Training-induced adaptation of oxidative phosphorylation in skeletal muscles.

Science.gov (United States)

Korzeniewski, Bernard; Zoladz, Jerzy A

2003-08-15

Muscle training/conditioning improves the adaptation of oxidative phosphorylation in skeletal muscles to physical exercise. However, the mechanisms underlying this adaptation are still not understood fully. By quantitative analysis of the existing experimental results, we show that training-induced acceleration of oxygen-uptake kinetics at the onset of exercise and improvement of ATP/ADP stability due to physical training are mainly caused by an increase in the amount of mitochondrial proteins and by an intensification of the parallel activation of ATP usage and ATP supply (increase in direct stimulation of oxidative phosphorylation complexes accompanying stimulation of ATP consumption) during exercise.

Synaptic contacts impaired by styrene-7,8-oxide toxicity

International Nuclear Information System (INIS)

Corsi, P.; D'Aprile, A.; Nico, B.; Costa, G.L.; Assennato, G.

2007-01-01

Styrene-7,8-oxide (SO), a chemical compound widely used in industrial applications, is a potential hazard for humans, particularly in occupational settings. Neurobehavioral changes are consistently observed in occupationally exposed individuals and alterations of neurotransmitters associated with neuronal loss have been reported in animal models. Although the toxic effects of styrene have been extensively documented, the molecular mechanisms responsible for SO-induced neurotoxicity are still unclear. A possible dopamine-mediated effect of styrene neurotoxicity has been previously demonstrated, since styrene oxide alters dopamine neurotransmission in the brain. Thus, the present study hypothesizes that styrene neurotoxicity may involve synaptic contacts. Primary striatal neurons were exposed to styrene oxide at different concentrations (0.1-1 mM) for different time periods (8, 16, and 24 h) to evaluate the dose able to induce synaptic impairments. The expression of proteins crucial for synaptic transmission such as Synapsin, Synaptophysin, and RAC-1 were considered. The levels of Synaptophysin and RAC-1 decreased in a dose-dependent manner. Accordingly, morphological alterations, observed at the ultrastructural level, primarily involved the pre-synaptic compartment. In SO-exposed cultures, the biochemical cascade of caspases was activated affecting the cytoskeleton components as their target. Thus the impairments in synaptic contacts observed in SO-exposed cultures might reflect a primarily morphological alteration of neuronal cytoskeleton. In addition, our data support the hypothesis developed by previous authors of reactive oxygen species (ROS) initiating events of SO cytotoxicity

Boys with Oppositional Defiant Disorder/Conduct Disorder Show Impaired Adaptation During Stress: An Executive Functioning Study.

Science.gov (United States)

Schoorl, Jantiene; van Rijn, Sophie; de Wied, Minet; van Goozen, Stephanie; Swaab, Hanna

2018-04-01

Evidence for problems in executive functioning (EF) in children with oppositional defiant disorder/conduct disorder (ODD/CD) is mixed and the impact stress may have on EF is understudied. Working memory, sustained attention, inhibition and cognitive flexibility of boys with ODD/CD (n = 65) and non-clinical controls (n = 32) were examined under typical and stressful test conditions. Boys with ODD/CD showed impaired working memory under typical testing conditions, and impairments in working memory and sustained attention under stressful conditions. In contrast to controls, performance on sustained attention, cognitive flexibility and inhibition was less influenced by stress in boys with ODD/CD. These results suggest that boys with ODD/CD show impairments in adaptation to the environment whereas typically developing boys show adaptive changes in EF.

Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

International Nuclear Information System (INIS)

Mercado, Nicolas; Thimmulappa, Rajesh; Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E.; Biswal, Shyam; Ito, Kazuhiro; Barnes, Peter J.

2011-01-01

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

Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

Energy Technology Data Exchange (ETDEWEB)

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

2011-03-11

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

Symbiosis-induced adaptation to oxidative stress.

Science.gov (United States)

Richier, Sophie; Furla, Paola; Plantivaux, Amandine; Merle, Pierre-Laurent; Allemand, Denis

2005-01-01

Cnidarians in symbiosis with photosynthetic protists must withstand daily hyperoxic/anoxic transitions within their host cells. Comparative studies between symbiotic (Anemonia viridis) and non-symbiotic (Actinia schmidti) sea anemones show striking differences in their response to oxidative stress. First, the basal expression of SOD is very different. Symbiotic animal cells have a higher isoform diversity (number and classes) and a higher activity than the non-symbiotic cells. Second, the symbiotic animal cells of A. viridis also maintain unaltered basal values for cellular damage when exposed to experimental hyperoxia (100% O(2)) or to experimental thermal stress (elevated temperature +7 degrees C above ambient). Under such conditions, A. schmidti modifies its SOD activity significantly. Electrophoretic patterns diversify, global activities diminish and cell damage biomarkers increase. These data suggest symbiotic cells adapt to stress while non-symbiotic cells remain acutely sensitive. In addition to being toxic, high O(2) partial pressure (P(O(2))) may also constitute a preconditioning step for symbiotic animal cells, leading to an adaptation to the hyperoxic condition and, thus, to oxidative stress. Furthermore, in aposymbiotic animal cells of A. viridis, repression of some animal SOD isoforms is observed. Meanwhile, in cultured symbionts, new activity bands are induced, suggesting that the host might protect its zooxanthellae in hospite. Similar results have been observed in other symbiotic organisms, such as the sea anemone Aiptasia pulchella and the scleractinian coral Stylophora pistillata. Molecular or physical interactions between the two symbiotic partners may explain such variations in SOD activity and might confer oxidative stress tolerance to the animal host.

ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

International Nuclear Information System (INIS)

Pi Jingbo; Zhang Qiang; Fu Jingqi; Woods, Courtney G.; Hou Yongyong; Corkey, Barbara E.; Collins, Sheila; Andersen, Melvin E.

2010-01-01

This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H 2 O 2 , act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function.

Poststroke Hemiparesis Impairs the Rate but not Magnitude of Adaptation of Spatial and Temporal Locomotor Features

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Savin, Douglas N.; Tseng, Shih-Chiao; Whitall, Jill; Morton, Susanne M.

2015-01-01

Background Persons with stroke and hemiparesis walk with a characteristic pattern of spatial and temporal asymmetry that is resistant to most traditional interventions. It was recently shown in nondisabled persons that the degree of walking symmetry can be readily altered via locomotor adaptation. However, it is unclear whether stroke-related brain damage affects the ability to adapt spatial or temporal gait symmetry. Objective Determine whether locomotor adaptation to a novel swing phase perturbation is impaired in persons with chronic stroke and hemiparesis. Methods Participants with ischemic stroke (14) and nondisabled controls (12) walked on a treadmill before, during, and after adaptation to a unilateral perturbing weight that resisted forward leg movement. Leg kinematics were measured bilaterally, including step length and single-limb support (SLS) time symmetry, limb angle center of oscillation, and interlimb phasing, and magnitude of “initial” and “late” locomotor adaptation rates were determined. Results All participants had similar magnitudes of adaptation and similar initial adaptation rates both spatially and temporally. All 14 participants with stroke and baseline asymmetry temporarily walked with improved SLS time symmetry after adaptation. However, late adaptation rates poststroke were decreased (took more strides to achieve adaptation) compared with controls. Conclusions Mild to moderate hemiparesis does not interfere with the initial acquisition of novel symmetrical gait patterns in both the spatial and temporal domains, though it does disrupt the rate at which “late” adaptive changes are produced. Impairment of the late, slow phase of learning may be an important rehabilitation consideration in this patient population. PMID:22367915

Plant-Adapted Escherichia coli Show Increased Lettuce Colonizing Ability, Resistance to Oxidative Stress and Chemotactic Response

Science.gov (United States)

Dublan, Maria de los Angeles; Ortiz-Marquez, Juan Cesar Federico; Lett, Lina; Curatti, Leonardo

2014-01-01

Background Escherichia coli is a widespread gut commensal and often a versatile pathogen of public health concern. E. coli are also frequently found in different environments and/or alternative secondary hosts, such as plant tissues. The lifestyle of E. coli in plants is poorly understood and has potential implications for food safety. Methods/Principal Findings This work shows that a human commensal strain of E. coli K12 readily colonizes lettuce seedlings and produces large microcolony-like cell aggregates in leaves, especially in young leaves, in proximity to the vascular tissue. Our observations strongly suggest that those cell aggregates arise from multiplication of single bacterial cells that reach those spots. We showed that E. coli isolated from colonized leaves progressively colonize lettuce seedlings to higher titers, suggesting a fast adaptation process. E. coli cells isolated from leaves presented a dramatic rise in tolerance to oxidative stress and became more chemotactic responsive towards lettuce leaf extracts. Mutant strains impaired in their chemotactic response were less efficient lettuce colonizers than the chemotactic isogenic strain. However, acclimation to oxidative stress and/or minimal medium alone failed to prime E. coli cells for enhanced lettuce colonization efficiency. Conclusion/Significance These findings help to understand the physiological adaptation during the alternative lifestyle of E. coli in/on plant tissues. PMID:25313845

Contribution Of Brain Tissue Oxidative Damage In Hypothyroidism-associated Learning and Memory Impairments

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Yousef Baghcheghi

2017-01-01

Full Text Available The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments.

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

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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.

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

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Noboru Toda

2016-08-01

Full Text Available 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.

Training-induced adaptation of oxidative phosphorylation in skeletal muscles.

OpenAIRE

Korzeniewski, Bernard; Zoladz, Jerzy A

2003-01-01

Muscle training/conditioning improves the adaptation of oxidative phosphorylation in skeletal muscles to physical exercise. However, the mechanisms underlying this adaptation are still not understood fully. By quantitative analysis of the existing experimental results, we show that training-induced acceleration of oxygen-uptake kinetics at the onset of exercise and improvement of ATP/ADP stability due to physical training are mainly caused by an increase in the amount of mitochondrial protein...

Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1.

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Floor Spaans

Full Text Available Syncytiotrophoblast extracellular vesicles (STBEVs are placenta derived particles that are released into the maternal circulation during pregnancy. Abnormal levels of STBEVs have been proposed to affect maternal vascular function. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1 is a multi-ligand scavenger receptor. Increased LOX-1 expression and activation has been proposed to contribute to endothelial dysfunction. As LOX-1 has various ligands, we hypothesized that, being essentially packages of lipoproteins, STBEVs are able to activate the LOX-1 receptor thereby impairing vascular function via the production of superoxide and decreased nitric oxide bioavailability. Uterine arteries were obtained in late gestation from Sprague-Dawley rats and incubated for 24h with or without human STBEVs (derived from a normal pregnant placenta in the absence or presence of a LOX-1 blocking antibody. Vascular function was assessed using wire myography. Endothelium-dependent maximal vasodilation to methylcholine was impaired by STBEVs (MCh Emax: 57.7±5.9% in STBEV-incubated arteries vs. 77.8±2.9% in controls, p<0.05. This was prevented by co-incubation of STBEV-incubated arteries with LOX-1 blocking antibodies (MCh Emax: 78.8±4.3%, p<0.05. Pre-incubation of the vessels with a nitric oxide synthase inhibitor (L-NAME demonstrated that the STBEV-induced impairment in vasodilation was due to decreased nitric oxide contribution (ΔAUC 12.2±11.7 in STBEV-arteries vs. 86.5±20 in controls, p<0.05, which was abolished by LOX-1 blocking antibody (ΔAUC 98.9±17, p<0.05. In STBEV-incubated vessels, LOX-1 inhibition resulted in an increased endothelial nitric oxide synthase expression (p<0.05, to a level similar to control vessels. The oxidant scavenger, superoxide dismutase, did not improve this impairment, nor were vascular superoxide levels altered. Our data support an important role for STBEVs in impairment of vascular function via activation of

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

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)

Lamp, Ole; Derno, Michael; Otten, Winfried; Mielenz, Manfred; Nürnberg, Gerd; Kuhla, Björn

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.

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.

Variance in exposed perturbations impairs retention of visuomotor adaptation.

