent antiseizure effects. Feretia apodanthera (150-200mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures, and generalized tonic-clonic seizures. The extract also improved the seizure score and decreased the number of myoclonic jerks. Pentylenetetrazole kindling induced significant oxidative stress and cognitive impairment which were reversed by pretreatment with F. apodanthera in a dose-dependent manner. The significant decrease in cholinesterase activity observed in the PTZ-kindled mice was reversed by pretreatment with the F. apodanthera extract. The results indicated that pretreatment with the aqueous extract of F. apodanthera antagonizes seizures, oxidative stress, and cognitive impairment in PTZ-kindled mice. The aqueous extract of F. apodanthera also showed anxiolytic activities, but the inhibition of memory impairment was not attributed to the anxiolytic activities of the plant. These results thus suggest the potential of F. apodanthera as an adjuvant in epilepsy both to prevent seizures as well as to protect against seizure-induced oxidative stress and memory impairment.

  17. Oleic Acid Increases Synthesis and Secretion of VEGF in Rat Vascular Smooth Muscle Cells: Role of Oxidative Stress and Impairment in Obesity

    Directory of Open Access Journals (Sweden)

    Mariella Trovati

    2013-09-01

    Full Text Available Obesity is characterized by poor collateral vessel formation, a process involving vascular endothelial growth factor (VEGF action on vascular smooth muscle cells (VSMC. Free fatty acids are involved in the pathogenesis of obesity vascular complications, and we have aimed to clarify whether oleic acid (OA enhances VEGF synthesis/secretion in VSMC, and whether this effect is impaired in obesity. In cultured aortic VSMC from lean and obese Zucker rats (LZR and OZR, respectively we measured the influence of OA on VEGF-A synthesis/secretion, signaling molecules and reactive oxygen species (ROS. In VSMC from LZR we found the following: (a OA increases VEGF-A synthesis/secretion by a mechanism blunted by inhibitors of Akt, mTOR, ERK-1/2, PKC-beta, NADPH-oxidase and mitochondrial electron transport chain complex; (b OA activates the above mentioned signaling pathways and increases ROS; (c OA-induced activation of PKC-beta enhances oxidative stress, which activates signaling pathways responsible for the increased VEGF synthesis/secretion. In VSMC from OZR, which present enhanced baseline oxidative stress, the above mentioned actions of OA on VEGF-A, signaling pathways and ROS are impaired: this impairment is reproduced in VSMC from LZR by incubation with hydrogen peroxide. Thus, in OZR chronically elevated oxidative stress causes a resistance to the action on VEGF that OA exerts in LZR by increasing ROS.

  18. Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis.

    Science.gov (United States)

    Engelen, Mariëlle P K J; Safar, Ahmed M; Bartter, Thaddeus; Koeman, Fari; Deutz, Nicolaas E P

    2016-07-01

    Reduced plasma arginine (ARG) concentrations are found in various types of cancer. ARG and its product nitric oxide (NO) are important mediators in the immune function and the defense against tumour cells. It remains unclear whether the diminished systemic ARG availability in cancer is related to insufficient endogenous ARG synthesis, negatively affecting NO synthesis, and whether a dietary amino acid mixture is able to restore this. In 13 patients with advanced non-small cell lung cancer (NSCLC) and 11 healthy controls, whole body ARG and CIT (citrulline) rates of appearance were measured by stable isotope methodology before and after intake of a mixture of amino acids as present in whey protein. The conversions of CIT to ARG (indicator of de novo ARG synthesis) and ARG to CIT (marker of NO synthesis), and ARG clearance (reflecting ARG disposal capacity) were calculated. Plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Conversions of CIT to ARG and ARG to CIT (P<0.05), and CIT rate of appearance (P=0.07) were lower in NSCLC. ARG rate of appearance and clearance were comparable suggesting no enhanced systemic ARG production and disposal capacity in NSCLC. After intake of the mixture, ARG rate of appearance and concentration increased (P<0.001), and ARG to CIT conversion was restored in NSCLC. In conclusion, an impaired endogenous ARG synthesis plays a role in the reduced systemic ARG availability and NO synthesis in advanced NSCLC. Nutritional approaches may restore systemic ARG availability and NO synthesis in cancer, but the clinical implication remains unclear. PMID:27129191

  19. 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.

  20. Swimming training induces liver mitochondrial adaptations to oxidative stress in rats submitted to repeated exhaustive swimming bouts.

    Directory of Open Access Journals (Sweden)

    Frederico D Lima

    Full Text Available BACKGROUND AND AIMS: Although acute exhaustive exercise is known to increase liver reactive oxygen species (ROS production and aerobic training has shown to improve the antioxidant status in the liver, little is known about mitochondria adaptations to aerobic training. The main objective of this study was to investigate the effects of the aerobic training on oxidative stress markers and antioxidant defense in liver mitochondria both after training and in response to three repeated exhaustive swimming bouts. METHODS: Wistar rats were divided into training (n = 14 and control (n = 14 groups. Training group performed a 6-week swimming training protocol. Subsets of training (n = 7 and control (n = 7 rats performed 3 repeated exhaustive swimming bouts with 72 h rest in between. Oxidative stress biomarkers, antioxidant activity, and mitochondria functionality were assessed. RESULTS: Trained group showed increased reduced glutathione (GSH content and reduced/oxidized (GSH/GSSG ratio, higher superoxide dismutase (MnSOD activity, and decreased lipid peroxidation in liver mitochondria. Aerobic training protected against exhaustive swimming ROS production herein characterized by decreased oxidative stress markers, higher antioxidant defenses, and increases in methyl-tetrazolium reduction and membrane potential. Trained group also presented higher time to exhaustion compared to control group. CONCLUSIONS: Swimming training induced positive adaptations in liver mitochondria of rats. Increased antioxidant defense after training coped well with exercise-produced ROS and liver mitochondria were less affected by exhaustive exercise. Therefore, liver mitochondria also adapt to exercise-induced ROS and may play an important role in exercise performance.

  1. Visual Impairment, Including Blindness

    Science.gov (United States)

    ... top Adapting the Environment Making adaptations to the environment where a child with a visual impairment lives, works, or plays ... can consult, depending on your role in the child’s life, are: Family Connect ... to the Physical Environment: Setting up a Classroom for Students with Visual ...

  2. High-fat, low-carbohydrate diet alters myocardial oxidative stress and impairs recovery of cardiac function after ischemia and reperfusion in obese rats.

    Science.gov (United States)

    Liu, Jian; Lloyd, Steven G

    2013-04-01

    Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats

  3. Oral supplements of aqueous extract of tomato seeds alleviate motor abnormality, oxidative impairments and neurotoxicity induced by rotenone in mice: relevance to Parkinson's disease.

    Science.gov (United States)

    Gokul, Krishna; Muralidhara

    2014-07-01

    Although tomato seeds (an industrial by-product) are known to contain several bioactive compounds, studies describing their health effects are limited. Previously, we evidenced that aqueous extract of tomato seeds (TSE) markedly attenuated rotenone (ROT)-induced oxidative stress and neurotoxicity in Drosophila system. This study investigated the neuroprotective effect of TSE in a chronic ROT model of neurotoxicity in mice. Initially, we assessed the potential of oral supplements of TSE to modulate the levels of endogenous markers of oxidative stress in brain regions of mice. Subsequently, employing a co-exposure paradigm, the propensity of TSE (100 mg/kg bw, 3 weeks) to attenuate ROT-induced behavioral phenotype (gait abnormalities, anxiety-like state), oxidative dysfunctions and neurotoxicity was examined. We found that mice provided with TSE supplements exhibited progressive improvement in gait pattern and exploratory behavior. TSE markedly offset ROT-induced oxidative impairments, restored reduced glutathione levels, antioxidant defenses (superoxide dismutase, glutathione peroxidase) and protein carbonyls content in brain regions. Specifically, TSE effectively diminished ROT induced elevation in the activity levels of acetylcholinesterase and restored the dopamine levels in striatum. Interestingly, in mitochondria, TSE was able to restore the activity of mitochondrial complexes and redox state. Collectively, our findings in the chronic ROT model demonstrate the ability of TSE to alleviate behavioral phenotype, oxidative stress, mitochondrial dysfunction and neurotoxicity. Further studies in dopaminergic cell models are necessary to understand the precise molecular mechanism/s by which tomato seed bioactives offer significant neuroprotection. PMID:24831121

  4. Albumin-bound fatty acids induce mitochondrial oxidant stress and impair antioxidant responses in proximal tubular cells

    NARCIS (Netherlands)

    Ishola, D. A.; Post, J. A.; van Timmeren, M. M.; Bakker, S. J. L.; Goldschmeding, R.; Koomans, H. A.; Braam, B.; Joles, J. A.

    2006-01-01

    Albumin induces oxidative stress and cytokine production in proximal tubular cells (PTECs). Albumin-bound fatty acids (FAs) enhance tubulopathic effects of albumin in vivo. We proposed that FA aggravation of albumin-induced oxidative stress in PTECs might be involved. We hypothesized that mitochondr

  5. 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…

  6. 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.

  7. Involvement of anti-oxidative enzymes, photosynthetic pigments and flavonoid metabolism in the adaptation of Reaumuria soongorica to salt stress

    Institute of Scientific and Technical Information of China (English)

    YuBing Liu; Bo Cao; MeiLing Liu

    2013-01-01

    Reaumuria soongorica is a short woody shrub widely found in semi-arid areas of China. It can survive severe environ-mental stress including high salinity in its natural habitat. Thus, we investigated the involvement of anti-oxidative enzymes, photosynthetic pigments and flavonoid metabolism in the adaptation of R. soongorica to saline environments. R. soon-gorica was treated with 0, 100, 200 and 400 mM NaCl solutions for 14 days. Soil salt content increased significantly by watering with high content of NaCl solution, and no variation between 8 and 14 days during treatment. The levels of pe-roxidation of lipid membranes (measured by malondialdehyde content) and the activities of three antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX)) increased under salt stress. Chlorophyll and carotenoid content decreased with increasing salt content. The ratio of Chl a/Chl b and carotenoid/Chl exhibited sig-nificant increase under 400 mM NaCl. However, total flavonoid and anthocyanin contents and key enzyme activities in the flavonoid pathway including phenylalanine ammonialyase (PAL) and Chalcone isomerase (CHI) decreased under salt stress. These findings possibly suggest that R. soongorica has an adaptation protection mechanism against salt-induced oxidative damage by inducing the activity of antioxidant enzymes and maintaining a steady level of carotenoid/Chl.

  8. Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain

    International Nuclear Information System (INIS)

    Recent global events have focused attention on the potential threat of international and domestic chemical terrorism, as well as the possibility of chemical warfare proliferation. Sulphur mustard (SM) is one of the potent chemical warfare agents (CWA), which initiates a cascade of events that converge on the redox mechanisms common to brain injury. The present study was designed to examine the effects of chronic SM exposure on neurobehavioral impairments, mitochondrial oxidative stress in male Swiss Albino mice and its role in inducing apoptotic neuronal cell death. The animals were divided into four groups (control, low, medium and high dose) of 5 animals each. Exposure to SM was given percutaneously daily for 12 weeks. The results demonstrated impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests in a dose dependent manner. There was a significant increase in lipid peroxidation and protein carbonyl content whereas, decrease in the activity of manganese superoxide dismutase (MnSOD), glutathione reductase and glutathione peroxidase suggesting impaired antioxidant defense system. Immunoblotting of cytochrome c, Bcl-2, Bax and activation of caspase-3 suggest induction of apoptosis in a dose dependent manner. Finally, increased p53 expression suggests that it may target the mitochondrial pathway for inducing apoptosis in response to DNA damage signals. In conclusion, chronic SM exposure may have the potential to generate oxidative stress which may trigger the release of cytochrome c as well as caspase-3 activation in neurons leading to cell death by apoptosis in a dose dependent manner which may in the end be responsible for the disruption of cognitive functions in mice.

  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. Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

    Science.gov (United States)

    Matsumoto, H.; Ohnishi, T.

    There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

  11. Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

    DEFF Research Database (Denmark)

    Zhang, Yaping; Zhang, Wei; Edvinsson, Lars;

    2014-01-01

    Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different concentra......B of LDL impairs vasodilation with damaging the endothelium and attenuating the NO-mediated endothelium-dependent relaxation, which might associate with lipid peroxidation and contribute to the development of cardiovascular disease....

  12. Selective Serotonin-norepinephrine Re-uptake Inhibition Limits Renovas-cular-hypertension Induced Cognitive Impairment, Endothelial Dysfunction, and Oxidative Stress Injury.

    Science.gov (United States)

    Singh, Prabhat; Sharma, Bhupesh

    2016-01-01

    Hypertension has been reported to induce cognitive decline and dementia of vascular origin. Serotonin- norepinephrine reuptake transporters take part in the control of inflammation, cognitive functions, motivational acts and deterioration of neurons. This study was carried out to examine the effect of venlafaxine; a specific serotonin-norepinephrine reuptake inhibitor (SNRI), in two-kidney-one-clip-2K1C (renovascular hypertension) provoked vascular dementia (VaD) in albino rats. 2K1C technique was performed to provoke renovascular-hypertension in adult male albino Wistar rats. Learning and memory were assessed by using the elevated plus maze and Morris water maze. Mean arterial blood pressure- MABP, as well as endothelial function, were assessed by means of BIOPAC system. Serum nitrosative stress (nitrite/ nitrate), aortic superoxide anion, brain oxidative stress, inflammation, cholinergic dysfunction and brain damage (2,3,5-triphenylterazolium chloride staining) were also assessed. 2K1C has increased MABP, endothelial dysfunction as well as learning and memory impairments. 2K1C method has increased serum nitrosative stress (reduced nitrite/nitrate level), oxidative stress (increased brain thiobarbituric acid reactive species and aortic superoxide anion content along with decreased levels of brain superoxide dismutase, glutathione, and catalase), brain inflammation (increased myeloperoxidase), cholinergic dysfunction (increased acetylcholinesterase activity) and brain damage. Treatment with venlafaxine considerably attenuated renovascular-hypertension induced cognition impairment, endothelial dysfunction, serum nitrosative stress, brain and aortic oxidative stress, cholinergic function, inflammation as well as cerebral damage. The finding of this study indicates that specific modulation of the serotonin-norepinephrine transporter perhaps regarded as potential interventions for the management of renovascular hypertension provoked VaD. PMID:26915517

  13. 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...

  14. Adaptation of the phosphotungstate method to determine reduced and oxidized vitamin C in blood plasma.

    Science.gov (United States)

    Rutkowski, Maciej; Grzegorczyk, Krzysztof; Greger, Janusz

    2004-01-01

    The phosphotungstate reagent (PTR) was used for quantitative spectrophotometric determination of physiological forms of vitamin C in blood plasma. An immediate action of PTR on the first half of the tested samples allowed to determine reduced vitamin C concentrations (I) at 700 nm. 10 mM dithiothreitol added to the second half of the samples reduced oxidized vitamin C in it--hence the total amount of this vitamin was reduced with a concentration (II) determined as above (remains of dithiothreitol were removed with N-ethylmaleimide). The difference of results (II) and (I) gave the concentration of oxidized vitamin C. The method is characterised by fault-less analytical parameters: correlation coefficients of analytical curves > 0.99, recovery factor 100.5%, variation coefficients intra- and inter-serial < 3% and < 5%, respectively, detection limit 0.05 microM. The simplicity of the method enables an easy control of the ratio of oxidized and reduced vitamin C concentrations in blood plasma--the biomarker of the level of oxidative damage to cells. PMID:15540612

  15. Mouse hepatic oval cells require Met-dependent PI3K to impair TGF-β-induced oxidative stress and apoptosis.

    Directory of Open Access Journals (Sweden)

    Adoración Martínez-Palacián

    Full Text Available We have previously shown that oval cells harboring a genetically inactivated Met tyrosine kinase (Met(-/- oval cells are more sensitive to TGF-β-induced apoptosis than cells expressing a functional Met (Met(flx/flx, demonstrating that the HGF/Met axis plays a pivotal role in oval cell survival. Here, we have examined the mechanism behind this effect and have found that TGF-β induced a mitochondria-dependent apoptotic cell death in Met(flx/flx and Met(-/- oval cells, associated with a marked increase in levels of the BH3-only proteins Bim and Bmf. Bmf plays a key role during TGF-β-mediated apoptosis since knocking down of BMF significantly diminished the apoptotic response in Met(-/- oval cells. TGF-β also induced oxidative stress accompanied by NADPH oxidase 4 (Nox4 mRNA up-regulation and decreased protein levels of antioxidant enzymes. Antioxidants inhibit both TGF-β-induced caspase 3 activity and Bmf up-regulation, revealing an oxidative stress-dependent Bmf regulation by TGF-β. Notably, oxidative stress-related events were strongly amplified in Met(-/- oval cells, emphasizing the critical role of Met in promoting survival. Pharmacological inhibition of PI3K did impair HGF-driven protection from TGF-β-induced apoptosis and increased sensitivity of Met(flx/flx oval cells to TGF-ß by enhancing oxidative stress, reaching apoptotic indices similar to those obtained in Met(-/- oval cells. Interestingly, both PI3K inhibition and/or knockdown itself resulted in caspase-3 activation and loss of viability in Met(flx/flx oval cells, whereas no effect was observed in Met(-/- oval cells. Altogether, results presented here provide solid evidences that both paracrine and autocrine HGF/Met signaling requires PI3K to promote mouse hepatic oval cell survival against TGF-β-induced oxidative stress and apoptosis.

  16. Graphene Oxides Decorated with Carnosine as an Adjuvant To Modulate Innate Immune and Improve Adaptive Immunity in Vivo.

    Science.gov (United States)

    Meng, Chunchun; Zhi, Xiao; Li, Chao; Li, Chuanfeng; Chen, Zongyan; Qiu, Xusheng; Ding, Chan; Ma, Lijun; Lu, Hongmin; Chen, Di; Liu, Guangqing; Cui, Daxiang

    2016-02-23

    Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4(+) T and CD8(+) T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo. PMID:26766427

  17. Graphene Oxides Decorated with Carnosine as an Adjuvant To Modulate Innate Immune and Improve Adaptive Immunity in Vivo.

    Science.gov (United States)

    Meng, Chunchun; Zhi, Xiao; Li, Chao; Li, Chuanfeng; Chen, Zongyan; Qiu, Xusheng; Ding, Chan; Ma, Lijun; Lu, Hongmin; Chen, Di; Liu, Guangqing; Cui, Daxiang

    2016-02-23

    Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4(+) T and CD8(+) T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo.

  18. 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.

  19. Modified Self-adaptive Immune Genetic Algorithm for Optimization of Combustion Side Reaction of p-Xylene Oxidation

    Institute of Scientific and Technical Information of China (English)

    陶莉莉; 孔祥东; 钟伟民; 钱锋

    2012-01-01

    In recent years, immune genetic algorithm (IGA) is gaining popularity for finding the optimal solution for non-linear optimization problems in many engineering applications. However, IGA with deterministic mutation factor suffers from the problem of premature convergence. In this study, a modified self-adaptive immune genetic algorithm (MSIGA) with two memory bases, in which immune concepts are applied to determine the mutation parameters, is proposed to improve the searching ability of the algorithm and maintain population diversity. Performance comparisons with other well-known population-based iterative algorithms show that the proposed method converges quickly to the global optimum and overcomes premature problem. This algorithm is applied to optimize a feed forward neural network to measure the content of products in the combustion side reaction of p-xylene oxidation, and satisfactory results are obtained.

  20. 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.

  1. Cyclooxygenase 2,pS2,inducible nitric oxide synthase and transforming growth factor alpha in gastric adaptation to stress

    Institute of Scientific and Technical Information of China (English)

    Shi-Nan Nie; Hai-Chen Sun; Xue-Hao Wu; Xiao-Ming Qian

    2004-01-01

    AIM: To determine the role of mucosal gene expression of cyclooxygenase 2 (COX-2), pS2 (belongs to trefoil peptides),inducible nitric oxide synthase (iNOS) and transforming growth factor alpha (TGFα) in gastric adaptation to water immersion and restraint stress (WRS) in rats.METHODS: Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 d. Gastric mucosal blood flow (GMBF) was measured by laser Doppler fiowmeter3. The extent of gastric mucosal lesions were evaluated grossly and histologically and expressions of COX-2, pS2,iNOS and TGFα were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot.RESULTS: The damage to the surface of gastric epithelium with focal areas of deep haemorrhagic necrosis was induced by repeated WRS.The adaptative cytoprotection against stress was developed with activation of cell proliferation in the neck regions of gastric glands. The ulcer index (UI) in groups Ⅱ, Ⅲ and Ⅳ was markedly reduced as compared with group Ⅰ (Ⅰ: 47.23±1.20; Ⅳ: 10.39±1.18,P<0.01). GMBF significantly decreased after first exposure to WRS with an adaptive increasement of GMBF in experimental groups after repetitive challenges with WRS. After the 4th WRS,the value of GMBF almost restored to normal level (Ⅰ:321.87±8.85; Ⅳ: 455.95±11.81,P<0.01). First WRS significantly decreased the expression of pS2 and significantly increased the expressions of COX-2, iNOS and TGFα. After repeated WRS, pS2 and TGFα expressions gradually increased (pS2: Ⅰ: 0.37±0.02; Ⅳ: 0.77±0.01; TGFα: Ⅰ:0.86±0.01; Ⅳ: 0.93±0.03, P<0.05) with a decrease in the expressions of COX-2 and iNOS (COX-2: Ⅰ: 0.45±0.02; Ⅳ:0.22±0.01; iNOS: Ⅰ: 0.93±0.01; Ⅳ: 0.56±0.01, P<0.01).Expressions of pS2, COX-2, iNOS and TGFα showed regular changes with a good relationship among them.CONCLUSION: Gastric adaptation to WRS injury involves enhanced cell proliferation, increased expression of pS2 and

  2. 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

    )), and normal pressure hydrocephalus (NPH, n = 15), as well as healthy controls (HC, n = 7). Fractions of three specific oxidative modifications (S-cysteinylation, S-cysteinylglycinylation, and S-glutathionylation) were quantitated relative to the total TTR protein. Results were correlated with diagnostic...

  3. Nitric oxide induces stomatal closure and enhances the adaptive plant responses against drought stress.

    Science.gov (United States)

    García-Mata, C; García Mata, C; Lamattina, L

    2001-07-01

    Nitric oxide (NO) is a very active molecule involved in many and diverse biological pathways where it has proved to be protective against damages provoked by oxidative stress conditions. In this work, we studied the effect of two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine SNP-treated on the response of wheat (Triticum aestivum) to water stress conditions. After 2 and 3 h of drought, detached wheat leaves pretreated with 150 microM SNP retained up to 15% more water than those pretreated with water or NO(2)(-)/NO(3)(-). The effect of SNP treatment on water retention was also found in wheat seedlings after 7 d of drought. These results were consistent with a 20% decrease in the transpiration rate of SNP-treated detached wheat leaves for the same analyzed time. In parallel experiments, NO was also able to induce a 35%, 30%, and 65% of stomatal closure in three different species, Tradescantia sp. (monocotyledonous) and two dicotyledonous, Salpichroa organifolia and fava bean (Vicia faba), respectively. In SNP-treated leaves of Tradescantia sp., the stomatal closure was correlated with a 10% increase on RWC. Ion leakage, a cell injury index, was 25% lower in SNP-treated wheat leaves compared with control ones after the recovery period. Carboxy-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), a specific NO scavenger, reverted SNP action by restoring the transpiration rate, stomatal aperture, and the ion leakage to the level found in untreated leaves. Northern-blot analysis showed that SNP-treated wheat leaves display a 2-fold accumulation of a group three late embryogenesis abundant transcript with respect to control leaves both after 2 and 4 h of drought periods. All together, these results suggest that the exogenous application of NO donors might confer an increased tolerance to severe drought stress conditions in plants. PMID:11457969

  4. Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice

    Directory of Open Access Journals (Sweden)

    Tanda Koichi

    2009-06-01

    Full Text Available Abstract Background Neuronal nitric oxide synthase (nNOS is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice. Results nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice. Conclusion These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders.

  5. 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.

  6. Electroacupuncture pretreatment prevents cognitive impairment induced by limb ischemia-reperfusion via inhibition of microglial activation and attenuation of oxidative stress in rats.

    Science.gov (United States)

    Chen, Ye; Zhou, Jun; Li, Jun; Yang, Shi-Bin; Mo, Li-Qun; Hu, Jie-Hui; Yuan, Wan-Li

    2012-01-13

    Limb ischemia-reperfusion (LI/R) is associated with high morbidity and mortality. Furthermore, critical trauma survivors can present cognitive impairment. Cognitive function, survival rate, oxidative stress and neuronal health were examined to elucidate (1) the magnitude of cognitive effects of prolonged reperfusion, (2) potential players in the mechanistic pathway mediating such effects, and (3) possible benefits of electroacupuncture (EA) pretreatment at Baihui (GV20), Yanglingquan (GB34), Taichong (LR3), Zusanli (ST36) and Xuehai (SP10) acupoints. LI/R was induced in rats by placing a rubber tourniquet on each hind limb for 3h, and the animals were evaluated periodically for 7d after LI/R. Rats subjected to LI/R had significantly lower survival rates, and displayed evidence of brain injury and cognitive dysfunction (as determined by the Morris water maze test) 1d and 3d after reperfusion compared to sham-operated controls. LI/R also resulted in higher levels of reactive oxygen species (ROS) and malondialdehyde (MDA), microglial activation, and decreased superoxide dismutase (SOD) activity within Cornu Ammonis area 1 (CA1) of the hippocampus. Depressed survival rates, microglial activation, oxidative damage, and histological changes, as well as cognitive dysfunction were partially or fully attenuated in rats that received 14d of EA prior to LI/R. These findings indicate that LI/R can result in cognitive dysfunction related to activated microglia and elevated oxidative stress, and that EA has neuroprotective potential mediated, at least in part, by inhibition of microglial activation and attenuation of oxidative stress. PMID:22129788

  7. Silibinin attenuates amyloid beta(25-35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice.

    Science.gov (United States)

    Lu, P; Mamiya, T; Lu, L L; Mouri, A; Niwa, M; Hiramatsu, M; Zou, L B; Nagai, T; Ikejima, T; Nabeshima, T

    2009-10-01

    In Alzheimer's disease (AD), the deposition of amyloid peptides is invariably associated with oxidative stress and inflammatory responses. Silibinin (silybin), a flavonoid derived from the herb milk thistle, has potent anti-inflammatory and antioxidant activities. However, it remains unclear whether silibinin improves amyloid beta (Abeta) peptide-induced neurotoxicity. In this study, we examined the effect of silibinin on the fear-conditioning memory deficits, inflammatory response, and oxidative stress induced by the intracerebroventricular injection of Abeta peptide(25-35) (Abeta(25-35)) in mice. Mice were treated with silibinin (2, 20, and 200 mg/kg p.o., once a day for 8 days) from the day of the Abeta(25-35) injection (day 0). Memory function was evaluated in cued and contextual fear-conditioning tests (day 6). Nitrotyrosine levels in the hippocampus and amygdala were examined (day 8). The mRNA expression of inducible nitric-oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in the hippocampus and amygdala was measured 2 h after the Abeta(25-35) injection. We found that silibinin significantly attenuated memory deficits caused by Abeta(25-35) in the cued and contextual fear-conditioning test. Silibinin significantly inhibited the increase in nitrotyrosine levels in the hippocampus and amygdala induced by Abeta(25-35). Nitrotyrosine levels in these regions were negatively correlated with memory performance. Moreover, real-time RT-PCR revealed that silibinin inhibited the overexpression of iNOS and TNF-alpha mRNA in the hippocampus and amygdala induced by Abeta(25-35). These findings suggest that silibinin (i) attenuates memory impairment through amelioration of oxidative stress and inflammatory response induced by Abeta(25-35) and (ii) may be a potential candidate for an AD medication. PMID:19638571

  8. A Combination Supplement of Fructo- and Xylo-Oligosaccharides Significantly Abrogates Oxidative Impairments and Neurotoxicity in Maternal/Fetal Milieu Following Gestational Exposure to Acrylamide in Rat.

    Science.gov (United States)

    Krishna, Gokul; Divyashri, Gangaraju; Prapulla, S G; Muralidhara

    2015-09-01

    Prebiotic oligosaccharides are demonstrated to confer a wide spectrum of physiological benefits during pregnancy. In view of this, focused attempts are being directed towards understanding their role as modulators of brain chemistry and behavior. Epidemiological studies have identified that exposure to neurotoxins during prenatal/early life can profoundly impact neurodevelopment/function. In this context, we have tested the hypothesis that a combination of prebiotic supplements during gestation has the propensity to attenuate acrylamide (ACR) induced oxidative impairments, mitochondrial dysfunction and neurotoxicity in maternal and fetal brain of rats. To achieve this, pregnant dams given oral supplements of a combination of fructo- and xylooligosaccharides (FOS + XOS, 3 g/kg/day) during gestation days (GD 0-19) were exposed to ACR (200 ppm in drinking water, GD 6-19). The behavioral analysis revealed that ACR dams fed prebiotics displayed higher exploratory behavior in the open field test. The prenatal evaluation showed that ACR-induced decrements of placental/fetal weights were markedly restored with prebiotic feeding. Prebiotics significantly offset markers of oxidative stress, restored enzymic antioxidants, cholinergic and mitochondrial function in the maternal and fetal brain. Concomitantly, prebiotics restored ACR-induced depletion in the levels of dopamine and γ-aminobutyric acid in the maternal cortex that positively correlated with cecal bacterial numbers. Collectively, these data suggest that prenatal prebiotic oligosaccharide supplements protect developing brain against oxidative stress-mediated neurotoxicity. While the underlying mechanism/s by which prebiotics abrogate the impact of neurotoxicants in the developing brain merits further studies, we speculate that it may be mediated predominantly through attenuation of oxidative stress and proliferation of enteric microbiota. PMID:26248513

  9. The architecture of iron microbial mats reflects the adaptation of chemolithotrophic iron oxidation in freshwater and marine environments

    Directory of Open Access Journals (Sweden)

    Clara S Chan

    2016-06-01

    Full Text Available Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respectively. If these biominerals are assembled into mat structures with similar functional morphology, this would suggest that mat architecture is adapted to serve roles specific to Fe oxidation. To evaluate this, we combined light, confocal, and scanning electron microscopy of intact Fe microbial mats with experiments on sheath formation in culture, in order to understand mat developmental history and subsequently evaluate the connection between Fe oxidation and mat morphology. We sampled a freshwater sheath mat from Maine and marine stalk and sheath mats from Loihi Seamount hydrothermal vents, Hawaii. Mat morphology correlated to niche: stalks formed in steeper O2 gradients while sheaths were associated with low to undetectable O2 gradients. Fe-biomineralized filaments, twisted stalks or hollow sheaths, formed the highly porous framework of each mat. The mat-formers are keystone species, with nascent marine stalk-rich mats comprised of novel and uncommon Zetaproteobacteria. For all mats, filaments were locally highly parallel with similar morphologies, indicating that cells were synchronously tracking a chemical or physical cue. In the freshwater mat, cells inhabited sheath ends at the growing edge of the mat. Correspondingly, time lapse culture imaging showed that sheaths are made like stalks, with cells rapidly leaving behind an Fe oxide filament. The distinctive architecture common to all observed Fe mats appears to serve specific functions related to

  10. 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.

  11. Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance

    OpenAIRE

    Keeney Paula M; Dunham Lisa D; Morton Stephanie L; Arthur Charles R; Bennett James P

    2009-01-01

    Abstract Background Sporadic Parkinson's disease (sPD) is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA...