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Canaveral, Cesar Augusto; Danion, Frédéric; Berrigan, Félix; Bernier, Pierre-Michel

2017-11-01

Sensorimotor control requires an accurate estimate of the state of the body. The brain optimizes state estimation by combining sensory signals with predictions of the sensory consequences of motor commands using a forward model. Given that both sensory signals and predictions are uncertain (i.e., noisy), the brain optimally weights the relative reliance on each source of information during adaptation. In support, it is known that uncertainty in the sensory predictions influences the rate and generalization of visuomotor adaptation. We investigated whether uncertainty in the sensory predictions affects the retention of a new visuomotor relationship. This was done by exposing three separate groups to a visuomotor rotation whose mean was common at 15° counterclockwise but whose variance around the mean differed (i.e., SD of 0°, 3.2°, or 4.5°). Retention was assessed by measuring the persistence of the adapted behavior in a no-vision phase. Results revealed that mean reach direction late in adaptation was similar across groups, suggesting it depended mainly on the mean of exposed rotations and was robust to differences in variance. However, retention differed across groups, with higher levels of variance being associated with a more rapid reversion toward nonadapted behavior. A control experiment ruled out the possibility that differences in retention were accounted for by differences in success rates. Exposure to variable rotations may have increased the uncertainty in sensory predictions, making the adapted forward model more labile and susceptible to change or decay. NEW & NOTEWORTHY The brain predicts the sensory consequences of motor commands through a forward model. These predictions are subject to uncertainty. We use visuomotor adaptation and modulate uncertainty in the sensory predictions by manipulating the variance in exposed rotations. Results reveal that variance does not influence the final extent of adaptation but selectively impairs the retention of

Stepping reaction time and gait adaptability are significantly impaired in people with Parkinson's disease: Implications for fall risk.

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Caetano, Maria Joana D; Lord, Stephen R; Allen, Natalie E; Brodie, Matthew A; Song, Jooeun; Paul, Serene S; Canning, Colleen G; Menant, Jasmine C

2018-02-01

Decline in the ability to take effective steps and to adapt gait, particularly under challenging conditions, may be important reasons why people with Parkinson's disease (PD) have an increased risk of falling. This study aimed to determine the extent of stepping and gait adaptability impairments in PD individuals as well as their associations with PD symptoms, cognitive function and previous falls. Thirty-three older people with PD and 33 controls were assessed in choice stepping reaction time, Stroop stepping and gait adaptability tests; measurements identified as fall risk factors in older adults. People with PD had similar mean choice stepping reaction times to healthy controls, but had significantly greater intra-individual variability. In the Stroop stepping test, the PD participants were more likely to make an error (48 vs 18%), took 715 ms longer to react (2312 vs 1517 ms) and had significantly greater response variability (536 vs 329 ms) than the healthy controls. People with PD also had more difficulties adapting their gait in response to targets (poorer stepping accuracy) and obstacles (increased number of steps) appearing at short notice on a walkway. Within the PD group, higher disease severity, reduced cognition and previous falls were associated with poorer stepping and gait adaptability performances. People with PD have reduced ability to adapt gait to unexpected targets and obstacles and exhibit poorer stepping responses, particularly in a test condition involving conflict resolution. Such impaired stepping responses in Parkinson's disease are associated with disease severity, cognitive impairment and falls. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diminished stress resistance and defective adaptive homeostasis in age-related diseases.

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Lomeli, Naomi; Bota, Daniela A; Davies, Kelvin J A

2017-11-01

Adaptive homeostasis is defined as the transient expansion or contraction of the homeostatic range following exposure to subtoxic, non-damaging, signaling molecules or events, or the removal or cessation of such molecules or events ( Mol. Aspects Med. (2016) 49, 1-7 ). Adaptive homeostasis allows us to transiently adapt (and then de-adapt) to fluctuating levels of internal and external stressors. The ability to cope with transient changes in internal and external environmental stress, however, diminishes with age. Declining adaptive homeostasis may make older people more susceptible to many diseases. Chronic oxidative stress and defective protein homeostasis (proteostasis) are two major factors associated with the etiology of age-related disorders. In the present paper, we review the contribution of impaired responses to oxidative stress and defective adaptive homeostasis in the development of age-associated diseases. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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

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

2015-01-01

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

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

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Bito, Tomohiro; Misaki, Taihei; Yabuta, Yukinori; Ishikawa, Takahiro; Kawano, Tsuyoshi; Watanabe, Fumio

2017-04-01

Oxidative stress is implicated in various human diseases and conditions, such as a neurodegeneration, which is the major symptom of vitamin B 12 deficiency, although the underlying disease mechanisms associated with vitamin B 12 deficiency are poorly understood. Vitamin B 12 deficiency was found to significantly increase cellular H 2 O 2 and NO content in Caenorhabditis elegans and significantly decrease low molecular antioxidant [reduced glutathione (GSH) and L-ascorbic acid] levels and antioxidant enzyme (superoxide dismutase and catalase) activities, indicating that vitamin B 12 deficiency induces severe oxidative stress leading to oxidative damage of various cellular components in worms. An NaCl chemotaxis associative learning assay indicated that vitamin B 12 deficiency did not affect learning ability but impaired memory retention ability, which decreased to approximately 58% of the control value. When worms were treated with 1mmol/L GSH, L-ascorbic acid, or vitamin E for three generations during vitamin B 12 deficiency, cellular malondialdehyde content as an index of oxidative stress decreased to the control level, but the impairment of memory retention ability was not completely reversed (up to approximately 50%). These results suggest that memory retention impairment formed during vitamin B 12 deficiency is partially attributable to oxidative stress. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

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Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai

2014-01-01

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. PMID:24672632

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

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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.

Oxidized DNA induces an adaptive response in human fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Kostyuk, Svetlana V., E-mail: svet.kostyuk@gmail.com [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Tabakov, Viacheslav J.; Chestkov, Valerij V.; Konkova, Marina S.; Glebova, Kristina V.; Baydakova, Galina V.; Ershova, Elizaveta S.; Izhevskaya, Vera L. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Baranova, Ancha, E-mail: abaranov@gmu.edu [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Center for the Study of Chronic Metabolic Diseases, School of System Biology, George Mason University, Fairfax, VA 22030 (United States); Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation)

2013-07-15

Highlights: • We describe the effects of gDNAOX on human fibroblasts cultivated in serum withdrawal conditions. • gDNAOX evokes an adaptive response in human fibroblasts. • gDNAOX increases the survival rates in serum starving cell populations. • gDNAOX enhances the survival rates in cell populations irradiated at 1.2 Gy dose. • gDNAOX up-regulates NRF2 and inhibits NF-kappaB-signaling. - Abstract: Cell-free DNA (cfDNA) released from dying cells contains a substantial proportion of oxidized nucleotides, thus, forming cfDNA{sup OX}. The levels of cfDNA{sup OX} are increased in the serum of patients with chronic diseases. Oxidation of DNA turns it into a stress signal. The samples of genomic DNA (gDNA) oxidized by H{sub 2}O{sub 2}in vitro (gDNA{sup OX}) induce effects similar to that of DNA released from damaged cells. Here we describe the effects of gDNA{sup OX} on human fibroblasts cultivated in the stressful conditions of serum withdrawal. In these cells, gDNA{sup OX} evokes an adaptive response that leads to an increase in the rates of survival in serum starving cell populations as well as in populations irradiated at the dose of 1.2 Gy. These effects are not seen in control populations of fibroblasts treated with non-modified gDNA. In particular, the exposure to gDNA{sup OX} leads to a decrease in the expression of the proliferation marker Ki-67 and an increase in levels of PSNA, a decrease in the proportion of subG1- and G2/M cells, a decrease in proportion of cells with double strand breaks (DSBs). Both gDNA{sup OX} and gDNA suppress the expression of DNA sensors TLR9 and AIM2 and up-regulate nuclear factor-erythroid 2 p45-related factor 2 (NRF2), while only gDNA{sup OX} inhibits NF-κB signaling. gDNA{sup OX} is a model for oxidized cfDNA{sup OX} that is released from the dying tumor cells and being carried to the distant organs. The systemic effects of oxidized DNA have to be taken into account when treating tumors. In particular, the damaged DNA

Adaptation of the Fresenius PD+ Cycler for a hearing-impaired patient.

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Kushner, A

2000-01-01

Continuous cycling peritoneal dialysis (CCPD) uses a cycler to perform dialysis exchanges and requires the patient to respond to an audible alarm signifying an interruption in the therapy. Consequently, an unassisted hearing-impaired patient could not use the system. By converting the standard alarm to a vibrating signal, the cycler was successfully adapted to accommodate the special needs of our hearing-impaired patient. The items required for the modification were the Sonic Alert Wake Up Alarm (Model SA-WA300: Sonic Alert, Troy, MI, U.S.A.) and the Sonic Alert Super Shaker Bed Vibrator (Model SA-SS120V: Sonic Alert). The patient can place the vibrator under either the pillow or the mattress. When the cycler alarm is activated, vibration wakens the patient. The equipment was purchased from Harris Communications (Eden Prairie, MN, U.S.A.) through a referral by the Easter Seal Society. Three days were needed to complete training compared to an average of one or two days for patients previously trained for continuous ambulatory peritoneal dialysis (CAPD). The patient remained on cycler therapy for approximately four months when the unrelated development of an abdominal hernia required termination of peritoneal dialysis and subsequent transfer to hemodialysis. In conclusion, a modified cycler can provide a safe and efficient renal replacement therapy option for a hearing-impaired patient.

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

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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.

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

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

2017-01-09

Multiple human diseases involving chronic oxidative stress show a significant sex bias, including neurodegenerative diseases, cancer, immune dysfunction, diabetes, and cardiovascular disease. However, a possible molecular mechanism for the sex bias in physiological adaptation to oxidative stress remains unclear. Here, we report that Drosophila melanogaster females but not males adapt to hydrogen peroxide stress, whereas males but not females adapt to paraquat (superoxide) stress. Stress adaptation in each sex requires the conserved mitochondrial Lon protease and is associated with sex-specific expression of Lon protein isoforms and proteolytic activity. Adaptation to oxidative stress is lost with age in both sexes. Transgenic expression of transformer gene during development transforms chromosomal males into pseudo-females and confers the female-specific pattern of Lon isoform expression, Lon proteolytic activity induction, and H 2 O 2 stress adaptation; these effects were also observed using adult-specific transformation. Conversely, knockdown of transformer in chromosomal females eliminates the female-specific Lon isoform expression, Lon proteolytic activity induction, and H 2 O 2 stress adaptation and produces the male-specific paraquat (superoxide) stress adaptation. Sex-specific expression of alternative Lon isoforms was also observed in mouse tissues. The results develop Drosophila melanogaster as a model for sex-specific stress adaptation regulated by the Lon protease, with potential implications for understanding sexual dimorphism in human disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

1987-01-01

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

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

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

2017-09-05

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

A Systematic Review of the Literature on Parenting of Young Children with Visual Impairments and the Adaptions for Video-Feedback Intervention to Promote Positive Parenting (VIPP).

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van den Broek, Ellen G C; van Eijden, Ans J P M; Overbeek, Mathilde M; Kef, Sabina; Sterkenburg, Paula S; Schuengel, Carlo

2017-01-01

Secure parent-child attachment may help children to overcome the challenges of growing up with a visual or visual-and-intellectual impairment. A large literature exists that provides a blueprint for interventions that promote parental sensitivity and secure attachment. The Video-feedback Intervention to promote Positive Parenting (VIPP) is based on that blueprint. While it has been adapted to several specific at risk populations, children with visual impairment may require additional adjustments. This study aimed to identify the themes that should be addressed in adapting VIPP and similar interventions. A Delphi-consultation was conducted with 13 professionals in the field of visual impairment to select the themes for relationship-focused intervention. These themes informed a systematic literature search. Interaction, intersubjectivity, joint attention, exploration, play and specific behavior were the themes mentioned in the Delphi-group. Paired with visual impairment or vision disorders, infants or young children (and their parents) the search yielded 74 articles, making the six themes for intervention adaptation more specific and concrete. The rich literature on six visual impairment specific themes was dominated by the themes interaction, intersubjectivity, and joint attention. These themes need to be addressed in adapting intervention programs developed for other populations, such as VIPP which currently focuses on higher order constructs of sensitivity and attachment.