  12. 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

  13. 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

    freeze lesion. In normal mice, the brain injury was followed by reactive astrogliosis and recruitment of macrophages from 1 day postlesion (dpl), peaking at 3-10 dpl, and by 20 dpl the transient immunoreactions were decreased, and a glial scar was present. In IL-6KO mice, the reactive astrogliosis...... and recruitment of macrophages were decreased throughout the experimental period. The expression of the antioxidant and anti-apoptotic factors metallothionein I+II (MT-I+II) was increased prominently by the freeze lesion, but this response was significantly reduced in the IL-6 KO mice. By contrast, the expression...... 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...

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

    OpenAIRE

    Bruno Pereira Carreira; Maria Inês Morte; Ana Isabel Santos; Ana Sofia Lourenço; António Francisco Ambrósio; Carvalho, Caetana M.; Araújo, Inês M.

    2014-01-01

    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 (NSCs), and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an...

  15. Chlorogenic acid protection of neuronal nitric oxide synthase-positive neurons in the hippocampus of mice with impaired learning and memory

    Institute of Scientific and Technical Information of China (English)

    Qiuyun Tu; Xiangqi Tang; Zhiping Hu

    2008-01-01

    BACKGROUND: Clinical practice and modern pharmacology have confirmed that ehlorogenic acid can ameliorate learning and memory impairments. OBJECTIVE: To observe the effects of chlorogenic acid on neuronal nitric oxide synthase (nNOS)-positive neurons in the mouse hippocampus, and to investigate the mechanisms underlying the beneficial effects of chlorogenic acid on learning and memory. DESIGN, TIME AND SETTING: The present randomized, controlled, neural cell morphological observation was performed at the Institute of Neurobiology, Central South University between January and May 2005.MATERIALS: Forty-eight female, healthy, adult, Kunming mice were included in this study. Learning and memory impairment was induced with an injection of 0.5 μL kainic acid (0.4 mg/mL) into the hippocampus.METHODS: The mice were randomized into three groups (n = 16): model, control, and chlorogenic acid-treated. At 2 days following learning and memory impairment induction, intragastric administration of physiological saline or chlorogenic acid was performed in the model and chlorogenic acid-treated groups, respectively. The control mice were administered 0.5 μ L physiological saline into the hippocampus, and 2 days later, they received an intragastric administration of physiological saline. Each mouse received two intragastric administrations (1 mL solution once) per day, for a total of 35 days. MAIN OUTCOME MEASURES: Detection of changes in hippocampal and cerebral cortical nNOS neurons by immunohistochemistry; determination of spatial learning and memory utilizing the Y-maze device.RESULTS: At day 7 and 35 after intervention, there was no significant difference in the number of nNOS-positive neurons in the cerebral cortex between the model, chlorogenic acid, and control groups (P > 0.05). Compared with the control group, the number of nNOS-positive neurons in the hippocampal CA1-4 region was significantly less in the model group (P 0.05). At day 7 following intervention, the number

  16. 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.

  17. Oral supplementation of standardized extract of Withania somnifera protects against diabetes-induced testicular oxidative impairments in prepubertal rats.

    Science.gov (United States)

    Kyathanahalli, Chandrashekara Nagaraj; Manjunath, Mallayya Jayawanth; Muralidhara

    2014-09-01

    Male reproductive dysfunctions and infertility are the common consequences of overt diabetes. Available evidence support oxidative stress to be the underlying mechanism for the manifestation of testicular complications during diabetes. In the present study, we assessed the attenuating effects of Withania somnifera root extract (WS) on diabetes-induced testicular oxidative disturbances in prepubertal rats. Four-week-old prepubertal rats were assigned into nondiabetic control, streptozotocin (STZ)-treated and STZ+WS supplemented (500 mg/kg b.w./d, oral, 15 days) groups. Experimental diabetes was induced by a single intraperitoneal injection of STZ (90 mg/kg b.w). Terminally, all animals were killed, and markers of oxidative stress were determined in the testis cytosol and mitochondrial fraction. Severe hyperglycemia and regression in testis size were apparent in diabetic rats. A decline in antioxidant defenses with subsequent elevation in the generation of reactive oxygen species and lipid peroxidation was discernible in testis cytosol and mitochondria of diabetic prepubertal rats, which was significantly reversed by WS. However, there was partial restoration of glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and 3-beta hydroxysteroid dehydrogenase activities in testis of diabetic prepubertal rats administered with WS. Taken together, data accrued suggest the potential of WS to improve diabetes-induced testicular dysfunctions in prepubertal rats. PMID:24488064

  18. Oral supplementation of standardized extract of Withania somnifera protects against diabetes-induced testicular oxidative impairments in prepubertal rats.

    Science.gov (United States)

    Kyathanahalli, Chandrashekara Nagaraj; Manjunath, Mallayya Jayawanth; Muralidhara

    2014-09-01

    Male reproductive dysfunctions and infertility are the common consequences of overt diabetes. Available evidence support oxidative stress to be the underlying mechanism for the manifestation of testicular complications during diabetes. In the present study, we assessed the attenuating effects of Withania somnifera root extract (WS) on diabetes-induced testicular oxidative disturbances in prepubertal rats. Four-week-old prepubertal rats were assigned into nondiabetic control, streptozotocin (STZ)-treated and STZ+WS supplemented (500 mg/kg b.w./d, oral, 15 days) groups. Experimental diabetes was induced by a single intraperitoneal injection of STZ (90 mg/kg b.w). Terminally, all animals were killed, and markers of oxidative stress were determined in the testis cytosol and mitochondrial fraction. Severe hyperglycemia and regression in testis size were apparent in diabetic rats. A decline in antioxidant defenses with subsequent elevation in the generation of reactive oxygen species and lipid peroxidation was discernible in testis cytosol and mitochondria of diabetic prepubertal rats, which was significantly reversed by WS. However, there was partial restoration of glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and 3-beta hydroxysteroid dehydrogenase activities in testis of diabetic prepubertal rats administered with WS. Taken together, data accrued suggest the potential of WS to improve diabetes-induced testicular dysfunctions in prepubertal rats.

  19. 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...

  20. Hepatic transcriptional analysis in rats treated with Cassia occidentalis seed: involvement of oxidative stress and impairment in xenobiotic metabolism as a putative mechanism of toxicity.

    Science.gov (United States)

    Panigrahi, Gati Krushna; Yadav, Ashish; Yadav, Anuradha; Ansari, Kausar M; Chaturvedi, Rajnish K; Vashistha, Vipin M; Raisuddin, S; Das, Mukul

    2014-08-17

    The present study was undertaken to investigate the effect of Cassia occidentalis (CO) seeds on the transcriptional expression patterns of mRNAs in rat liver by microarray analysis. The results indicated that exposure of CO (0.5%) seeds in diet to rats differentially regulated 60 transcripts belonging to various metabolic pathways including, oxidative stress, xenobiotic metabolism, carbohydrate metabolism, cell cycle, apoptosis etc. The expression of AKT1, CAT, SOD1, CYP1A1, CYP2B1, TGF-β, BAX, CREB1, JNK1 and IL-6 were validated by the qRT-PCR. In addition, involvement of oxidative stress was observed due to marked depletion of glutathione, increase in lipid peroxidation and modulation of antioxidant enzymes in hepatic tissue of rats treated with 0.5-2.0% CO in diet. Furthermore, significant decrease in the levels of Phase 1 (EROD, MROD and PROD) and Phase 2 (QR and GST) enzymes following 0.5-2.0% CO exposure indicates the impairment of xenobiotic metabolism and possible accumulation of toxic ingredients of the seeds in liver. Overall, the study predicts the involvement of multiple pathways and related biomolecules in CO induced hepatotoxicity and the data may be useful in formulating strategies for therapeutic interventions of suspected CO poisoning study cases.

  1. Pretreatment with Rhodiola Rosea Extract Reduces Cognitive Impairment Induced by Intracerebroventricular Streptozotocin in Rats: Implication of Anti-oxidative and Neuroprotective Effects

    Institute of Scientific and Technical Information of China (English)

    ZE-QIANG QU; YAN ZHOU; YUAN-SHAN ZENGt; YAN LI; PETER CHUNG

    2009-01-01

    Objectives 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). Methods 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. Results 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). Conclusion 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.

  2. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat.

    Science.gov (United States)

    Yousef, Mokhtar I; Omar, Sahar A M; El-Guendi, Marwa I; Abdelmegid, Laila A

    2010-11-01

    The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine.

  3. Gain of Cellular Adaptation Due to Prolonged p53 Impairment Leads to Functional Switchover from p53 to p73 during DNA Damage in Acute Myeloid Leukemia Cells*

    OpenAIRE

    Chakraborty, Juni; Banerjee, Shuvomoy; Ray, Pallab; Hossain, Dewan Md Sakib; Bhattacharyya, Sankar; Adhikary, Arghya; Chattopadhyay, Sreya; Das, Tanya; Sa, Gaurisankar

    2010-01-01

    Tumor suppressor p53 plays the central role in regulating apoptosis in response to genotoxic stress. From an evolutionary perspective, the activity of p53 has to be backed up by other protein(s) in case of any functional impairment of this protein, to trigger DNA damage-induced apoptosis in cancer cells. We adopted multiple experimental approaches to demonstrate that in p53-impaired cancer cells, DNA damage caused accumulation of p53 paralogue p73 via Chk-1 that strongly impacted Bax expressi...

  4. Contribution of nitric oxide radicals in bystander and adaptive responses induced by heavy ion-beams

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate whether radioadaptive responses were induced after irradiation with accelerated ion beams through nitric oxide-mediated bystander response in cultured cells in vitro and in some organs of mice in vivo. Human non-small cell lung carcinoma cells transfected with wild-type p53 (H1299/wtp53 cells) were used. The cells were irradiated with accelerated carbon ion beams (290 MeV/u, 31 keV/μm or 135 MeV/u, 31 keV/μm). Then, the cells were allowed forming colonies. ICR male mice (Jcl: ICR) were used. The mice were irradiated on 2 days with accelerated carbon ion beams (290 MeV/u, 13 keV/μm or 135 MeV/u, 25 keV/μm) or argon ion beams (500 MeV/u, 90 keV/μm). The small intestine and testis were excised 2 days after the last irradiation. These excised tissues were fixed, embedded in paraffin and made of thin-sections on slide glasses. Then the TUNEL- and activated caspase-3-positive cells in the thin-sections of tissues were detected by the immunohistochemical method. A significant elevated surviving fractions of cells was observed when the cells were challengingly irradiated after the priming irradiation with accelerate carbon ion beams. This enhancement was partially suppressed by Nitric oxide (NO) radical scavenger, carboxy-PTIO (c-PTIO). The bystander-induced apoptotic and activated caspase-3-positive cells were obviously observed in the unirradiated small intestine and testis when mice were irradiated with carbon or argon ion beams across the upper body. In addition, a significant reduction of apoptotic cells in the intestine and testis, when mice were challengingly irradiated after the priming irradiation with accelerate carbon or argon ion beams. These observations were partially suppressed by c-PTIO into the peritoneal cavity. Furthermore, it is suggested that the apoptosis may be induced in the tissue stem cells of small intestine and testis. (author)

  5. 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.' PMID:23558301

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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. PMID:26060181

  9. Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production.

    Science.gov (United States)

    Suman, Shubhankar; Rodriguez, Olga C; Winters, Thomas A; Fornace, Albert J; Albanese, Chris; Datta, Kamal

    2013-08-01

    Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice two and twelve months after exposure to a γ radiation dose (2 Gy) commonly employed in fractionated radiotherapy. For a comparative study, effects of 1.6 Gy heavy ion 56Fe radiation on cerebral cortex were also investigated, which has implications for space exploration. Radiation exposure was associated with increased chronic oxidative stress, oxidative DNA damage, lipid peroxidation, and apoptosis. These results when considered with decreased cortical thickness, activation of cell-cycle arrest pathway, and inhibition of DNA double strand break repair factors led us to conclude to our knowledge for the first time that radiation caused aging-like pathology in cerebral cortical cells and changes after heavy ion radiation were more pronounced than γ radiation. PMID:23928451

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

    AIM: 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.METHODS: Either 200 ml/L ethanol, 50 g/L NaCl or 0.3 mol/LHCl 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.RESULTS: 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.CONCLUSION: 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 nongastritis 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.

  11. Contribution of nitric oxide radicals in bystander and adaptive responses induced by heavy ion-beams

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate whether radioadaptive responses were induced after irradiation with accelerated ion beams through nitric oxide-mediated bystander response in cultured cells in vitro and in some organs of mice in vivo. Human non-small cell lung carcinoma cells transfected with wild-type p53 (H1299/wtp53 cells) were used. The cells were irradiated with accelerated neon (400 MeV/u, 31 keV/μm) or iron (500 MeV/u, 200 keV/μm) ion beams. Then, the cells were allowed forming colonies, were cultured for 48 h to obtained samples for Western blot analysis, or were cultured for several weeks to fix mutations in the locus of hprt gene. ICR male mice (Jcl:ICR) were used. The mice were irradiated on 2 days with accelerated carbon ion beams (290 MeV/u, 13 keV/μm) or argon ion beams (500 MeV/u, 90 keV/μm). The intestine and testis were excised 2 days after the last irradiation. These excised tissues were fixed, embedded in paraffin and made of thin-sections on slide glasses. Then the TdT-mediated dUTP-biotin nick end-labeling (TUNEL)- and activated caspase-3-positive cells in the thin-sections of tissues were detected by the immunohistochemical method. A significant reduction of mutation rate of the hprt gene was observed when the cells were challengingly irradiated after the priming irradiation with accelerate neon or iron ion beams. This reduction was partially suppressed by NO radical scavenger, carboxy-PTIO. The bystander-induced apoptotic and activated caspase-3-positive cells were obviously observed in unirradiated intestine and testis when mice were irradiated with carbon or argon ion beams across the upper body. These observations were partially suppressed by carboxy-PTIO into the peritoneal cavity. (author)

  12. 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.

  13. 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. PMID:24704229

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

    Science.gov (United States)

    Sobinoff, A P; Pye, V; Nixon, B; Roman, S D; McLaughlin, E A

    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 (1.5mg/kg/daily) and high (3mg/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.

  15. 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 retinol...

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

    Science.gov (United States)

    Gao, Fei; Gao, Ying; Liu, Yang-Feng; Wang, Li; Li, Ya-Jun

    2014-01-01

    Though new antiepileptic drugs are emerging, approximately a third of epileptic patients still suffer from recurrent convulsions and cognitive dysfunction. Therefore, we tested whether berberine (Ber), a vegetable drug, has an anticonvulsant property and attenuates memory impairment in a pilocarpine (Pilo)-induced epilepsy model in rats. The rats were injected with 400 mg/kg Pilo to induce convulsions, and Ber 25, 50, and 100 mg/kg were administrated by the intragastric route once daily 7 days before Pilo injection until the experiment was over. Convulsions were observed after Pilo injection. For the rats that developed status epilepticus (SE), malondialdehyde, glutathione levels, superoxide dismutase, and catalase activity in the hippocampus were measured 24 hours after SE. The rats received the Morris water-maze test 2 weeks after SE, and then were killed for fluoro-jade B staining to detect the degenerating neurons. We found Ber delayed latency to the first seizure and the time to develop SE in a dose-dependent manner. Malondialdehyde levels were decreased, while glutathione and catalase activity were strengthened in Ber-injected SE rats. In the Morris water-maze test, Ber decreased escape latency compared to saline-treated SE rats. Additionally, Ber reduced the number of fluoro-jade B-positive cells in the 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.

  17. Endogenous nitric oxide mediates He-Ne laser-induced adaptive responses in salt stressed-tall fescue leaves.

    Science.gov (United States)

    Li, Yongfeng; Gao, Limei; Han, Rong

    2016-10-01

    The aim of this study was to investigate the role of endogenous nitric oxide in protective effects of He-Ne laser on salt stressed-tall fescue leaves. Salt stress resulted in significant increases of membrane injury, reactive oxygen species (ROS) production, polyamine accumulation, and activities of SOD, POD, and APX, while pronounced decreases of antioxidant contents, CAT activity and intracellular Ca(2+) concentration in seedlings leaves. He-Ne laser illumination caused a distinct alleviation of cellular injury that was reflected by the lower MDA amounts, polyamine accumulation and ROS levels at the stress period. In contrast, the laser treatment displayed a higher Ca(2+) concentration, antioxidant amounts, NO release, antioxidant enzyme, and NOS activities. These responses could be blocked due to the inhibition of NO biosynthesis by PTIO (NO scavenger) or LNNA (NOS inhibitor). The presented results demonstrated that endogenous NO might be involved in the progress of He-Ne laser-induced plant antioxidant system activation and ROS degradation in order to enhance adaptive responses of tall fescue to prolonged saline conditions. PMID:27309569

  18. Mitigation of peroxynitrite-mediated nitric oxide (NO) toxicity as a mechanism of induced adaptive NO resistance in the CNS.

    Science.gov (United States)

    Bishop, Amy; Gooch, Renea; Eguchi, Asuka; Jeffrey, Stephanie; Smallwood, Lorraine; Anderson, James; Estevez, Alvaro G

    2009-04-01

    During CNS injury and diseases, nitric oxide (NO) is released at a high flux rate leading to formation of peroxynitrite (ONOO(*)) and other reactive nitrogenous species, which nitrate tyrosines of proteins to form 3-nitrotyrosine (3NY), leading to cell death. Previously, we have found that motor neurons exposed to low levels of NO become resistant to subsequent cytotoxic NO challenge; an effect dubbed induced adaptive resistance (IAR). Here, we report IAR mitigates, not only cell death, but 3NY formation in response to cytotoxic NO. Addition of an NO scavenger before NO challenge duplicates IAR, implicating reactive nitrogenous species in cell death. Addition of uric acid (a peroxynitrite scavenger) before cytotoxic NO challenge, duplicates IAR, implicating peroxynitrite, with subsequent 3NY formation, in cell death, and abrogation of this pathway as a mechanism of IAR. IAR is dependent on the heme-metabolizing enzyme, heme oxygenase-1 (HO1), as indicated by the elimination of IAR by a specific HO1 inhibitor, and by the finding that neurons isolated from HO1 null mice have increased NO sensitivity with concomitant increased 3NY formation. This data indicate that IAR is an HO1-dependent mechanism that prevents peroxynitrite-mediated NO toxicity in motor neurons, thereby elucidating therapeutic targets for the mitigation of CNS disease and injury. PMID:19183270

  19. 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.

  20. Impaired Nitric Oxide Mediated Vasodilation In The Peripheral Circulation In The R6/2 Mouse Model Of Huntington's Disease.

    Science.gov (United States)

    Kane, Andrew D; Niu, Youguo; Herrera, Emilio A; Morton, A Jennifer; Giussani, Dino A

    2016-01-01

    Recent evidence shows that the Huntington's disease (HD) extends beyond the nervous system to other sites, including the cardiovascular system. Further, the cardiovascular pathology pre-dates neurological decline, however the mechanisms involved remain unclear. We investigated in the R6/2 mouse model of HD nitric oxide (NO) dependent and independent endothelial mechanisms. Femoral artery reactivity was determined by wire myography in wild type (WT) and R6/2 mice at 12 and 16 weeks of adulthood. WT mice showed increased endothelial relaxation between 12 and 16 weeks (Rmax: 72 ± 7% vs. 97 ± 13%, P R6/2 mice showed enhanced endothelial relaxation already by 12 weeks (Rmax at 12w: 72 ± 7% vs. 94 ± 5%, WT vs. R6/2, P R6/2, P R6/2 mouse developed overt endothelial dysfunction due to an inability to increase NO dependent vasodilation. The data add to the growing literature of non-neural manifestations of HD and implicate NO depletion as a key mechanism underlying the HD pathophysiology in the peripheral vasculature. PMID:27181166

  1. 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.

  2. Calycosin ameliorates diabetes-induced cognitive impairments in rats by reducing oxidative stress via the PI3K/Akt/GSK-3β signaling pathway.

    Science.gov (United States)

    Wang, Xiang; Zhao, Linhui

    2016-04-29

    Diabetic encephalopathy is one of the most prevalent chronic complications of diabetes mellitus (DM), but there is currently no effective method of prevention nor proven therapeutic regimen for it. In this study, we investigated the effects of calycosin on cognitive behavior and the potential mechanism involved in streptozocin-induced diabetic rats. The effects of diabetes and calycosin treatment on spatial learning and memory were evaluated using the Morris Water Maze, passive avoidance and motor coordination tests. Histological analysis of the hippocampus cornu ammonis 1 (CA1) region was conducted in rats. The decreased expression of the synapsin (SYN) and postsynatptic density protein (PSD-95), as well as brain-derived neurotrophic factor (BDNF) in diabetic rats was measured by quantitative real-time PCR and western blot. Treatment with calycosin promoted a reduction in the expression of SYN, PSD-95 and BDNF. In addition, diabetic rats showed increased MDA levels, and decreased SOD levels and GSH-Px activities in the hippocampus, as well as increased AChE activity in the cerebral cortex; these changes were reversed by calycosin supplementation. Thus, the impairment of learning and memory in STZ-induced diabetic rats was alleviated by calycosin, and that the degree of alleviation was associated with oxidative stress. We also found that calycosin treatment significantly stimulated Akt phosphorylation and decreased GSK-3β and tau phosphorylation, and that these changes could be restored by the PI3K/Akt inhibitor LY294002. In conclusion, calycosin had a beneficial effect on the amelioration, prevention and treatment of diabetes-associated cognitive deficits, through its involvement in oxidative stress, synaptic function and the PI3K/Akt/GSK-3β pathway. PMID:26970304

  3. Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice

    Science.gov (United States)

    Rhein, Virginie; Song, Xiaomin; Wiesner, Andreas; Ittner, Lars M.; Baysang, Ginette; Meier, Fides; Ozmen, Laurence; Bluethmann, Horst; Dröse, Stefan; Brandt, Ulrich; Savaskan, Egemen; Czech, Christian; Götz, Jürgen; Eckert, Anne

    2009-01-01

    Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ)-containing plaques, neurofibrillary tangles, and neuron and synapse loss. Tangle formation has been reproduced in P301L tau transgenic pR5 mice, whereas APPswPS2N141I double-transgenic APP152 mice develop Aβ plaques. Cross-breeding generates triple transgenic (tripleAD) mice that combine both pathologies in one model. To determine functional consequences of the combined Aβ and tau pathologies, we performed a proteomic analysis followed by functional validation. Specifically, we obtained vesicular preparations from tripleAD mice, the parental strains, and nontransgenic mice, followed by the quantitative mass-tag labeling proteomic technique iTRAQ and mass spectrometry. Within 1,275 quantified proteins, we found a massive deregulation of 24 proteins, of which one-third were mitochondrial proteins mainly related to complexes I and IV of the oxidative phosphorylation system (OXPHOS). Notably, deregulation of complex I was tau dependent, whereas deregulation of complex IV was Aβ dependent, both at the protein and activity levels. Synergistic effects of Aβ and tau were evident in 8-month-old tripleAD mice as only they showed a reduction of the mitochondrial membrane potential at this early age. At the age of 12 months, the strongest defects on OXPHOS, synthesis of ATP, and reactive oxygen species were exhibited in the tripleAD mice, again emphasizing synergistic, age-associated effects of Aβ and tau in perishing mitochondria. Our study establishes a molecular link between Aβ and tau protein in AD pathology in vivo, illustrating the potential of quantitative proteomics. PMID:19897719

  4. 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.

  5. Lung diffusion capacity for nitric oxide and carbon monoxide is impaired similarly following short-term graded exercise.

    Science.gov (United States)

    Zavorsky, Gerald S; Lands, Larry C

    2005-02-01

    Study aimed to determine whether short-term graded exercise affects single-breath lung diffusion capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) similarly, and whether the DLNO/DLCO ratios during rest are altered post-exercise compared to pre-exercise. Eleven healthy subjects (age=29+/-6 years; weight=76.6+/-13.2 kg; height=177.9+/-13.2 cm; and maximal oxygen uptake or V(.-)(O(2max) = 52.7 +/- 9.3 ml kg(-1) min(-1))performed simultaneous single-breath DLNO and DLCO measurements at rest (inspired NO concentration=43.2+/-4.1 ppm, inspired CO concentration=0.30%) 15 min before and 2h after a graded exercise test to exhaustion (exercise duration=593+/-135 s). Resting DLNO and DLCO was similarly reduced 2h post-exercise (DLNO=-7.8+/-3.5%, DLCO=-10.3+/-6.9%, and PDLNO post-exercise such that 68% of the variance in the change in DLCO was accounted for by the variance in the change in DLNO (PDLNO/DLCO ratio was not altered post-exercise (5.87+/-0.37) compared to pre-exercise (5.70+/-0.34). We conclude that the decrease in single-breath DLNO and DLCO from pre- to post-exercise is similar, the magnitude of the change in DLCO closely reflects that of the change in DLNO, and single-breath DLNO/DLCO ratios are independent of the timing of measurement suggesting that using NO and CO transfer gases are valid in looking at short-term changes in lung diffusional conductance.

  6. Impaired functions of neural stem cells by abnormal nitric oxide-mediated signaling in an in vitro model of Niemann-Pick type C disease

    Institute of Scientific and Technical Information of China (English)

    Sun-Jung Kim; Myung-Sin Lim; Soo-Kyung Kang; Yong-Soon Lee; Kyung-Sun Kang

    2008-01-01

    Nitric oxide (NO) has been implicated in the promotion of neurodegeneration.However,little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells (NSCs) in neurodegenerative disease.In this study,we investigated the effect of NO on self-renewal of NSCs in an animal model for Niemann-Pick type C (NPC) disease.We found that NO production was significantly increased in NSCs from NPC1-deficient mice (NPC1-/-),which showed reduced NSC self-renewal.The number of nestin-positive cells and the size of neurospheres were both significantly decreased.The expression of NO synthase (NOS) was increased in neurospheres derived from the brain of NPC1-/- mice in comparison to wild-type neurospheres.NO-mediated activation of glycogen synthase kinase-3β(GSK3β) and caspase-3 was also observed in NSCs from NPC1-/- mice.The self-renewal ability of NSCs from NPC1-/- mice was restored by an NOS inhibitor,L-NAME,which resulted in the inhibition of GSK3β and caspase-3.In addition,the differentiation ability of NSCs was partially restored and the number of Fluoro-Jade C-positive degenerating neurons was reduced.These data suggest that overproduction of NO in NPC disease impaired the self-renewal of NSCs.Control of NO production may be key for the treatment of NPC disease.

  7. Cardiomyocyte-Restricted Deletion of PPARβ/δ in PPARα-Null Mice Causes Impaired Mitochondrial Biogenesis and Defense, but No Further Depression of Myocardial Fatty Acid Oxidation

    Directory of Open Access Journals (Sweden)

    Jian Liu

    2011-01-01

    Full Text Available It is well documented that PPARα and PPARβ/δ share overlapping functions in regulating myocardial lipid metabolism. However, previous studies demonstrated that cardiomyocyte-restricted PPARβ/δ deficiency in mice leads to severe cardiac pathological development, whereas global PPARα knockout shows a benign cardiac phenotype. It is unknown whether a PPARα-null background would alter the pathological development in mice with cardiomyocyte-restricted PPARβ/δ deficiency. In the present study, a mouse model with long-term PPARβ/δ deficiency in PPARα-null background showed a comparably reduced cardiac expression of lipid metabolism to those of single PPAR-deficient mouse models. The PPARα-null background did not rescue or aggravate the cardiac pathological development linked to cardiomyocyte-restricted PPARβ/δ deficiency. Moreover, PPARα-null did not alter the phenotypic development in adult mice with the short-term deletion of PPARβ/δ in their hearts, which showed mitochondrial abnormalities, depressed cardiac performance, and cardiac hypertrophy with attenuated expression of key factors in mitochondrial biogenesis and defense. The present study demonstrates that cardiomyocyte-restricted deletion of PPARβ/δ in PPARα-null mice causes impaired mitochondrial biogenesis and defense, but no further depression of fatty acid oxidation. Therefore, PPARβ/δ is essential for maintaining mitochondrial biogenesis and defense in cardiomyocytes independent of PPARα.

  8. 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.

  9. The Relationship between Visual Impairment and Gestures.

    Science.gov (United States)

    Frame, Melissa J.

    2000-01-01

    A study found the gestural activity of 15 adolescents with visual impairments differed from that of 15 adolescents with sight. Subjects with visual impairments used more adapters (especially finger-to-hand gestures) and fewer conversational gestures. Differences in gestural activity by degree of visual impairment and grade in school were also…

  10. Impaired Driving

    Science.gov (United States)

    ... help prevent injuries and deaths from alcohol-impaired driving. The Problem Risk Factors BAC Effects Prevention Additional Resources How big is the problem? In 2014, 9,967 people were killed in alcohol-impaired driving crashes, accounting for nearly one-third (31%) of ...

  11. The RosR transcription factor is required for gene expression dynamics in response to extreme oxidative stress in a hypersaline-adapted archaeon

    Directory of Open Access Journals (Sweden)

    Sharma Kriti

    2012-07-01

    Full Text Available Abstract Background Previous work has shown that the hypersaline-adapted archaeon, Halobacterium salinarum NRC-1, is highly resistant to oxidative stress caused by exposure to hydrogen peroxide, UV, and gamma radiation. Dynamic alteration of the gene regulatory network (GRN has been implicated in such resistance. However, the molecular functions of transcription regulatory proteins involved in this response remain unknown. Results Here we have reanalyzed several existing GRN and systems biology datasets for H. salinarum to identify and characterize a novel winged helix-turn-helix transcription factor, VNG0258H, as a regulator required for reactive oxygen species resistance in this organism. This protein appears to be unique to the haloarchaea at the primary sequence level. High throughput quantitative growth assays in a deletion mutant strain implicate VNG0258H in extreme oxidative stress resistance. According to time course gene expression analyses, this transcription factor is required for the appropriate dynamic response of nearly 300 genes to reactive oxygen species damage from paraquat and hydrogen peroxide. These genes are predicted to function in repair of oxidative damage to proteins and DNA. In vivo DNA binding assays demonstrate that VNG0258H binds DNA to mediate gene regulation. Conclusions Together these results suggest that VNG0258H is a novel archaeal transcription factor that regulates gene expression to enable adaptation to the extremely oxidative, hypersaline niche of H. salinarum. We have therefore renamed VNG0258H as RosR, for reactive oxygen species regulator.

  12. 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

    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......) 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......., 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...

  13. Calpastatin overexpression reduces oxidative stress-induced mitochondrial impairment and cell death in human neuroblastoma SH-SY5Y cells by decreasing calpain and calcineurin activation, induction of mitochondrial fission and destruction of mitochondrial fusion.

    Science.gov (United States)

    Tangmansakulchai, Kulvadee; Abubakar, Zuroida; Kitiyanant, Narisorn; Suwanjang, Wilasinee; Leepiyasakulchai, Chaniya; Govitrapong, Piyarat; Chetsawang, Banthit

    2016-09-01

    Calpain is an intracellular Ca(2+)-dependent protease, and the activation of calpain has been implicated in neurodegenerative diseases. Calpain activity can be regulated by calpastatin, an endogenous specific calpain inhibitor. Several lines of evidence have demonstrated a potential role of calpastatin in preventing calpain-mediated pathogenesis. Additionally, several studies have revealed that calpain activation and mitochondrial damage are involved in the cell death process; however, recent evidence has not clearly indicated a neuroprotective mechanism of calpastatin against calpain-dependent mitochondrial impairment in the process of neuronal cell death. Therefore, the purpose of this study was to investigate the potential ability of calpastatin to inhibit calpain activation and mitochondrial impairment in oxidative stress-induced neuron degeneration. Calpastatin was stably overexpressed in human neuroblastoma SH-SY5Y cells. In non-calpastatin overexpressing SH-SY5Y cells, hydrogen peroxide significantly decreased cell viability, superoxide dismutase activity, mitochondrial membrane potential, ATP production and mitochondrial fusion protein (Opa1) levels in the mitochondrial fraction but increased reactive oxygen species formation, calpain and calcineurin activation, mitochondrial fission protein (Fis1 and Drp1) levels in the mitochondrial fraction and apoptotic cells. Nevertheless, these toxic effects were abolished in hydrogen peroxide-treated calpastatin-overexpressing SH-SY5Y cells. The results of the present study demonstrate the potential ability of calpastatin to diminish calpain and calcineurin activation and mitochondrial impairment in neurons that are affected by oxidative damage. PMID:27453331

  14. 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.

  15. Adaptation of a thermo assay balance to the study of oxidation by water vapor and / or oxygen at high temperatures

    International Nuclear Information System (INIS)

    The construction of an apparatus which allows the continuous follow-up of oxidation in the presence of steam, with different addition of O2 is described. This apparatus permits to abserve the initial kinetics of oxidation of the stainless steel type 18-10 in mixtures steam/oxygen. (A.R.)

  16. Effect of Modified Wuzi Yanzong Granule(加味五子衍宗颗粒)on Patients with Mild Cognitive Impairment from Oxidative Damage Aspect

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To observe the effects of modified Wuzi Yanzong Granule(加味五子洐宗颗粒,WYG)on memory function and the activity of serum superoxide dismutase(SOD),malondialdehyde(MDA)levels,leukocyte mitochondrial DNA(mtDNA)deletion rate and β-amyloid protein1-28(Aβ1-28 )in patients with mild cognitive impairment(MCI).Methods:Thirty-six patients with MCI were selected based on the internationally recognized Petersen's criteria,and equally and randomly assigned to two groups.The treated group was treated with WYG and the control group was treated with placebo for 3 months.In addition,20 healthy subjects were included in the study as the normal control group.Changes of memory function,SOD activity,MDA content,leukocyte mtDNA deletion rate and Aβ1-28 content were observed before and after treatment.Results:Compared with the normal control group,the memory quotient and SOD activity in patients with MCI decreased significantly(P<0.01),while MDA,Aβ1-28 levels and the leukocyte mtDNA deletion rate increased significantly(P<0.01).After treatment,levels of memory quotient and serum SOD activity increased while the serum MDA level,leukocyte mtDNA deletion rate and Aβ1-28 level decreased in the treated group compared with those before treatment(P<0.01,P<0.05).Meanwhile,leukocyte mtDNA deletion rate and Aβ1-28 content in the treated group were all lower than those in the control group(P<0.05).Conclusion:WYG could improve memory function in patients with MCI and the therapeutic mechanism is possibly related to the increased activity of anti-oxidase,the improved free radical metabolism and the alleviation of leukocyte mtDNA oxidation damage.WYG shows clinical significance in delaying the progression of MCI.

  17. Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil, L-NAME, and L-arginine treatments.

    Science.gov (United States)

    Zaobornyj, Tamara; Valdez, Laura B; Iglesias, Darío E; Gasco, Manuel; Gonzales, Gustavo F; Boveris, Alberto

    2009-06-01

    Rats submitted to high altitude (Cerro de Pasco, Perú, 4,340 m, Po(2) = 12.2 kPa) for up to 84 days showed a physiological adaptive response with decreased body weight gain (15%), increased right ventricle weight (100%), and increased hematocrit (40%) compared with sea level animals. These classical parameters of adaptation to high altitude were accompanied by an increase in heart mitochondrial enzymes: complexes I-III activity by 34% and mitochondrial nitric oxide synthase (mtNOS) activity and expression by >75%. The hyperbolic increase for mtNOS activity during adaptation to high altitude was similar to the observed pattern for hematocrit. Hematocrit and mtNOS activity mean values correlated linearly (r(2) = 0.75, P oxide (NO) production by mtNOS accounts for approximately 49% of total cellular NO production in sea level rats and for approximately 54% in rats exposed to high altitude for 84 days. It is concluded that mtNOS is a substantial source of cardiac NO, a factor in the adaptive response to sustained heart hypoxia that is susceptible to be modified by pharmacological treatments.

  18. 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

  19. Identification of the SLAM Adapter Molecule EAT-2 as a Lupus-Susceptibility Gene That Acts through Impaired Negative Regulation of Dendritic Cell Signaling.

    Science.gov (United States)

    Talaei, Nafiseh; Yu, Tao; Manion, Kieran; Bremner, Rod; Wither, Joan E

    2015-11-15

    We showed previously that C57BL/6 congenic mice with an introgressed homozygous 70 cM (125.6 Mb) to 100 cM (179.8 Mb) interval on c1 from the lupus-prone New Zealand Black (NZB) mouse develop high titers of antinuclear Abs and severe glomerulonephritis. Using subcongenic mice, we found that a genetic locus in the 88-96 cM region was associated with altered dendritic cell (DC) function and synergized with T cell functional defects to promote expansion of pathogenic proinflammatory T cell subsets. In this article, we show that the promoter region of the NZB gene encoding the SLAM signaling pathway adapter molecule EWS-activated transcript 2 (EAT-2) is polymorphic, which results in an ∼ 70% reduction in EAT-2 in DC. Silencing of the EAT-2 gene in DC that lacked this polymorphism led to increased production of IL-12 and enhanced differentiation of T cells to a Th1 phenotype in T cell-DC cocultures, reproducing the phenotype observed for DC from congenic mice with the NZB c1 70-100 cM interval. SLAM signaling was shown to inhibit production of IL-12 by CD40L-activated DCs. Consistent with a role for EAT-2 in this inhibition, knockdown of EAT-2 resulted in increased production of IL-12 by CD40-stimulated DC. Assessment of downstream signaling following CD40 cross-linking in the presence or absence of SLAM cross-linking revealed that SLAM coengagement blocked activation of p38 MAPK and JNK signaling pathways in DC, which was reversed in DC with the NZB EAT-2 allele. We conclude that EAT-2 negatively regulates cytokine production in DC downstream of SLAM engagement and that a genetic polymorphism that disturbs this process promotes the development of lupus.

  20. Hearing Impairment

    Science.gov (United States)

    ... hearing loss is present at birth. Acquired hearing loss happens later in life — during childhood, the teen years, or in adulthood — ... for your ears to avoid a permanent hearing loss. See your doctor right away ... basis. What's Life Like for People Who Are Hearing Impaired? For ...

  1. Environmental Interpretation for the Visually Impaired.

    Science.gov (United States)

    Seven, Steven M.

    1980-01-01

    The paper concerns itself with the art of environmental interpretation and addresses its application specifically to the visually impaired, considering the adaptations and alterations available which will make the environmental interpretation a beneficial and meaningful experience for the visually impaired. (Author)

  2. Overexpressed neuroglobin raises threshold for nitric oxide-induced impairment of mitochondrial respiratory activities and stress signaling in primary cortical neurons.

    Science.gov (United States)

    Singh, Shilpee; Zhuo, Ming; Gorgun, Falih M; Englander, Ella W

    2013-08-01

    Surges of nitric oxide compromise mitochondrial respiration primarily by competitive inhibition of oxygen binding to cytochrome c oxidase (complex IV) and are particularly injurious in neurons, which rely on oxidative phosphorylation for all their energy needs. Here, we show that transgenic overexpression of the neuronal globin protein, neuroglobin, helps diminish protein nitration, preserve mitochondrial function and sustain ATP content of primary cortical neurons challenged by extended nitric oxide exposure. Specifically, in transgenic neurons, elevated neuroglobin curtailed nitric oxide-induced alterations in mitochondrial oxygen consumption rates, including baseline oxygen consumption, consumption coupled with ATP synthesis, proton leak and spare respiratory capacity. Concomitantly, activation of genes involved in sensing and responding to oxidative/nitrosative stress, including the early-immediate c-Fos gene and the phase II antioxidant enzyme, heme oxygenase-1, was diminished in neuroglobin-overexpressing compared to wild-type neurons. Taken together, these differences reflect a lesser insult produced by similar concentrations of nitric oxide in neuroglobin-overexpressing compared to wild-type neurons, suggesting that abundant neuroglobin buffers nitric oxide and raises the threshold of nitric oxide-mediated injury in neurons.

  3. 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

  4. 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

  5. The Architecture of Iron Microbial Mats Reflects the Adaptation of Chemolithotrophic Iron Oxidation in Freshwater and Marine Environments

    OpenAIRE

    Chan, Clara S.; McAllister, Sean M.; Leavitt, Anna H.; Brian T. Glazer; Krepski, Sean T.; Emerson, David

    2016-01-01

    Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respecti...

  6. Application of adaptive neuro-fuzzy inference system techniques and artificial neural networks to predict solid oxide fuel cell performance in residential microgeneration installation

    Energy Technology Data Exchange (ETDEWEB)

    Entchev, Evgueniy; Yang, Libing [Integrated Energy Systems Laboratory, CANMET Energy Technology Centre, 1 Haanel Dr., Ottawa, Ontario (Canada)

    2007-06-30

    This study applies adaptive neuro-fuzzy inference system (ANFIS) techniques and artificial neural network (ANN) to predict solid oxide fuel cell (SOFC) performance while supplying both heat and power to a residence. A microgeneration 5 kW{sub el} SOFC system was installed at the Canadian Centre for Housing Technology (CCHT), integrated with existing mechanical systems and connected in parallel to the grid. SOFC performance data were collected during the winter heating season and used for training of both ANN and ANFIS models. The ANN model was built on back propagation algorithm as for ANFIS model a combination of least squares method and back propagation gradient decent method were developed and applied. Both models were trained with experimental data and used to predict selective SOFC performance parameters such as fuel cell stack current, stack voltage, etc. The study revealed that both ANN and ANFIS models' predictions agreed well with variety of experimental data sets representing steady-state, start-up and shut-down operations of the SOFC system. The initial data set was subjected to detailed sensitivity analysis and statistically insignificant parameters were excluded from the training set. As a result, significant reduction of computational time was achieved without affecting models' accuracy. The study showed that adaptive models can be applied with confidence during the design process and for performance optimization of existing and newly developed solid oxide fuel cell systems. It demonstrated that by using ANN and ANFIS techniques SOFC microgeneration system's performance could be modelled with minimum time demand and with a high degree of accuracy. (author)

  7. ECONOMIC EFFICIENT PRODUCTION OF BIOMASS ADAPTED TO THE SUBSTRATE OF OIL OXIDIZING ACTINOBACILLOSIS USED IN BIOREMEDIATION PROCESSES

    Directory of Open Access Journals (Sweden)

    Khudokormov A. A.

    2013-10-01

    Full Text Available In the article we have studied the technology of obtaining a biomass of oil oxidizing microorganisms in a nutrient medium containing vegetable oil as the sole source of carbon and energy. In vitro and in soil experiment we have confirmed the effectiveness of the resulting biomass at work on bioremediation of oil contaminated sites. It is shown that the use of vegetable oil during culturing allows obtaining the same amount of biomass and carbohydrate raw materials, but the efficiency of its use is 20% higher, in average

  8. 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...... 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....

  9. 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.

  10. Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model

    OpenAIRE

    Keller, Amy C.; Knaub, Leslie A; P. Mason McClatchey; Chelsea A. Connon; Ron Bouchard; Miller, Matthew W.; Kate E. Geary; Walker, Lori A.; Klemm, Dwight J.; Reusch, Jane E. B.

    2016-01-01

    Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. ...

  11. Oxidative stress indicators and metabolic adaptations in response to the omission of the dry period in dairy cows.

    Science.gov (United States)

    Mantovani, Roberto; Sgorlon, Sandy; Marinelli, Lieta; Bailoni, Lucia; Bittante, Giovanni; Gabai, Gianfranco

    2010-08-01

    The effects of dry period omission on oxidative stress and metabolic indicators around calving were studied. Seventeen Italian Friesian cows were randomly assigned to two groups, homogeneous for milk yield and parity, and managed either with a traditional 55-d dry off period (n=8) or continuously milked till parturition (n=9). Between 60 d before expected calving and 90 d after calving, body condition (BCS) was recorded and blood samples were collected to measure cortisol, urea, cholesterol, glucose, NEFA, triglycerides, insulin, malondialdehyde (MDA), total glutathione (GSH) and glutathione peroxidase (GPx) activity. BCS changes after calving were not different between the two groups. The normally dried group showed lower (Pmilked cows after calving (Pmilking up to parturition (Pmilk secretion. The differences in plasma GSH observed after calving may depend upon sulphur amino acid sparing in continuously milked cows.

  12. Nitric oxide derived from L-arginine impairs cytoplasmic pH regulation by vacuolar-type H+ ATPases in peritoneal macrophages

    OpenAIRE

    1991-01-01

    The ability of macrophages (Mos) to function within an acidic environment has been shown to depend on cytoplasmic pH (pHi) regulation by vacuolar-type H+ ATPases. Mos metabolize L-arginine via an oxidative pathway that generates nitric oxide, nitrate, and nitrite. Since each of these products could potentially inhibit vacuolar-type H+ ATPases, we investigated the effect of L-arginine metabolism on Mo pHi regulation in thioglycolate-elicited murine peritoneal Mos. H+ ATPase- mediated pHi recov...

  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. Metabolic adaptations to ammonia-induced oxidative stress in leaves of the submerged macrophyte Vallisneria natans (Lour.) Hara.

    Science.gov (United States)

    Wang, Chao; Zhang, Song He; Wang, Pei Fang; Hou, Jun; Li, Wei; Zhang, Wen Jing

    2008-04-28

    Ammonia (i.e. the total of NH(3) and NH(4)(+)) has been one of the main causes of the decline of macrophytes in fresh water. In order to study the effects of ammonia toxicity, plants of the submersed macrophyte Vallisneria natans (Lour.) Hara were treated with various concentrations of NH(4)Cl (0.1, 0.4, 1.2, 2 and 2.8mM) for 4 days or with 2mM NH(4)Cl for different lengths of time (12h, 1, 2, 4 and 8 days). The toxic effect and oxidative stress caused by NH(4)Cl resulted in a reduction of total chlorophyll (chlorophyll a and b) and an increase in the levels of reactive oxygen species (ROS) O(2)(-) and H(2)O(2), with an increased concentration of NH(4)Cl and duration of exposure. Meanwhile, weak chlorosis and water-soaked symptoms were observed in older leaves exposed to 2.8mM NH(4)Cl for 4 days. The activity of superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (POD), ascorbate peroxidase (APX) and glutathione reductase (GR) was up-regulated in leaves treated with 1.2, 2 and 2.8mM NH(4)Cl for 4 days or with 2mM NH(4)Cl for 1, 2 and 4 days, when compared with controls. Among these enzymes, the activity of superoxide dismutase, ascorbate peroxidase and glutathione reductase was significantly up-regulated in plants treated with 0.4mM NH(4)Cl for 4 days, while they were down-regulated at 4 and 8 days from their peak values in leaves treated with 2mM NH(4)Cl. The content of ascorbic acid decreased significantly in leaves treated with 0.4-2.8mM NH(4)Cl for 4 days or with 2mM NH(4)Cl for 2-8 days. The content of total glutathione (tGSH; reduced and oxidized glutathione) increased in leaves treated with NH(4)Cl at 0.4, 1.2 and 2mM for 4 days or with 2mM NH(4)Cl at 1, 2 and 4 days, while tGSH was decreased below the level of controls by treatment with 2.8mM NH(4)Cl for 4 days or to the level of controls by treatment with 2mM NH(4)Cl for 8 days. However, the content of malondialdehyde (MDA) decreased with increased concentration of NH(4)Cl and duration of

  15. 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.

  16. Liquid fructose downregulates Sirt1 expression and activity and impairs the oxidation of fatty acids in rat and human liver cells.

    Science.gov (United States)

    Rebollo, Alba; Roglans, Núria; Baena, Miguel; Sánchez, Rosa M; Merlos, Manel; Alegret, Marta; Laguna, Juan C

    2014-04-01

    Fructose ingestion is associated with the production of hepatic steatosis and hypertriglyceridemia. For fructose to attain these effects in rats, simultaneous induction of fatty acid synthesis and inhibition of fatty acid oxidation is required. We aimed to determine the mechanism involved in the inhibition of fatty acid oxidation by fructose and whether this effect occurs also in human liver cells. Female rats were supplemented or not with liquid fructose (10% w/v) for 7 or 14 days; rat (FaO) and human (HepG2) hepatoma cells, and human hepatocytes were incubated with fructose 25mM for 24h. The expression and activity of the enzymes and transcription factors relating to fatty acid β-oxidation were evaluated. Fructose inhibited the activity of fatty acid β-oxidation only in livers of 14-day fructose-supplemented rats, as well as the expression and activity of peroxisome proliferator activated receptor α (PPARα). Similar results were observed in FaO and HepG2 cells and human hepatocytes. PPARα downregulation was not due to an osmotic effect or to an increase in protein-phosphatase 2A activity caused by fructose. Rather, it was related to increased content in liver of inactive and acetylated peroxisome proliferator activated receptor gamma coactivator 1α, due to a reduction in sirtuin 1 expression and activity. In conclusion, fructose inhibits liver fatty acid oxidation by reducing PPARα expression and activity, both in rat and human liver cells, by a mechanism involving sirtuin 1 down-regulation.

  17. Liquid fructose downregulates Sirt1 expression and activity and impairs the oxidation of fatty acids in rat and human liver cells.

    Science.gov (United States)

    Rebollo, Alba; Roglans, Núria; Baena, Miguel; Sánchez, Rosa M; Merlos, Manel; Alegret, Marta; Laguna, Juan C

    2014-04-01

    Fructose ingestion is associated with the production of hepatic steatosis and hypertriglyceridemia. For fructose to attain these effects in rats, simultaneous induction of fatty acid synthesis and inhibition of fatty acid oxidation is required. We aimed to determine the mechanism involved in the inhibition of fatty acid oxidation by fructose and whether this effect occurs also in human liver cells. Female rats were supplemented or not with liquid fructose (10% w/v) for 7 or 14 days; rat (FaO) and human (HepG2) hepatoma cells, and human hepatocytes were incubated with fructose 25mM for 24h. The expression and activity of the enzymes and transcription factors relating to fatty acid β-oxidation were evaluated. Fructose inhibited the activity of fatty acid β-oxidation only in livers of 14-day fructose-supplemented rats, as well as the expression and activity of peroxisome proliferator activated receptor α (PPARα). Similar results were observed in FaO and HepG2 cells and human hepatocytes. PPARα downregulation was not due to an osmotic effect or to an increase in protein-phosphatase 2A activity caused by fructose. Rather, it was related to increased content in liver of inactive and acetylated peroxisome proliferator activated receptor gamma coactivator 1α, due to a reduction in sirtuin 1 expression and activity. In conclusion, fructose inhibits liver fatty acid oxidation by reducing PPARα expression and activity, both in rat and human liver cells, by a mechanism involving sirtuin 1 down-regulation. PMID:24434080

  18. Toxicity of cobalt ferrite (CoFe2O4) nanobeads in Chlorella vulgaris: interaction, adaptation and oxidative stress.

    Science.gov (United States)

    Ahmad, Farooq; Yao, Hongzhou; Zhou, Ying; Liu, Xiaoyi

    2015-11-01

    The potential toxicity of CoFe2O4 nanobeads (NBs) in Chlorella vulgaris was observed up to 72h. Algal cell morphology, membrane integrity and viability were severely compromised due to adsorption and aggregation of NBs on algal surfaces, release of Fe(3+) and Co(2+) ions and possible mechanical damage by NBs. Interactions with NBs and effective decrease in ions released by aggregation and exudation of algal cells as a self defense mechanism were observed by Fourier transform infrared attenuated total reflectance (FTIR-ATR) and inductively coupled plasma mass spectrometry (ICP-MS). The results corroborated CoFe2O4 NBs induced ROS triggered oxidative stress, leading to a reduction in catalase activity, activation of the mutagenic glutathione s-transferase (mu-GST) and acid phosphatase (AP) antioxidant enzymes, and an increase in genetic aberrations, metabolic and cellular signal transduction dysfunction. Circular dichroism (CD) spectra indicated the weak interactions of NBs with BSA, with slight changes in the α-helix structure of BSA confirming conformational changes in structure, hence the potential for functional interactions with biomolecules. Possible interferences of CoFe2O4 NBs with assay techniques and components indicated CoFe2O4 NBs at lower concentration do not show any significant interference with ROS, catalase, mu-GST and no interference with CD measurements. This study showed ROS production is one of the pathways of toxicity initiated by CoFe2O4 NBs and illustrates the complex processes that may occur between organisms and NBs in natural complex ecosystem. PMID:26291677

  19. 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.

  20. Adaptive Inverse Control Based on Least Square Support Vector Machines for Solid Oxide Fuel Cell%基于LS-SVM的SOFC系统自适应逆控制

    Institute of Scientific and Technical Information of China (English)

    刘宗辉; 王阳华; 杨慧君

    2013-01-01

    The operating temperature and voltage are the key parameters affecting the performance of Solid Oxide Fuel Cell( SOFC) . Aiming at the strong nonlinear of SOFC and conventional mature linear theory does not apply, the paper adopted an adaptive inverse control strategy based on least square support vector machine. First, the principle dynamic model of SOFC was constructed. Then, the LS-SVM method was used to establish the inverse dynamics model of SOFC. Based on the inverse dynamic model acquired, a control algorithm based on recursive least squares support vector machine(RLS-SVM) of inverse dynamics was designed. In this adaptive inverse control mechanism, the inverse dynamic model was updated by RLS algorithm. The parameters of controller were adjusted on—line with e—filtering. The simulations of SOFC system identification and control show that the method is credibility, the inverse dynamic model identified has high precision and the designed controller has good control performance. The simulation results can provide certain theoretical basis for the practical and industrialization of SOFC.%关于固体氧化物燃料电池(Solid Oxide Fuel Cell,SOFC)性能的优化问题,其中工作温度和电压是关键参数.针对固体氧化物燃料具有较强的非线性且常规成熟线性理论不适用的特点,提出了一种最小二乘支持向量机(LS-SVM)的自适应逆控制策略.首先建立了SOFC的机理模型,然后采用LS-SVM方法建立了SOFC系统的逆动力学模型.在获得逆动力学模型的基础上,设计了一种逆动力学递推最小二乘支持向量机的控制方法.在自适应逆控制下,逆模型通过RLS算法更新,控制器依据ε-滤波进行在线调整.SOFC系统辨识和仿真结果表明,改进方法的可信性,辨识出的逆动力模型具有较高的精度,所设计的控制器能获得较好的控制性能.仿真结果可以为SOFC的实用化和产业化提供一定的理论依据.

  1. 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.

  2. Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance

    Directory of Open Access Journals (Sweden)

    Keeney Paula M

    2009-09-01

    Full Text Available Abstract Background Sporadic Parkinson's disease (sPD is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA, heteroplasmic mtDNA point mutations and levels of electron transport chain proteins. We sought to determine if sPD brains possess any mtDNA genotype-respiratory phenotype relationships. Results Treatment of sPD brain mtDNA with the mitochondrial base-excision repair enzyme 8-oxyguanosine glycosylase-1 (hOGG1 inhibited, in an age-dependent manner, qPCR amplification of overlapping ~2 kbase products; amplification of CTL brain mtDNA showed moderate sensitivity to hOGG1 not dependent on donor age. hOGG1 mRNA expression was not different between sPD and CTL brains. Heteroplasmy analysis of brain mtDNA using Surveyor nuclease® showed asymmetric distributions and levels of heteroplasmic mutations across mtDNA but no patterns that statistically distinguished sPD from CTL. sPD brain mitochondria displayed reductions of nine respirasome proteins (respiratory complexes I-V. Reduced levels of sPD brain mitochondrial complex II, III and V, but not complex I or IV proteins, correlated closely with rates of NADH-driven electron flow. mtDNA levels and PGC-1α expression did not differ between sPD and CTL brains. Conclusion PD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age

  3. Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle.

    Science.gov (United States)

    Ukropcova, Barbara; Sereda, Olga; de Jonge, Lilian; Bogacka, Iwona; Nguyen, Tuong; Xie, Hui; Bray, George A; Smith, Steven R

    2007-03-01

    Insulin resistance is associated with metabolic inflexibility, impaired switching of substrate oxidation from fatty acids to glucose in response to insulin. Impaired switching to fat oxidation in response to a high-fat diet (HFD) is hypothesized to contribute to insulin resistance. The objective of this study was to test the hypothesis that defects in substrate switching in response to insulin and a HFD are linked to reduced mitochondrial biogenesis and occur before the development of diabetes. Metabolic flexibility was measured in young sedentary men with (n = 16) or without (n = 34) a family history of diabetes by euglycemic-hyperinsulinemic clamp. Flexibility correlated with fat oxidation measured in a respiratory chamber after a 3-day HFD. Muscle mitochondrial content was higher in flexible subjects with high fat oxidation after a HFD and contributed 49% of the variance. Subjects with a family history of diabetes were inflexible and had reduced HFD-induced fat oxidation and muscle mitochondrial content but did not differ in the amount of body or visceral fat. Metabolic inflexibility, lower adaptation to a HFD, and reduced muscle mitochondrial mass cluster together in subjects with a family history of diabetes, supporting the role of an intrinsic metabolic defect of skeletal muscle in the pathogenesis of insulin resistance. PMID:17327442

  4. Saponin-rich fraction from Clematis chinensis Osbeck roots protects rabbit chondrocytes against nitric oxide-induced apoptosis via preventing mitochondria impairment and caspase-3 activation.

    Science.gov (United States)

    Wu, Wenjun; Gao, Xinghua; Xu, Xianxiang; Luo, Yubin; Liu, Mei; Xia, Yufeng; Dai, Yue

    2013-03-01

    Our previous study reported that the saponin-rich fraction from Clematis chinensis Osbeck roots (SFC) could effectively alleviate experimental osteoarthritis induced by monosodium iodoacetate in rats through protecting articular cartilage and inhibiting local inflammation. The present study was performed to investigate the preventive effects of SFC on articular chondrocyte, and explore the underlying mechanisms. Primary rabbit chondrocytes were cultured and exposed to sodium nitroprusside (SNP), a NO donor. After treatment with different concentrations of SFC (30, 100, 300, 1,000 μg/ml) for 24 h, nucleic morphology, apoptotic rate, mitochondrial function and caspase-3 activity of chondrocytes were examined. The results showed that SNP induced remarkable apoptosis of rabbit chondrocytes evidenced by Hoechst 33258 staining and flow cytometry analysis, and SFC prevented the apoptosis in a concentration-dependent manner. Further studies indicated that SFC could prevent the depolarization of mitochondrial membrane potential (∆ψm) in SNP-treated chondrocytes and suppress the activation of caspase-3. It can be concluded that the protection of SFC on articular chondrocytes is associated with the anti-apoptosis effects via inhibiting the mitochondrion impairment and caspase-3 activation. PMID:22821055

  5. Gestural Interfaces for Hearing-Impaired Communication

    OpenAIRE

    Aran, Oya; Burger, Thomas; Akarun, Lale; Caplier, Alice

    2008-01-01

    International audience Gestural interfaces, besides providing natural means of human computer interaction for everyone, enable the hearing impaired to use sign language or better understand speech through vision. This chapter overviews (1) the various modalities involved in gestured languages (2) the mean to automatically apprehend them individually and (3) to fuse them in order to provide a communication medium adapted to hearing-impaired. We present two example applications, a sign langu...

  6. Ameliorating of Memory Impairment and Apoptosis in Amyloid β-Injected Rats Via Inhibition of Nitric Oxide Synthase: Possible Participation of Autophagy

    Science.gov (United States)

    Shariatpanahi, Marjan; Khodagholi, Fariba; Ashabi, Ghorbangol; Aghazadeh Khasraghi, Azar; Azimi, Leila; Abdollahi, Mohammad; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Noorbakhsh, Farshid; Sharifzadeh, Mohammad

    2015-01-01

    It has been proposed that appearance of amyloid beta (Aβ) in hippocampus is one of the characteristic features of Alzheimer’s disease (AD). The role of Nitric oxide (NO) in neurodegenerative disorders is controversy in different contexts. Here, we examined the effect of NO on spatial memory. For this purpose, we compared the effects of three different concentrations of L-NG-Nitroarginine Methyl Ester (L-NAME) as a nitric oxide synthase (NOS) inhibitor. We used Morris water maze (MWM) for evaluation of behavioral alterations. We also assessed the apoptosis and autophagy markers as two possible interfering pathways with NO signaling by western blot method. We found that in Aβ pretreated rats, intra-hippocampal injection of 1or 2 (μg/side) of L-NAME caused a significant reduction in escape latency and traveled distance comparing to Aβ-treatment group. Our molecular findings revealed that L-NAME could induce autophagy and attenuate apoptosis dose dependently. The protective role of autophagy and the deteriorative role of apoptosis is the hypothesis that can vindicate our findings. Thus using NOS inhibitors at low concentrations can be one of the therapeutic approaches in the future studies. PMID:26330869

  7. Antagonism of lycopene on pulmonary oxidative impairment induced by O3 in rats%番茄红素对臭氧致大鼠肺氧化损伤的拮抗作用

    Institute of Scientific and Technical Information of China (English)

    潘洪志; 万丽葵; 常东

    2004-01-01

    ,差异有显著性意义(P<0 05).结论:吸入臭氧能够造成机体氧化损伤,番茄红素可以拮抗臭氧造成的氧化损伤.%BACKGROUND: O3 is a kind of strong oxidant, which induces lipid peroxidation, impairs organic anti-oxidase and results in oxidative impairment. Lung is the main organ in charge of air exchange between the human body and outer environment. Since it connects with the outer environment directly, the lung is the first organ to be attacked earliest by O3 and results in oxidative impairment. Lycopene is a kind of important carotenoid with various biological functions, such as antioxidation, anti-carcinoma, inducing message connection among inter-cells, etc.OBJECTIVE: To probe into the oxidative impairment of O3 in rats and protection of lycopene.DESIGN: A randomized controlled experimental study.SETTINGS: Sanitary Test Center, College of Public Health, Harbin Medical University; Heilongjiang Center for Disease Control and Prevention; Department of Laboratory, the First Affiliated Hospital of Harbin Medical University.PARTICIPANTS: The experiment was performed in the Animal Room of College of Public Health, Harbin Medical University. Forty pure male SD rats were emplored, provided by the Experimental Animal Center of the Second Affiliated Hospital of Haerbin Medical University.INTERVENTIONS: To divide normal control, O3 impaired model group,low dosage of lycopene group( 10 mg/kg) and high dosage of lycopene group (20 mg/kg). Except in the control, the rats in the rest groups were poisoned by O3. Lycopene was applied for lycopene groups except model and control groups. The rats were sacrificed 3 weeks later and the serum and pulmonary tissues were collected to prepare homogenate.MAIN OUTCOME MEASURES: Activity of superoxide dismutase(SOD), activity of glutathione peroxides(GSH-Px) and content of malondi aldehyde(MDA) in serum and pulmonary homogenate.RESULTS: O3 could remarkably affect the activity of anti-oxidase, reduce SOD activity[(4 645.60±891.85) μkat/L in

  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. Role of nitric oxide in the impairment of circular muscle contractility of distended, uninflamed mid-colon in TNBS-induced acute distal colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Luciano Onori; Giovanni Latella; Annalisa Aggio; Simona D'Alo'; Paola Muzi; Maria Grazia Cifone; Gabriella Mellillo; Rachele Ciccocioppo; Gennaro Taddei; Giuseppe Frieri

    2005-01-01

    AIM: To evaluate the role of nitric oxide (NO) in the motor disorders of the dilated uninflamed mid-colon (DUMC)from trinitrobenzene sulfonic acid (TNBS)-induced acute distal colitis in rats.METHODS: Colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of TNBS.Control rats received an enema of 0.9% saline. The rats were killed 48 h after TNBS or saline administration.Macroscopic and histologic lesions of the colon were evaluated. Myeloperoxidase (MPO) and nitric oxide synthase (NOS) activity were measured on the colonic tissue. In TNBS rats, we evaluated spontaneous and evoked contractile activity in circular muscle strips derived from DUMC in comparison to the same colonic segment of control rats, both in the presence and in the absence of a non-selective NOS isoforms inhibitor N-nitro-Larginine (L-NNA). Pharmacological characterization of electric field stimulation (EFS)-evoked contractile responses was also performed.RESULTS: In TNBS rats, the distal colon showed severe histological lesions and a high MPO activity, while the DUMC exhibited normal histology and MPO activity.Constitutive NOS activity was similar in TNBS and control rats, whereas inducible NOS activity was significantly increased only in the injured distal colon of TNBS rats.Isometrically recorded mechanical activity of circular muscle strips from DUMC of TNBS rats showed a marked reduction of the force and frequency of spontaneous contractions compared to controls, as well as of the contractile responses to a contracting stimulus. In the presence of L-NNA, the contractile activity and responses displayed a significantly greater enhancement compared to controls. The pharmacological characterization of EFS contractile responses showed that a cooperative-like interaction between cholinergic muscarinic and tachykinergic neurokinin 1 and 2 receptors mediated transmission in DUMC of TNBS rats vs a simple additive interaction in controls.CONCLUSION: The results of this

  10. 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. PMID:27067728

  11. 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.