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

KAUST Repository

Zhang, Weipeng; Wang, Yong; Lee, On On; Tian, Renmao; Cao, Huiluo; Gao, Zhaoming; Li, Yongxin; Yu, Li; Xu, Ying; Qian, Pei-Yuan

2013-01-01

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.

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.

Modulation of Hypercholesterolemia-Induced Oxidative/Nitrative Stress in the Heart

Science.gov (United States)

Sárközy, Márta; Pipicz, Márton; Dux, László; Csont, Tamás

2016-01-01

Hypercholesterolemia is a frequent metabolic disorder associated with increased risk for cardiovascular morbidity and mortality. In addition to its well-known proatherogenic effect, hypercholesterolemia may exert direct effects on the myocardium resulting in contractile dysfunction, aggravated ischemia/reperfusion injury, and diminished stress adaptation. Both preclinical and clinical studies suggested that elevated oxidative and/or nitrative stress plays a key role in cardiac complications induced by hypercholesterolemia. Therefore, modulation of hypercholesterolemia-induced myocardial oxidative/nitrative stress is a feasible approach to prevent or treat deleterious cardiac consequences. In this review, we discuss the effects of various pharmaceuticals, nutraceuticals, some novel potential pharmacological approaches, and physical exercise on hypercholesterolemia-induced oxidative/nitrative stress and subsequent cardiac dysfunction as well as impaired ischemic stress adaptation of the heart in hypercholesterolemia. PMID:26788247

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

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

2015-12-01

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

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

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Stefane A Aguiar

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

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.

[Role of restricted nitric oxide overproduction in the cardioprotective effect of adaptation to intermittent hypoxia].

Science.gov (United States)

goriacheva, A V; Belkina, L M; Terekhina, O L; Dawney, H F; Mallet, R T; Smirin, B V; Smirnova, E A; Mashina, S Iu; Manukhina, E B

2012-01-01

Adaptation to intermittent normobaric hypoxia is cardioprotective and can stimulate nitric oxide (NO) synthesis. However the role of nitric oxide (NO) in prevention of ischemia-reperfusion (IR) injury of myocardium is controversial. This study was focused on evaluating the effect of adaptation to hypoxia and IR on NO production and development of nitrative stress in the myocardium. Adaptation to hypoxia tended to increase NO production, which was determined by the total level of plasma nitrite and nitrate, and prevented IR-induced NO overproduction. The IR-induced NO overproduction was associated with significant 3-nitrotyrosine (3-NT) accumulation in the left ventricle but not in septum or aorta. In hypoxia-adapted rats, 3-NT after IR was similar to that of control rats without IR. IHC induced marked accumulation of HIF-1alpha in the left ventricle. We suggest that HIF-1alpha contributes to NO-synthase expression during adaptation to hypoxia and thereby facilitates the increase in NO production. NO, in turn, may subsequently prevent NO overproduction during IR by a negative feedback mechanism.

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

Science.gov (United States)

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

2016-10-01

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

Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses.

Science.gov (United States)

Mahanty, Siddhartha; Hutchinson, Karen; Agarwal, Sudhanshu; McRae, Michael; Rollin, Pierre E; Pulendran, Bali

2003-03-15

Acute infection of humans with Ebola and Lassa viruses, two principal etiologic agents of hemorrhagic fevers, often results in a paradoxical pattern of immune responses: early infection, characterized by an outpouring of inflammatory mediators such as TNF-alpha, IL-1 beta, and IL-6, vs late stage infections, which are associated with poor immune responses. The mechanisms underlying these diverse outcomes are poorly understood. In particular, the role played by cells of the innate immune system, such as dendritic cells (DC), is not known. In this study, we show that Ebola and Lassa viruses infect human monocyte-derived DC and impair their function. Monocyte-derived DC exposed to either virus fail to secrete proinflammatory cytokines, do not up-regulate costimulatory molecules, and are poor stimulators of T cells. These data represent the first evidence for a mechanism by which Ebola and Lassa viruses target DC to impair adaptive immunity.

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.

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

International Nuclear Information System (INIS)

Won, Eun-Ji; Lee, Jae-Seong

2014-01-01

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

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...

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

Science.gov (United States)

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

2014-01-01

Extracorporeal membrane oxygenation (ECMO) provides a rescue for children with severe cardiac failure. It has previously been shown that triiodothyronine (T3) improves cardiac function by modulating pyruvate oxidation during weaning. This study focused on fatty acid (FA) metabolism modulated by T3 for weaning from ECMO after cardiac injury. METHODS AND RESULTS: Nineteen immature piglets (9.1-15.3 kg) were separated into 3 groups with ECMO (6.5 h) and wean: normal circulation (Group-C); transient coronary occlusion (10 min) for ischemia-reperfusion (IR) followed by ECMO (Group-IR); and IR with T3 supplementation (Group-IR-T3). 13-Carbon ((13)C)-labeled lactate, medium-chain and long-chain FAs, was infused as oxidative substrates. Substrate fractional contribution (FC) to the citric acid cycle was analyzed by(13)C-nuclear magnetic resonance. ECMO depressed circulating T3 levels to 40% of the baseline at 4 h 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 [adenosine triphosphate]/[adenosine diphosphate] without either decreasing FC-FAs or elevating myocardial oxygen consumption over Group-C or -IR. T3 releases inhibition of lactate oxidation following IR 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.

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

Science.gov (United States)

Ke, Xiubin; Lu, Yahai

2012-04-01

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

Impaired fat oxidation after a single high-fat meal in insulin-sensitive nondiabetic individuals with a family history of type 2 diabetes.

Science.gov (United States)

Heilbronn, Leonie K; Gregersen, Søren; Shirkhedkar, Deepali; Hu, Dachun; Campbell, Lesley V

2007-08-01

Individuals with insulin resistance and type 2 diabetes have an impaired ability to switch appropriately between carbohydrate and fatty acid oxidation. However, whether this is a cause or consequence of insulin resistance is unclear, and the mechanism(s) involved in this response is not completely elucidated. Whole-body fat oxidation and transcriptional regulation of genes involved in lipid metabolism in skeletal muscle were measured after a prolonged fast and after consumption of either high-fat (76%) or high-carbohydrate (76%) meals in individuals with no family history of type 2 diabetes (control, n = 8) and in age- and fatness-matched individuals with a strong family history of type 2 diabetes (n = 9). Vastus lateralis muscle biopsies were performed before and 3 h after each meal. Insulin sensitivity and fasting measures of fat oxidation were not different between groups. However, subjects with a family history of type 2 diabetes had an impaired ability to increase fatty acid oxidation in response to the high-fat meal (P FAT)/CD36 (P fat meal in both groups, but it was not changed after the high-carbohydrate meal. In conclusion, an impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals. PGC1alpha and FAT/CD36 are likely candidates in mediating this response.

OXIDATIVE STRESS IN MUSCLE GROWTH AND ADAPTATION TO PHYSICAL EXERCISE

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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.

Sensorimotor and Cognitive Predictors of Impaired Gait Adaptability in Older People.

Science.gov (United States)

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

2017-09-01

The ability to adapt gait when negotiating unexpected hazards is crucial to maintain stability and avoid falling. This study investigated whether impaired gait adaptability in a task including obstacle and stepping targets is associated with cognitive and sensorimotor capacities in older adults. Fifty healthy older adults (74±7 years) were instructed to either (a) avoid an obstacle at usual step distance or (b) step onto a target at either a short or long step distance projected on a walkway two heel strikes ahead and then continue walking. Participants also completed cognitive and sensorimotor function assessments. Stroop test and reaction time performance significantly discriminated between participants who did and did not make stepping errors, and poorer Trail-Making test performance predicted shorter penultimate step length in the obstacle avoidance condition. Slower reaction time predicted poorer stepping accuracy; increased postural sway, weaker quadriceps strength, and poorer Stroop and Trail-Making test performances predicted increased number of steps taken to approach the target/obstacle and shorter step length; and increased postural sway and higher concern about falling predicted slower step velocity. Superior executive function, fast processing speed, and good muscle strength and balance were all associated with successful gait adaptability. Processing speed appears particularly important for precise foot placements; cognitive capacity for step length adjustments; and early and/or additional cognitive processing involving the inhibition of a stepping pattern for obstacle avoidance. This information may facilitate fall risk assessments and fall prevention strategies. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reduced host cell invasiveness and oxidative stress tolerance in double and triple csp gene family deletion mutants of Listeria monocytogenes.

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Loepfe, Chantal; Raimann, Eveline; Stephan, Roger; Tasara, Taurai

2010-07-01

The cold shock protein (Csp) family comprises small, highly conserved proteins that bind nucleic acids to modulate various bacterial gene expressions. In addition to cold adaptation functions, this group of proteins is thought to facilitate various cellular processes to promote normal growth and stress adaptation responses. Three proteins making up the Listeria monocytogenes Csp family (CspA, CspB, and CspD) promote both cold and osmotic stress adaptation functions in this bacterium. The contribution of these three Csps in the host cell invasion processes of L. monocytogenes was investigated based on human Caco-2 and murine macrophage in vitro cell infection models. The DeltacspB, DeltacspD, DeltacspAB, DeltacspAD, DeltacspBD, and DeltacspABD strains were all significantly impaired in Caco-2 cell invasion compared with the wild-type strain, whereas in the murine macrophage infection assay only, the double (DeltacspBD) and triple (DeltacspABD) csp mutants were also significantly impaired in cell invasion compared with the wild-type strain. The DeltacspBD and DeltacspABD mutants displayed the most severely impaired invasion phenotypes. The invasion ability of these two mutant strains was also further analyzed using cold-stress-exposed organisms. In both cell infection models a significant reduction in invasiveness was observed after cold stress exposure of Listeria organisms. The negative impact of cold stress on subsequent cell invasion ability was, however, more severe in cold-sensitive csp mutants (DeltacspBD and DeltacspABD) compared with the wild type. The impaired macrophage invasion and intracellular growth of DeltacspBD and DeltacspABD also led us to examine oxidative stress resistance capacity in these two mutant strains. Both strains also displayed higher oxidative stress sensitivity relative to the wild-type strain. Our data indicate that besides cold and osmotic stress adaptation roles, Csp family proteins also promote efficient host cell invasion and

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

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

2017-01-01

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

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

Science.gov (United States)

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

2018-01-01

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

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.

Adaptive stress response to menadione-induced oxidative stress in Saccharomyces cerevisiae KNU5377.

Science.gov (United States)

Kim, Il-Sup; Sohn, Ho-Yong; Jin, Ingnyol

2011-10-01

The molecular mechanisms involved in the ability of yeast cells to adapt and respond to oxidative stress are of great interest to the pharmaceutical, medical, food, and fermentation industries. In this study, we investigated the time-dependent, cellular redox homeostasis ability to adapt to menadione-induced oxidative stress, using biochemical and proteomic approaches in Saccharomyces cerevisiae KNU5377. Time-dependent cell viability was inversely proportional to endogenous amounts of ROS measured by a fluorescence assay with 2',7'-dichlorofluorescin diacetate (DCFHDA), and was hypersensitive when cells were exposed to the compound for 60 min. Morphological changes, protein oxidation and lipid peroxidation were also observed. To overcome the unfavorable conditions due to the presence of menadione, yeast cells activated a variety of cell rescue proteins including antioxidant enzymes, molecular chaperones, energy-generating metabolic enzymes, and antioxidant molecules such as trehalose. Thus, these results show that menadione causes ROS generation and high accumulation of cellular ROS levels, which affects cell viability and cell morphology and there is a correlation between resistance to menadione and the high induction of cell rescue proteins after cells enter into this physiological state, which provides a clue about the complex and dynamic stress response in yeast cells.

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.

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

Science.gov (United States)

Gomes, Elisa Couto; Silva, Albená Nunes; de Oliveira, Marta Rubino

2012-01-01

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. PMID:22701757

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.