  12. Amelioration of aspirin induced oxidative impairment and apoptotic cell death by a novel antioxidant protein molecule isolated from the herb Phyllanthus niruri.

    Directory of Open Access Journals (Sweden)

    Sudip Bhattacharyya

    Full Text Available 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.

  13. 视功能损害眼病患者的心理社会适应对生活质量影响的研究进展%Research development in impact of psychosocial adaptation on life quality of patients with visual impairment

    Institute of Scientific and Technical Information of China (English)

    张秀杰; 王爱平

    2010-01-01

    目的 了解国内外关于视功能损害眼病患者的心理社会适应、生活质量以及两者之间关系的研究进展.方法 对视功能损害眼病患者心理社会适应对生活质量影响的相关研究进行文献检索,并对结果进行分析.结果 白内障、青光眼、视网膜脱离、糖尿病性视网膜病变和年龄相关性黄斑变性等眼病造成不同程度的视功能损害,进而影响患者的生理、心理社会适应以及生活质量.国内外也有学者编制了一些量表测量这些因素对患者的影响程度,但缺乏测量视功能损害眼病患者的心理社会适应的工具.根据文献我们也筛选出了对生活质量有影响的人口统计学变量.结论 针对单一眼病对患者生活质量影响的研究比较多,而对视功能损害眼病患者心理社会适应与生活质量关系的研究相对甚少;研制我国视功能损害眼病患者心理社会适应测量工具是非常必要的.%Objective To understand the development of psychosocial adaptation and life quality of patients with visual impairment, as well as their relationship. Methods Researches about impact of psychosocial adaptation on life quality of patients with visual impairment underwent document retrieval and the results went through analysis. Results Cataract, glaucoma, retinal detachment, diabetic retinopathy, age-related macular degeneration caused different degree of visual impairment, furthermore influence physical, psychosocial adaptation and life quality of these patients. Some scales were compiled by some scholars at home and abroad to evaluate the influence degree of these factors, but tools to test psychosocial adaptation lacked. Conclusions Researches on quality of life for a single eye impairment are more than those on the relationship between psychosocial adaptation and quality of life. At the same time, it is necessary to develop a tool to measure psychosocial adaptation of visual function impairment.

  14. Impaired renal endothelial nitric oxide synthase and reticulocyte production as modulators of hypertension induced by rHuEPO in the rat.

    Science.gov (United States)

    Ribeiro, Sandra; Garrido, Patrícia; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Costa, Elísio; Belo, Luís; Reis, Flávio; Santos-Silva, Alice

    2016-04-15

    Our aim was to study the effect of a broad range of recombinant human erythropoietin (rHuEPO) doses on hematological and biochemical parameters, blood pressure (BP), renal function and damage in the rat, focusing on endothelial nitric oxide synthase (eNOS) and hypoxia-inducible factors (HIFs). Male Wistar rats were divided in 5 groups receiving different doses of rHuEPO (100, 200, 400 and 600IU/kg body weight (BW)/week) and saline solution (control), during 3weeks. Blood and 24h urine were collected to perform hematological and biochemical analysis. BP was measured by the tail-cuff method. Kidney tissue was collected to mRNA and protein expression assays and to characterize renal lesions. A dose-dependent increase in red blood cells count, hematocrit and hemoglobin levels was found with rHuEPO therapy, in rHuEPO200, rHuEPO400 and rHuEPO600 groups. Increased reticulocyte count was found in rHuEPO400 and rHuEPO600 groups. BP raised in all groups receiving rHuEPO. The rHuEPO200 and rHuEPO600 groups presented increased kidney protein levels of HIF2α, a reduction in kidney protein levels of eNOS, and the highest grade of vascular and tubular renal lesions. Our study showed that rHuEPO-induced hypertension is present before significant hematological changes occur and, therefore, might involve direct (renal) and indirect (hematological) effects, which varies according to the dose used. The presence of renal hypoxia reduces eNOS activity. Excessive erythrocytosis increases blood hyperviscosity, which can be modulated by an increase in reticulocytes. Hypertension leads to early renal damage without alterations in traditional markers of renal function, thus underestimating the serious adverse effects and risks. PMID:26924494

  15. Neutralization by Acetyl Salicylic Acid of the Testosterone induced Impaired Maspin Synthesis Stimulated by Estriol in Neutrophils through Nitric Oxide Synthesis

    Science.gov (United States)

    Manna, Emili; Bank, Sarbashri; Maiti, Smarajit; Jana, Pradipta; Sinha, Asru K.

    2015-01-01

    Purpose: Maspin, an anti breast cancer protein in the mammary cell and normal neutrophil has been reported to be synthesised by the stimulation of NO production induced by estriol. The role of testosterone was investigated in the synthesis of maspin in relation to that of estriol. Methods: Fifty normal female between the ages of 25-65 years old participated in the study. Maspin synthesis was demonstrated by in vitro translation of maspin mRNA, followed by the quantification of maspin by enzyme linked immune absorbent assay. NO was determined by methomoglobin method. Results: Incubation of the neutrophils in HBSS both with 30 nM estriol resulted in the synthesis of 1.8 ngm maspin with simultaneous increase of NO synthesis. In contrast incubating neutrophils with 20 nM testosterone in the presence of estriol inhibited maspin synthesis to 0.33 nM with simultaneous inhibition of NO synthesis from 1.89 nM to 0 nM at the same time. Addition of 0.2 μM flutamide, a testosterone receptor blocker to the incubation mixture restored the synthesis of maspin by 60.64 %. Incubation of 25 μM aspirin that stimulated NO synthesis restored the inhibition of maspin synthesis by testosterone by 79.1%. I-NAME, an inhibitor of nitric oxide synthase, abolished both maspin and NO synthesis. Scatchard plot of estriol binding in the presence of testosterone demonstrated that the male sex hormone inhibited the female sex hormone binding to its receptor by “cross talk” between the receptors. It was found that while 1.02 × 103 molecules of estriol bind each neutrophil at equilibrium, in the presence of testosterone (20 nM) in the binding mixture decreases the binding of estriol to 0.5 × 103 with little change in the dissociation constant compared to controls. Conclution: Estriol was found to stimulate maspin synthesis through the stimulation of NO, testosterone inhibited maspin synthesis through the inhibition of NO synthesis. PMID:26759534

  16. 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.

  17. 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

  18. Space Activities for the Visually Impaired

    Science.gov (United States)

    Ries, J. G.; Baguio, M.

    2005-12-01

    To a visually impaired person celestial objects or concepts of space exploration are likely to be more abstract than to other people, but they encounter news about the universe through their daily life. A partnership between Texas Space Grant Consortium, The University of Texas at Austin, and the Texas School for the Blind and Visually Impaired provided the opportunity to assist visually impaired students increase their understanding of astronomy and space science. The activities helped visually impaired students activity engage in inquiry-based, hands-on astronomy activities. The experiences provided during the educator workshops, adapted instructional classroom activities, and tactile learning aids will be shared in the hopes that others may be able to incorporate these lessons into their regular teaching activities.

  19. Oxidative stress and anxiety

    OpenAIRE

    Bouayed, Jaouad; Rammal, Hassan; Soulimani, Rachid

    2009-01-01

    High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal ...

  20. Evaluation of packet loss impairment on streaming video

    Institute of Scientific and Technical Information of China (English)

    RUI Hua-xia; LI Chong-rong; QIU Sheng-ke

    2006-01-01

    Video compression technologies are essential in video streaming application because they could save a great amount of network resources. However compressed videos are also extremely sensitive to packet loss which is inevitable in today's best effort IP network. Therefore we think accurate evaluation of packet loss impairment on compressed video is very important. In this work, we develop an analytic model to describe these impairments without the reference of the original video (NR) and propose an impairment metric based on the model, which takes into account both impairment length and impairment strength. To evaluate an impaired frame or video, we design a detection and evaluation algorithm (DE algorithm) to compute the above metric value. The DE algorithm has low computational complexity and is currently being implemented in the real-time monitoring module of our HDTV over IP system. The impairment metric and DE algorithm could also be used in adaptive system or be used to compare diffeient error concealment strategies.

  1. 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.

  2. Adaptive Lighting

    OpenAIRE

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive LightingAdaptive 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 i...

  3. Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages

    Science.gov (United States)

    Kiltz, U; van der Heijde, D; Boonen, A; Bautista-Molano, W; Burgos-Vargas, R; Chiowchanwisawakit, P; Duruoz, T; El-Zorkany, B; Essers, I; Gaydukova, I; Géher, P; Gossec, L; Grazio, S; Gu, J; Khan, M A; Kim, T J; Maksymowych, W P; Marzo-Ortega, H; Navarro-Compán, V; Olivieri, I; Patrikos, D; Pimentel-Santos, F M; Schirmer, M; van den Bosch, F; Weber, U; Zochling, J; Braun, J

    2016-01-01

    Introduction The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages. Methods Translation and cross-cultural adaptation has been carried out following the forward–backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included. Results The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option ‘not applicable’ was added to two items of the ASAS HI to improve appropriateness. Discussion This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures. PMID:27752358

  4. The Role of Spirituality in Coping with Visual Impairment

    Science.gov (United States)

    Yampolsky, Maya A.; Wittich, Walter; Webb, Gail; Overbury, Olga

    2008-01-01

    Spirituality and coping behaviors were measured in 85 individuals with visual impairments aged 23 to 97. A regression analysis indicated that the religious well-being subscale of the Spiritual Well-Being Scale is a significant predictor of adaptive coping behaviors, indicating that higher religious well-being facilitates adaptive coping. (Contains…

  5. The Influence of green tea on oxidative stress r esponse of patients with vascular cognitive impairment%绿茶对血管性认知功能障碍患者氧化应激反应的影响

    Institute of Scientific and Technical Information of China (English)

    徐艳; 肖云月; 杨英; 鞠洁阳; 张磊; 訚亚涛

    2015-01-01

    目的:探讨饮用绿茶对血管性认知功能障碍( VCI)患者体内氧化应激反应的影响。方法将入选的VCI患者依据饮用绿茶的习惯分为两组,即饮茶者组和非饮茶者组,采用简易精神状态检查表(MMSE)和蒙特利尔认识评估量表(MoCA)检测认知功能,取肘静脉血测定丙二醛(MDA)、4-羟基壬烯醛(4-HNE)及8-羟化脱氧鸟苷(8-OHdG )的含量。结果所入选的 VCI 患者中,饮茶者组的 MMSE 评分(26.62±0.41)稍高于非饮茶者组(26.17±0.38),统计学分析显示两组差异无统计学意义(P>0.05)。但饮茶者组的MoCA评分(23.29±0.61)高于非饮用绿茶者组(21.12±0.50),差异具有统计学意义(P<0.05)。饮茶者外周血的 MDA 含量(2.345±0.3697)低于非饮茶者(4.437±0.3710),以及饮茶者外周血4-HNE 含量(4.919±0.9378)低于非饮茶者(8.660±0.7883),差异均具有统计学意义(P<0.01),而饮茶者8-OHdG浓度(1845±121.5)虽低于非饮茶者(2322±203.4),但差异无统计学意义(P>0.05)。结论常饮绿茶可能具有抑制VCI患者的氧化应激反应,改善认知功能的作用,但绿茶对抑制氧化性DNA损伤的作用较弱。%Objective To explore the influence of drinking green tea on oxidative stress response of patients with vascular cognitive impairment( VCI) .Methods The involved patients with vascular cognitive impairment were divided into two groups according to the habit of drinking green tea:drinking green tea group and non-drinking green tea group.The cognitive function was measured by Mini Mental State Examination ( MMSE)and Montreal Cognitive Assessment ( MoCA ) .The oxidative stress response was evaluated by the level of malondialdehyde ( MDA ) , 4-hydroxynonenal(4-HNE) and 8-hydroxy-2ˊ-deoxyguanosine (8 -OHdG) in elbow venous blood.Results Of all participants with VCI, the

  6. Muscle adaptation and disability in late poliomyelitis.

    Science.gov (United States)

    Einarsson, G

    1991-01-01

    Persons who suffered poliomyelitis 3 or more decades ago now report functional decline and symptoms designated as "post-polio syndrome". The objects of this investigation were to identify subjects fulfilling the criteria of this syndrome, to describe their motor impairment and resulting disabilities/handicaps, to study the adaptive changes in the muscle structure and effects of a resistance exercise program. Forty-one late-polio subjects, 40-65 years old, volunteered for the studies of motor impairment, subgroups of those volunteered to further studies of long-term and short-term adaptations. Seventy-five per cent of the subjects met the criteria for the post-polio syndrome. Complete manual muscle tests and dynamometer measurements of knee muscle strength revealed severe motor impairment predominantly in the lower extremities, the strength of the latter correlating to the degree of mobility handicap. In biopsies from the vastus lateralis muscle, type grouping was frequent. Half of the subjects demonstrated over 70% occurrence of type I fibers with negative significant correlation to strength in the female subjects. Cross-section areas of muscle fibers were on average twice the normal, with negative significant correlation to strength values in male subjects. Muscle enzymatic activity values showed large individual variations; oxidative activities (citrate synthase) were low or very low, while average glycolytic activities were nearly normal. Macro EMG and single-fiber EMG measurements in the vastus lateralis muscle demonstrated large macro motor unit potentials and increased fiber density. Neuromuscular transmission was disturbed as identified by jitter and blockings in most subjects regardless of the occurrence of new muscular symptoms. A statistically significant increase in strength (25-30%) resulted from a 6 weeks' heavy resistance exercise program, utilizing a dynamometer, without any obvious side-effects. Strength improvement was maintained for 6-12 months

  7. Oxidative stress as a significant factor for development of an adaptive response in irradiated and nonirradiated human lymphocytes after inducing the bystander effect by low-dose X-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ermakov, Aleksei V., E-mail: avePlato@mail.ru [Research Centre for Medical Genetics, Russian Academy of Medical Science, ul. Moskvorechye, 1, Moscow 115478 (Russian Federation); Konkova, Marina S.; Kostyuk, Svetlana V.; Egolina, Natalya A.; Efremova, Liudmila V.; Veiko, Natalya N. [Research Centre for Medical Genetics, Russian Academy of Medical Science, ul. Moskvorechye, 1, Moscow 115478 (Russian Federation)

    2009-10-02

    X-radiation (10 cGy) was shown to induce in human lymphocytes transposition of homologous chromosomes loci from the membrane towards the centre of the nucleus and activation of the chromosomal nucleolus-forming regions (NFRs). These effects are transmitted by means of extracellular DNA (ecDNA) fragments to nonirradiated cells (the so-called bystander effect, BE). We demonstrated that in the development of the BE an important role is played by oxidative stress (which is brought about by low radiation doses and ecDNA fragments of the culture medium of the irradiated cells), by an enzyme of apoptosis called caspase-3, and by DNA-binding receptors of the bystander cells, presumably TLR9. Proposed herein is a scheme of the development of an adaptive response and the BE on exposure to radiation. Ionizing radiation induces apoptosis of the radiosensitive fraction of cells due to the development of the 'primary' oxidative stress (OS). DNA fragments of apoptotic cells are released into the intercellular space and interact with the DNA-binding receptors of the bystander cells. This interaction activates in lymphocytes signalling pathways associated with synthesis of the reactive oxygen species and nitrogen species, i.e., induces secondary oxidative stress accompanied by apoptosis of part of the cells, etc. Hence, single exposure to radiation may be followed by relatively long-lasting in the cellular population oxidative stress contributing to the development of an adaptive response. We thus believe that ecDNA of irradiated apoptotic lymphocytes is a significant factor of stress-signalling.

  8. Depression in Cognitive Impairment

    Science.gov (United States)

    Pellegrino, Laurel D.; Lyketsos, Constantine G.; Marano, Christopher M.

    2014-01-01

    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. PMID:23933974

  9. Metabolic inflexibility is a common feature of impaired fasting glycaemia and impaired glucose tolerance.

    Science.gov (United States)

    Færch, Kristine; Vaag, Allan

    2011-12-01

    Metabolic flexibility reflects the ability to switch from lipid to carbohydrate oxidation during insulin stimulation. Impaired metabolic flexibility is related to insulin resistance and type 2 diabetes, but whether metabolic flexibility is impaired in individuals with the pre-diabetic states isolated impaired fasting glycaemia (i-IFG) and isolated impaired glucose tolerance (i-IGT) is unknown. Using the gold standard euglycaemic hyperinsulinaemic clamp technique combined with indirect calorimetry, we measured peripheral insulin sensitivity, lipid and glucose oxidation, and thus metabolic flexibility in 66 individuals with normal glucose tolerance (NGT, n = 20), i-IFG (n = 18) and i-IGT (n = 28). During insulin stimulation, individuals with i-IGT displayed reduced insulin sensitivity including reduced glucose oxidation. Interestingly, those with i-IFG exhibited reduced glucose oxidation and a slightly elevated lipid oxidation rate during insulin infusion despite having normal total peripheral glucose disposal. Thus, metabolic flexibility was significantly reduced in individuals with both i-IFG and i-IGT even after adjustment for BMI and insulin sensitivity. The data indicate that metabolic inflexibility may precede the development of overt peripheral insulin resistance in pre-diabetic individuals. However, prospective studies are needed to confirm this notion. PMID:21207234

  10. 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.

  11. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    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...... distributed 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...

  12. 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 e

  13. Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring.

    Science.gov (United States)

    da Silva Aragão, Raquel; Guzmán-Quevedo, Omar; Pérez-García, Georgina; Manhães-de-Castro, Raul; Bolaños-Jiménez, Francisco

    2014-08-14

    Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition. PMID:24823946

  14. 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 Glyceria maxima had a strong positive effect on numbers and activities of the nitrifying bacteria in its root zone in spring and e

  15. 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

  16. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    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...... the investigations of lighting scenarios carried out in two test installations: White Cube and White Box. The test installations are discussed as large-scale experiential instruments. In these test installations we examine what could potentially occur when light using LED technology is integrated and...

  17. Adaptive Computing.

    Science.gov (United States)

    Harrell, William

    1999-01-01

    Provides information on various adaptive technology resources available to people with disabilities. (Contains 19 references, an annotated list of 129 websites, and 12 additional print resources.) (JOW)

  18. 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...

  19. Speech impairment (adult)

    Science.gov (United States)

    ... brain tumors or degenerative diseases that affect the language areas of the brain. This term does not apply to children who ... gradually, but anyone can develop a speech and language impairment ... Brain tumor (more common in aphasia than dysarthria) Dementia ...

  20. 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 ...

  1. 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.

  2. Kids' Quest: Vision Impairment

    Science.gov (United States)

    ... and neighborhood . Step 8: Now see if your attitudes have changed. Take the Fact Checkup again. ... impairment also have at least one other developmental disability, such as intellectual disabilities, cerebral palsy, hearing loss, ...

  3. 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.

  4. Vascular cognitive impairment

    OpenAIRE

    Rebecca F. Gottesman; Hillis, Argye E.

    2014-01-01

    The term vascular cognitive impairment (VCI) has been proposed to encompass all people with cognitive impairment of cerebrovascular origin. VCI is not a single condition, but has several clinical presentations, etiologies, and treatment. VCI forms a spectrum that includes vascular dementia, mixed Alzheimer’s disease with a vascular component, and VCI that does not meet dementia criteria. Multiple pathophysiological mechanisms contribute to VCI, accounting for its heterogeneity. Although main ...

  5. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment

    OpenAIRE

    Vasconcelos, Andrea R; Yshii, Lidia M; Viel, Tania A; Buck, Hudson S; Mark P Mattson; Scavone, Cristoforo; Kawamoto, Elisa M

    2014-01-01

    Background 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. Methods Rats on ...

  6. Impairment of Methotrexate Transport Is Common in Osteosarcoma Tumor Samples

    OpenAIRE

    Richard Gorlick; Levy, Adam S.; John H. Healey; Paul A. Meyers; Wenzel, Bethanne D.; Condon Richardson; Rebecca Sowers

    2010-01-01

    Osteosarcoma does not respond well to conventional dose methotrexate but does respond to high-dose methotrexate. Previous work has indicated that this resistance may be due to impaired transport of methotrexate across the cell membrane. In this study, the PT430 competitive displacement assay was adapted to evaluate methotrexate transport in 69 high-grade osteosarcoma tumor samples. All samples studied were shown to have relatively impaired methotrexate transport by PT430 assay. Ninety-nine pe...

  7. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies

    OpenAIRE

    Hove, Michael J.; Peter E Keller

    2015-01-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson’s disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients’ gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize...

  8. Work at high altitude and oxidative stress: antioxidant nutrients.

    Science.gov (United States)

    Askew, E W

    2002-11-15

    A significant portion of the world's geography lies above 10,000 feet elevation, an arbitrary designation that separates moderate and high altitude. Although the number of indigenous people living at these elevations is relatively small, many people travel to high altitude for work or recreation, exposing themselves to chronic or intermittent hypoxia and the associated risk of acute mountain sickness (AMS) and less frequently, high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The symptoms of AMS (headache, nausea, anorexia, fatigue, lassitude) occur in those who travel too high, too fast. Some investigators have linked the development of these symptoms with the condition of altered blood-brain barrier permeability, possibly related to hypoxia induced free radical formation. The burden of oxidative stress increases during the time spent at altitude and may even persist for some time upon return to sea level. The physiological and medical consequences of increased oxidative stress engendered by altitude is unclear; indeed, hypoxia is believed to be the trigger for the cascade of signaling events that ultimately leads to adaptation to altitude. These signaling events include the generation of reactive oxygen species (ROS) that may elicit important adaptive responses. If produced in excess, however, these ROS may contribute to impaired muscle function and reduced capillary perfusion at altitude or may even play a role in precipitating more serious neurological and pulmonary crisis. Oxidative stress can be observed at altitude without strenuous physical exertion; however, environmental factors other than hypoxia, such as exercise, UV light exposure and cold exposure, can also contribute to the burden. Providing antioxidant nutrients via the diet or supplements to the diet can reduce oxidative stress secondary to altitude exposure. In summary, the significant unanswered question concerning altitude exposure and antioxidant supplementation is

  9. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning

    2006-01-01

    expression analysis and proteomics have pointed to abnormalities in mitochondrial oxidative phosphorylation and cellular stress in muscle of type 2 diabetic subjects, and recent work suggests that impaired mitochondrial activity is another early defect in the pathogenesis of type 2 diabetes. This review...... will discuss the latest advances in the understanding of the molecular mechanisms underlying insulin resistance in human skeletal muscle in type 2 diabetes with focus on possible links between impaired glycogen synthase activity and mitochondrial dysfunction....

  10. 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. 

  11. Is adaptation. Truly an adaptation? Is adaptation. Truly an adaptation?

    Directory of Open Access Journals (Sweden)

    Thais Flores Nogueira Diniz

    2008-04-01

    Full Text Available The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition, joined with the study of recycling, remaking, and every form of retelling. The film deals with the attempt by the scriptwriter Charles Kaufman, cast by Nicholas Cage, to adapt/translate a non-fictional book to the cinema, but ends up with a kind of film which is by no means what it intended to be: a film of action in the model of Hollywood productions. During the process of creation, Charles and his twin brother, Donald, undergo a series of adventures involving some real persons from the world of film, the author and the protagonist of the book, all of them turning into fictional characters in the film. In the film, adaptation then signifies something different from itstraditional meaning. The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition

  12. Research the mobile phone operation interfaces for vision-impairment.

    Science.gov (United States)

    Yao, Yen-Ting; Leung, Cherng-Yee

    2012-01-01

    Due to the vision-impaired users commonly having difficulty with mobile-phone function operations and adaption any manufacturer's user interface design, the goals for this research are established for evaluating how to improve for them the function operation convenience and user interfaces of either mobile phones or electronic appliances in the market currently. After applying collecting back 30 effective questionnaires from 30 vision-impairment, the comments have been concluded from this research include: (1) All mobile phone manufactures commonly ignorant of the vision-impairment difficulty with operating mobile phone user interfaces; (2) The vision-impairment preferential with audio alert signals; (3) The vision-impairment incapable of mobile-phone procurement independently unless with assistance from others; (4) Preferential with adding touch-usage interface design by the vision-impairment; in contrast with the least requirement for such functions as braille, enlarging keystroke size and diversifying-function control panel. With exploring the vision-impairment's necessary improvements and obstacles for mobile phone interface operation, this research is established with goals for offering reference possibly applied in electronic appliance design and . Hopefully, the analysis results of this research could be used as data references for designing electronic and high-tech products and promoting more usage convenience for those vision-impaired.

  13. Specific Language Impairment

    Science.gov (United States)

    ... to distinguish between children who are struggling to learn a new language and children with true language impairments. After studying a large group of Hispanic children who speak English as a second language, NIDCD-funded researchers have developed a dual ...

  14. Setting Up a Library Accessible Area for the Blind or Visually Impaired: Considerations.

    Science.gov (United States)

    Henson, Dawn

    1997-01-01

    Discusses library planning for services for blind and visually impaired users, including access needs of patrons, available library space, appropriate adaptive technology, equipment costs and budget resources, Internet access, and staff training. A list of pertinent resources is appended. (LRW)

  15. 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....

  16. 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...... concepts of strategic renewal, dynamic managerial capabilities, dynamic capabilities, and strategic response capabilities are discussed and contextualized against strategic responsiveness. The insights derived from this article are used to outline the contours of a dynamic process of strategic adaptation....... 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....

  17. Adaptive management

    Science.gov (United States)

    Allen, Craig R.; Garmestani, Ahjond S.

    2015-01-01

    Adaptive management is an approach to natural resource management that emphasizes learning through management where knowledge is incomplete, and when, despite inherent uncertainty, managers and policymakers must act. Unlike a traditional trial and error approach, adaptive management has explicit structure, including a careful elucidation of goals, identification of alternative management objectives and hypotheses of causation, and procedures for the collection of data followed by evaluation and reiteration. The process is iterative, and serves to reduce uncertainty, build knowledge and improve management over time in a goal-oriented and structured process.

  18. Resilience in Parents of Young Adults with Visual Impairments

    Science.gov (United States)

    de Klerk, Heidi; Greeff, Abraham P.

    2011-01-01

    This article reports on a study of the adaptation of parents with children with visual impairment in South Africa. The results showed that familial values (such as attitude toward the disability, religious faith, and familial closeness) permit a process of inclusion (through the use of resources and acceptance of help) and the development of a…

  19. 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…

  20. 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.

  1. Moving towards adaptive management of cyanotoxin-impaired water bodies.

    Science.gov (United States)

    Paerl, Hans W; Otten, Timothy G; Joyner, Alan R

    2016-09-01

    The cyanobacteria are a phylum of bacteria that have played a key role in shaping the Earth's biosphere due to their pioneering ability to perform oxygenic photosynthesis. Throughout their history, cyanobacteria have experienced major biogeochemical changes accompanying Earth's geochemical evolution over the past 2.5+ billion years, including periods of extreme climatic change, hydrologic, nutrient and radiation stress. Today, they remain remarkably successful, exploiting human nutrient over-enrichment as nuisance "blooms." Cyanobacteria produce an array of unique metabolites, the functions and biotic ramifications of which are the subject of diverse ecophysiological studies. These metabolites are relevant from organismal and ecosystem function perspectives because some can be toxic and fatal to diverse biota, including zooplankton and fish consumers of algal biomass, and high-level consumers of aquatic food sources and drinking water, including humans. Given the long history of environmental extremes and selection pressures that cyanobacteria have experienced, it is likely that that these toxins serve ecophysiological functions aimed at optimizing growth and fitness during periods of environmental stress. Here, we explore the molecular and ecophysiological mechanisms underlying cyanotoxin production, with emphasis on key environmental conditions potentially controlling toxin production. Based on this information, we offer potential management strategies for reducing cyanotoxin potentials in natural waters; for cyanotoxins with no clear drivers yet elucidated, we highlight the data gaps and research questions that are still lacking. We focus on the four major classes of toxins (anatoxins, cylindrospermopsins, microcystins and saxitoxins) that have thus far been identified as relevant from environmental health perspectives, but caution there may be other harmful metabolites waiting to be elucidated. PMID:27418325

  2. Free Recall Behaviour in Children with and without Spelling Impairment: The Impact of Working Memory Subcapacities

    Science.gov (United States)

    Malstadt, Nadine; Hasselhorn, Marcus; Lehmann, Martin

    2012-01-01

    This study examined supraspan free recall in children with and without spelling impairment. A repeated free recall task involving overt rehearsal and three computer-based adaptive working memory tasks were administered to 54 eight-year-old children. Children without spelling impairments tended to recall more items than did those children with…

  3. Cryotherapy impairs proprioception function?

    OpenAIRE

    Cordeiro, Nuno; Henriques, Sara

    2014-01-01

    INTRODUCTION: Cryotherapy application over a joint causes a nerve conduction velocity decrease and proprioceptive changes. OBJECTIVE: This study aims to determine if cryotherapy impairs proprioception acuity. METHODS: Proprioception was assessed by joint position sense (JPS), measured with an isokinetic dynamometer Biodex System 3, in twenty one females on experimental group, before 15 minutes cryotherapy (T0) and immediately after (T1). A control group (n=20) performed also the JPS...

  4. Impairment of Methotrexate Transport Is Common in Osteosarcoma Tumor Samples

    Directory of Open Access Journals (Sweden)

    Rebecca Sowers

    2011-01-01

    Full Text Available Osteosarcoma does not respond well to conventional dose methotrexate but does respond to high-dose methotrexate. Previous work has indicated that this resistance may be due to impaired transport of methotrexate across the cell membrane. In this study, the PT430 competitive displacement assay was adapted to evaluate methotrexate transport in 69 high-grade osteosarcoma tumor samples. All samples studied were shown to have relatively impaired methotrexate transport by PT430 assay. Ninety-nine percent of the samples had less than 20% PT430 displacement by methotrexate. Eighty-eight percent exhibited displacement by methotrexate at less than 50% of the displacement by trimetrexate. The high frequency of impaired transport suggests the presence of decreased functionality of the reduced folate carrier protein. The overwhelming presence of impaired transport may explain why methotrexate needs to be given in high doses to be effective in osteosarcoma therapy and suggests that reduced folate carrier-independent antifolates should be explored.

  5. Oxidants, Antioxidants, and the Beneficial Roles of Exercise-Induced Production of Reactive Species

    Directory of Open Access Journals (Sweden)

    Elisa Couto Gomes

    2012-01-01

    Full Text Available This review offers an overview of the influence of reactive species produced during exercise and their effect on exercise adaptation. Reactive species and free radicals are unstable molecules that oxidize other molecules in order to become stable. Although they play important roles in our body, they can also lead to oxidative stress impairing diverse cellular functions. During exercise, reactive species can be produced mainly, but not exclusively, by the following mechanisms: electron leak at the mitochondrial electron transport chain, ischemia/reperfusion and activation of endothelial xanthine oxidase, inflammatory response, and autooxidation of catecholamines. Chronic exercise also leads to the upregulation of the body's antioxidant defence mechanism, which helps minimize the oxidative stress that may occur after an acute bout of exercise. Recent studies show a beneficial role of the reactive species, produced during a bout of exercise, that lead to important training adaptations: angiogenesis, mitochondria biogenesis, and muscle hypertrophy. The adaptations occur depending on the mechanic, and consequently biochemical, stimulus within the muscle. This is a new area of study that promises important findings in the sphere of molecular and cellular mechanisms involved in the relationship between oxidative stress and exercise.

  6. Neurological Impairment: Nomenclature and Consequences.

    Science.gov (United States)

    Spears, Catherine E.; Weber, Robert E.

    Neurological impairment as discussed includes a range of disabilities referred to as neurological impairment: minimal brain dysfunction/damage, developmental disability, perceptual handicap, learning disability, hyperkinetic behavioral syndrome, and others. Defined are causes of neurological impairment and methods of diagnosis. Symptoms…

  7. Impairment, disability, and handicap.

    Science.gov (United States)

    Mooney, V

    1987-08-01

    It seems clear that the orthopedic surgeon cannot separate impairment from disability. The measurement of impairment is clouded by the inability to measure dynamic function. A range of motion demonstrated by a patient in the doctor's office does not fully describe the functional potential of either the extremity or the spine. Moreover, the rules by which disability is defined are interpreted with a natural sympathy of the physician's care for the patient. The physician may have less sympathy if the individual being reviewed is a client of an insurance company or of an attorney, compared to being a "private" patient. In the future, the orthopedic surgeon would focus on the musculoskeletal handicap rather than disability, or function rather than impairment. Function must be measured in a dynamic manner. The guidelines for definition of function or dysfunction should be similar to those used in sports medicine regarding the decision as to when the athlete can resume sports. What was the capacity before injury? How close to the normal capacity has medical care restored function? This includes measurements of passage of time and consideration of the desire to return to previous activity. The goal is the development of methods that will accurately measure dynamic musculoskeletal function. Visceral organ systems have biochemical standards of measurement; comparable standards must be devised for the musculoskeletal system. PMID:2955986

  8. 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.

  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...... 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...

  10. 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.

  11. Adaptive noise

    OpenAIRE

    Viney, Mark; Reece, Sarah E.

    2013-01-01

    In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise ...

  12. Adaptable positioner

    International Nuclear Information System (INIS)

    This paper describes the circuits and programs in assembly language, developed to control the two DC motors that give mobility to a mechanical arm with two degrees of freedom. As a whole, the system is based in a adaptable regulator designed around a 8 bit microprocessor that, starting from a mode of regulation based in the successive approximation method, evolve to another mode through which, only one approximation is sufficient to get the right position of each motor. (Author) 22 fig. 6 ref

  13. Test Anxiety, Computer-Adaptive Testing and the Common Core

    Science.gov (United States)

    Colwell, Nicole Makas

    2013-01-01

    This paper highlights the current findings and issues regarding the role of computer-adaptive testing in test anxiety. The computer-adaptive test (CAT) proposed by one of the Common Core consortia brings these issues to the forefront. Research has long indicated that test anxiety impairs student performance. More recent research indicates that…

  14. The visually impaired child.

    Science.gov (United States)

    Thompson, Lisa; Kaufman, Lawrence M

    2003-02-01

    This article discusses the causes of childhood blindness and how the primary care provider may begin the appropriate steps toward diagnosing and managing the visually impaired child. Community resources (see Box 3) and low-vision programs in schools should be used so that parents do not need to reinvent strategies to raise a blind child. Worldwide, childhood blindness, which places is a tremendous burden on families and communities of the third world, is mostly preventable with improved hygiene, diet, and immunization. PMID:12713115

  15. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    International Nuclear Information System (INIS)

    Highlights: → In 3T3-L1 adipocytes iAs3+ decreases insulin-stimulated glucose uptake. → iAs3+ attenuates insulin-induced phosphorylation of AKT S473. → iAs3+ activates the cellular adaptive oxidative stress response. → iAs3+ impairs insulin-stimulated ROS signaling. → iAs3+ 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 μM) inorganic arsenite (iAs3+) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs3+ 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 iAs3+ 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 expression may also be involved in arsenic-induced insulin resistance in adipocytes

  16. 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

  17. Niche specialization of terrestrial archaeal ammonia oxidizers

    OpenAIRE

    Gubry-Rangin, Cécile; Hai, Brigitte; Quince, Christopher; Engel, Marion; Thomson, Bruce C.; James, Phillip; Schloter, Michael; Robert I. Griffiths; Prosser, James I.; Nicol, Graeme W.

    2011-01-01

    Soil pH is a major determinant of microbial ecosystem processes and potentially a major driver of evolution, adaptation, and diversity of ammonia oxidizers, which control soil nitrification. Archaea are major components of soil microbial communities and contribute significantly to ammonia oxidation in some soils. To determine whether pH drives evolutionary adaptation and community structure of soil archaeal ammonia oxidizers, sequences of amoA, a key functional gene of ammonia oxidation, were...

  18. Specific language impairment.

    Science.gov (United States)

    Kamhi, Alan G; Clark, Mary Kristen

    2013-01-01

    The acquisition of language is one of the most important achievements in young children, in part because most children appear to acquire language with little effort. Some children are not so fortunate, however. There is a large group of children who also have difficulty learning language, but do not have obvious neurological, cognitive, sensory, emotional, or environmental deficits. Clinicians often refer to these children as language disordered or language impaired. Researchers tend to refer to these children as specific language impaired (SLI). Children with SLI have intrigued researchers for many years because there is no obvious reason for their language learning difficulties. SLI has been found to be an enduring condition that begins in early childhood and often persists into adolescence and adulthood. The language problems of children with SLI are not limited to spoken language; they also affect reading and writing and thus much of academic learning. Knowledge of the characteristics of SLI should aid physicians, pediatricians, and early childhood specialists to identify these children during the preschool years and ensure that they receive appropriate services. With high-quality language intervention and literacy instruction, most children with SLI should be able to perform and function adequately in school and beyond. PMID:23622167

  19. Fertility impairment in radiotherapy.

    Science.gov (United States)

    Biedka, Marta; Kuźba-Kryszak, Tamara; Nowikiewicz, Tomasz; Żyromska, Agnieszka

    2016-01-01

    Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient's sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect. The aim of this article is to raise the issue of infertility in these patients. It is of growing importance due to the increase in the number of children and young adults who underwent radiotherapy in the past. The progress in antineoplastic therapy improves treatment results, but at the same time requires a deeper look at existential needs of the patient. Reproductive function is an integral element of self-esteem and should be taken into account during therapy planning. PMID:27647982

  20. Validity and suitability of the Bayley-III Low Motor/Vision version : A comparative study among young children with and without motor and/or visual impairments

    NARCIS (Netherlands)

    Visser, Linda; Ruiter, Selma; van der Meulen, Bieuwe; Ruijssenaars, Wied; Timmerman, Marieke

    2013-01-01

    The aim of the present study was to examine the validity of the Bayley-III Low Motor/Vision version, and its suitability for children with motor and/or visual impairment(s). This version contains accommodated items, that is, adaptations to minimize impairment bias, without altering what the test mea

  1. 基于免疫系统的自适应差分进化算法及在水银氧化动力学参数估计中的应用%An immune self-adaptive differential evolution algorithm with application to estimate kinetic parameters for homogeneous mercury oxidation

    Institute of Scientific and Technical Information of China (English)

    胡春平; 颜学峰

    2009-01-01

    A new version of differential evolution(DE)algorithm,in which immurle concepts and methods are applied to determine the parameter setting.named immune self-adaptive difierential evolution(ISDE),iS proposed to improve the performance of the DE algorithm.During the actual operation.ISDE seeks the optimal parameters arising from the evolutionary process.which enable ISDE to alter the algorithm for different optimization problems and improve the performance Of ISDE bv the control parameters'self-adaptation.The performance of the proposed method is studied with the use of nine benchmark problems and compared with original DE algorithm and other well-known self-adaptive DE algorithms.The experiments conducted show that the ISDE clearly outperforms the othcr DE algorithms in all benchmark functions.Furthermore.ISDE iS applied to develop the kinetic model for homogeneous mercury (Hg) oxidation in tlue gas,and satistactory results are obtained.

  2. Vascular cognitive impairment and dementia.

    Science.gov (United States)

    Gorelick, Philip B; Counts, Scott E; Nyenhuis, David

    2016-05-01

    Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26704177

  3. [Multilingualism and specific language impairment].

    Science.gov (United States)

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja

    2013-01-01

    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  4. Adaptive management

    DEFF Research Database (Denmark)

    Rist, Lucy; Campbell, Bruce Morgan; Frost, Peter

    2013-01-01

    in scientific articles, policy documents and management plans, but both understanding and application of the concept is mixed. This paper reviews recent literature from conservation and natural resource management journals to assess diversity in how the term is used, highlight ambiguities and consider how...... a management framework, as well as of identified challenges and pathologies, are needed. Further discussion and systematic assessment of the approach is required, together with greater attention to its definition and description, enabling the assessment of new approaches to managing uncertainty, and AM itself.......Adaptive management (AM) emerged in the literature in the mid-1970s in response both to a realization of the extent of uncertainty involved in management, and a frustration with attempts to use modelling to integrate knowledge and make predictions. The term has since become increasingly widely used...

  5. Astrocytes Underlie Neuroinflammatory Memory Impairment

    OpenAIRE

    Osso, LA; Chan, JR

    2015-01-01

    © 2015 Elsevier Inc. All rights reserved. Neuroinflammation is being increasingly recognized as a potential mediator of cognitive impairments in various neurological conditions. Habbas et al. demonstrate that the pro-inflammatory cytokine tumor necrosis factor alpha signals through astrocytes to alter synaptic transmission and impair cognition in a mouse model of multiple sclerosis.

  6. Coordinated balancing of muscle oxidative metabolism through PGC-1α increases metabolic flexibility and preserves insulin sensitivity

    International Nuclear Information System (INIS)

    Highlights: → PGC-1α enhances muscle oxidative capacity. → PGC-1α promotes concomitantly positive and negative regulators of lipid oxidation. → Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. → Balanced oxidation prevents detrimental acylcarnitine and ROS generation. → Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) 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-1α on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1α in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1α 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-1α enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1α 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-1α 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-1α does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1α mimic the beneficial effects of endurance training on muscle metabolism in this context.

  7. Locomotion and Grasping impairment in preschoolers with autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Francesca Fulceri

    2015-08-01

    Full Text Available Objective: To investigate expressiveness of motor impairment in autism spectrum disorder (ASD and its correlation with developmental and clinical features of ASD. Method: Thirty-five male preschoolers with ASD completed the Peabody Developmental Motor Scales-2 (PDMS-2; Folio and Fewell, 2000 and underwent a multidisciplinary assessment including medical examination, standardized assessment of cognitive abilities, administration of Autism_Diagnostic_Observation_Schedule (ADOS and a parent interview about adaptive skills. Results: Results revealed a substantial impairment in locomotion and grasping skills. Both fine and gross motor skills were significantly correlated with non verbal IQ and adaptive behaviours (p<0.01 but not with chronological age or ADOS scores. Children with weaker motor skills have greater cognitive and adaptive behaviours deficits. Conclusions: Motor development in ASD can be detected at preschool age and locomotion and grasping skills are substantially the most impaired area. These findings support the need to assess motor skills in preschoolers with ASD in addition to other developmental skill areas. Along with the increasingly acknowledged importance of motor skills for subsequent social, cognitive, and communicative development our findings support the need to consider motor intervention as a key area in therapeutic program to improve outcome in preschoolers with ASD.

  8. Oficinas de estimulação cognitiva adaptadas para idosos analfabetos com transtorno cognitivo leve Talleres de estimulación cognitiva adaptadas para ancianos analfabetos con deterioro cognitivo leve Workshops for cognitive stimulation adapted for elderly illiterate individuals with mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Izabel Borges dos Santos

    2012-12-01

    los talleres y conferencias produjeron mejora en la memoria de los ancianos en la funcionalidad y en la socialización/integración.The aim of this study was to assess the self-perception of memory in elderly illiterate with mild cognitive impairment, before and after workshops of cognitive stimulation adapted for illiterate individuals. The research was qualitative, held at the Health Unit of Taguatinga-DF, involving 63 elderly illiterate: 22 in the experimental group (EG, with 10 workshops; 21 in control group 1 (CG1, with 10 lectures; and 20 in the control group 2 (GC2, without intervention. Semi-structured interviews were carried on before and after the interventions, asking about memory status. The activities offered weekly to EG and CG1 have had two hours of duration. The mean age of the participants was 72.8 years, and 92% were female. In pre-intervention, 82% reported worsening memory during the last year. In post-intervention, CG1 and CG2 kept memory changes, while EG improved cognition. One concludes that the provided workshops and lectures improved functionality and socialization / integration.

  9. A hypoxia-inducible factor (HIF)-3α splicing variant, HIF-3α4 impairs angiogenesis in hypervascular malignant meningiomas with epigenetically silenced HIF-3α4

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Hitoshi [Department of Neurosurgery, Nagoya University School of Medicine, Nagoya (Japan); Department of Neurosurgery, Fukushima Medical University School of Medicine, Fukushima (Japan); Natsume, Atsushi, E-mail: anatsume@med.nagoya-u.ac.jp [Department of Neurosurgery, Nagoya University School of Medicine, Nagoya (Japan); Iwami, Kenichiro; Ohka, Fumiharu [Department of Neurosurgery, Nagoya University School of Medicine, Nagoya (Japan); Kuchimaru, Takahiro; Kizaka-Kondoh, Shinae [Department of Biomolecular Engineering, Tokyo Institute of Technology Graduate School of Bioscience and Biotechnology, Yokohama (Japan); Ito, Kengo [National Center for Geriatrics and Gerontology, Aichi (Japan); Saito, Kiyoshi [Department of Neurosurgery, Fukushima Medical University School of Medicine, Fukushima (Japan); Sugita, Sachi; Hoshino, Tsuneyoshi [MICRON Inc.Medical Facilities Support Department, Aichi (Japan); Wakabayashi, Toshihiko [Department of Neurosurgery, Nagoya University School of Medicine, Nagoya (Japan)

    2013-03-29

    Highlights: ► HIF-3α4 is silenced by DNA methylation in meningiomas. ► Induction of HIF-3α4 impaired angiogenesis in meningiomas. ► Induction of HIF-3α4 impaired proliferation and oxygen-dependent metabolism. -- Abstract: Hypoxia inducible factor is a dominant regulator of adaptive cellular responses to hypoxia and controls the expression of a large number of genes regulating angiogenesis as well as metabolism, cell survival, apoptosis, and other cellular functions in an oxygen level-dependent manner. When a neoplasm is able to induce angiogenesis, tumor progression occurs more rapidly because of the nutrients provided by the neovasculature. Meningioma is one of the most hypervascular brain tumors, making anti-angiogenic therapy an attractive novel therapy for these tumors. HIF-3α has been conventionally regarded as a dominant-negative regulator of HIF-1α, and although alternative HIF-3α splicing variants are extensively reported, their specific functions have not yet been determined. In this study, we found that the transcription of HIF-3α4 was silenced by the promoter DNA methylation in meningiomas, and inducible HIF-3α4 impaired angiogenesis, proliferation, and metabolism/oxidation in hypervascular meningiomas. Thus, HIF-3α4 could be a potential molecular target in meningiomas.

  10. A hypoxia-inducible factor (HIF)-3α splicing variant, HIF-3α4 impairs angiogenesis in hypervascular malignant meningiomas with epigenetically silenced HIF-3α4

    International Nuclear Information System (INIS)

    Highlights: ► HIF-3α4 is silenced by DNA methylation in meningiomas. ► Induction of HIF-3α4 impaired angiogenesis in meningiomas. ► Induction of HIF-3α4 impaired proliferation and oxygen-dependent metabolism. -- Abstract: Hypoxia inducible factor is a dominant regulator of adaptive cellular responses to hypoxia and controls the expression of a large number of genes regulating angiogenesis as well as metabolism, cell survival, apoptosis, and other cellular functions in an oxygen level-dependent manner. When a neoplasm is able to induce angiogenesis, tumor progression occurs more rapidly because of the nutrients provided by the neovasculature. Meningioma is one of the most hypervascular brain tumors, making anti-angiogenic therapy an attractive novel therapy for these tumors. HIF-3α has been conventionally regarded as a dominant-negative regulator of HIF-1α, and although alternative HIF-3α splicing variants are extensively reported, their specific functions have not yet been determined. In this study, we found that the transcription of HIF-3α4 was silenced by the promoter DNA methylation in meningiomas, and inducible HIF-3α4 impaired angiogenesis, proliferation, and metabolism/oxidation in hypervascular meningiomas. Thus, HIF-3α4 could be a potential molecular target in meningiomas

  11. Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance.

    Science.gov (United States)

    Lira, Vitor A; Okutsu, Mitsuharu; Zhang, Mei; Greene, Nicholas P; Laker, Rhianna C; Breen, David S; Hoehn, Kyle L; Yan, Zhen

    2013-10-01

    Pathological and physiological stimuli, including acute exercise, activate autophagy; however, it is unknown whether exercise training alters basal levels of autophagy and whether autophagy is required for skeletal muscle adaptation to training. We observed greater autophagy flux (i.e., a combination of increased LC3-II/LC3-I ratio and LC3-II levels and reduced p62 protein content indicating a higher rate of initiation and resolution of autophagic events), autophagy protein expression (i.e., Atg6/Beclin1, Atg7, and Atg8/LC3) and mitophagy protein Bnip3 expression in tonic, oxidative muscle compared to muscles of either mixed fiber types or of predominant glycolytic fibers in mice. Long-term voluntary running (4 wk) resulted in increased basal autophagy flux and expression of autophagy proteins and Bnip3 in parallel to mitochondrial biogenesis in plantaris muscle with mixed fiber types. Conversely, exercise training promoted autophagy protein expression with no significant increases of autophagy flux and mitochondrial biogenesis in the oxidative soleus muscle. We also observed increased basal autophagy flux and Bnip3 content without increases in autophagy protein expression in the plantaris muscle of sedentary muscle-specific Pgc-1α transgenic mice, a genetic model of augmented mitochondrial biogenesis. These findings reveal that endurance exercise training-induced increases in basal autophagy, including mitophagy, only take place if an enhanced oxidative phenotype is achieved. However, autophagy protein expression is mainly dictated by contractile activity independently of enhancements in oxidative phenotype. Exercise-trained mice heterozygous for the critical autophagy protein Atg6 showed attenuated increases of basal autophagy flux, mitochondrial content, and angiogenesis in skeletal muscle, along with impaired improvement of endurance capacity. These results demonstrate that increased basal autophagy is required for endurance exercise training-induced skeletal

  12. 美满霉素改善血管性痴呆大鼠认知功能损伤并抑制氧化应激%Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion

    Institute of Scientific and Technical Information of China (English)

    蔡志友; 晏勇; 孙善全; 张骏; 黄良国; 晏宁; 吴芳; 李洁颖

    2008-01-01

    Objective Nitric oxide(NO)was speculated to play an important role in the pathophysiology of cerebral ischemia.Minocycline,a tetracycline derivative,reduced inflammation and protected against cerebral ischemia.To study the neuroprotection mechanism of minocycline for vascular dementia,the influences of minocycline on expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were observed in the brains of Wistar rats.Methods The vascular dementia rat model was established by permanent bilateral common carotid arteries occlusion (BCCAO).Wistar rats were divideded into 3 groups randomly: sham-operation group (S group),vascular dementia model group (M group),and minocycline treatment group (MT group).The behaviour was tested with Morris water maze and open-field task.Expressions of iNOS and eNOS were measured by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR).The optical density value was measured by imaging analysis.Percentage of positive cells with iNOS and eNOS expression was analyzed with optical microscope.Results Minocycline attenuated cognitive impairment.Inducible NOS was significantly down-regulated in MT group,compared with that in M group (P<0.01),while eNOS was significantly up-regulated,compared with that in M group (P<0.01).The expressions of iNOS and eNOS in M and MT groups were higher than those in S group (P<0.01).Conclusion Minocycline can down-regulate the expression of iNOS and up-regulate the expression of eNOS in vascular dementia,which restrains apoptosis and oxidative stress to protect neural function.%目的 观察美满霉素(minocycline)对血管性痴呆大鼠学习记忆功能和脑组织内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达的影响,探讨美满霉素对血管性痴呆的脑保护作用的机制.方法 Wistar大鼠随机分为假手术组(S组)、痴呆模

  13. The aging of the adaptive immune system

    OpenAIRE

    Grubeck-Loebenstein, B.; Weinberger, B.; Herndler-Brandstetter, D.; Weiskopf, D.; Pfister, G.

    2011-01-01

    Adaptive immune responses are severely affected by the aging process as reflected by an increased morbidity and mortality from infectious diseases and a low efficacy of vaccination in elderly persons. Age-related changes within the bone marrow and thymus lead to an impaired generation of new T and B cells severely compromising the maintenance of a diverse and balanced T and B cell repertoire in old age. The maintenance of a balanced T cell repertoire is further challenged by latent persistent...

  14. Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling

    Directory of Open Access Journals (Sweden)

    Manuel A. Fernández-Rojo

    2013-07-01

    Full Text Available Caveolae and caveolin-1 (CAV1 have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1−/− mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1−/− mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1 hepatic lipid homeostasis and (2 nuclear hormone receptor (PPARα, FXRα, and SHP and bile acid signaling.

  15. Management of impaired fracture healing: Historical aspects

    OpenAIRE

    Gajdobranski Đorđe; Micić Ivan; Mitković Milorad B.; Mladenović Desimir; Milankov Miroslav

    2005-01-01

    Introduction Establishing continuity of long bones in cases of impaired bone healing and pseudo-arthrosis is one of the most complex problems in orthopedics. Impaired bone healing The problem of impaired fracture healing is not new. As in other areas of human life, the roots of modern treatment of impaired bone healing lie in ancient medicine. A relatively high percentage of impaired bone healing, as well as unsatisfactory results of standard therapies of impaired bone healing and pseudoarthr...

  16. Adaptively robust filtering with classified adaptive factors

    Institute of Scientific and Technical Information of China (English)

    CUI Xianqiang; YANG Yuanxi

    2006-01-01

    The key problems in applying the adaptively robust filtering to navigation are to establish an equivalent weight matrix for the measurements and a suitable adaptive factor for balancing the contributions of the measurements and the predicted state information to the state parameter estimates. In this paper, an adaptively robust filtering with classified adaptive factors was proposed, based on the principles of the adaptively robust filtering and bi-factor robust estimation for correlated observations. According to the constant velocity model of Kalman filtering, the state parameter vector was divided into two groups, namely position and velocity. The estimator of the adaptively robust filtering with classified adaptive factors was derived, and the calculation expressions of the classified adaptive factors were presented. Test results show that the adaptively robust filtering with classified adaptive factors is not only robust in controlling the measurement outliers and the kinematic state disturbing but also reasonable in balancing the contributions of the predicted position and velocity, respectively, and its filtering accuracy is superior to the adaptively robust filter with single adaptive factor based on the discrepancy of the predicted position or the predicted velocity.

  17. EEG in Specific Language Impairment

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-11-01

    Full Text Available The value of routine wake electroencephalography in children with specific language impairment was reviewed retrospectively in 111 children examined over a 10-year interval at Montreal Children’s Hospital, Quebec, Çanada.

  18. Intracerebral hemorrhage and cognitive impairment.

    Science.gov (United States)

    Xiong, Li; Reijmer, Yael D; Charidimou, Andreas; Cordonnier, Charlotte; Viswanathan, Anand

    2016-05-01

    Vascular cognitive impairment and vascular dementia are composed of cognitive deficits resulted from a range of vascular lesions and pathologies, including both ischemic and hemorrhagic. However the contribution of spontaneous intracerebral hemorrhage presumed due to small vessel diseases on cognitive impairment is underestimated, in contrast to the numerous studies about the role of ischemic vascular disorders on cognition. In this review we summarize recent findings from clinical studies and appropriate basic science research to better elucidate the role and possible mechanisms of intracerebral hemorrhage in cognitive impairment and dementia. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

  19. [Cognitive Impairment in Multiple Sclerosis].

    Science.gov (United States)

    Niino, Masaaki; Miyazaki, Yusei

    2016-04-01

    While cognitive impairment is a major symptom of multiple sclerosis (MS), it is commonly overlooked. This may be explained by the fact that it is difficult to evaluate cognitive function in patients with MS using screening batteries for the detection of dementia such as the mini-mental state examination. Further more, cognitive impairment in MS typically involves domain-specific deficits such as imparement of sustained attention and information processing speed rather than global cognitive decline. Cognitive impairment may influence the daily living and social lines of affected patients. This review discusses the characteristics of cognitive impairment, appropreate tests to evaluate its symptoms, and the current status of clinical trials for the treatment of MS. PMID:27056855

  20. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

    Directory of Open Access Journals (Sweden)

    Tohru Tanigawa

    Full Text Available Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG, one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV, which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  1. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Ignacio Negrón-Oyarzo

    2016-01-01

    Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

  2. ENVIRONMENTAL INJUSTICE AND MOBILITY IMPAIRMENT

    Directory of Open Access Journals (Sweden)

    Michael Cahill

    2013-06-01

    Full Text Available The study of mobility is a growth area in the social sciences.  The car system (automobility has had as one of its consequences reduced opportunities for mobility impaired people to walk in their local environment. Immobility has resulted for many people with disabilities. Despite the promotion of physical activity by public health guidance local environments are often hazardous for mobility impaired people.  In particular, there is a problem with cars parking on pavements and pavement cycling.

  3. Vascular contributions to cognitive impairment

    OpenAIRE

    Wright, Clinton B.; Flores, Alan

    2015-01-01

    Unlike many neurodegenerative causes of cognitive impairment and dementia, vascular damage is preventable. Despite the heterogeneity of vascular cognitive impairment (VCI) and the complexity of its clinical presentations, the potential for limiting progression and changing the trajectory of damage makes it all the more important for physicians to be educated about the syndrome and to remain vigilant when taking care of patients. In this review, we outline an approach to patients with possible...

  4. Chemistry for the Visually Impaired

    Science.gov (United States)

    Ratliff, Judy L.

    1997-06-01

    Methods used to try to provide a valuable experience for visually impaired students in a general education or an introductory chemistry class are discussed. Modifications that can be made cheaply and with little time commitment which will allow visually impaired students to participate productively in the laboratory are examined. A conductivity tester that cost less than $4.00 to construct, is easy to assemble, very rugged, and provides a great deal of entertainment for sighted and non-sighted students is described.

  5. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    OpenAIRE

    Ignacio Negrón-Oyarzo; Francisco Aboitiz; Pablo Fuentealba

    2016-01-01

    Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral response...

  6. Low Motor Assessment: A Comparative Pilot Study with Young Children With and Without Motor Impairment

    OpenAIRE

    Ruiter, Selma Anne José; Nakken, Han; van der Meulen, Bieuwe F.; Lunenborg, Carolien B.

    2009-01-01

    Most of the developmental instruments that measure cognitive development in children rely heavily on fine motor skills, especially for young children whose language skills are not yet well developed. This is problematic when evaluating the cognitive development of young children with motor impairment. The purpose of this study is to assess the need for a Low Motor adapation of a standardized instrument when testing children with motor impairment. To accomplish this, we have adapted the proced...

  7. Staged membrane oxidation reactor system

    Science.gov (United States)

    Repasky, John Michael; Carolan, Michael Francis; Stein, VanEric Edward; Chen, Christopher Ming-Poh

    2012-09-11

    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.

  8. Impaired mitochondrial function in chronically ischemic human heart

    DEFF Research Database (Denmark)

    Stride, Nis Ottesen; Larsen, Steen; Hey-Mogensen, Martin;

    2013-01-01

    , and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared.......05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found....

  9. Computer interfaces for the visually impaired

    Science.gov (United States)

    Higgins, Gerry

    1991-01-01

    Information access via computer terminals extends to blind and low vision persons employed in many technical and nontechnical disciplines. Two aspects are detailed of providing computer technology for persons with a vision related handicap. First, research into the most effective means of integrating existing adaptive technologies into information systems was made. This was conducted to integrate off the shelf products with adaptive equipment for cohesive integrated information processing systems. Details are included that describe the type of functionality required in software to facilitate its incorporation into a speech and/or braille system. The second aspect is research into providing audible and tactile interfaces to graphics based interfaces. Parameters are included for the design and development of the Mercator Project. The project will develop a prototype system for audible access to graphics based interfaces. The system is being built within the public domain architecture of X windows to show that it is possible to provide access to text based applications within a graphical environment. This information will be valuable to suppliers to ADP equipment since new legislation requires manufacturers to provide electronic access to the visually impaired.

  10. Adaptive Image Denoising by Mixture Adaptation.

    Science.gov (United States)

    Luo, Enming; Chan, Stanley H; Nguyen, Truong Q

    2016-10-01

    We propose an adaptive learning procedure to learn patch-based image priors for image denoising. The new algorithm, called the expectation-maximization (EM) adaptation, takes a generic prior learned from a generic external database and adapts it to the noisy image to generate a specific prior. Different from existing methods that combine internal and external statistics in ad hoc ways, the proposed algorithm is rigorously derived from a Bayesian hyper-prior perspective. There are two contributions of this paper. First, we provide full derivation of the EM adaptation algorithm and demonstrate methods to improve the computational complexity. Second, in the absence of the latent clean image, we show how EM adaptation can be modified based on pre-filtering. The experimental results show that the proposed adaptation algorithm yields consistently better denoising results than the one without adaptation and is superior to several state-of-the-art algorithms. PMID:27416593

  11. Inhibition of HIF-prolyl-4-hydroxylases prevents mitochondrial impairment and cell death in a model of neuronal oxytosis

    NARCIS (Netherlands)

    Neitemeier, S; Dolga, A M; Honrath, B; Karuppagounder, S S; Alim, I; Ratan, R R; Culmsee, C

    2016-01-01

    Mitochondrial impairment induced by oxidative stress is a main characteristic of intrinsic cell death pathways in neurons underlying the pathology of neurodegenerative diseases. Therefore, protection of mitochondrial integrity and function is emerging as a promising strategy to prevent neuronal dama

  12. [What is impaired consciousness? Revisiting impaired consciousness as psychiatric concept].

    Science.gov (United States)

    Kanemoto, Kousuke

    2004-01-01

    For decades, psychiatrists have considered that concepts of impaired consciousness in the study of psychiatry were inconsistent with those applied in the field of neurology, in which the usefulness of the concept of consciousness has long been seriously doubted. Gloor concluded that the concept of consciousness does not further the understanding of seizure mechanisms or brain function, which is the current representative opinion of most epileptologists. Loss of consciousness tends to be reduced to aggregates of individual impairments of higher cognitive functions, and the concept of consciousness is preferably avoided by neurologists by assigning various behavioral disturbances during disturbed consciousness to particular neuropsychological centers. In contrast, psychiatrists, especially those in Europe, are more likely to include phenomena involving problems related to phenomenological intentionality in impaired consciousness. For the present study, we first divided consciousness into vigilance and recursive consciousness, and then attempted to determine what kind of impaired consciousness would be an ideal candidate to represent pure disturbance of recursive consciousness. Then, 4 patients, 1 each with pure amnestic states followed immediately by complex partial seizures, an akinetic mutistic state caused by absence status, and mental diplopia as a manifestation of postictal psychosis, as well as a patient with Alzheimer's disease who gracefully performed Japanese tea ceremony, were studied. Based on our findings, we concluded that impaired consciousness as a generic term in general medicine does not indicate any unitary entity corresponding to some well-demarcated physiological function or constitute a base from which recursive consciousness emerges as a superstructure. From that, we stressed that a pure form of impairment of recursive consciousness could occur without the impaired consciousness named generically in general medicine. Second, following

  13. [What is impaired consciousness? Revisiting impaired consciousness as psychiatric concept].