Developmental Programming in Response to Intrauterine Growth Restriction Impairs Myoblast Function and Skeletal Muscle Metabolism

Science.gov (United States)

Yates, D. T.; Macko, A. R.; Nearing, M.; Chen, X.; Rhoads, R. P.; Limesand, S. W.

2012-01-01

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. PMID:22900186

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.

Peripheral blood lymphocytes: a model for monitoring physiological adaptation to high altitude.

Science.gov (United States)

Mariggiò, Maria A; Falone, Stefano; Morabito, Caterina; Guarnieri, Simone; Mirabilio, Alessandro; Pilla, Raffaele; Bucciarelli, Tonino; Verratti, Vittore; Amicarelli, Fernanda

2010-01-01

Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.

Multi-objective optimization of p-xylene oxidation process using an improved self-adaptive differential evolution algorithm

Institute of Scientific and Technical Information of China (English)

Lili Tao; Bin Xu; Zhihua Hu; Weimin Zhong

2017-01-01

The rise in the use of global polyester fiber contributed to strong demand of the Terephthalic acid (TPA). The liquid-phase catalytic oxidation of p-xylene (PX) to TPA is regarded as a critical and efficient chemical process in industry [1]. PX oxidation reaction involves many complex side reactions, among which acetic acid combustion and PX combustion are the most important. As the target product of this oxidation process, the quality and yield of TPA are of great concern. However, the improvement of the qualified product yield can bring about the high energy consumption, which means that the economic objectives of this process cannot be achieved simulta-neously because the two objectives are in conflict with each other. In this paper, an improved self-adaptive multi-objective differential evolution algorithm was proposed to handle the multi-objective optimization prob-lems. The immune concept is introduced to the self-adaptive multi-objective differential evolution algorithm (SADE) to strengthen the local search ability and optimization accuracy. The proposed algorithm is successfully tested on several benchmark test problems, and the performance measures such as convergence and divergence metrics are calculated. Subsequently, the multi-objective optimization of an industrial PX oxidation process is carried out using the proposed immune self-adaptive multi-objective differential evolution algorithm (ISADE). Optimization results indicate that application of ISADE can greatly improve the yield of TPA with low combustion loss without degenerating TA quality.

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

DEFF Research Database (Denmark)

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

2013-01-01

Alveld is a hepatogenous photosensitivity disorder in lambs. The aim of the study was to investigate if alveld affected lambs had a reduced capacity to handle oxidative stress induced from either endogenous and/or exogenous photosensitizers. Serum samples from alveld lambs (n=33) were compared...... to serum samples from control lambs (n=31) and exposed to a controlled amount of singlet oxygen ((1)O2). The sera from alveld lambs were found to have an impaired ability to deactivate reactive oxygen species (ROS) compared to control sera. A higher degree of initial hemolysis and a higher concentration...... in pooled serum from alveld lambs that showed a high degree of hemolysis. It was concluded that alveld photosensitivity is likely to be initiated by a photodynamic reaction involving PP and possibly also PP IX followed by a light-independent reaction involving hemoglobin-related products and catalysis...

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

Directory of Open Access Journals (Sweden)

Masaaki Adachi

2009-11-01

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

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

Science.gov (United States)

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

2017-07-25

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

Inefficient skeletal muscle oxidative function flanks impaired motor neuron recruitment in Amyotrophic Lateral Sclerosis during exercise.

Science.gov (United States)

Lanfranconi, F; Ferri, A; Corna, G; Bonazzi, R; Lunetta, C; Silani, V; Riva, N; Rigamonti, A; Maggiani, A; Ferrarese, C; Tremolizzo, L

2017-06-07

This study aimed to evaluate muscle oxidative function during exercise in amyotrophic lateral sclerosis patients (pALS) with non-invasive methods in order to assess if determinants of reduced exercise tolerance might match ALS clinical heterogeneity. 17 pALS, who were followed for 4 months, were compared with 13 healthy controls (CTRL). Exercise tolerance was assessed by an incremental exercise test on cycle ergometer measuring peak O 2 uptake ([Formula: see text]O 2peak ), vastus lateralis oxidative function by near infrared spectroscopy (NIRS) and breathing pattern ([Formula: see text]E peak ). pALS displayed: (1) 44% lower [Formula: see text]O 2peak vs. CTRL (p motor units recruitment, is a major determinant of pALS clinical heterogeneity and working capacity exercise tolerance. CPET and NIRS are useful tools for detecting early stages of oxidative deficiency in skeletal muscles, disclosing individual impairments in the O 2 transport and utilization chain.

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)

Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E.; Pi, Jingbo

2011-01-01

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

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

Dysfunction of Rapid Neural Adaptation in Dyslexia.

Science.gov (United States)

Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

2016-12-21

Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

Impaired oxidation of carbon-labeled galactose by alcoholic or diabetic liver in vivo

International Nuclear Information System (INIS)

Shreeve, W.W.

1987-01-01

Because of the organ and enzyme specificity of the metabolism of galactose, evaluation of various kinds of liver disease can be done by measuring the formation of labeled breath CO 2 from carbon-labeld galactose in vivo. As shown earlier with uniformly 14 C- or 13 C-labeld galactose, a further study of alcoholic cirrhotic patients and controls with cheaper 1- 14 C-galactose indicates a superior discriminatory value of this test compared with common liver functions tests. The oxidation test is easier to perform and more acceptable to patients than the standard galactose tolerance blood test. Output of 14 CO 2 showed slight correlations with serum albumin and 99m Tc-sulfur colloid scan grade, but not with other function tests (SGOT, alkaline phosphatase, bilirubin). Comparison with five-year clinical outcome (two groups: with or without known liver-related death) in 29 of 43 total cirrhotic patients (U- 14 C or 1- 14 C-galactose) showed a low (75% probability) significance of prognosis for the galactose oxidation test, but none for any of the other tests. A two-part test of oxidation of 14 C-galactose (with and without an acute dose of ethanol) in 19 possibly or likely alcoholic (but non-cirrhotic) persons indicated, by correlation with other liver function tests and drinking history, some possibly enhanced sensitivity of the two-part versus the single test for recognizing early liver damage. A preliminary study of the single galactose oxidation test in 7 patients with Type II diabetes suggests moderate impairment of oxidation, which might be applied to evaluate the hepatic disorder in diabetes. (orig.) [de

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

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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.

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

-hydro-5-methylimidazolone (MG-H1) was detected with an antibody against MG-H1 and quantified with ultra-performance liquid chromatography (tandem) mass spectrometry. Reactive oxygen species formation was measured with a 5-(and-6)-chloromethyl-2'7'-dichlorodihydrofluorescein diacetate acetyl ester probe...... for AGE ligand S100b did (p cells and adventitia by fivefold accompanied by an eightfold increase in the oxidative stress marker nitrotyrosine. Antioxidant pre-incubation prevented methylglyoxal......-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....

Maximal lipid oxidation in patients with type 2 diabetes is normal and shows an adequate increase in response to aerobic training

DEFF Research Database (Denmark)

Mogensen, M; Vind, B F; Højlund, K

2009-01-01

AIM: Insulin resistance in subjects with type 2 diabetes (T2D) and obesity is associated with an imbalance between the availability and the oxidation of lipids. We hypothesized that maximal whole-body lipid oxidation during exercise (FATmax) is reduced and that training-induced metabolic adaptation...... in response to aerobic training in obese subjects with and without T2D. These metabolic adaptations to training seem to be unrelated to changes in insulin sensitivity and indicate that an impaired capacity for lipid oxidation is not a major cause of insulin resistance in T2D....... subjects after training (all p Insulin-stimulated glucose disappearance rate (Rd) was lower in T2D vs. control subjects both before and after training. Rd increased...

Impaired myogenic tone in mesenteric arteries from overweight rats

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Sweazea Karen L

2012-03-01

Full Text Available Abstract Background Rats fed high fat (HFD or high sucrose (HSD diets develop increased adiposity as well as impaired vasodilatory responsiveness stemming from oxidative stress. Moreover, HFD rats become hypertensive compared to either control (Chow or HSD fed rats, suggesting elevated vascular tone. We hypothesized that rats with increased adiposity and oxidative stress demonstrate augmented pressure-induced vasoconstriction (i.e. myogenic tone that could account for the hypertensive state. Methods Male Sprague-Dawley rats were fed Chow, HFD or HSD for 6 weeks. The effects of oxidative stress and endogenous nitric oxide on myogenic responses were examined in small mesenteric arteries by exposing the arteries to incremental intraluminal pressure steps in the presence of antioxidants or an inhibitor of nitric oxide synthase, LNNA (100 μM. Results Contrary to the hypothesis, rats fed either HSD or HFD had significantly impaired myogenic responses despite similar vascular morphology and passive diameter responses to increasing pressures. Vascular smooth muscle (VSM calcium levels were normal in HFD arteries suggesting that diminished calcium sensitivity was responsible for the impaired myogenic response. In contrast, VSM calcium levels were reduced in HSD arteries but were increased with pre-exposure of arteries to the antioxidants tiron (10 mM and catalase (1200 U/mL, also resulting in enhanced myogenic tone. These findings show that oxidative stress impairs myogenic tone in arteries from HSD rats by decreasing VSM calcium. Similarly, VSM calcium responses were increased in arteries from HFD rats following treatment with tiron and catalase, but this did not result in improved myogenic tone. Nitric oxide is involved in the impaired myogenic response in HFD, but not HSD, rats since inhibition with LNNA resulted in maximal myogenic responses at lower intraluminal pressures and VSM calcium levels, further implicating reduced calcium sensitivity in

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

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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.

Reducing barriers to healthy weight: Planned and responsive adaptations to a lifestyle intervention to serve people with impaired mobility.

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Betts, Andrea C; Froehlich-Grobe, Katherine; Driver, Simon; Carlton, Danielle; Kramer, M Kaye

2018-04-01

People with impaired mobility (IM) disabilities have a higher prevalence of obesity and obesity-related chronic conditions; however, lifestyle interventions that address the unique needs of people with IM are lacking. This paper describes an adapted evidence-based lifestyle intervention developed through community-based participatory research (CBPR). Individuals with IM, health professionals, disability group representatives, and researchers formed an advisory board to guide the process of thoroughly adapting the Diabetes Prevention Program Group Lifestyle Balance (DPP GLB) intervention after a successful pilot in people with IM. The process involved two phases: 1) planned adaptations to DPP GLB content and delivery, and 2) responsive adaptations to address issues that emerged during intervention delivery. Planned adaptations included combining in-person sessions with conference calls, providing arm-based activity trackers, and adding content on adaptive cooking, adaptive physical activity, injury prevention, unique health considerations, self-advocacy, and caregiver support. During the intervention, participants encountered numerous barriers, including health and mental health issues, transportation, caregivers, employment, adjusting to disability, and functional limitations. We addressed barriers with responsive adaptations, such as supporting electronic self-monitoring, offering make up sessions, and adding content and activities on goal setting, problem solving, planning, peer support, reflection, and motivation. Given the lack of evidence on lifestyle change in people with disabilities, it is critical to involve the community in intervention planning and respond to real-time barriers as participants engage in change. A randomized controlled trial (RCT) is underway to examine the usability, feasibility, and preliminary effectiveness of the adapted intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

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

NARCIS (Netherlands)

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

Purpose: To investigate whether the adapted version of the Gross Motor Function Measure 88 (GMFM-88) for children with Cerebral Palsy (CP) and Cerebral Visual Impairment (CVI) results in higher scores. This is most likely to be a reflection of their gross motor function, however it may be the result

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

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Malkus Kristen A

2009-06-01

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

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

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Pushpalatha Bunadri

2013-01-01

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

Impairment of PPARα and the Fatty Acid Oxidation Pathway Aggravates Renal Fibrosis during Aging.