    Science.gov (United States)

    Kanemoto, Kousuke

    2004-01-01

    For decades, psychiatrists have considered that concepts of impaired consciousness in the study of psychiatry were inconsistent with those applied in the field of neurology, in which the usefulness of the concept of consciousness has long been seriously doubted. Gloor concluded that the concept of consciousness does not further the understanding of seizure mechanisms or brain function, which is the current representative opinion of most epileptologists. Loss of consciousness tends to be reduced to aggregates of individual impairments of higher cognitive functions, and the concept of consciousness is preferably avoided by neurologists by assigning various behavioral disturbances during disturbed consciousness to particular neuropsychological centers. In contrast, psychiatrists, especially those in Europe, are more likely to include phenomena involving problems related to phenomenological intentionality in impaired consciousness. For the present study, we first divided consciousness into vigilance and recursive consciousness, and then attempted to determine what kind of impaired consciousness would be an ideal candidate to represent pure disturbance of recursive consciousness. Then, 4 patients, 1 each with pure amnestic states followed immediately by complex partial seizures, an akinetic mutistic state caused by absence status, and mental diplopia as a manifestation of postictal psychosis, as well as a patient with Alzheimer's disease who gracefully performed Japanese tea ceremony, were studied. Based on our findings, we concluded that impaired consciousness as a generic term in general medicine does not indicate any unitary entity corresponding to some well-demarcated physiological function or constitute a base from which recursive consciousness emerges as a superstructure. From that, we stressed that a pure form of impairment of recursive consciousness could occur without the impaired consciousness named generically in general medicine. Second, following

  14. 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.

  15. Impairment aware routing with service differentiation in heterogeneous WDM networks

    Science.gov (United States)

    Jirattigalachote, Amornrat; Wosinska, Lena; Monti, Paolo; Katrinis, Kostas; Tzanakaki, Anna

    2009-11-01

    In transparent Wavelength Division Multiplexing (WDM) networks, the signal is transported from source to destination in the optical domain through all-optical channels, or lightpaths. A lightpath may traverse several fiber segments and optical components that in general degrade the optical signal. This effect introduces the need for considering physical layer impairments during the connection-provisioning phase. Physical layer impairments can be divided into linear and non-linear. Both types of impairments are highly dependent on the fiber characteristics, which in turn are sensitive to length, temperature and age. A close look at the fiber infrastructure of today's network operators reveals a situation where old and newly deployed fibers coexist in the network. This heterogeneous fiber plant presents a challenge. A tradeoff should be found between the QoS requirements of connection requests and the use of the available (old and new) network resources. This calls for a provisioning mechanism able to adapt to the various fiber composition scenarios. In parallel, given the need for service differentiation, the authors recently proposed an Impairment Constraint Based Routing (ICBR) algorithm, referred to as ICBR-Diff, supporting differentiation of services at the BER (Bit Error Rate) level in a network with a homogeneous fiber infrastructure. In this paper the ICBR-Diff algorithm is extended to heterogeneous network; particularly, it is evaluated in WDM networks with fiber links having varying Polarization Mode Dispersion characteristics, i.e., with old and new fiber coexisting. Simulation results show that the ICBR-Diff algorithm exhibits high adaptability in a heterogeneous fiber composition scenario. This translates into improved performance in terms of blocking probability, when compared to traditional impairment aware routing algorithms.

  16. Assessing functional impairment in individuals with mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Patrícia Belchior

    2016-04-01

    Full Text Available To date, there is no consensus on how to assess functional impairment in individuals with mild cognitive impairment (MCI, and this lack of consensus is reflected in the clinical practice. Since the criterion used in the literature is very vague, clinicians are still left without much guidance in this area. Thus, the main goal of this study was to examine how functional impairment in individuals with MCI has been assessed in the literature. An electronic database search strategy was developed in consultation with an experienced librarian. Four databases (CINAHL, PsycINFO, PubMed, and MEDLINE were searched from 2000 to May 2014 to provide a comprehensive coverage of the literature. The literature search yielded 14 tools that assessed functional impairment in MCI. Among those, nine tools were performance-based measures in which participants were observed while executing a task in a simulated environment using real life material. In terms of questionnaires (either informant- or self-reports, five tools were found. Different functional domains have been assessed in each tool. According to this review, the characteristics of the instruments used in the literature to assess functional impairment in individuals with MCI vary greatly. Nonetheless, results of this study allow clinicians to make better-informed decisions when choosing a functional assessment for this population.

  17. The self-concepts of visually impaired and normally sighted middle school children.

    Science.gov (United States)

    Obiakor, F E; Stile, S W

    1990-03-01

    The self-concepts of visually impaired (n = 61) and normally sighted (n = 229) American school children in Grades 6, 7, and 8 were compared. Self-concept was measured with the Student Self-Assessment Inventory (SSAI; Muller, Larned, Leonetti, & Muller, 1984, 1986), which assesses children's self-knowledge, self-ideal, and self-esteem as related to physical maturity, peer relations, academic success, and school adaptiveness. Visually impaired students scored higher than normally sighted children on 5 of the 12 SSAI subscales, refuting the notion that visually impaired children have poorer self-concepts than normally sighted children.

  18. Experimental Adaptive Digital Performance Monitoring for Optical DP-QPSK Coherent Receiver

    DEFF Research Database (Denmark)

    Borkowski, Robert; Zhang, Xu; Zibar, Darko;

    2011-01-01

    We report on a successful experimental demonstration of a digital optical performance monitoring (OPM) yielding satisfactory estimation accuracy along with adaptive impairment equalization. No observable penalty is measured when equalizer is driven by monitoring module.......We report on a successful experimental demonstration of a digital optical performance monitoring (OPM) yielding satisfactory estimation accuracy along with adaptive impairment equalization. No observable penalty is measured when equalizer is driven by monitoring module....

  19. Adaptive compressive sensing camera

    Science.gov (United States)

    Hsu, Charles; Hsu, Ming K.; Cha, Jae; Iwamura, Tomo; Landa, Joseph; Nguyen, Charles; Szu, Harold

    2013-05-01

    We have embedded Adaptive Compressive Sensing (ACS) algorithm on Charge-Coupled-Device (CCD) camera based on the simplest concept that each pixel is a charge bucket, and the charges comes from Einstein photoelectric conversion effect. Applying the manufactory design principle, we only allow altering each working component at a minimum one step. We then simulated what would be such a camera can do for real world persistent surveillance taking into account of diurnal, all weather, and seasonal variations. The data storage has saved immensely, and the order of magnitude of saving is inversely proportional to target angular speed. We did design two new components of CCD camera. Due to the matured CMOS (Complementary metal-oxide-semiconductor) technology, the on-chip Sample and Hold (SAH) circuitry can be designed for a dual Photon Detector (PD) analog circuitry for changedetection that predicts skipping or going forward at a sufficient sampling frame rate. For an admitted frame, there is a purely random sparse matrix [Φ] which is implemented at each bucket pixel level the charge transport bias voltage toward its neighborhood buckets or not, and if not, it goes to the ground drainage. Since the snapshot image is not a video, we could not apply the usual MPEG video compression and Hoffman entropy codec as well as powerful WaveNet Wrapper on sensor level. We shall compare (i) Pre-Processing FFT and a threshold of significant Fourier mode components and inverse FFT to check PSNR; (ii) Post-Processing image recovery will be selectively done by CDT&D adaptive version of linear programming at L1 minimization and L2 similarity. For (ii) we need to determine in new frames selection by SAH circuitry (i) the degree of information (d.o.i) K(t) dictates the purely random linear sparse combination of measurement data a la [Φ]M,N M(t) = K(t) Log N(t).

  20. Adaptive Technology that Provides Access to Computers. DO-IT Program.

    Science.gov (United States)

    Washington Univ., Seattle.

    This brochure describes the different types of barriers individuals with mobility impairments, blindness, low vision, hearing impairments, and specific learning disabilities face in providing computer input, interpreting output, and reading documentation. The adaptive hardware and software that has been developed to provide functional alternatives…

  1. Patterns of Semantic Memory Impairment in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Sven Joubert

    2008-01-01

    Full Text Available Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment. The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.

  2. Unimpaired Neuro-Adaptive Plasticity in an Elderly Astronaut

    Science.gov (United States)

    Paloski, William H.; Black, F. Owen; Metter, E. Jeffrey; Dawson, David L. (Technical Monitor)

    1999-01-01

    Quantitative analyses of a 77 year old astronaut's balance control performances on a standardized test battery revealed few differences between his neuro-adaptive responses to space flight and those of a group of younger astronauts tested following missions of similar duration. This finding suggests that the physiological changes associated with age do not necessarily impair adaptive plasticity in the human following removal and subsequent reintroduction of gravity.

  3. Adaptive Modular Playware

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Þorsteinsson, Arnar Tumi

    2011-01-01

    In this paper, we describe the concept of adaptive modular playware, where the playware adapts to the interaction of the individual user. We hypothesize that there are individual differences in user interaction capabilities and styles, and that adaptive playware may adapt to the individual user’s...

  4. Chronic Melatonin Treatment Prevents Memory Impairment Induced by Chronic Sleep Deprivation.

    Science.gov (United States)

    Alzoubi, Karem H; Mayyas, Fadia A; Khabour, Omar F; Bani Salama, Fatima M; Alhashimi, Farah H; Mhaidat, Nizar M

    2016-07-01

    Sleep deprivation (SD) has been associated with memory impairment through induction of oxidative stress. Melatonin, which promotes the metabolism of many reactive oxygen species (ROS), has antioxidant and neuroprotective properties. In this study, the effect of melatonin on memory impairment induced by 4 weeks of SD was investigated using rat animal model. Animals were sleep deprived using modified multiple platform model. Melatonin was administered via oral gavage (100 mg/kg/day). Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers in the hippocampus following treatments were measured using ELISA procedure. The result revealed that SD impaired both short- and long-term memory (P sleep-deprived rats (P  0.05). In conclusion, SD induced memory impairment, which was prevented by melatonin. This was correlated with normalizing hippocampus antioxidant mechanisms during chronic SD. PMID:26084441

  5. Changes in integrity of the gill during histidine deficiency or excess due to depression of cellular anti-oxidative ability, induction of apoptosis, inflammation and impair of cell-cell tight junctions related to Nrf2, TOR and NF-κB signaling in fish.

    Science.gov (United States)

    Jiang, Wei-Dan; Feng, Lin; Qu, Biao; Wu, Pei; Kuang, Sheng-Yao; Jiang, Jun; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang

    2016-09-01

    This study firstly explored the possible effects of dietary histidine on structural integrity and the related signaling factor gene expression in the gills of fish. Young grass carp (Ctenopharyngodon idella) were fed with six diets containing gradual levels of histidine for 8 weeks. The results firstly demonstrated that histidine deficiency caused increases in reactive oxygen species (ROS) contents, and severe oxidative damage (lipid peroxidation and protein oxidation) in the gills of fish, which was partially due to the decreased glutathione (GSH) content and antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)]. Further investigations indicated that histidine deficiency caused depressions of those antioxidant enzyme activities are related to the down-regulation of corresponding antioxidant enzyme genes and the related signaling factor Nrf2 mRNA levels. Meanwhile, histidine deficiency induced DNA fragmentation via up-regulation of caspase-3, caspase-8 and caspase-9 expressions that referring to the down-regulation of TOR and S6K mRNA levels. Furthermore, His deficiency down-regulated claudin-b, claudin-c, claudin-3, claudin-12, claudin-15, occludin and ZO-1 transcription in fish gills. These effects were partially related to the up-regulation of pro-inflammatory cytokines, interleukin 1β (IL-1β), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α) and related signaling factor nuclear factor κB P65 (NF-κB P65) mRNA levels, and the down-regulation of anti-inflammatory cytokines, interleukin 10 (IL-10), transforming growth factor β1 (TGF-β1) and related signaling factor IκBα mRNA levels. Excessive histidine exhibited negative effects that were similar to histidine deficiency, whereas the optimal histidine levels reversed those negative effects. Taken together, our results showed that histidine deficiency or excess impaired the structural

  6. Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates

    OpenAIRE

    Chadderdon, Scott M.; Belcik, J. Todd; Smith, Elise; Pranger, Lindsay; Kievit, Paul; Grove, Kevin L.; Lindner, Jonathan R

    2012-01-01

    Insulin produces capillary recruitment in skeletal muscle through a nitric oxide (NO)-dependent mechanism. Capillary recruitment is blunted in obese and diabetic subjects and contributes to impaired glucose uptake. This study's objective was to define whether inactivity, in the absence of obesity, leads to impaired capillary recruitment and contributes to insulin resistance (IR). A comprehensive metabolic and vascular assessment was performed on 19 adult male rhesus macaques (Macaca mulatta) ...

  7. Language Impairment and Generative Analysis

    Directory of Open Access Journals (Sweden)

    Andrej Stopar

    2004-12-01

    Full Text Available This article deals with different types of language impairment from the perspective of generative grammar. The paper focuses on syntactic deficiencies observed in aphasic and SLI (specific language impairment patients. We show that the observed ungrammatical structures do not appear in a random fashion but can be predicted by that theory of universal sentence structure which posits a strict hierarchy of its constituent parts. The article shows that while the hierarchically lower elements remain unaffected, the higher positions in the hierarchy show various degrees of syntactic impairment. The paper supports the implementation of recent developments in the field of generative grammar with the intention of encouraging further theoretical, experimental and therapeutic research in the field.

  8. Vascular contributions to cognitive impairment

    Science.gov (United States)

    Flores, Alan

    2015-01-01

    Summary Unlike many neurodegenerative causes of cognitive impairment and dementia, vascular damage is preventable. Despite the heterogeneity of vascular cognitive impairment (VCI) and the complexity of its clinical presentations, the potential for limiting progression and changing the trajectory of damage makes it all the more important for physicians to be educated about the syndrome and to remain vigilant when taking care of patients. In this review, we outline an approach to patients with possible VCI, summarize current treatment and prevention guidelines, and provide an overview with case examples. PMID:26124978

  9. Expressing Adaptation Strategies Using Adaptation Patterns

    Science.gov (United States)

    Zemirline, N.; Bourda, Y.; Reynaud, C.

    2012-01-01

    Today, there is a real challenge to enable personalized access to information. Several systems have been proposed to address this challenge including Adaptive Hypermedia Systems (AHSs). However, the specification of adaptation strategies remains a difficult task for creators of such systems. In this paper, we consider the problem of the definition…

  10. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies.

    Science.gov (United States)

    Hove, Michael J; Keller, Peter E

    2015-03-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

  11. Cognitive impairment and mortality among nonagenarians

    DEFF Research Database (Denmark)

    Andersen, Kjeld; Nybo, Hanne; Gaist, David;

    2002-01-01

    Cognitive impairment has been associated with increased mortality. Most studies, however, have only included small numbers, if at all, of the very old. In a large nationwide survey of all Danes born in 1905 and still alive in 1998, where the baseline examination was conducted, we examined...... interval) of 1.24 (1.00-1.55) for mildly impaired and 1.73 (1.37-2.20) for severely impaired Danes compared to individuals with no impairment. Cognitive impairment predicts mortality among the very old, even after controlling for most known predictors of mortality....... the impact of cognitive impairment on mortality over a 2-year period. No cognitive impairment was defined as a score of 24-30 points on the Mini Mental State Examination, mild cognitive impairment was defined as a score of 18-23 points, and severe impairment was defined as a score of 0-17 points. Cox...

  12. Language Impairment in Autistic Children.

    Science.gov (United States)

    Deaton, Ann Virginia

    Discussed is the language impairment of children with infantile autism. The speech patterns of autistic children, including echolalia, pronomial reversal, silent language, and voice imitation, are described. The clinical picture of the autistic child is compared to that of children with such other disorders as deafness, retardation, and…

  13. Cognitive Impairment in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Farnaz Etesam

    2014-01-01

    Full Text Available Cognitive impairment can emerge in the earliest phases of multiple sclerosis. It strongly impacts different aspects of Multiple Sclerosis (MS patients' lives, like employment, social relationships and the overall quality of life; thus, its on-time recognition and treatment is mandatory. This paper discusses issues, diagnostic methods and treatment options for cognitive dysfunctions in MS. This paper is a descriptive review of the related studies in the recent 10 years, performing a keyword search in the main databases4T. Cognitive impairment mostly involves aspects of information processing, memory and executive functioning in MS. Neuropsychological tests like MACFIMS and BRB-N are recommended for its assessment. Still, there is no fully efficient treatment for cognitive impairment. Researchers have shown some positive effects, using disease-modifying therapies and cognitive rehabilitation. Depression, pain, fatigue and other factors influencing cognitive functions must be paid attention to4T. Recognizing cognitive impairment as a major symptom for MS, makes studying this subject one of the priorities in dealing with the disease. Therefore, a consecutive research for identification and management of this part of quality of life in MS patients is obligatory4T.4T

  14. Electrophysiology in visually impaired children

    NARCIS (Netherlands)

    Genderen, Maria Michielde van

    2006-01-01

    Inherited retinal disorders and posterior visual pathway abnormalities are important causes of visual impairment in children. Visual electrophysiology often is indispensable in diagnosing these conditions. This thesis shows the wide range of use of pediatric electro-ophthalmology, and demonstrates i

  15. Oceanography for the Visually Impaired

    Science.gov (United States)

    Fraser, Kate

    2008-01-01

    Amy Bower is a physical oceanographer and senior scientist at the Woods Hole Oceanographic Institution (WHOI) in Woods Hole, Massachusetts--she has also been legally blind for 14 years. Through her partnership with the Perkins School for the Blind in Watertown, Massachusetts, the oldest K-12 school for the visually impaired in the United States,…

  16. Language Impairment in Cerebellar Ataxia

    NARCIS (Netherlands)

    van Gaalen, Judith; de Swart, Bert J. M.; Oostveen, Judith; Knuijt, Simone; van de Warrenburg, Bart P. C.; Kremer, Berry (H. ) P. H.

    2014-01-01

    Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients

  17. 糖调节受损与新诊断2型糖尿病患者氧化应激与抗氧化状态研究%Oxidative stress and antioxidant status in patients with impaired glucose regulation and newly diagnosed Type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    姜少琼; 荣莹

    2013-01-01

    Objective To investigate oxidative stress status in patients with impaired glucose regulation (IGR) and newly diagnosed type 2 diabetes ( NDD) and postulate the association between oxidative stress and type 2 diabetes (T2D). Methods 92 subjects with normal glucose tolerance (NGT) , 78 patients with IGR and 113 patients with NDD were studied. A standard questionnaire was used to collect basic information. All of the study subjects underwent a complete physical examination. At the same time, baseline biochemistry detection and biomarkers of antioxidant status were determined. Results Compared with subjects with NGT, patients with IGR had reduced erythrocyte superoxide dis-mutase (SOD) activity. Patients with diabetes had a higher plasma malondialdehyde (MDA) concentration, but a lower plasma total antioxidative capacity (TAC) level and erythrocyte SOD activity, than the NGT group. Correlation analysis revealed a strong positive association between insulin resistance and MDA concentration, but negative correlation with TAC status and SOD activity. With respect to β-cell function, a positive association with TAC status and an inverse correlation with GSH respectively, were observed. Conclusions The results of the present study suggest that hyperglycaemia in an IGR state caused the predominance of oxidative stress over antioxidative defence systems, which possibly contributed to pancreatic β-cell dysfunction, insulin resistance and more pronounced hyperglycaemia. This vicious circle finally induced deterioration to diabetes.%目的 通过对糖调节受损(IGR)和新诊断2型糖尿病(NDD)患者氧化应激水平的检测探讨氧化应激与2型糖尿病(T2D)的关系.方法 纳入78名IGR患者,113名NDD患者和92名血糖正常(NGT)对照,进行问卷调查、体格检测和基本的生化、抗氧化指标检测.结果 与NGT对照相比,IGR患者红细胞过氧化物歧化酶(SOD)活性降低.NDD患者血浆丙二醛(MDA)水平较NGT对照升高,但血浆总

  18. Cognitive impairments in cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    A. Yu. Emelin

    2014-01-01

    Full Text Available Cerebrovascular diseases belong to a group of the major causes of cognitive impairments, in the elderly in particular. The paper presents current ideas on the etiology and pathogenesis of vascular cognitive impairments (VCI. The etiological factors of VCI may be divided into genetic, sociodemographic, and common risk factors for vascular and other diseases. The pathogenesis of VCI is multifactorial; cognitive function decrement results from brain damage due to cerebral circulatory disorders. Damage to the deep white matter portions and basal ganglions plays a leading role in the development of cognitive deficit in cerebral circulatory insufficiency, disrupting the connections between the frontal lobes and subcortical structures (a dissociation phenomenon. Regulatory functions are impaired; instability of volitional attention develops; the speed of thinking processes and the performance of professional and everyday skills are suffered, mnestic functions being impaired to a lesser extent. Impairments in other higher cortical functions, such as speech, gnosis, praxis, thinking, generally occur in the later stages of cognitive deficit. The comprehensive approach to examining patients with cognitive dysfunctions, which encompasses physical examination with a mandatory evaluation of neurological symptoms, neuropsychological testing, laboratory studies, instrumental diagnostic methods, and structural and functional neuroimaging techniques, are most justified now. VCI therapy is a challenging task requiring the specific features of different types of cognitive deficit to be analyzed, by providing a rationale for the choice of medications. Therapeutic effectiveness may be enhanced by rational combined multimodal therapy, by keeping in mind a variety of factors for the pathogenesis of VCI.

  19. Cognitive impairments may mimic delusions.

    Science.gov (United States)

    Eterović, Marija; Kozarić-Kovačić, Dragica

    2015-12-01

    Delusions are often recognized as key to the concept of psychosis. What is delusion is one of the basic questions of psychopathology. The common denominator of definitions of delusions is the divergence between the strong conviction in the delusional belief and superior evidences to the contrary which are continually ignored. An implicit, sustainably unspoken assumption is that the person with delusional belief has cognitive capacities to process the (counter-)arguments relevant to their delusion. However, individual's cognitive capacities are not being emphasized when delusions are evaluated. Moreover, the impact of cognitive decline on formation of delusions is neglected, both in theory and practice. We elaborate that cognitive deficits may facilitate, oppose, or mimic delusions. We focus on the last, which can lead to diagnosing as delusion what could be explained by cognitive decline and better called pseudo-delusion. The risk is significant when cognition is impaired, as in demented people; an issue which has not yet been debated. True delusions are incompatible with person's cognitive capacities, i.e., if we take into account person's cognitive status, we still cannot understand how the person holds the strange belief with an extraordinary conviction. Pseudo-delusions would be beliefs, thoughts or judgments that at first seem delusional (they are false, subculturally atypical beliefs that are strongly maintained in the face of counterargument), but lose the essence of delusions after we take cognitive impairment into account. Pseudo-delusions could actually be explained or understood by person's cognitive impairments, they "fit into" them. The reported reality-based contents of delusions in the elderly, poor response to antipsychotics and lack of association with early or family history of psychiatric disorders could in part be accounted for by the bias of misdiagnosing the cognitive impairment as the delusion. Not recognizing that the cognitive impairment

  20. Mitochondrial oxidative function and type 2 diabetes

    DEFF Research Database (Denmark)

    Rabøl, Rasmus; Boushel, Robert; Dela, Flemming

    2006-01-01

    biochemical measurements of oxidative enzyme and electron transport activity, isolation of mitochondria for measurements of respiration, and ATP production and indirect measurements of ATP production using nuclear magnetic resonance (NMR) - spectroscopy. Biochemical markers of mitochondrial content are also...... discussed. Several studies show reduced activity of oxidative enzymes in skeletal muscle of type 2 diabetics. The reductions are independent of muscle fiber type, and are accompanied by visual evidence of damaged mitochondria. In most studies, the reduced oxidative enzyme activity is explained by decreases...... in mitochondrial content; thus, evidence of a functional impairment in mitochondria in type 2 diabetes is not convincing. These impairments in oxidative function and mitochondrial morphology could reflect the sedentary lifestyle of the diabetic subjects, and the influence of physical activity on oxidative activity...

  1. Frailty and Vascular Cognitive Impairment: Mechanisms Behind the Link.

    Science.gov (United States)

    Aguilar-Navarro, Sara Gloria; Mimenza-Alvarado, Alberto José; Anaya-Escamilla, Antonio; Gutiérrez-Robledo, Luis Miguel

    2016-01-01

    The relationship between frailty and cognitive impairment has been recognized for decades, but it was not until a few years ago that the interest in this relationship increased and is now being understood. Epidemiological evidence suggests that physical frailty may be linked to cognitive impairment since both conditions share pathophysiological mechanisms at the cellular and systemic levels. Aging itself promotes multiple vascular changes, making the brain susceptible to cognitive decline through mechanisms such as thinning of blood vessels, increased collagen accumulation, rupture of the blood-brain barrier, inflammation, and oxidative damage. The prevalence of frailty and cognitive decline increases as individuals become older, and cognitive impairment attributable to cerebrovascular disease has become a major public health problem since vascular dementia is now the second most common subtype of dementia. However, full understanding of the mechanisms underlying the relationship between frailty and vascular cognitive impairment remains fragmented. This review examines the link between frailty and vascular cognitive decline and also explores the role of vascular changes in the genesis of both conditions. PMID:27028174

  2. Adaptive Rationality, Adaptive Behavior and Institutions

    Directory of Open Access Journals (Sweden)

    Volchik Vyacheslav, V.

    2015-12-01

    Full Text Available The economic literature focused on understanding decision-making and choice processes reveals a vast collection of approaches to human rationality. Theorists’ attention has moved from absolutely rational, utility-maximizing individuals to boundedly rational and adaptive ones. A number of economists have criticized the concepts of adaptive rationality and adaptive behavior. One of the recent trends in the economic literature is to consider humans irrational. This paper offers an approach which examines adaptive behavior in the context of existing institutions and constantly changing institutional environment. It is assumed that adaptive behavior is a process of evolutionary adjustment to fundamental uncertainty. We emphasize the importance of actors’ engagement in trial and error learning, since if they are involved in this process, they obtain experience and are able to adapt to existing and new institutions. The paper aims at identifying relevant institutions, adaptive mechanisms, informal working rules and practices that influence actors’ behavior in the field of Higher Education in Russia (Rostov Region education services market has been taken as an example. The paper emphasizes the application of qualitative interpretative methods (interviews and discourse analysis in examining actors’ behavior.

  3. Walking Flexibility after Hemispherectomy: Split-Belt Treadmill Adaptation and Feedback Control

    Science.gov (United States)

    Choi, Julia T.; Vining, Eileen P. G.; Reisman, Darcy S.; Bastian, Amy J.

    2009-01-01

    Walking flexibility depends on use of feedback or reactive control to respond to unexpected changes in the environment, and the ability to adapt feedforward or predictive control for sustained alterations. Recent work has demonstrated that cerebellar damage impairs feedforward adaptation, but not feedback control, during human split-belt treadmill…

  4. Exploring the Early Literacy Practices of Teachers of Infants, Toddlers, and Preschoolers with Visual Impairments

    Science.gov (United States)

    Murphy, Jeanne Lovo; Hatton, Deborah; Erickson, Karen A.

    2008-01-01

    Practices endorsed by 192 teachers of young children with visual impairments who completed an online early literacy survey included facilitating early attachment (70%), providing early literacy support to families (74%), and providing adaptations to increase accessibility (55%). Few teachers reported using assistive technology, providing…

  5. Behavioral Flexibility and Response Selection Are Impaired after Limited Exposure to Oxycodone

    Science.gov (United States)

    Seip-Cammack, Katharine M.; Shapiro, Matthew L.

    2014-01-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on…

  6. Effect of functional electrostimulation on impaired skin vasodilator responses to local heating in spinal cord injury.

    NARCIS (Netherlands)

    Duijnhoven, N.T.L. van; Janssen, T.W.; Green, D.J.; Minson, C.T.; Hopman, M.T.E.; Thijssen, D.H.J.

    2009-01-01

    Spinal cord injury (SCI) induces vascular adaptations below the level of the lesion, such as impaired cutaneous vasodilation. However, the mechanisms underlying these differences are unclear. The aim of this study is to examine arm and leg cutaneous vascular conductance (CVC) responses to local heat

  7. Principles of adaptive optics

    CERN Document Server

    Tyson, Robert

    2010-01-01

    History and BackgroundIntroductionHistoryPhysical OpticsTerms in Adaptive OpticsSources of AberrationsAtmospheric TurbulenceThermal BloomingNonatmospheric SourcesAdaptive Optics CompensationPhase ConjugationLimitations of Phase ConjugationArtificial Guide StarsLasers for Guide StarsCombining the LimitationsLinear AnalysisPartial Phase ConjugationAdaptive Optics SystemsAdaptive Optics Imaging SystemsBeam Propagation Syst

  8. Impaired glycemia increases disease progression in mild cognitive impairment

    OpenAIRE

    Morris, Jill K.; Vidoni, Eric D.; Honea, Robyn A.; Burns, Jeffrey M.

    2013-01-01

    Insulin resistance and Type 2 Diabetes are associated with cognitive decline and increased risk for Alzheimer’s disease (AD). Relatively few studies have assessed the impact of metabolic dysfunction on conversion to AD in mild cognitive impairment (MCI), and it is unclear whether glycemic status is associated with clinically-relevant measures of cognitive decline and brain structure in MCI. This study used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to examine the relation...

  9. 阿尔茨海默病转基因小鼠早期记忆功能障碍与氧化应激损伤关系的实验研究%Relationship between early memory impairment and oxidative stress in transgenic mouse model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    刘柳; 毛妮; 郝键; 张文均; 叶芸; 张巍; 苗建亭

    2011-01-01

    Objective To investigate the spatial learning and memory ability,the changes of indicators of oxidative stress,and their relationship in transgenic APP/PS1 mouse model of Alzheimer's disease(APP/PS1 mice). Methods The spatial learning and memory ability were assessed by Morris water maze test,and the activity or content of SOD, GSH-PX, MDA, and protein carbonyl in brain tissues were measured by ELISA in the APP/PS1 and wild type (WT) mice. Furthermore, the relationship between the learning and memory performances and the indicators of oxidative stress was examined. Results No significant difference in the spatial learning was observed between the APP/PS1 and WT mice (P <0. 05). The spatial memory which was measured as the percentage of time traveling in the targeted quadrant to the total traveling time was significantlydeclined in the APP/PS1 mice(29. 02 ± 4. 27) % as compared with the WT mice(47. 39 ± 6. 01) %(t =0. 000 ,P <0. 05). The percentage of length of traveling in the targeted quadrant to the total length traveled was significantly lower in the APP/PS1 mice(28. 85 ±3.77)% compared with the WT mice(46. 70 ±5.60)% (t =0. 000,P <0. 05). These findings indicated that the spatial learning and memory ability of APP/PS1 mice was significantly decreased compared to WT mice. There was no significant difference in activity or content of SOD,GSH-PX,and MDA in brain tissues between the APP/PS1 and WT mice (P < 0. 05), while the content of protein carbonyl was significantly elevated in the APP/PS1 mice (2. 67 ±0. 19) than in the WT mice (2. 38 ±0. 15)(t = 0. 008, P < 0. 05). Correlation analysis revealed that the elevated protein carbonyl was negatively correlated with the percentage of length traveled in the targeted quadrant(r = - 0. 639, P < 0. 05) and the percentage of time traveled in the targeted quadrant(r = - 0. 636 ,P < 0. 05). Conclusion The spatial memory impairment was negatively correlated with the elevated protein carbonyl in the APP

  10. Adaptation to climate change

    NARCIS (Netherlands)

    J. Carmin; K. Tierney; E. Chu; L.M. Hunter; J.T. Roberts; L. Shi

    2015-01-01

    Climate change adaptation involves major global and societal challenges such as finding adequate and equitable adaptation funding and integrating adaptation and development programs. Current funding is insufficient. Debates between the Global North and South center on how best to allocate the financ

  11. Protein oxidation and ageing

    DEFF Research Database (Denmark)

    Linton, S; Davies, Michael Jonathan; Dean, R T

    2001-01-01

    of redox-active metal ions that could catalyse oxidant formation. As a result of this decrease in antioxidant defences, and increased rate of ROS formation, it is possible that the impact of ROS increases with age. ROS are known to oxidise biological macromolecules, with proteins an important target....... If the argument that the impact of ROS increases with age is true, then proteins would be expected to accumulate oxidised materials with age, and the rate of such accumulation should increase with time, reflecting impaired inefficiency of homeostasis. Here we review the evidence for the accumulation of oxidised......, or modified, extra- and intra-cellular proteins in vivo....