Science.gov (United States)

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

2018-04-01

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

Behavioral Impairment and Oxidative Damage Induced by Chronic Application of Nonylphenol

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Zhen Mao

2010-12-01

Full Text Available Nonylphenol (NP is a degradation product of nonylphenol polyethoxylates, which are widely used in the production of industrial and consumer surfactants. The aim of the present study was to evaluate the effect of NP on the antioxidant capacity and cognitive ability of mice. NP was given orally by gavages at doses of 0, 50, 100, and 200 mg kg−1 d−1 for 90 days. The results showed that NP significantly decreased the activity of superoxide dismutases (SOD, catalase (CAT, glutathione peroxidase (GPx, and glutathione reductase (GR and at the same time increased malondialdehyde (MDA levels in mice brains. Exploration, memory function and ability to learn a novel task were significantly decreased in NP fed mice. These results indicate that chronic high dose of NP exposure has the potential to generate oxidative stress and induce the cognitive impairment in male mice.

Walnut supplementation reverses the scopolamine-induced memory impairment by restoration of cholinergic function via mitigating oxidative stress in rats: a potential therapeutic intervention for age related neurodegenerative disorders.

Science.gov (United States)

Haider, Saida; Batool, Zehra; Ahmad, Saara; Siddiqui, Rafat Ali; Haleem, Darakhshan Jabeen

2018-02-01

The brain is highly susceptible to the damaging effects of oxidative reactive species. The free radicals which are produced as a consequence of aerobic respiration can cause cumulative oxygen damage which may lead to age-related neurodegeneration. Scopolamine, the anti-muscarinic agent, induces amnesia and oxidative stress similar to that observed in the older age. Studies suggest that antioxidants derived from plant products may provide protection against oxidative stress. Therefore, the present study was designed to investigate the attenuation of scopolamine-induced memory impairment and oxidative stress by walnut supplementation in rats. Rats in test group were administrated with walnut suspension (400 mg/kg/day) for four weeks. Both control and walnut-treated rats were then divided into saline and scopolamine-treated groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg dissolved in saline) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM), and novel object recognition task (NOR) followed by estimation of regional acetylcholine levels and acetylcholinesterase activity. In the next phase, brain oxidative status was determined by assaying lipid peroxidation, and measuring superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Results showed that scopolamine-treatment impaired memory function, caused cholinergic dysfunction, and induced oxidative stress in rats compared to that saline-treated controls. These impairments were significantly restored by pre-administration of walnut. This study demonstrates that antioxidant properties of walnut may provide augmented effects on cholinergic function by reducing oxidative stress and thus improving memory performance.

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.

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.

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.

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

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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.

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

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Carles Lerin

2016-10-01

Full Text Available 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 to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28. We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. 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 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. Keywords: Insulin sensitivity, BCAA, Fatty acid oxidation, TCA cycle

Adapted physical education for a student with visual impairment

OpenAIRE

Debevec, Karin

2016-01-01

Pupils with special needs, among which are blind and visually impaired children, are involved in various educational programs and attend all educational subjects, including physical education. However, teachers lack experience with teaching blind and visually impaired pupils and often find it challenging to find a way to include such pupils in physical activities. The purpose of this master's thesis was to identify the most common issues and adjustments that need to be made to individual p...

The role of oxidative, inflammatory and neuroendocrinological systems during exercise stress in athletes: implications of antioxidant supplementation on physiological adaptation during intensified physical training.

Science.gov (United States)

Slattery, Katie; Bentley, David; Coutts, Aaron J

2015-04-01

During periods of intensified physical training, reactive oxygen species (ROS) release may exceed the protective capacity of the antioxidant system and lead to dysregulation within the inflammatory and neuroendocrinological systems. Consequently, the efficacy of exogenous antioxidant supplementation to maintain the oxidative balance in states of exercise stress has been widely investigated. The aim of this review was to (1) collate the findings of prior research on the effect of intensive physical training on oxidant-antioxidant balance; (2) summarise the influence of antioxidant supplementation on the reduction-oxidation signalling pathways involved in physiological adaptation; and (3) provide a synopsis on the interactions between the oxidative, inflammatory and neuroendocrinological response to exercise stimuli. Based on prior research, it is evident that ROS are an underlying aetiology in the adaptive process; however, the impact of antioxidant supplementation on physiological adaptation remains unclear. Equivocal results have been reported on the impact of antioxidant supplementation on exercise-induced gene expression. Further research is required to establish whether the interference of antioxidant supplementation consistently observed in animal-based and in vivo research extends to a practical sports setting. Moreover, the varied results reported within the literature may be due to the hormetic response of oxidative, inflammatory and neuroendocrinological systems to an exercise stimulus. The collective findings suggest that intensified physical training places substantial stress on the body, which can manifest as an adaptive or maladaptive physiological response. Additional research is required to determine the efficacy of antioxidant supplementation to minimise exercise-stress during intensive training and promote an adaptive state.

Factors influencing radiation-induced impairment of rat liver mitochondrial oxidative phosphorylation

International Nuclear Information System (INIS)

Alexander, K.C.; Aiyar, A.S.; Sreenivasan, A.

1975-01-01

The influence of some experimental conditions on the radiation-induced impairment of oxidative phosphorylation in rat liver mitochondria has been studied. Shielding of the liver during whole body irradiation of the animal does not significantly alter the decreased efficiency of phosphorylation. There exists a great disparity in the in vivo and in vitro radiation doses required for the manifestation of damage to liver mitochondria. While these observations point to the abscopal nature of the radiation effects, direct involvement of the adrenals has been ruled out by studies with adrenalectomised rats. Prior administration of the well known radio-protective agents, serotonin or 2-aminoethyl isothiouronium bromide hydrobromide, is effective in preventing the derangement of mitochondrial function following radioexposure. The hypocholesterolemic drug ethyl-α-p-chlorophenoxy isobutyrate, which is known to influence hepatic mitochondrial turnover, does not afford any significant protection against either mitochondrial damage or the mortality of the animals due to whole body irradiation. (author)

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

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

Development of the Italian version of the trunk impairment scale in subjects with acute and chronic stroke. Cross-cultural adaptation, reliability, validity and responsiveness.

Science.gov (United States)

Monticone, Marco; Ambrosini, Emilia; Verheyden, Geert; Brivio, Flavia; Brunati, Roberto; Longoni, Luca; Mauri, Gaia; Molteni, Alessandro; Nava, Claudia; Rocca, Barbara; Ferrante, Simona

2017-09-10

To cross-culturally adapt and psychometrically analyse the Italian version of the Trunk Impairment Scale on acute (cohort 1) and chronic stroke patients (cohort 2). The Trunk Impairment Scale was culturally adapted in accordance with international standards. The psychometric testing included: internal consistency (Cronbach's alpha), inter- and intra-rater reliability (intraclass correlation coefficient; standard error of measurement and minimal detectable change), construct validity by comparing Trunk Impairment Scale score with Barthel Index, motor subscale of Functional Independence Measure, and Trunk Control Test (Pearson's correlation), and responsiveness (Effect Size, Effect Size with Guyatt approach, standardized response mean, and Receiver Operating Characteristics curves). The Trunk Impairment Scale was administered to 125 and 116 acute and chronic stroke patients, respectively. Internal consistency was acceptable (α > 0.7), inter- and intra-rater reliability (ICC > 0.9, Minimal Detectable Change for total score  0.4) with all scales but the motor Functional Independence Measure in cohort 2. Distribution-based methods showed large effects in cohort 1 and moderate to large effects in cohort 2. The Minimal Important Difference was 3.5 both from patient's and therapist's perspective in cohort 1 and 2.5 and 1.5 from patient's and therapist's perspective, respectively, in cohort 2. The Trunk Impairment Scale was successfully translated into Italian and proved to be reliable, valid, and responsive. Its use is recommended for clinical and research purposes. Implications for Rehabilitation Trunk control is an essential part of balance and postural control, constituting an important prerequisite for daily activities and function. The TIS administered in subjects with subacute and chronic stroke was reliable, valid and responsive. The TIS is expected to help clinicians and researchers by identifying key functional processes related to disability in people

Prerequisites for the development of the concept of health-forming technologies in the process of adaptive physical education of school-age children with hearing impairment

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Vitaliy Kashuba

2018-03-01

Full Text Available Prerequisites for the development of the concept of health-forming technologies in the process of adaptive physical education of school-age children with hearing impairment Prerequisites for the development of the concept of health-forming technologies in the process of adaptive physical education of school-age children with hearing impairment National University of Physical Education and Sports of Ukraine, Kyiv. Actuality. The leading position of the contemporary issues of health-forming activity of children and youth presented in the form of a methodological basis for the formation of a positive motivation for a healthy lifestyle of the younger generation, especially with specific disabilities in the state of health, separates the central component of this process from the humanistic approach, the essence of which is creating a favorable situation for the readiness of the present youth to perceive and adequately respond to the educational activities of the school and social environment that are implemented in the process of their physical education. Objectives of the study: determination of priority directions of optimization of the process of physical education of students with hearing impairments, selection of rational means and methods that fully satisfy the specific needs of this contingent based on the study of their interests not only during physical education, but also correctional activities, self-organized motor activity Research results. The data obtained during the study showed that most children with hearing impairments understood the problems of their own health and had a desire to carry out activities aimed at improving their level, defining for themselves as the main criterion the physical state of their organism. The results of the questionnaire survey of 236 schoolchildren aged 13 to 19 years with different established hearing disorders supplemented the systematization of preconditions and scientifically substantiated the

Adaptive Assessment of Young Children with Visual Impairment

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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…

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

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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.

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

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Xue, Peng; Hou, Yongyong; Zhang, Qiang; Woods, Courtney G; Yarborough, Kathy; Liu, Huiyu; Sun, Guifan; Andersen, Melvin E; Pi, Jingbo

2011-04-08

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. Taken together our studies suggest that prolonged low-level iAs³(+) exposure activates the cellular adaptive oxidative stress response, which impairs insulin-stimulated ROS signaling that is involved in ISGU, and thus causes insulin resistance in adipocytes. Copyright © 2011 Elsevier Inc. All rights reserved.

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

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Shabala, Sergey; Bækgaard, Lone; Shabala, Lana

2011-01-01

Although the role of Ca2+ influx channels in oxidative stress signaling and cross-tolerance in plants is well established, little is known about the role of active Ca2+ efflux systems in this process. In our recent paper,17 we reported Potato Virus X (PVX)-induced acquired resistance to oxidative...... 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...... stress in Nicotiana benthamiana and showed the critical role of plasma membrane Ca2+/H+ exchangers in this process. The current study continues this research. Using biochemical and electrophysiological approaches, we reveal that both endomembrane P2A and P2B Ca2+-ATPases play significant roles...

Screening tools for the identification of dementia for adults with age-related acquired hearing or vision impairment: a scoping review.

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Pye, Annie; Charalambous, Anna Pavlina; Leroi, Iracema; Thodi, Chrysoulla; Dawes, Piers

2017-11-01

Cognitive screening tests frequently rely on items being correctly heard or seen. We aimed to identify, describe, and evaluate the adaptation, validity, and availability of cognitive screening and assessment tools for dementia which have been developed or adapted for adults with acquired hearing and/or vision impairment. Electronic databases were searched using subject terms "hearing disorders" OR "vision disorders" AND "cognitive assessment," supplemented by exploring reference lists of included papers and via consultation with health professionals to identify additional literature. 1,551 papers were identified, of which 13 met inclusion criteria. Four papers related to tests adapted for hearing impairment; 11 papers related to tests adapted for vision impairment. Frequently adapted tests were the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MOCA). Adaptations for hearing impairment involved deleting or creating written versions for hearing-dependent items. Adaptations for vision impairment involved deleting vision-dependent items or spoken/tactile versions of visual tasks. No study reported validity of the test in relation to detection of dementia in people with hearing/vision impairment. Item deletion had a negative impact on the psychometric properties of the test. While attempts have been made to adapt cognitive tests for people with acquired hearing and/or vision impairment, the primary limitation of these adaptations is that their validity in accurately detecting dementia among those with acquired hearing or vision impairment is yet to be established. It is likely that the sensitivity and specificity of the adapted versions are poorer than the original, especially if the adaptation involved item deletion. One solution would involve item substitution in an alternative sensory modality followed by re-validation of the adapted test.

Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise

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Mankowski, Robert T.; Anton, Stephen D.; Buford, Thomas W.; Leeuwenburgh, Christiaan

2015-01-01

Adaptive responses to exercise training (ET) are crucial in maintaining physiological homeostasis and health span. Exercise-induced aerobic bioenergetic reactions in mitochondria and cytosol increase production of reactive oxygen species (ROSs), where excess of ROS can be scavenged by enzymatic as well as non-enzymatic antioxidants to protect against deleterious oxidative stress. Free radicals, however, have recently been recognized as crucial signaling agents that promote adaptive mechanisms to ET, such as mitochondrial biogenesis, antioxidant (AO) enzyme activity defense system upregulation, insulin sensitivity, and glucose uptake in skeletal muscle. Commonly used non-enzymatic AO supplements, such as vitamins C and E, a-lipoic acid, and polyphenols, in combination with ET, have been proposed as ways to prevent exercise-induced oxidative stress and hence improve adaptation responses to endurance training. Preclinical and clinical studies to date have shown inconsistent results indicating either positive or negative effects of endurance training combined with different blends of AO supplements (mostly vitamins C and E and a-lipoic acid) on redox status, mitochondrial biogenesis pathways, and insulin sensitivity. Preclinical reports on ET combined with resveratrol, however, have shown consistent positive effects on exercise performance, mitochondrial biogenesis, and insulin sensitivity, with clinical trials reporting mixed effects. Relevant clinical studies have been few and have used inconsistent results and methodology (types of compounds, combinations, and supplementation time). The future studies would investigate the effects of specific antioxidants and other popular supplements, such as a-lipoic acid and resveratrol, on training effects in humans. Of particular importance are older adults who may be at higher risk of age-related increased oxidative stress, an impaired AO enzyme defense system, and comorbidities such as hypertension, insulin resistance, and

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

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Tatiana Barichello

2011-01-01

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

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

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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. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal muscle integrity

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Lantier, Louise; Fentz, Joachim; Mounier, Rémi

2014-01-01

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that plays a central role in skeletal muscle metabolism. We used skeletal muscle-specific AMPKα1α2 double-knockout (mdKO) mice to provide direct genetic evidence of the physiological importance of AMPK in regulating muscle...... diminished maximal ADP-stimulated mitochondrial respiration, showing an impairment at complex I. This effect was not accompanied by changes in mitochondrial number, indicating that AMPK regulates muscle metabolic adaptation through the regulation of muscle mitochondrial oxidative capacity and mitochondrial...

IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice.

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Toth, Peter; Tucsek, Zsuzsanna; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2014-12-01

Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice (Igf1(f/f)+TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype.

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

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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.

Food Preparation: An Instructional Package with Adaptations for Visually Impaired Individuals.

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Crawford, Glinda B.; And Others

This instructional package, developed for the home economics teacher of mainstreamed visually impaired students, provides food preparation lesson plans appropriate for the junior high level. First, teacher guidelines are given, including characteristics of the visually impaired, orienting such students to the classroom, orienting class members to…

Experimentally induced hyperthyroidism influences oxidant and antioxidant status and impairs male gonadal functions in adult rats.

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Asker, M E; Hassan, W A; El-Kashlan, A M

2015-08-01

The objective of the present experiment was to study the effect of hyperthyroidism on male gonadal functions and oxidant/antioxidant biomarkers in testis of adult rats. Induction of hyperthyroidism by L-thyroxine (L-T4, 300 μg kg(-1) body weight) treatment once daily for 3 or 8 weeks caused a decrease in body weight gain as well as in absolute genital sex organs weight. The epididymal sperm counts and their motility were significantly decreased in a time-dependent manner following L-T4 treatment. Significant decline in serum levels of luteinising hormone, follicle stimulating hormone and testosterone along with significant increase in serum estradiol level was observed in hyperthyroid rats compared with euthyroid ones. Significant increase in malondialdehyde and nitric oxide concentration associated with significant decrease in superoxide dismutase and catalase activity was also noticed following hyperthyroidism induction. Both reduced glutathione content and glutathione peroxidase activity were increased in hyperthyroid rats compared with control rats. Marked histopathological alterations were observed in testicular section of hyperthyroid rats. These results provide evidence that hypermetabolic state induced by excess level of thyroid hormones may be a causative factor for the impairment of testicular physiology as a consequence of oxidative stress. © 2014 Blackwell Verlag GmbH.

Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain.

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Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Ataee, Ramin; Moghaddam, Shiva Nasiraei

2010-08-01

Aging is the major risk factor for neurodegenerative diseases and oxidative stress and is involved in their pathophysiology. Oxidative stress can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (5, 15, or 45 mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intracerebroventricular injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests, were evaluated 24 hours after the last injection of curcumin or vehicle. Results indicated that Hcy induces lipid peroxidation and increases malondialdehyde (MDA) and superoxide anion (SOA) levels in whole rat brain. In addition, Hcy impaired memory retention in the passive avoidance learning test. However, curcumin treatment significantly decreased MDA and SOA levels and improved learning and memory in rats. These results suggest that Hcy may induce lipid peroxidation in rat brain and that polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against oxidative stress.

Saponins from Panax japonicus attenuate D-galactose-induced cognitive impairment through its anti-oxidative and anti-apoptotic effects in rats.

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Wang, Ting; Di, Guojie; Yang, Li; Dun, Yaoyan; Sun, Zhiwei; Wan, Jingzhi; Peng, Ben; Liu, Chaoqi; Xiong, Guangrun; Zhang, Changcheng; Yuan, Ding

2015-09-01

To investigate the neuroprotective effects of saponins from Panax japonicus (SPJ) on D-galactose (D-gal)-induced brain ageing, and further explore the underlying mechanisms. SPJ were analysed using high-pressure liquid chromatography. Male Wistar rats weighing 200 ± 20 g were randomly divided into four groups: control group (saline), D-gal-treated group (400 mg/kg, subcutaneously), D-gal + SPJ groups (50, 100 and 200 mg/kg, orally) and vitamin E group (100 mg/kg). Rats were injected corresponding drugs once daily for 8 weeks. Neuroprotective effects of SPJ were evaluated by Morris water maze, histopathological observations, biochemical assays, western blot analysis and quantitative real-time polymerase chain reaction (PCR) analysis in vivo as well as reactive oxygen species (ROS) measurement and apoptosis assay in vitro. Our present study showed that D-gal had a neurotoxic effect in rats and in SH-SY5Y cells due to oxidative stress induction, including decreased total anti-oxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase activity, ultimately leading to spatial learning and memory impairment in rats and ROS accumulation in SH-SY5Y cells. SPJ improved spatial learning and memory deficits, attenuated hippocampus histopathological injury and restored impaired anti-oxidative as well as anti-apoptotic capacities in D-gal-induced ageing rats. In addition, SPJ remarkably decreased lipofuscin levels, increased hippocampus nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homologue (SIRT1) protein levels and anti-oxidant genes expression such as manganese superoxide dismutase (Mn-SOD), heme oxygenase (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1) and cysteine ligase catalytic (GCLC) in D-gal-induced brain ageing. Our data suggested that D-gal induced multiple molecular and functional changes in brain similar to natural ageing process. SPJ protected brain from D-gal-induced neuronal

Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress.

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Patki, Gaurav; Solanki, Naimesh; Atrooz, Fatin; Allam, Farida; Salim, Samina

2013-11-20

In the present study, we have examined the behavioral and biochemical effect of induction of psychological stress using a modified version of the resident-intruder model for social stress (social defeat). At the end of the social defeat protocol, body weights, food and water intake were recorded, depression and anxiety-like behaviors as well as memory function was examined. Biochemical analysis including oxidative stress measurement, inflammatory markers and other molecular parameters, critical to behavioral effects were examined. We observed a significant decrease in the body weight in the socially defeated rats as compared to the controls. Furthermore, social defeat increased anxiety-like behavior and caused memory impairment in rats (PSocially defeated rats made significantly more errors in long term memory tests (Psocially defeated rats, when compared to control rats. We suggest that social defeat stress alters ERK1/2, IL-6, GLO1, GSR1, CAMKIV, CREB, and BDNF levels in specific brain areas, leading to oxidative stress-induced anxiety-depression-like behaviors and as well as memory impairment in rats. © 2013 Published by Elsevier B.V.

Adaptation, validation and application of the chemo-thermal oxidation method to quantify black carbon in soils

International Nuclear Information System (INIS)

Agarwal, Tripti; Bucheli, Thomas D.

2011-01-01

The chemo-thermal oxidation method at 375 o C (CTO-375) has been widely used to quantify black carbon (BC) in sediments. In the present study, CTO-375 was tested and adapted for application to soil, accounting for some matrix specific properties like high organic carbon (≤39%) and carbonate (≤37%) content. Average recoveries of standard reference material SRM-2975 ranged from 25 to 86% for nine representative Swiss and Indian samples, which is similar to literature data for sediments. The adapted method was applied to selected samples of the Swiss soil monitoring network (NABO). BC content exhibited different patterns in three soil profiles while contribution of BC to TOC was found maximum below the topsoil at all three sites, however at different depths (60-130 cm). Six different NABO sites exhibited largely constant BC concentrations over the last 25 years, with short-term (6 months) prevailing over long-term (5 years) temporal fluctuations. - Research highlights: → The CTO-375 method was adapted and validated for BC analysis in soils. → Method validation figures of merit proofed satisfactory. → Application is shown with soil cores and topsoil temporal variability. → BC content can be elevated in subsurface soils. → BC contents in surface soils were largely constant over the last 25 years. - Although widely used also for soils, the chemo-thermal oxidation method at 375 o C to quantify black carbon has never been properly validated for this matrix before.

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

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

2016-10-01

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

Macrophage mitochondrial damage from StAR transport of 7-hydroperoxycholesterol: implications for oxidative stress-impaired reverse cholesterol transport.

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Korytowski, Witold; Wawak, Katarzyna; Pabisz, Pawel; Schmitt, Jared C; Girotti, Albert W

2014-01-03

StAR family proteins in vascular macrophages participate in reverse cholesterol transport (RCT). We hypothesize that under pathophysiological oxidative stress, StARs will transport not only cholesterol to macrophage mitochondria, but also pro-oxidant cholesterol hydroperoxides (7-OOHs), thereby impairing early-stage RCT. Upon stimulation with dibutyryl-cAMP, RAW264.7 macrophages exhibited a strong time-dependent induction of mitochondrial StarD1 and plasma membrane ABCA1, which exports cholesterol. 7α-OOH uptake by stimulated RAW cell mitochondria (like cholesterol uptake) was strongly reduced by StarD1 knockdown, consistent with StarD1 involvement. Upon uptake by mitochondria, 7α-OOH (but not redox-inactive 7α-OH) triggered lipid peroxidation and membrane depolarization while reducing ABCA1 upregulation. These findings provide strong initial support for our hypothesis. Copyright © 2013. Published by Elsevier B.V.

Conflict adaptation in schizophrenia: reviewing past and previewing future efforts.

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Abrahamse, Elger; Ruitenberg, Marit; Duthoo, Wout; Sabbe, Bernard; Morrens, Manuel; van Dijck, Jean-Philippe

2016-05-01

Cognitive control impairments have been suggested to be a critical component in the overall cognitive deficits observed in patients diagnosed with schizophrenia. Here, we zoom in on a specific function of cognitive control, conflict adaptation. Abnormal neural activity patterns have been observed for patients diagnosed with schizophrenia in core conflict adaptation areas such as anterior cingulate cortex and prefrontal cortex. On the one hand, this strongly indicates that conflict adaptation is affected. On the other hand, however, outcomes at the behavioural level are needed to create a window into a precise interpretation of this abnormal neural activity. We present a narrative review of behavioural work within the context of conflict adaptation in schizophrenia, focusing on various major conflict adaptation markers: congruency sequence effects, proportion congruency effects, and post-error and post-conflict slowing. The review emphasises both methodological and theoretical aspects that are relevant to the understanding of conflict adaptation in schizophrenia. Based on the currently available set of behavioural studies on conflict adaptation, no clear-cut answer can be provided as to the precise conflict adaptation processes that are impaired (and to what extent) in schizophrenia populations. Future work is needed in state-of-the-art designs in order to reach better insight into the specifics of conflict adaptation impairments associated with schizophrenia.