  12. Verbal learning impairment in euthymic bipolar disorder: BDI v BDII

    OpenAIRE

    Bourne, Corin; Bilderbeck, Amy; Drennan, Rebecca; Atkinson, Lauren; Price, Jonathan; Geddes, John R.; Goodwin, Guy M.

    2015-01-01

    Objectives Cognitive impairment is known to occur in bipolar disorder (BD), even in euthymic patients, with largest effect sizes often seen in Verbal Learning and Memory Tasks (VLT). However, comparisons between BD Type-I and Type-II have produced inconsistent results partly due to low sample sizes. Methods This study compared the performance of 183 BDI with 96 BDII out-patients on an adapted version of the Rey Verbal Learning Task. Gender, age, years of education, mood scores and age at onse...

  13. Saccade adaptation in autism and Asperger's disorder.

    Science.gov (United States)

    Johnson, B P; Rinehart, N J; White, O; Millist, L; Fielding, J

    2013-07-23

    Autism and Asperger's disorder (AD) are neurodevelopmental disorders primarily characterized by deficits in social interaction and communication, however motor coordination deficits are increasingly recognized as a prevalent feature of these conditions. Although it has been proposed that children with autism and AD may have difficulty utilizing visual feedback during motor learning tasks, this has not been directly examined. Significantly, changes within the cerebellum, which is implicated in motor learning, are known to be more pronounced in autism compared to AD. We used the classic double-step saccade adaptation paradigm, known to depend on cerebellar integrity, to investigate differences in motor learning and the use of visual feedback in children aged 9-14 years with high-functioning autism (HFA; IQ>80; n=10) and AD (n=13). Performance was compared to age and IQ matched typically developing children (n=12). Both HFA and AD groups successfully adapted the gain of their saccades in response to perceived visual error, however the time course for adaptation was prolonged in the HFA group. While a shift in saccade dynamics typically occurs during adaptation, we revealed aberrant changes in both HFA and AD groups. This study contributes to a growing body of evidence centrally implicating the cerebellum in ocular motor dysfunction in autism. Specifically, these findings collectively imply functional impairment of the cerebellar network and its inflow and outflow tracts that underpin saccade adaptation, with greater disturbance in HFA compared to AD. PMID:23562581

  14. Perioperative care of the visually impaired.

    Science.gov (United States)

    Dobson, F

    1991-07-01

    Eighty-three per cent of sensory input is received optically. Sight impaired patients thus experience substantial sensory deficit, so nursing any visually impaired patient through surgery requires special considerations.

  15. 20 CFR 404.1523 - Multiple impairments.

    Science.gov (United States)

    2010-04-01

    ....1523 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and Blindness Evaluation of Disability § 404.1523 Multiple... combination of impairments, the combined impact of the impairments will be considered throughout...

  16. Markers of neurodevelopmental impairments in early-onset psychosis

    Directory of Open Access Journals (Sweden)

    Petruzzelli MG

    2015-07-01

    Full Text Available Maria Giuseppina Petruzzelli,1 Lucia Margari,1 Francesco Craig,1 Maria Gloria Campa,1 Domenico Martinelli,2 Adriana Pastore,3 Marta Simone,1 Francesco Margari3 1Child and Adolescence Neuropsychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University “Aldo Moro” of Bari, 2Department of Medical and Surgical Sciences; University of Foggia, Foggia, 3Psychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organ, University “Aldo Moro” of Bari, Bari, Italy Background: The aim of this study was to assess the association between the clinical and neurobiological markers of neurodevelopmental impairments and early-onset schizophrenia spectrum psychosis. Methods: A sample of 36 patients with early-onset schizophrenia spectrum psychosis was compared to a control sample of 36 patients with migraine. We assessed early childhood neurodevelopmental milestones using a modified version of the General Developmental Scale, general intellectual ability using the Wechsler Intelligence Scale for Children–Revised or Leiter International Performance Scale–Revised for patients with speech and language abnormalities, and neurological soft signs with specific regard to subtle motor impairment. Results: Subjects with early-onset psychosis had a higher rate of impaired social development (P=0.001, learning difficulties (P=0.04, enuresis (P=0.0008, a lower intelligence quotient (P<0.001, and subtle motor impairments (P=0.005 than control subjects. Conclusion: We suggest that neurodevelopment in early-onset psychosis is characterized by a global impairment of functional and adaptive skills that manifests from early childhood, rather than a delay or limitation in language and motor development. The current evidence is based on a small sample and should be investigated in larger samples in future research. Keywords: early-onset psychosis, early-onset schizophrenia, neurodevelopment, social cognition

  17. Impairments of astrocytes are involved in the D-galactose-induced brain aging

    International Nuclear Information System (INIS)

    Astrocyte dysfunction is implicated in course of various age-related neurodegenerative diseases. Chronic injection of D-galactose can cause a progressive deterioration in learning and memory capacity and serve as an animal model of aging. To investigate the involvement of astrocytes in this model, oxidative stress biomarkers, biochemical and pathological changes of astrocytes were examined in the hippocampus of the rats with six weeks of D-galactose injection. D-galactose-injected rats displayed impaired antioxidant systems, an increase in nitric oxide levels, and a decrease in reduced glutathione levels. Consistently, western blotting and immunostaining of glial fibrillary acidic protein showed extensive activation of astrocytes. Double-immunofluorescent staining further showed activated astrocytes highly expressed inducible nitric oxide synthase. Electron microscopy demonstrated the degeneration of astrocytes, especially in the aggregated area of synapse and brain microvessels. These findings indicate that impairments of astrocytes are involved in oxidative stress-induced brain aging by chronic injection of D-galactose

  18. Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model.

    Science.gov (United States)

    Keller, Amy C; Knaub, Leslie A; McClatchey, P Mason; Connon, Chelsea A; Bouchard, Ron; Miller, Matthew W; Geary, Kate E; Walker, Lori A; Klemm, Dwight J; Reusch, Jane E B

    2016-01-01

    Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets. PMID:27034743

  19. Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model

    Directory of Open Access Journals (Sweden)

    Amy C. Keller

    2016-01-01

    Full Text Available Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS, and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS- mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK and the Wistar control rat were exposed to high glucose (25 mM. At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p<0.05. Mitochondrial superoxide increased with high glucose in Wistar SMCs (p<0.05 with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets.

  20. Endocrine Risk Factors for Cognitive Impairment

    OpenAIRE

    Moon, Jae Hoon

    2016-01-01

    Cognitive impairment, including Alzheimer's disease and other kinds of dementia, is a major health problem in older adults worldwide. Although numerous investigators have attempted to develop effective treatment modalities or drugs, there is no reasonably efficacious strategy for preventing or recovering from cognitive impairment. Therefore, modifiable risk factors for cognitive impairment have received attention, and the growing literature of metabolic risk factors for cognitive impairment h...

  1. Diagnosis advances in vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    Hua Zhou; Zhong Zhao

    2009-01-01

    Vascular cognitive impairment(VCI) encompasses the entire range of cognitive deficits associated with cerebrovascular disease(CVD), from mild deficits with little or no functional impairment, such as vascular cognitive impairment-no dementia(VCIND), to full-blown vascular dementia(VaD). Accurate diagnosis of vascular cognitive impairment is important but may be difficult. In this review we report advances in VCI in the following areas: etiology, subtypes, neuropsychology, biomarkers, neuroimaging, and diagnostic criteria.

  2. Oxidative Stress and Anxiety: Relationship and Cellular Pathways

    OpenAIRE

    Jaouad Bouayed; Hassan Rammal; Rachid Soulimani

    2009-01-01

    High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal ...

  3. Impaired sleep and allostatic load

    DEFF Research Database (Denmark)

    Clark, Alice Jessie; Dich, Nadya; Lange, Theis;

    2014-01-01

    Objective: Understanding the mechanisms linking sleep impairment to morbidity and mortality is important for future prevention, but these mechanisms are far from elucidated. We aimed to determine the relation between impaired sleep, both in terms of duration and disturbed sleep, and allostatic load...... Biobank with comprehensive information on sleep duration, disturbed sleep, objective measures of an extensive range of biological risk markers, and physical conditions. Results: Long sleep (mean difference 0.23; 95% confidence interval, 0.13, 0.32) and disturbed sleep (0.14; 0.06, 0.22) were associated...... with higher AL as well as with high-risk levels of risk markers from the anthropometric, metabolic, and immune system. Sub-analyses suggested that the association between disturbed sleep and AL might be explained by underlying disorders. Whereas there was no association between short sleep and AL...

  4. Nutrition in neurologically impaired children

    OpenAIRE

    2009-01-01

    Malnutrition, either under- or overnutrition, is a common condition among neurologically impaired children. Energy needs are difficult to define in this heterogeneous population, and there is a lack of information on what normal growth should be in these children. Non-nutritional factors may influence growth, but nutritional factors such as insufficient caloric intake, excessive nutrient losses and abnormal energy metabolism also contribute to growth failure. Malnutrition is associated with s...

  5. Multilingualism and Specific Language Impairment

    OpenAIRE

    Engel de Abreu, Pascale

    2014-01-01

    Is a multilingual education beneficial for children? What are the optimal conditions under which a child can become perfectly multilingual? When should we be concerned about a multilingual child's language skills? What are the signs of Specific Language Impairment in a child who speaks more than one language? Developmental psychologist and Associate Professor in multilingual cognitive development at the University of Luxembourg Pascale Engel de Abreu will address these questions based on what...

  6. Electrophysiology in visually impaired children

    OpenAIRE

    Genderen, Maria Michielde van

    2006-01-01

    Inherited retinal disorders and posterior visual pathway abnormalities are important causes of visual impairment in children. Visual electrophysiology often is indispensable in diagnosing these conditions. This thesis shows the wide range of use of pediatric electro-ophthalmology, and demonstrates its value in establishing diagnoses and predicting the course of a disease, with consequences for the rehabilitation process. The electrophysiological results also contribute to the understanding of...

  7. Impaired Leydig cell function in infertile men

    DEFF Research Database (Denmark)

    Andersson, A-M; Jørgensen, N; Frydelund-Larsen, L;

    2004-01-01

    of the fertile levels.Thus, the group of infertile men showed significant signs of impaired Leydig cell function in parallel to their impaired spermatogenesis. The association of decreased spermatogenesis and impaired Leydig cell function might reflect a disturbed paracrine communication between the seminiferous...

  8. Alcohol and the Physically Impaired: Special Focus.

    Science.gov (United States)

    Boros, Alexander, Ed.

    1989-01-01

    The articles in this special issue explore the connections between the dual disabilities of alcohol abuse and physical impairment, and reflect progress made in exploring the causes and treatments of alcohol abuse among the physically impaired. Selected articles include: "Results of a Model Intervention Program for Physically Impaired Persons"…

  9. Inferential Functioning in Visually Impaired Children

    Science.gov (United States)

    Puche-Navarro, Rebeca; Millan, Rafael

    2007-01-01

    The current study explores the inferential abilities of visually impaired children in a task presented in two formats, manipulative and verbal. The results showed that in the group of visually impaired children, just as with children with normal sight, there was a wide range of inference types. It was found that the visually impaired children…

  10. Cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Cosgrove, Jeremy; Alty, Jane Elizabeth; Jamieson, Stuart

    2015-04-01

    Cognitive impairment is a significant non-motor symptom of Parkinson's disease (PD). Longitudinal cohort studies have demonstrated that approximately 50% of those with PD develop dementia after 10 years, increasing to over 80% after 20 years. Deficits in cognition can be identified at the time of PD diagnosis in some patients and this mild cognitive impairment (PD-MCI) has been studied extensively over the last decade. Although PD-MCI is a risk factor for developing Parkinson's disease dementia there is evidence to suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. The major pathological correlate of Parkinson's disease dementia is Lewy body deposition in the limbic system and neocortex although Alzheimer's related pathology is also an important contributor. Pathological damage causes alteration to neurotransmitter systems within the brain, producing behavioural change. Management of cognitive impairment in PD requires a multidisciplinary approach and accurate communication with patients and relatives is essential. PMID:25814509

  11. Protective Effects of Punica Granatum Seeds Extract Against Aging and Scopolamine Induced Cognitive Impairments in Mice

    OpenAIRE

    Kumar, Sokindra; Maheshwari, Kamal Kishore; Singh, Vijender

    2008-01-01

    Dementia is one of the age related mental problems and characteristic symptom of various neurodegenerative diseases including Alzheimer's disease. This impairment probably is due to the vulnerability of the brain cells to increased oxidative stress during aging process. Many studies have shown that certain phenolic antioxidants attenuate neuronal cell death induced by oxidative stress. The present work was undertaken to assess the effect of ethanolic extract of Punica granatum seeds on cognit...

  12. The trypanocidal benznidazole promotes adaptive response to oxidative injury: Involvement of the nuclear factor-erythroid 2-related factor-2 (Nrf2) and multidrug resistance associated protein 2 (MRP2).

    Science.gov (United States)

    Rigalli, Juan Pablo; Perdomo, Virginia Gabriela; Ciriaci, Nadia; Francés, Daniel Eleazar Antonio; Ronco, María Teresa; Bataille, Amy Michele; Ghanem, Carolina Inés; Ruiz, María Laura; Manautou, José Enrique; Catania, Viviana Alicia

    2016-08-01

    Oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. Benznidazole (BZL) is the only trypanocidal agent available for treatment of Chagas disease in endemic areas. Its use is associated with side effects, including increases in biomarkers of hepatotoxicity. However, BZL potential to cause oxidative stress has been poorly investigated. Here, we evaluated the effect of a pharmacologically relevant BZL concentration (200μM) at different time points on redox status and the counteracting mechanisms in the human hepatic cell line HepG2. BZL increased reactive oxygen species (ROS) after 1 and 3h of exposure, returning to normality at 24h. Additionally, BZL increased glutathione peroxidase activity at 12h and the oxidized glutathione/total glutathione (GSSG/GSSG+GSH) ratio that reached a peak at 24h. Thus, an enhanced detoxification of peroxide and GSSG formation could account for ROS normalization. GSSG/GSSG+GSH returned to control values at 48h. Expression of the multidrug resistance-associated protein 2 (MRP2) and GSSG efflux via MRP2 were induced by BZL at 24 and 48h, explaining normalization of GSSG/GSSG+GSH. BZL activated the nuclear erythroid 2-related factor 2 (Nrf2), already shown to modulate MRP2 expression in response to oxidative stress. Nrf2 participation was confirmed using Nrf2-knockout mice in which MRP2 mRNA expression was not affected by BZL. In summary, we demonstrated a ROS increase by BZL in HepG2 cells and a glutathione peroxidase- and MRP2 driven counteracting mechanism, being Nrf2 a key modulator of this response. Our results could explain hepatic alterations associated with BZL therapy. PMID:27180241

  13. Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella Pneumoniae in mice

    Directory of Open Access Journals (Sweden)

    Patterson Craig M

    2012-05-01

    Full Text Available Abstract Background Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS fluticasone propionate (FP. There is limited work describing FP effects on host defenses against bacterial pneumonia. Methods C57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with Klebsiella pneumoniae. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured. Results Inhaled FP increased bacterial burden in lungs and blood 48 h after infection but affected neither in vivo phagocytosis of bacteria by alveolar macrophages (AM nor alveolar neutrophil recruitment. AM from FP-treated mice showed impaired expression of infection induced TNF-alpha, IP-10 (CXCL-10, and interleukin 6 (IL-6, and AM also showed a trend towards impaired intracellular pathogen control following in vivo infection. In vitro FP treatment resulted in a dose-dependent impairment of cytokine expression by AM. Furthermore, infection-induced nitric oxide (but not hydrogen peroxide production was impaired by FP in vivo and in vitro. FP decreased survival in this model. Conclusions Exposure to inhaled FP impairs pulmonary clearance of K. pneumoniae in mice, an effect associated with greater systemic bacteremia and death. Decreased AM cytokine and nitric oxide expression parallel the failure to control infection. These results support the study of ICS effects on human pulmonary host defenses.

  14. Hyperglycaemia and diabetes impair gap junctional communication among astrocytes

    Directory of Open Access Journals (Sweden)

    Gautam K Gandhi

    2010-03-01

    Full Text Available Sensory and cognitive impairments have been documented in diabetic humans and animals, but the pathophysiology of diabetes in the central nervous system is poorly understood. Because a high glucose level disrupts gap junctional communication in various cell types and astrocytes are extensively coupled by gap junctions to form large syncytia, the influence of experimental diabetes on gap junction channel-mediated dye transfer was assessed in astrocytes in tissue culture and in brain slices from diabetic rats. Astrocytes grown in 15–25 mmol/l glucose had a slow-onset, poorly reversible decrement in gap junctional communication compared with those grown in 5.5 mmol/l glucose. Astrocytes in brain slices from adult STZ (streptozotocin-treated rats at 20–24 weeks after the onset of diabetes also exhibited reduced dye transfer. In cultured astrocytes grown in high glucose, increased oxidative stress preceded the decrement in dye transfer by several days, and gap junctional impairment was prevented, but not rescued, after its manifestation by compounds that can block or reduce oxidative stress. In sharp contrast with these findings, chaperone molecules known to facilitate protein folding could prevent and rescue gap junctional impairment, even in the presence of elevated glucose level and oxidative stress. Immunostaining of Cx (connexin 43 and 30, but not Cx26, was altered by growth in high glucose. Disruption of astrocytic trafficking of metabolites and signalling molecules may alter interactions among astrocytes, neurons and endothelial cells and contribute to changes in brain function in diabetes. Involvement of the microvasculature may contribute to diabetic complications in the brain, the cardiovascular system and other organs.

  15. ANALYSIS OF BIOLOGICAL SCIENCES FOR TEACHING STUDENTS WITH VISUAL IMPAIRMENT IN DISTRITO FEDERAL’S SCHOOLS

    Directory of Open Access Journals (Sweden)

    Júlia Carvalho Mota de Souza

    2014-05-01

    Full Text Available Visual impairment is a limitation that occurs in the sensory part of the vision, and can be classified as blindness, low vision or subnormal vision. The people with visually impaired have guaranteed rights to study in regular schools or special education schools. Therefore, a differentiated teaching is necessary for the learning of visually impaired students to happen effectively and ensure educational inclusion within the school. The aim of this study was to qualitatively analyze the teaching of Biological Sciences for the visually impaired in schools of the Distrito Federal, noting the institution, teachers and visually impaired students. The study was conducted using semi-structured interviews analyzed epistemologically. The results showed that: the institutions do not have adequate physical infrastructure; Biology teachers have no qualifications required; teachers of resource rooms are able to meet visually impaired students, even if resources are not sufficient, and the students do not understand all the benefits they could have. Therefore, it is necessary to adapt the teaching and learning materials to allow for a better education for visually impaired students and thus ensure appropriate learning for all students within the same educational institution.

  16. Teacher perceptions of communication impairment at screening stage in preschool children living in Patras, Greece.

    Science.gov (United States)

    Okalidou, A; Kampanaros, M

    2001-01-01

    The general aim was to obtain piloting data for a series of experiments about the prevalence of communication impairment in preschool children in Greece. At this screening stage of the overall project, teacher perceptions of communication impairment in 57 kindergartens servicing 1113 children were examined via a questionnaire distributed in the urban region of Patras. The specific research goals were (1) to screen for specific categories of communication impairment such as articulation/phonology, receptive language, expressive language and pragmatics, hearing, stuttering, and voice, as they appear in the mainstreamed kindergarten population and (2) to offer comparative information on sex differences in communication impairment(s). The information was gathered by administration of a Greek-adapted version of the Communication Checklist for Pre-school Teachers, which was administered three times to obtain validity and reliability measures. The results were analysed separately for two studies (original and follow-up) and indicated teacher estimates of 14.4-18.7% for communication impairment in kindergarten children of the Patras region. Prevalence was higher for boys than for girls. Analysis of specific communication areas revealed that prevalence varies according to gender and category of communicative impairment. The limitations and follow-up needs of this study are discussed.

  17. Neuromuscular adaptations to electrostimulation resistance training.

    Science.gov (United States)

    Maffiuletti, Nicola A; Zory, Raphael; Miotti, Danilo; Pellegrino, Maria A; Jubeau, Marc; Bottinelli, Roberto

    2006-02-01

    A combination of in vivo and in vitro analyses was performed to investigate muscular and neural adaptations of the weaker (nondominant) quadriceps femoris muscle of one healthy individual to short-term electrostimulation resistance training. The increase in maximal voluntary strength (+12%) was accompanied by neural (cross-education effect and increased muscle activation) and muscle adaptations (impairment of whole-muscle contractile properties). Significant changes in myosin heavy chain (MHC) isoforms relative content (+22% for MHC-2A and -28% for MHC-2X), single-fiber cross-sectional area (+27% for type 1 and +6% for type 2A muscle fibers), and specific tension of type 1 (+67%) but not type 2A fibers were also observed after training. Plastic changes in neural control confirm the possible involvement of both spinal and supraspinal structures to electrically evoked contractions. Changes at the single muscle fiber level induced by electrostimulation resistance training were significant and preferentially affected slow, type 1 fibers.

  18. Quality assessment of adaptive 3D video streaming

    Science.gov (United States)

    Tavakoli, Samira; Gutiérrez, Jesús; García, Narciso

    2013-03-01

    The streaming of 3D video contents is currently a reality to expand the user experience. However, because of the variable bandwidth of the networks used to deliver multimedia content, a smooth and high-quality playback experience could not always be guaranteed. Using segments in multiple video qualities, HTTP adaptive streaming (HAS) of video content is a relevant advancement with respect to classic progressive download streaming. Mainly, it allows resolving these issues by offering significant advantages in terms of both user-perceived Quality of Experience (QoE) and resource utilization for content and network service providers. In this paper we discuss the impact of possible HAS client's behavior while adapting to the network capacity on enduser. This has been done through an experiment of testing the end-user response to the quality variation during the adaptation procedure. The evaluation has been carried out through a subjective test of the end-user response to various possible clients' behaviors for increasing, decreasing, and oscillation of quality in 3D video. In addition, some of the HAS typical impairments during the adaptation has been simulated and their effects on the end-user perception are assessed. The experimental conclusions have made good insight into the user's response to different adaptation scenarios and visual impairments causing the visual discomfort that can be used to develop the adaptive streaming algorithm to improve the end-user experience.

  19. Technology transfer for adaptation

    Science.gov (United States)

    Biagini, Bonizella; Kuhl, Laura; Gallagher, Kelly Sims; Ortiz, Claudia

    2014-09-01

    Technology alone will not be able to solve adaptation challenges, but it is likely to play an important role. As a result of the role of technology in adaptation and the importance of international collaboration for climate change, technology transfer for adaptation is a critical but understudied issue. Through an analysis of Global Environment Facility-managed adaptation projects, we find there is significantly more technology transfer occurring in adaptation projects than might be expected given the pessimistic rhetoric surrounding technology transfer for adaptation. Most projects focused on demonstration and early deployment/niche formation for existing technologies rather than earlier stages of innovation, which is understandable considering the pilot nature of the projects. Key challenges for the transfer process, including technology selection and appropriateness under climate change, markets and access to technology, and diffusion strategies are discussed in more detail.

  20. Diffusion Adaptation over Networks

    CERN Document Server

    Sayed, Ali H

    2012-01-01

    Adaptive networks are well-suited to perform decentralized information processing and optimization tasks and to model various types of self organized and complex behavior encountered in nature. Adaptive networks consist of a collection of agents with processing and learning abilities. The agents are linked together through a connection topology, and they cooperate with each other through local interactions to solve distributed inference problems in real-time. The continuous diffusion of information across the network enables agents to adapt their performance in relation to changing data and network conditions; it also results in improved adaptation and learning performance relative to non-cooperative networks. This article provides an overview of diffusion strategies for adaptation and learning over networks. The article is divided into several sections: 1. Motivation; 2. Mean-Square-Error Estimation; 3. Distributed Optimization via Diffusion Strategies; 4. Adaptive Diffusion Strategies; 5. Performance of Ste...

  1. Origins of adaptive immunity.

    Science.gov (United States)

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  2. Functional MRI in investigating cognitive impairment in multiple sclerosis.

    Science.gov (United States)

    Rocca, M A; De Meo, E; Filippi, M

    2016-09-01

    There is increasing evidence that the severity of the clinical manifestations of multiple sclerosis (MS) does not simply result from the extent of tissue destruction, but it rather represents a complex balance between tissue damage, tissue repair, and cortical reorganization. Functional magnetic resonance imaging (fMRI) provides information about the plasticity of the human brain. Therefore, it has the potential to provide important pieces of information about brain reorganization following MS-related structural damage. When investigating cognitive systems, fMRI changes have been described in virtually all patients with MS and different clinical phenotypes. These functional changes have been related to the extent of brain damage within and outside T2-visible lesions as well as to the involvement of specific central nervous system structures. It has also been suggested that a maladaptive recruitment of specific brain regions might be associated with the appearance of clinical symptoms in MS, such as fatigue and cognitive impairment. fMRI studies from clinically (and cognitively) impaired MS patients may be influenced by different task performances between patients and controls. As a consequence, new strategies have been introduced to assess the role, if any, of brain reorganization in severely impaired patients, including the analysis of resting-state networks. The enhancement of any beneficial effects of this brain adaptive plasticity should be considered as a potential target of therapy for MS. PMID:27580905

  3. Communication Partners’ Journey through Their Partner’s Hearing Impairment

    Directory of Open Access Journals (Sweden)

    Vinaya K. C. Manchaiah

    2013-01-01

    Full Text Available The objective of this study was to further develop the Ida Institute model on communication partners’ (CPs journey through experiences of person with hearing impairment (PHI, based on the perspectives of CPs. Nine CPs of hearing aid users participated in this study, recruited through the Swansea hearing impaired support group. Semi-structured interviews were conducted, the data were analysed using qualitative thematic analysis and presented with the use of process mapping approach. Seven main phases were identified in the CP journey which includes: (1 contemplation, (2 awareness, (3 persuasion, (4 validation, (5 rehabilitation, (6 adaptation, and (7 resolution. The Ida Institute model (based on professionals’ perspective was compared with the new template developed (based on CPs’ perspectives. The results suggest some commonalities and differences between the views of professionals and CPs. A new phase, adaptation, was identified from CPs reported experiences, which was not identified by professionals in the Ida Institute model. The CP’s journey model could be a useful tool during audiological enablement/rehabilitation sessions to promote discussion between the PHI and the CP. In addition, it can be used in the training of hearing healthcare professionals.

  4. The Adaptive Organization

    DEFF Research Database (Denmark)

    Andersen, Torben Juul; Hallin, Carina Antonia

    2016-01-01

    Contemporary organizations operate under turbulent business conditions and must adapt their strategies to ongoing changes. This article argues that sustainable organizational performance is achieved when top management directs and coordinates interactive processes anchored in emerging organizatio......Contemporary organizations operate under turbulent business conditions and must adapt their strategies to ongoing changes. This article argues that sustainable organizational performance is achieved when top management directs and coordinates interactive processes anchored in emerging...... the adaptive organization....

  5. Human Adaptations: Free divers

    OpenAIRE

    Tournat, Troy Z.

    2014-01-01

    Freediving has been around for thousands of years and was only way to dive until the inventionof oxygen tanks in the 19th century. Around the world, people dove for goods such as pearls, andtoday people freedive for sport. Divers stretch the limit of their body and mind’s capabilitiesthrough psychological adaptations from thermal, respiratory, and cardiovascular responses.Findings conclude that thermal adaptations are a similar process to cold adaptive response. Withthe implementation of wets...

  6. Consciousness And Adaptive Behavior

    OpenAIRE

    Sieb, Richard/A.

    2005-01-01

    Consciousness has resisted scientific explanation for centuries. The main problem in explaining consciousness is its subjectivity. Subjective systems may be adaptive. Humans can produce voluntary new or novel intentional (adaptive) action and such action is always accompanied by consciousness. Action normally arises from perception. Perception must be rerepresented in order to produce new or novel adaptive action. The internal explicit states produced by a widespread nonlinear emergen...

  7. Quantifying the adaptive cycle

    Science.gov (United States)

    Angeler, David G.; Allen, Craig R.; Garmestani, Ahjond S.; Gunderson, Lance H.; Hjerne, Olle; Winder, Monika

    2015-01-01

    The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation) in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994–2011) data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and adaptation provides opportunities to cope with the intricacies and uncertainties associated with fast ecological change, driven by shifting system controls. Ultimately, combining traditional ecological paradigms with heuristics of complex system dynamics using quantitative approaches may help refine ecological theory and improve our understanding of the resilience of ecosystems.

  8. Adaptive Wireless Transceiver Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Wireless technologies are an increasingly attractive means for spatial data, input, manipulation, and distribution. Mobitrum is proposing an innovative Adaptive...

  9. Diabetes mellitus and cognitive impairments.

    Science.gov (United States)

    Saedi, Elham; Gheini, Mohammad Reza; Faiz, Firoozeh; Arami, Mohammad Ali

    2016-09-15

    There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer's disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings. PMID:27660698

  10. Impaired follistatin secretion in cirrhosis

    DEFF Research Database (Denmark)

    Rinnov, Anders Rasmussen; Plomgaard, Peter; Pedersen, Bente Klarlund;

    2016-01-01

    compared to healthy control participants. DESIGN, SETTING, PARTICIPANTS: To experimentally increase the glucagon-insulin ratio (mimicking the hormonal effect of exercise), we infused glucagon / somatostatin (to inhibit insulin secretion) and compared the acute follistatin increase in eight male cirrhosis...... compared to healthy controls (27.6 ± 3.8 % versus 34.5 ± 2.9 %, respectively; p = 0.001). CONCLUSIONS: Patients with cirrhosis show impaired capacity to acutely secrete follistatin. The decrease in acute follistatin release may contribute to loss of muscle mass in liver cirrhosis....

  11. Diabetes mellitus and cognitive impairments

    Science.gov (United States)

    Saedi, Elham; Gheini, Mohammad Reza; Faiz, Firoozeh; Arami, Mohammad Ali

    2016-01-01

    There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer’s disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings. PMID:27660698

  12. Ammonia-oxidizing archaea have more important role than ammonia-oxidizing bacteria in ammonia oxidation of strongly acidic soils

    OpenAIRE

    Zhang, Li-Mei; Hu, Hang-Wei; Shen, Ju-Pei; He, Ji-Zheng

    2011-01-01

    Increasing evidence demonstrated the involvement of ammonia-oxidizing archaea (AOA) in the global nitrogen cycle, but the relative contributions of AOA and ammonia-oxidizing bacteria (AOB) to ammonia oxidation are still in debate. Previous studies suggest that AOA would be more adapted to ammonia-limited oligotrophic conditions, which seems to be favored by protonation of ammonia, turning into ammonium in low-pH environments. Here, we investigated the autotrophic nitrification activity of AOA...

  13. Magnesium Oxide

    Science.gov (United States)

    Magnesium is an element your body needs to function normally. Magnesium oxide may be used for different reasons. Some ... to relieve heartburn, sour stomach, or acid indigestion. Magnesium oxide also may be used as a laxative ...

  14. Adaptive Multimedia Retrieval: Semantics, Context, and Adaptation

    DEFF Research Database (Denmark)

    This book constitutes the thoroughly refereed post-conference proceedings of the 10th International Conference on Adaptive Multimedia Retrieval, AMR 2012, held in Copenhagen, Denmark, in October 2012. The 17 revised full papers presented were carefully reviewed and selected from numerous submissi...

  15. Empathy in schizophrenia: impaired resonance.

    Science.gov (United States)

    Haker, Helene; Rössler, Wulf

    2009-09-01

    Resonance is the phenomenon of one person unconsciously mirroring the motor actions as basis of emotional expressions of another person. This shared representation serves as a basis for sharing physiological and emotional states of others and is an important component of empathy. Contagious laughing and contagious yawning are examples of resonance. In the interpersonal contact with individuals with schizophrenia we can often experience impaired empathic resonance. The aim of this study is to determine differences in empathic resonance-in terms of contagion by yawning and laughing-in individuals with schizophrenia and healthy controls in the context of psychopathology and social functioning. We presented video sequences of yawning, laughing or neutral faces to 43 schizophrenia outpatients and 45 sex- and age-matched healthy controls. Participants were video-taped during the stimulation and rated regarding contagion by yawning and laughing. In addition, we assessed self-rated empathic abilities (Interpersonal Reactivity Index), psychopathology (Positive and Negative Syndrome Scale in the schizophrenia group resp. Schizotypal Personality Questionnaire in the control group), social dysfunction (Social Dysfunction Index) and executive functions (Stroop, Fluency). Individuals with schizophrenia showed lower contagion rates for yawning and laughing. Self-rated empathic concern showed no group difference and did not correlate with contagion. Low rate of contagion by laughing correlated with the schizophrenia negative syndrome and with social dysfunction. We conclude that impaired resonance is a handicap for individuals with schizophrenia in social life. Blunted observable resonance does not necessarily reflect reduced subjective empathic concern. PMID:19377866

  16. [Postvagotomy adaptation syndrome].

    Science.gov (United States)

    Shapovalov, V A

    1998-01-01

    It was established in experiment, that the changes of the natural resistance of organism indexes and of the peritoneal cavity cytology has compensatory-adaptational character while the denervation-adaptational syndrome occurrence and progress, which may be assessed as eustress. Vagotomy and operative trauma cause qualitatively different reactions of an organism.

  17. Adaptive Wavelet Transforms

    Energy Technology Data Exchange (ETDEWEB)

    Szu, H.; Hsu, C. [Univ. of Southwestern Louisiana, Lafayette, LA (United States)

    1996-12-31

    Human sensors systems (HSS) may be approximately described as an adaptive or self-learning version of the Wavelet Transforms (WT) that are capable to learn from several input-output associative pairs of suitable transform mother wavelets. Such an Adaptive WT (AWT) is a redundant combination of mother wavelets to either represent or classify inputs.

  18. Behavioral Adaptation and Acceptance

    NARCIS (Netherlands)

    Martens, M.H.; Jenssen, G.D.

    2012-01-01

    One purpose of Intelligent Vehicles is to improve road safety, throughput, and emissions. However, the predicted effects are not always as large as aimed for. Part of this is due to indirect behavioral changes of drivers, also called behavioral adaptation. Behavioral adaptation (BA) refers to uninte

  19. Behavioural adaptation and acceptance

    NARCIS (Netherlands)

    Martens, M.H.; Jenssen, G.D.; Eskandarian, A.

    2012-01-01

    One purpose of Intelligent Vehicles is to improve road safety, throughput, and emissions. However, the predicted effects are not always as large as aimed for. Part of this is due to indirect behavioral changes of drivers, also called behavioral adaptation. Behavioral adaptation (BA) refers to uninte

  20. Validation of the Dutch version of the quick mild cognitive impairment screen (Qmci-D).

    LENUS (Irish Health Repository)

    Bunt, Steven

    2015-10-01

    Differentiating mild cognitive impairment (MCI) from dementia is important, as treatment options differ. There are few short (<5 min) but accurate screening tools that discriminate between MCI, normal cognition (NC) and dementia, in the Dutch language. The Quick Mild Cognitive Impairment (Qmci) screen is sensitive and specific in differentiating MCI from NC and mild dementia. Given this, we adapted the Qmci for use in Dutch-language countries and validated the Dutch version, the Qmci-D, against the Dutch translation of the Standardised Mini-Mental State Examination (SMMSE-D).

  1. Oxidative stress and DNA repair and detoxification gene expression in adolescents exposed to heavy metals living in the Milazzo-Valle del Mela area (Sicily, Italy

    Directory of Open Access Journals (Sweden)

    Gabriele Pizzino

    2014-01-01

    Conclusions: Continuous exposure at relatively low concentrations of heavy metals is associated with increased oxidative DNA damage and impaired expression of DNA repair and detoxification genes in adolescents.

  2. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s)....

  3. Adaptive noise cancellation

    CERN Document Server

    Akram, N

    1999-01-01

    In this report we describe the concept of adaptive noise canceling, an alternative method of estimating signals corrupted by additive noise of interference. The method uses 'primary' input containing the corrupted signal and a 'reference' input containing noise correlated in some unknown way with the primary noise, the reference input is adaptively filtered and subtracted from the primary input to obtain the signal estimate. Adaptive filtering before subtraction allows the treatment of inputs that are deterministic or stochastic, stationary or time variable. When the reference input is free of signal and certain other conditions are met then noise in the primary input can be essentially eliminated without signal distortion. It is further shown that the adaptive filter also acts as notch filter. Simulated results illustrate the usefulness of the adaptive noise canceling technique.

  4. Appraising Adaptive Management

    Directory of Open Access Journals (Sweden)

    Kai N. Lee

    1999-12-01

    Full Text Available Adaptive management is appraised as a policy implementation approach by examining its conceptual, technical, equity, and practical strengths and limitations. Three conclusions are drawn: (1 Adaptive management has been more influential, so far, as an idea than as a practical means of gaining insight into the behavior of ecosystems utilized and inhabited by humans. (2 Adaptive management should be used only after disputing parties have agreed to an agenda of questions to be answered using the adaptive approach; this is not how the approach has been used. (3 Efficient, effective social learning, of the kind facilitated by adaptive management, is likely to be of strategic importance in governing ecosystems as humanity searches for a sustainable economy.

  5. Adaptive signal processor

    International Nuclear Information System (INIS)

    An experimental, general purpose adaptive signal processor system has been developed, utilizing a quantized (clipped) version of the Widrow-Hoff least-mean-square adaptive algorithm developed by Moschner. The system accommodates 64 adaptive weight channels with 8-bit resolution for each weight. Internal weight update arithmetic is performed with 16-bit resolution, and the system error signal is measured with 12-bit resolution. An adapt cycle of adjusting all 64 weight channels is accomplished in 8 μsec. Hardware of the signal processor utilizes primarily Schottky-TTL type integrated circuits. A prototype system with 24 weight channels has been constructed and tested. This report presents details of the system design and describes basic experiments performed with the prototype signal processor. Finally some system configurations and applications for this adaptive signal processor are discussed

  6. When sustained attention impairs perception

    OpenAIRE

    Ling, Sam; Carrasco, Marisa

    2006-01-01

    Virtually all behavioral and neurophysiological studies have shown that sustained (endogenous, conceptually driven) attention enhances perception. But can this enhancement be held indefinitely? We assessed the time course of attention’s effects on contrast sensitivity, reasoning that if attention does indeed boost stimulus strength, the strengthened representation could result in stronger adaptation over time. We found that attention initially enhances contrast sensitivity, but that over time...

  7. Visual Impairments in Children with Cerebral Palsy

    OpenAIRE

    Alimović, Sonja

    2012-01-01

    Cerebral palsy (CP) is the neurological developmental disorder mainly affecting motor abilities. Considering the high rate of associated impairments even the definition of CP is revised and changed. Visual impairment is one of the most common associated impairment. Unfortunately, it is often unrecognized and considered to be a normal consequence of motor problems. Sense of sight is most important for early child development, motivation, learning through imitation. It is, therefore, indispensa...

  8. Vascular cognitive impairment, a cardiovascular complication

    OpenAIRE

    Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah

    2016-01-01

    Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke an...

  9. The Differences Between Revaluation and Assets Impairment

    Directory of Open Access Journals (Sweden)

    BOBIȚAN Nicolae

    2013-05-01

    Full Text Available Impairment and revaluation are terms closely related to one another, with subtle differences. Revaluation and impairment both require the company to evaluate the assets for their fair value, and then take appropriate action in updating the accounting books. The major difference between the two is that a revaluation can be made upwards (to increase the value of the asset to market value or downwards (to ecrease the value. An impairment, on the other hand, only refers to one of the two, a fall in the market value which is then written down. The purpose of the paper is to establish what are the differences between revaluation and impairment of assets.

  10. Information entropy-based fitting of the disease trajectory of brain ischemia-induced vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    Lin Liu; Ju Huo; Ying Zhao; Yu Tian

    2012-01-01

    The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories.Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model.The fitting curves for each factor were obtained using Matlab software.Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors.Our results demonstrated that vascular cognitive impairment involves multiple factors.These factors include excitatory amino acid toxicity and nitric oxide toxicity.These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury.

  11. Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability

    OpenAIRE

    Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E.; Lacy, D. Brooks; McGuinness, Owen P.

    2009-01-01

    Glucose, fat, and glucagon availability are increased in diabetes. The normal response of the liver to chronic increases in glucose availability is to adapt to become a marked consumer of glucose. Yet this fails to occur in diabetes. The aim was to determine whether increased glucagon and lipid interact to impair the adaptation to increased glucose availability. Chronically catheterized well controlled depancreatized conscious dogs (n = 21) received 3 days of continuous parenteral nutrition (...

  12. Cognitive impairment related changes in the elemental concentration in the brain of old rat

    Energy Technology Data Exchange (ETDEWEB)

    Serpa, R.F.B. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil)]. E-mail: renata@lin.ufrj.br; Jesus, E.F.O. de [University of Rio de Janeiro State, Physics Institute, RJ (Brazil); Anjos, M.J. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil); University of Rio de Janeiro State, Physics Institute, RJ (Brazil); Lopes, R.T. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil); Carmo, M.G.T. do [Federal University of Rio de Janeiro, Nutrition Institute, RJ (Brazil); Rocha, M.S. [Federal University of Rio de Janeiro, Department of Basics and Clinic Pharmacy, RJ (Brazil); Rodrigues, L.C. [Federal University of Rio de Janeiro, Department of Basics and Clinic Pharmacy, RJ (Brazil); Moreira, S. [University of Campinas State, Civil Engineering Department, SP (Brazil); Martinez, A.M.B. [Federal University of Rio de Janeiro, Department of Histology and Embryology, RJ (Brazil)

    2006-11-15

    In order to evaluate the elemental concentration as a function of learning and memory deficiency, six different structures of the brain were analyzed by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). To evaluate the cognitive processes, the animals were tested in an adaptation of the Morris water maze. After the test, the animals were divided into two groups: cognitively healthy (control group) and cognitively impaired. The measurements were carried out at XRF beam line at Light Synchrotron Brazilian laboratory, Campinas, Brazil. The following elements were identified: Al, P, S, Cl, K, Ca, Ti, Cr, Fe, Cu, Zn, Br and Rb. K concentration was higher in all regions of the brain studied for control group than the cognitively impaired group. Moreover, the control group presented higher levels for P and Fe in the entorhinal cortex, in the temporal cortex (only P), in the hypothalamus and in the thalamus, than the cognitively impaired group. Br concentration in the animals which presented cognitive impairment was three times larger in the hypothalamus and thalamus, twice larger in temporal cortex and higher in visual cortex than the cognitively healthy group. Cu was more remarkable in the hippocampus and hypothalamus from the animals with cognitive impairment than the control group. We observed that the cognitively impaired group presented highest concentrations of Br and Cu in certain areas than the control group, on the other hand, this group presented highest levels of K for all brain areas studied.

  13. [Issues in psychiatric evaluation of children and adolescents with visual impairment].

    Science.gov (United States)

    Saisky, Yaniv; Hasid, Soli; Ebert, Tanya; Kosov, Irene

    2014-02-01

    Approximately 8% from those who are defined as blind in Israel are children and adolescents. Visual impairment is correlated with a high rate of psychopathology. However, some of these children and adolescents do not receive appropriate diagnosis and treatment. Often, the clinicians and those who treat the children/adolescents lack the proper professional knowledge related to the unique diagnosis and treatment of children/ adolescents who are visually impaired. Visual impairment might influence different aspects of the psychiatric diagnosis. These aspects include the influence of the impairment on different developmental axes; the reciprocal relationship between the child and his/her environment; the clinical presentation of different psychopathologies; and the different treatment modalities. In this review we discuss these issues. Moreover, we raise the question as to whether there is a need to adapt the psychiatric evaluation and the treatment specifically to the visually impaired child. The review is based on the existing literature in addition to our clinical experience, which stems from our work with children and adolescents who are at the "Jewish Institute for the Blind", an institute for children and adolescents with visual impairment in Israel.

  14. Cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Ransmayr, Gerhard

    2015-12-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy. PMID:26609664

  15. Cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Ransmayr, Gerhard

    2015-12-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy.

  16. The Effect of Nitric Oxide Donor in Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    N Dashti

    2003-10-01

    Full Text Available Diabetes is characterized by a nitric oxide deficiency at the wound site. Diabetes is a factor that influences all stages of wound healing. In animals with acute experimental diabetes induced by streptozotocin (STZ, the early inflammatory responses after wounding is impaired, fibroblast and endothelial cell proliferation is reduced as well as accumulation of reparative collagen and gain in wound breaking strenght. This study investigated whether exogenous nitric oxide supplimentation with nitric oxide donor DETA NONOate could reverse impaired healing in diabetes. The results suggest nitric oxide donor DETA NONOate can reverse impaired healing associated with diabetes (P<0.001 and urinary nitrate (NO-3 output may reflect the extent of repair in this wound model (P<0.001.

  17. Impairment of pancreatic islet β cell function induced by intermittent high glucose through oxidative and endoplasmic reticulum stress:experiment with rat pancreatic islet β cells%高糖波动诱导氧化应激及内质网应激损伤胰岛β细胞功能

    Institute of Scientific and Technical Information of China (English)

    侯志强; 李宏亮; 赵家军; 李光伟

    2008-01-01

    .04 respectively,both significantly lower than that of the control group(1.67±0.23,both P<0.05).The intracellularinsulin contents of the IHG and SHG groupswere(10.91±0.14)and(11.08±O.03)μU/μg respectively,both significantly lower than that of the control group[(12.37±0.37)μU/μg,both Pimpairment in pancreatic islet β cell functions,especially IHG,which is closely associated with the aggravation of oxidative stress and endoplasmic reticulum stress triggered by intermittent high glucose.

  18. Clean Water Act 303(d) Listed Impaired Waters and their Causes of Impairment from All Years

    Data.gov (United States)

    U.S. Environmental Protection Agency — Waters identified as impaired as well as their associated causes of impairment from all approved Clean Water Act 303(d) lists submitted by the states. Includes all...

  19. Adaptive Behavior Ratings Correlate with Symptomatology and IQ among Individuals with High-Functioning Autism Spectrum Disorders

    Science.gov (United States)

    Kenworthy, Lauren; Case, Laura; Harms, Madeline B.; Martin, Alex; Wallace, Gregory L.

    2010-01-01

    Caregiver report on the Adaptive Behavior Assessment System-II (ABAS) for 40 high-functioning individuals with Autism Spectrum Disorders (ASD) and 30 typically developing (TD) individuals matched for age, IQ, and sex ratio revealed global adaptive behavior deficits in ASD, with social skills impairments particularly prominent. Within the ASD…

  20. Adapt or Become Extinct!

    DEFF Research Database (Denmark)

    Goumas, Georgios; McKee, Sally A.; Själander, Magnus;

    2011-01-01

    boundaries (walls) for applications which limit software development (parallel programming wall), performance (memory wall, communication wall) and viability (power wall). The only way to survive in such a demanding environment is by adaptation. In this paper we discuss how dynamic information collected...... static analysis (either during ahead-of-time or just-in-time) compilation. We extend the notion of information-driven adaptation and outline the architecture of an infrastructure designed to enable information ow and adaptation throughout the life-cycle of an application....

  1. Adaptation investments and homeownership

    DEFF Research Database (Denmark)

    Hansen, Jørgen Drud; Skak, Morten

    2008-01-01

    This article develops a model where ownership improves efficiency of the housing market as it enhances the utility of housing consumption for some consumers. The model is based on an extended Hotelling-Lancaster utility approach in which the ideal variant of housing is obtainable only by adapting...... the home through a supplementary investment. Ownership offers low costs of adaptation, but has high contract costs compared with renting. Consumers simultaneously decide housing demand and tenure, and because of the different cost structure only consumers with strong preferences for individual adaptation...

  2. [Adaptive optics for ophthalmology].

    Science.gov (United States)

    Saleh, M

    2016-04-01

    Adaptive optics is a technology enhancing the visual performance of an optical system by correcting its optical aberrations. Adaptive optics have already enabled several breakthroughs in the field of visual sciences, such as improvement of visual acuity in normal and diseased eyes beyond physiologic limits, and the correction of presbyopia. Adaptive optics technology also provides high-resolution, in vivo imaging of the retina that may eventually help to detect the onset of retinal conditions at an early stage and provide better assessment of treatment efficacy.

  3. Adaptive network countermeasures.

    Energy Technology Data Exchange (ETDEWEB)

    McClelland-Bane, Randy; Van Randwyk, Jamie A.; Carathimas, Anthony G.; Thomas, Eric D.

    2003-10-01

    This report describes the results of a two-year LDRD funded by the Differentiating Technologies investment area. The project investigated the use of countermeasures in protecting computer networks as well as how current countermeasures could be changed in order to adapt with both evolving networks and evolving attackers. The work involved collaboration between Sandia employees and students in the Sandia - California Center for Cyber Defenders (CCD) program. We include an explanation of the need for adaptive countermeasures, a description of the architecture we designed to provide adaptive countermeasures, and evaluations of the system.

  4. Introduction to adaptive arrays

    CERN Document Server

    Monzingo, Bob; Haupt, Randy

    2011-01-01

    This second edition is an extensive modernization of the bestselling introduction to the subject of adaptive array sensor systems. With the number of applications of adaptive array sensor systems growing each year, this look at the principles and fundamental techniques that are critical to these systems is more important than ever before. Introduction to Adaptive Arrays, 2nd Edition is organized as a tutorial, taking the reader by the hand and leading them through the maze of jargon that often surrounds this highly technical subject. It is easy to read and easy to follow as fundamental concept

  5. The process of organisational adaptation through innovations, and organisational adaptability

    OpenAIRE

    Tikka, Tommi

    2010-01-01

    This study is about the process of organisational adaptation and organisational adaptability. The study generates a theoretical framework about organisational adaptation behaviour and conditions that have influence on success of organisational adaptation. The research questions of the study are: How does an organisation adapt through innovations, and which conditions enhance or impede organisational adaptation through innovations? The data were gathered from five case organisations withi...

  6. Cognitive functions in drivers with brain injury : Anticipation and adaption

    OpenAIRE

    Lundqvist, Anna

    2001-01-01

    The purpose of this thesis was to improve the understanding of what cognitive functions are important for driving performance, investigate the impact of impaired cognitive functions on drivers with brain injury, and study adaptation strategies relevant for driving performance after brain injury. Finally, the predictive value of a neuropsychological test battery was evaluated for driving performance. Main results can be summarized in the following conclusions: (a) Cognitive functions in terms ...

  7. Adapt or Die

    DEFF Research Database (Denmark)

    Brody, Joshua Eric; Larsen, Kasper Green

    2015-01-01

    In this paper, we study the role non-adaptivity plays in maintaining dynamic data structures. Roughly speaking, a data structure is non-adaptive if the memory locations it reads and/or writes when processing a query or update depend only on the query or update and not on the contents of previously...... read cells. We study such non-adaptive data structures in the cell probe model. This model is one of the least restrictive lower bound models and in particular, cell probe lower bounds apply to data structures developed in the popular word-RAM model. Unfortunately, this generality comes at a high cost...... several different notions of non-adaptivity and identify key properties that must be dealt with if we are to prove polynomial lower bounds without restrictions on the data structures. Finally, our results also unveil an interesting connection between data structures and depth-2 circuits. This allows us...

  8. Adaptations, exaptations, and spandrels.

    Science.gov (United States)

    Buss, D M; Haselton, M G; Shackelford, T K; Bleske, A L; Wakefield, J C

    1998-05-01

    Adaptation and natural selection are central concepts in the emerging science of evolutionary psychology. Natural selection is the only known causal process capable of producing complex functional organic mechanisms. These adaptations, along with their incidental by-products and a residue of noise, comprise all forms of life. Recently, S. J. Gould (1991) proposed that exaptations and spandrels may be more important than adaptations for evolutionary psychology. These refer to features that did not originally arise for their current use but rather were co-opted for new purposes. He suggested that many important phenomena--such as art, language, commerce, and war--although evolutionary in origin, are incidental spandrels of the large human brain. The authors outline the conceptual and evidentiary standards that apply to adaptations, exaptations, and spandrels and discuss the relative utility of these concepts for psychological science. PMID:9612136

  9. Adaptive Architectural Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Kirkegaard, Poul Henning

    2010-01-01

    Recent years have seen an increasing variety of applications of adaptive architectural structures for improvement of structural performance by recognizing changes in their environments and loads, adapting to meet goals, and using past events to improve future performance or maintain serviceability....... The general scopes of this paper are to develop a new adaptive kinetic architectural structure, particularly a reconfigurable architectural structure which can transform body shape from planar geometries to hyper-surfaces using different control strategies, i.e. a transformation into more than one or two...... different shape alternatives. The adaptive structure is a proposal for a responsive building envelope which is an idea of a first level operational framework for present and future investigations towards performance based responsive architectures through a set of responsive typologies. A mock- up concept...

  10. Asimovian Adaptive Agents

    CERN Document Server

    Gordon, D F

    2011-01-01

    The goal of this research is to develop agents that are adaptive and predictable and timely. At first blush, these three requirements seem contradictory. For example, adaptation risks introducing undesirable side effects, thereby making agents' behavior less predictable. Furthermore, although formal verification can assist in ensuring behavioral predictability, it is known to be time-consuming. Our solution to the challenge of satisfying all three requirements is the following. Agents have finite-state automaton plans, which are adapted online via evolutionary learning (perturbation) operators. To ensure that critical behavioral constraints are always satisfied, agents' plans are first formally verified. They are then reverified after every adaptation. If reverification concludes that constraints are violated, the plans are repaired. The main objective of this paper is to improve the efficiency of reverification after learning, so that agents have a sufficiently rapid response time. We present two solutions: ...

  11. The genomics of adaptation.

    Science.gov (United States)

    Radwan, Jacek; Babik, Wiesław

    2012-12-22

    The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far are beginning to challenge some widespread views of the way in which natural selection operates at the genomic level. Papers in this Special Feature of Proceedings of the Royal Society B illustrate various aspects of the broad field of adaptation genomics. This introductory article sets up a context and, on the basis of a few selected examples, discusses how genomic data can advance our understanding of the process of adaptation.

  12. Statistical Physics of Adaptation

    CERN Document Server

    Perunov, Nikolai; England, Jeremy

    2014-01-01

    All living things exhibit adaptations that enable them to survive and reproduce in the natural environment that they inhabit. From a biological standpoint, it has long been understood that adaptation comes from natural selection, whereby maladapted individuals do not pass their traits effectively to future generations. However, we may also consider the phenomenon of adaptation from the standpoint of physics, and ask whether it is possible to delineate what the difference is in terms of physical properties between something that is well-adapted to its surrounding environment, and something that is not. In this work, we undertake to address this question from a theoretical standpoint. Building on past fundamental results in far-from-equilibrium statistical mechanics, we demonstrate a generalization of the Helmholtz free energy for the finite-time stochastic evolution of driven Newtonian matter. By analyzing this expression term by term, we are able to argue for a general tendency in driven many-particle systems...

  13. Islands, resettlement and adaptation

    Science.gov (United States)

    Barnett, Jon; O'Neill, Saffron J.

    2012-01-01

    Resettlement of people living on islands in anticipation of climate impacts risks maladaptation, but some forms of population movement carry fewer risks and larger rewards in terms of adapting to climate change.

  14. Adaptive Heat Engine

    Science.gov (United States)

    Allahverdyan, A. E.; Babajanyan, S. G.; Martirosyan, N. H.; Melkikh, A. V.

    2016-07-01

    A major limitation of many heat engines is that their functioning demands on-line control and/or an external fitting between the environmental parameters (e.g., temperatures of thermal baths) and internal parameters of the engine. We study a model for an adaptive heat engine, where—due to feedback from the functional part—the engine's structure adapts to given thermal baths. Hence, no on-line control and no external fitting are needed. The engine can employ unknown resources; it can also adapt to results of its own functioning that make the bath temperatures closer. We determine resources of adaptation and relate them to the prior information available about the environment.

  15. Adaptive digital filters

    CERN Document Server

    Kovačević, Branko; Milosavljević, Milan

    2013-01-01

    Adaptive Digital Filters” presents an important discipline applied to the domain of speech processing. The book first makes the reader acquainted with the basic terms of filtering and adaptive filtering, before introducing the field of advanced modern algorithms, some of which are contributed by the authors themselves. Working in the field of adaptive signal processing requires the use of complex mathematical tools. The book offers a detailed presentation of the mathematical models that is clear and consistent, an approach that allows everyone with a college level of mathematics knowledge to successfully follow the mathematical derivations and descriptions of algorithms.   The algorithms are presented in flow charts, which facilitates their practical implementation. The book presents many experimental results and treats the aspects of practical application of adaptive filtering in real systems, making it a valuable resource for both undergraduate and graduate students, and for all others interested in m...

  16. Limits to adaptation

    Science.gov (United States)

    Dow, Kirstin; Berkhout, Frans; Preston, Benjamin L.; Klein, Richard J. T.; Midgley, Guy; Shaw, M. Rebecca

    2013-04-01

    An actor-centered, risk-based approach to defining limits to social adaptation provides a useful analytic framing for identifying and anticipating these limits and informing debates over society's responses to climate change.

  17. The genomics of adaptation.

    Science.gov (United States)

    Radwan, Jacek; Babik, Wiesław

    2012-12-22

    The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far are beginning to challenge some widespread views of the way in which natural selection operates at the genomic level. Papers in this Special Feature of Proceedings of the Royal Society B illustrate various aspects of the broad field of adaptation genomics. This introductory article sets up a context and, on the basis of a few selected examples, discusses how genomic data can advance our understanding of the process of adaptation. PMID:23097510

  18. The Walking Trail-Making Test is an early detection tool for mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Perrochon A

    2014-01-01

    Full Text Available Anaick Perrochon, Gilles Kemoun Laboratoire Mobilité, Vieillissement, Exercice (MOVE, EA 6314, Faculté des Sciences du Sport, Université de Poitiers, 8 Allée Jean Monnet, 86000 Poitiers, France; ISIS, Research Institute on Handicap and Aging, Paris, France Background: Executive function impairment (in particular, mental flexibility in the elderly, and in patients with mild cognitive impairment (MCI, is strongly correlated with difficulties in performing complex walking tasks. The aim of this study was to determine if the adaptation of a neuropsychological test (the Trail-Making Test, to evaluate executive functions during walking, can be an early detection tool for cognitive impairment. Methods: Fifty subjects (15 young, 20 older, presumably healthy, and 15 MCI were first evaluated for cognitive functions (Mini-Mental State Examination, Frontal Assessment Battery, and Trail-Making Test and motor functions (10-meter walking test. All subjects then performed a spatial navigation, or a complex walking test (the Walking Trail-Making Test: [WTMT], and their spatiotemporal walking variables were analyzed using cluster analysis. Results: Following evaluation of WTMT locomotor performance, cluster analysis revealed three groups that were distinctly different in age and cognitive abilities: a group of young subjects, a group of healthy older subjects, MCI subjects with amnestic impairment, and a group of MCI subjects with executive function impairment. The WTMT enabled early detection, (ie, borderline MCI of dysexecutive impairment, with 78% sensitivity and 90% specificity. Conclusion: The WTMT is of interest in that it can help provide early detection of dysexecutive cognitive impairment. Keywords: spatial navigation, walking, trail making test, detection, mild cognitive impairment

  19. RNA oxidation

    DEFF Research Database (Denmark)

    Kjaer, L. K.; Cejvanovic, V.; Henriken, T.;

    2015-01-01

    RNA modification has attracted increasing interest as it is realized that epitranscriptomics is important in disease development. In type 2 diabetes we have suggested that high urinary excretion of 8-oxo-2'-Guanosine (8oxoGuo), as a measure of global RNA oxidation, is associated with poor survival.......9 significant hazard ratio for death compared with the quartile with the lowest 8oxoGuo excretion when adjusted for age, sex, BMI, smoker status, s-HbA1c, urine protein excretion and s-cholesterol. We conclude that it is now established that RNA oxidation is an independent risk factor for death in type 2...... diabetes. In agreement with our previous finding, DNA oxidation did not show any prognostic value. RNA oxidation represents oxidative stress intracellularly, presumably predominantly in the cytosol. The mechanism of RNA oxidation is not clear, but hypothesized to result from mitochondrial dysfunction...

  20. Feasibility of the adaptive and automatic presentation of tasks (ADAPT system for rehabilitation of upper extremity function post-stroke

    Directory of Open Access Journals (Sweden)

    Choi Younggeun

    2011-08-01

    Full Text Available Abstract Background Current guidelines for rehabilitation of arm and hand function after stroke recommend that motor training focus on realistic tasks that require reaching and manipulation and engage the patient intensively, actively, and adaptively. Here, we investigated the feasibility of a novel robotic task-practice system, ADAPT, designed in accordance with such guidelines. At each trial, ADAPT selects a functional task according to a training schedule and with difficulty based on previous performance. Once the task is selected, the robot picks up and presents the corresponding tool, simulates the dynamics of the tasks, and the patient interacts with the tool to perform the task. Methods Five participants with chronic stroke with mild to moderate impairments (> 9 months post-stroke; Fugl-Meyer arm score 49.2 ± 5.6 practiced four functional tasks (selected out of six in a pre-test with ADAPT for about one and half hour and 144 trials in a pseudo-random schedule of 3-trial blocks per task. Results No adverse events occurred and ADAPT successfully presented the six functional tasks without human intervention for a total of 900 trials. Qualitative analysis of trajectories showed that ADAPT simulated the desired task dynamics adequately, and participants reported good, although not excellent, task fidelity. During training, the adaptive difficulty algorithm progressively increased task difficulty leading towards an optimal challenge point based on performance; difficulty was then continuously adjusted to keep performance around the challenge point. Furthermore, the time to complete all trained tasks decreased significantly from pretest to one-hour post-test. Finally, post-training questionnaires demonstrated positive patient acceptance of ADAPT. Conclusions ADAPT successfully provided adaptive progressive training for multiple functional tasks based on participant's performance. Our encouraging results establish the feasibility of ADAPT; its