The Protective Role of Tempol Against Oxidative Stress-Related Renal Impairment Induced by Gamma Rays in Rats

International Nuclear Information System (INIS)

Mekawy, H.M.S.; Elkhouly, W.A.; Tawfik, S.S.

2015-01-01

Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1 oxyl) is a naturally occurring substance that counteracts the harmful and damaging effects of oxidation in animal tissues and has been reported to permeate the biological membranes. In this study, tempol with dose of 18 mg/kg/day for 2 weeks has been shown to be effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage. Adult rats were exposed to a total dose of 6 Gy gamma rays to determine the protective role of tempol on the biochemistry of the injured kidney because gamma rays displayed significant augmentation in renal oxidative modifications markers.The results indicated that plasma renal function tests; urea (Ur), creatinine (Cr), uric acid (UA) and sodium (Na), and plasma renal tubular injury markers; γ -glutamyltransferase ( γ -GT), aspartate aminotransferase (AST), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH), were increased significantly in gamma rays group. In addition, the renal oxidative stress parameters; malondialdehyde (MDA), total cholesterol (TC) and protein carbonyl (PC), were increased significantly, and reduced glutathione (GSH) was decreased significantly in gamma rays group. Moreover, the levels of renal antioxidant enzymes; superoxide dismutase (SOD) and catalase (CAT), were decreased significantly, and myeloperoxidase (MPO) was in creased significantly in gamma rays group.The antioxidant treatment with tempol ameliorates gamma rays-induced biochemical alterations and dysfunction of kidney.Tempol, at levels within tolerable nutritional strategy, reduced the oxidative modification-related renal impairment induced by gamma radiation in rats.

Cth2 Protein Mediates Early Adaptation of Yeast Cells to Oxidative Stress Conditions.

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Laia Castells-Roca

Full Text Available Cth2 is an mRNA-binding protein that participates in remodeling yeast cell metabolism in iron starvation conditions by promoting decay of the targeted molecules, in order to avoid excess iron consumption. This study shows that in the absence of Cth2 immediate upregulation of expression of several of the iron regulon genes (involved in high affinity iron uptake and intracellular iron redistribution upon oxidative stress by hydroperoxide is more intense than in wild type conditions where Cth2 is present. The oxidative stress provokes a temporary increase in the levels of Cth2 (itself a member of the iron regulon. In such conditions Cth2 molecules accumulate at P bodies-like structures when the constitutive mRNA decay machinery is compromised. In addition, a null Δcth2 mutant shows defects, in comparison to CTH2 wild type cells, in exit from α factor-induced arrest at the G1 stage of the cell cycle when hydroperoxide treatment is applied. The cell cycle defects are rescued in conditions that compromise uptake of external iron into the cytosol. The observations support a role of Cth2 in modulating expression of diverse iron regulon genes, excluding those specifically involved in the reductive branch of the high-affinity transport. This would result in immediate adaptation of the yeast cells to an oxidative stress, by controlling uptake of oxidant-promoting iron cations.

Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans

NARCIS (Netherlands)

Wanders, Ronald J. A.; Komen, Jasper; Kemp, Stephan

2011-01-01

Fatty acids (FAs) can be degraded via different mechanisms including alpha-, beta- and omega-oxidation. In humans, a range of different genetic diseases has been identified in which either mitochondrial FA beta-oxidation, peroxisomal FA beta-oxidation or FA alpha-oxidation is impaired. Treatment

Adapting Art Instruction for Students with Disabilities.

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Platt, Jennifer M.; Janeczko, Donna

1991-01-01

This article presents adaptations for teaching art to students with disabilities. Various techniques, methods, and materials are described by category of disability, including students with mental disabilities, visual impairments, hearing impairments, learning disabilities, emotional disabilities, and physical disabilities. (JDD)

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

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Qi Wang

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

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

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Wang, Qi; Hu, Weina; Lei, Mingming; Wang, Yong; Yan, Bing; Liu, Jun; Zhang, Ren; Jin, Yuanzhe

2013-01-01

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

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

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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

Robust adaptive control for a hybrid solid oxide fuel cell system

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Snyder, Steven

2011-12-01

Solid oxide fuel cells (SOFCs) are electrochemical energy conversion devices. They offer a number of advantages beyond those of most other fuel cells due to their high operating temperature (800-1000°C), such as internal reforming, heat as a byproduct, and faster reaction kinetics without precious metal catalysts. Mitigating fuel starvation and improving load-following capabilities of SOFC systems are conflicting control objectives. However, this can be resolved by the hybridization of the system with an energy storage device, such as an ultra-capacitor. In this thesis, a steady-state property of the SOFC is combined with an input-shaping method in order to address the issue of fuel starvation. Simultaneously, an overall adaptive system control strategy is employed to manage the energy sharing between the elements as well as to maintain the state-of-charge of the energy storage device. The adaptive control method is robust to errors in the fuel cell's fuel supply system and guarantees that the fuel cell current and ultra-capacitor state-of-charge approach their target values and remain uniformly, ultimately bounded about these target values. Parameter saturation is employed to guarantee boundedness of the parameters. The controller is validated through hardware-in-the-loop experiments as well as computer simulations.

Fasting exacerbates hepatic growth differentiation factor 15 to promote fatty acid β-oxidation and ketogenesis via activating XBP1 signaling in liver

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Meiyuan Zhang

2018-06-01

Full Text Available Liver coordinates a series of metabolic adaptations to maintain systemic energy balance and provide adequate nutrients for critical organs, tissues and cells during starvation. However, the mediator(s implicated in orchestrating these fasting-induced adaptive responses and the underlying molecular mechanisms are still obscure. Here we show that hepatic growth differentiation factor 15 (GDF15 is regulated by IRE1α-XBP1s branch and promotes hepatic fatty acids β-oxidation and ketogenesis upon fasting. GDF15 expression was exacerbated in liver of mice subjected to long-term fasted or ketogenic diet feeding. Abrogation of hepatic Gdf15 dramatically attenuated hepatic β-oxidation and ketogenesis in fasted mice or mice with STZ-initiated type I diabetes. Further study revealed that XBP1s activated Gdf15 transcription via binding to its promoter. Elevated GDF15 in liver reduced lipid accumulation and impaired NALFD development in obese mice through enhancing fatty acids oxidation in liver. Therefore, our results demonstrate a novel and critical role of hepatic GDF15 activated by IRE1α-XBP1s branch in regulating adaptive responses of liver upon starvation stress. Keywords: Fasting, Fatty acid β-oxidation, Ketogenesis, GDF15, XBP1, NAFLD

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

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

2017-07-06

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

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

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V. A. Sergeeva

2017-01-01

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

About subjective evaluation of adaptive video streaming

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Tavakoli, Samira; Brunnström, Kjell; Garcia, Narciso

2015-03-01

The usage of HTTP Adaptive Streaming (HAS) technology by content providers is increasing rapidly. Having available the video content in multiple qualities, using HAS allows to adapt the quality of downloaded video to the current network conditions providing smooth video-playback. However, the time-varying video quality by itself introduces a new type of impairment. The quality adaptation can be done in different ways. In order to find the best adaptation strategy maximizing users perceptual quality it is necessary to investigate about the subjective perception of adaptation-related impairments. However, the novelties of these impairments and their comparably long time duration make most of the standardized assessment methodologies fall less suited for studying HAS degradation. Furthermore, in traditional testing methodologies, the quality of the video in audiovisual services is often evaluated separated and not in the presence of audio. Nevertheless, the requirement of jointly evaluating the audio and the video within a subjective test is a relatively under-explored research field. In this work, we address the research question of determining the appropriate assessment methodology to evaluate the sequences with time-varying quality due to the adaptation. This was done by studying the influence of different adaptation related parameters through two different subjective experiments using a methodology developed to evaluate long test sequences. In order to study the impact of audio presence on quality assessment by the test subjects, one of the experiments was done in the presence of audio stimuli. The experimental results were subsequently compared with another experiment using the standardized single stimulus Absolute Category Rating (ACR) methodology.

Motivation and Physical Activity in Adolescents with Visual Impairments

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Kozub, Francis M.

2006-01-01

It is found that individuals with visual impairments have levels of intrinsic and extrinsic motivation and amotivation that influence their use of free time and lead to adaptive or maladaptive outcomes. As such, inactive individuals with visual impairments, lacking motivation to engage in physical activity, become dependent members of society who…

Conflict adaptation in patients diagnosed with schizophrenia.

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Abrahamse, Elger; Ruitenberg, Marit; Boddewyn, Sarah; Oreel, Edith; de Schryver, Maarten; Morrens, Manuel; van Dijck, Jean-Philippe

2017-11-01

Cognitive control impairments may contribute strongly to the overall cognitive deficits observed in patients diagnosed with schizophrenia. In the current study we explore a specific cognitive control function referred to as conflict adaptation. Previous studies on conflict adaptation in schizophrenia showed equivocal results, and, moreover, were plagued by confounded research designs. Here we assessed for the first time conflict adaptation in schizophrenia with a design that avoided the major confounds of feature integration and stimulus-response contingency learning. Sixteen patients diagnosed with schizophrenia and sixteen healthy, matched controls performed a vocal Stroop task to determine the congruency sequence effect - a marker of conflict adaptation. A reliable congruency sequence effect was observed for both healthy controls and patients diagnosed with schizophrenia. These findings indicate that schizophrenia is not necessarily accompanied by impaired conflict adaptation. As schizophrenia has been related to abnormal functioning in core conflict adaptation areas such as anterior cingulate and dorsolateral prefrontal cortex, further research is required to better understand the precise impact of such abnormal brain functioning at the behavioral level. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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Carmen Vida

2018-01-01

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

Winter-swimming as a building-up body resistance factor inducing adaptive changes in the oxidant/antioxidant status.

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Lubkowska, Anna; Dołęgowska, Barbara; Szyguła, Zbigniew; Bryczkowska, Iwona; Stańczyk-Dunaj, Małgorzata; Sałata, Daria; Budkowska, Marta

2013-01-01

The aim of our research was to examine whether winter-swimming for five consecutive months results in adaptational changes improving tolerance to stress induced by exposure to cryogenic temperatures during whole-body cryostimulation (WBC). The research involved 15 healthy men, with normal bodyweight, who had never been subjected to either WBC or cold water immersion. During the experiment, the participants were twice subjected to WBC (3 min/- 130°C), namely before the winter-swimming season and after the season. Blood was taken seven times: In the morning before each cryostimulation, 30 min after each cryostimulation and the next morning. Additionally, control blood was collected in the middle of the winter season, in February. Our analysis concerned changes in hematological parameters as well as in reduced glutathione and oxidized glutathione, total oxidant status, total antioxidant status and in components of the antioxidant system: Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and 8-Isoprostanes as a sensitive indicator of oxidative stress. We found significant changes in hemoglobin concentration, the number of red blood cells, the hematocrit index and mean corpuscular volume of red blood cell and the percentage of monocytes and granulocytes after the winter swimming season. The response to cryogenic temperatures was milder after five months of winter-swimming. The obtained results may indicate positive adaptive changes in the antioxidant system of healthy winter-swimmers. These changes seem to increase the readiness of the human body to stress factors.

Temporal Structure of Adaptation to Disability.

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Livneh, Hanoch; Antonak, Richard F.

1991-01-01

Used cross-sectional design to collect data on phases of adaptation to disability as measured by the Reactions to Impairment and Disability Inventory among 112 inpatients and 92 outpatients at rehabilitation facilities. Results generally support the existence of a psychosocial adaptation process to physical disability. Incongruities between the…

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

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Sharma, Deep Raj; Sunkaria, Aditya; Bal, Amanjit; Bhutia, Yangchen D.; Vijayaraghavan, R.; Flora, S.J.S.; Gill, Kiran Dip

2009-01-01

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.

Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers

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Ross, Megan L.; Garvican‐Lewis, Laura A.; Welvaert, Marijke; Heikura, Ida A.; Forbes, Sara G.; Mirtschin, Joanne G.; Cato, Louise E.; Strobel, Nicki; Sharma, Avish P.; Hawley, John A.

2017-01-01

Key points Three weeks of intensified training and mild energy deficit in elite race walkers increases peak aerobic capacity independent of dietary support.Adaptation to a ketogenic low carbohydrate, high fat (LCHF) diet markedly increases rates of whole‐body fat oxidation during exercise in race walkers over a range of exercise intensities.The increased rates of fat oxidation result in reduced economy (increased oxygen demand for a given speed) at velocities that translate to real‐life race performance in elite race walkers.In contrast to training with diets providing chronic or periodised high carbohydrate availability, adaptation to an LCHF diet impairs performance in elite endurance athletes despite a significant improvement in peak aerobic capacity. Abstract We investigated the effects of adaptation to a ketogenic low carbohydrate (CHO), high fat diet (LCHF) during 3 weeks of intensified training on metabolism and performance of world‐class endurance athletes. We controlled three isoenergetic diets in elite race walkers: high CHO availability (g kg−1 day−1: 8.6 CHO, 2.1 protein, 1.2 fat) consumed before, during and after training (HCHO, n = 9); identical macronutrient intake, periodised within or between days to alternate between low and high CHO availability (PCHO, n = 10); LCHF (diets providing chronic or periodised high‐CHO availability, and despite a significant improvement in V˙O2 peak , adaptation to the topical LCHF diet negated performance benefits in elite endurance athletes, in part due to reduced exercise economy. PMID:28012184

The Role of Spirituality in Coping with Visual Impairment

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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…

Sox17 regulates liver lipid metabolism and adaptation to fasting.

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Samuel Rommelaere

Full Text Available Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.

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

2014-05-06

Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels. Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior.

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Parnaudeau, Sébastien; Taylor, Kathleen; Bolkan, Scott S; Ward, Ryan D; Balsam, Peter D; Kellendonk, Christoph

2015-03-01

Cognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction, we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions remain about the elementary cognitive processes that account for the deficit. Using the Designer Receptors Exclusively Activated by Designer Drugs system, we reversibly decreased MD activity during behavioral tasks assessing elementary cognitive processes inherent to flexible goal-directed behaviors, including extinction, contingency degradation, outcome devaluation, and Pavlovian-to-instrumental transfer (n = 134 mice). While MD hypofunction impaired reversal learning, it did not affect the ability to learn about nonrewarded cues or the ability to modulate action selection based on the outcome value. In contrast, decreasing MD activity delayed the ability to adapt to changes in the contingency between actions and their outcomes. In addition, while Pavlovian learning was not affected by MD hypofunction, decreasing MD activity during Pavlovian learning impaired the ability of conditioned stimuli to modulate instrumental behavior. Mediodorsal thalamus hypofunction causes cognitive inflexibility reflected by an impaired ability to adapt actions when their consequences change. Furthermore, it alters the encoding of environmental stimuli so that they cannot be properly utilized to guide behavior. Modulating MD activity could be a potential therapeutic strategy for promoting adaptive behavior in human subjects with cognitive inflexibility. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Cordyceps militaris extract attenuates D-galactose-induced memory impairment in mice.

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Li, Zaixin; Zhang, Zhi; Zhang, Jinshan; Jia, Jing; Ding, Jie; Luo, Rongzhen; Liu, Zhangqin

2012-12-01

Memory impairment is one of main clinical symptoms of brain senescence. To address the effects of Cordyceps militaris Link extract (CE) on memory impairment, a D-galactose (D-Gal)-induced aging mouse model was employed. Mice injected with D-Gal showed a significant learning and memory impairment that was rescued by CE treatment. The mechanism was further investigated by analyzing the protein level and activity of oxidant and antioxidant molecules, including malondialdehyde (MDA), monoamine oxidase (MAO), total super-oxide dismutase (T-SOD), total antioxidant capacity (T-AOC), glutathione (GSH), and glutathione peroxidase (GSH-px), which played critical roles in the development of brain senescence. The results showed that CE treatment resulted in a significant decrease in the oxidative activity of MAO and the level of MDA, and significantly increased the antioxidant activities of T-SOD and T-AOC in the cerebral cortices. Moreover, the level of GSH and the activity of antioxidant enzymes GSH-px in serum were significantly upregulated after CE treatment. Taken together, our results suggest that Cordyceps militaris extract could ameliorate experimental memory impairment in mice with D-Gal-induced aging through its potent antioxidant activities.

Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice.

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Rajasekar, N; Dwivedi, Subhash; Tota, Santosh Kumar; Kamat, Pradeep Kumar; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

2013-09-05

Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca(2+))i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca(2+))i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment. © 2013 Elsevier B.V. All rights reserved.

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

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

2011-04-01

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

Stroke survivors' views and experiences on impact of visual impairment.

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Rowe, Fiona J

2017-09-01

We sought to determine stroke survivors' views on impact of stroke-related visual impairment to quality of life. Stroke survivors with visual impairment, more than 1 year post stroke onset, were recruited. Semistructured biographical narrative interviews were audio-recorded and transcribed verbatim. A thematic approach to analysis of the qualitative data was adopted. Transcripts were systematically coded using NVivo10 software. Thirty-five stroke survivors were interviewed across the UK: 16 females, 19 males; aged 20-75 years at stroke onset. Five qualitative themes emerged: "Formal care," "Symptoms and self," "Adaptations," "Daily life," and "Information." Where visual problems existed, they were often not immediately recognized as part of the stroke syndrome and attributed to other causes such as migraine. Many participants did not receive early vision assessment or treatment for their visual problems. Visual problems included visual field loss, double vision, and perceptual problems. Impact of visual problems included loss in confidence, being a burden to others, increased collisions/accidents, and fear of falling. They made many self-identified adaptations to compensate for visual problems: magnifiers, large print, increased lighting, use of white sticks. There was a consistent lack of support and provision of information about visual problems. Poststroke visual impairment causes considerable impact to daily life which could be substantially improved by simple measures including early formal visual assessment, management and advice on adaptive strategies and self-management options. Improved education about poststroke visual impairment for the public and clinicians could aid earlier diagnosis of visual impairments.

Oxidant/Antioxidant Balance in Animal Nutrition and Health: The Role of Protein Oxidation

OpenAIRE

Celi, Pietro; Gabai, Gianfranco

2015-01-01

This review examines the role that oxidative stress (OS), and protein oxidation in particular, plays in nutrition, metabolism, and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functi...

Oxidant/antioxidant balance in animal nutrition and health: the role of protein oxidation

OpenAIRE

Pietro eCeli; Pietro eCeli; Gianfranco eGabai

2015-01-01

This review examines the role that oxidative stress, and protein oxidation in particular, plays in nutrition, metabolism and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functional m...

Fluxomic evidence for impaired contribution of short-chain acyl-CoA dehydrogenase to mitochondrial palmitate β-oxidation in symptomatic patients with ACADS gene susceptibility variants.

Science.gov (United States)

Dessein, Anne-Frédérique; Fontaine, Monique; Joncquel-Chevalier Curt, Marie; Briand, Gilbert; Sechter, Claire; Mention-Mulliez, Karine; Dobbelaere, Dries; Douillard, Claire; Lacour, Arnaud; Redonnet-Vernhet, Isabelle; Lamireau, Delphine; Barth, Magalie; Minot-Myhié, Marie-Christine; Kuster, Alice; de Lonlay, Pascale; Gregersen, Niels; Acquaviva, Cécile; Vianey-Saban, Christine; Vamecq, Joseph

2017-08-01

Despite ACADS (acyl-CoA dehydrogenase, short-chain) gene susceptibility variants (c.511C>T and c.625G>A) are considered to be non-pathogenic, encoded proteins are known to exhibit altered kinetics. Whether or not, they might affect overall fatty acid β-oxidation still remains, however, unclear. De novo biosynthesis of acylcarnitines by whole blood samples incubated with deuterated palmitate (16- 2 H 3 ,15- 2 H 2 -palmitate) is suitable as a fluxomic exploration to distinguish between normal and disrupted β-oxidation, abnormal profiles and ratios of acylcarnitines with different chain-lengths being indicative of the site for enzymatic blockade. Determinations in 301 control subjects of ratios between deuterated butyrylcarnitine and sum of deuterated C2 to C14 acylcarnitines served here as reference values to state specifically functional SCAD impairment in patients addressed for clinical and/or biological suspicion of a β-oxidation disorder. Functional SCAD impairment was found in 39 patients. The 27 patients accepting subsequent gene studies were all positive for ACADS mutations. Twenty-six of 27 patients were positive for c.625G>A variant. Twenty-three of 27 patients harbored susceptibility variants as sole ACADS alterations (18 homozygous and 3 heterozygous for c.625G>A, 2 compound heterozygous for c.625G>A/c.511C>T). Our present fluxomic assessment of SCAD suggests a link between ACADS susceptibility variants and abnormal β-oxidation consistent with known altered kinetics of these variants. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Edaravone attenuates intracerebroventricular streptozotocin-induced cognitive impairment in rats.

Science.gov (United States)

Reeta, K H; Singh, Devendra; Gupta, Yogendra K

2017-04-01

Alzheimer's disease is a major cause of dementia worldwide. Edaravone, a potent free radical scavenger, is reported to be neuroprotective. The present study was designed to investigate the effect of chronic edaravone administration on intracerebroventricular-streptozotocin (ICV-STZ) induced cognitive impairment in male Wistar rats. Cognitive impairment was developed by single ICV-STZ (3 mg/kg) injection bilaterally on day 1. Edaravone (1, 3 and 10 mg/kg, orally, once daily) was administered for 28 days. Morris water maze and passive avoidance tests were used to assess cognitive functions at baseline and on days 14 and 28. ICV-STZ caused cognitive impairment as evidenced by increased escape latency and decreased time spent in target quadrant in the Morris water maze test and reduced retention latency in the passive avoidance test. STZ caused increase in oxidative stress, cholinesterases, inflammatory cytokines and protein expression of ROCK-II and decrease in protein expression of ChAT. Edaravone ameliorated the STZ-induced cognitive impairment. STZ-induced increase in oxidative stress and increased levels of pro-inflammatory cytokines (TNF-α, IL-1β) were mitigated by edaravone. Edaravone also prevented STZ-induced increased protein expression of ROCK-II. Moreover, edaravone significantly prevented STZ-induced increased activity of cholinesterases in the cortex and hippocampus. The decreased expression of ChAT caused by STZ was brought towards normal by edaravone in the hippocampus. The results thus show that edaravone is protective against STZ-induced cognitive impairment, oxidative stress, cholinergic dysfunction and altered protein expressions. This study thus suggests the potential of edaravone as an adjuvant in the treatment of Alzheimer's disease. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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....

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

NARCIS (Netherlands)

Nur, Erfan; Kim, Yu-Sok; Truijen, Jasper; van Beers, Eduard J.; Davis, Shyrin C. A. T.; Brandjes, Dees P.; Biemond, Bart J.; van Lieshout, Johannes J.

2009-01-01

Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxide-bioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO2 responsiveness is nitric oxide dependent and has been

Obstructive sleep apnea and cognitive impairment: Addressing the blood–brain barrier

Science.gov (United States)

Lim, Diane C.; Pack, Allan I.

2013-01-01

SUMMARY Increasing data support a connection between obstructive sleep apnea (OSA) and cognitive impairment but a causal link has yet to be established. Although neuronal loss has been linked to cognitive impairment, emerging theories propose that changes in synaptic plasticity can cause cognitive impairment. Studies demonstrate that disruption to the blood–brain barrier (BBB), which is uniquely structured to tightly maintain homeostasis inside the brain, leads to changes in the brain’s microenvironment and affects synaptic plasticity. Cyclical intermittent hypoxia is a stressor that could disrupt the BBB via molecular responses already known to occur in either OSA patients or animal models of intermittent hypoxia. However, we do not yet know if or how intermittent hypoxia can cause cognitive impairment by mechanisms operating at the BBB. Therefore, we propose that initially, adaptive homeostatic responses at the BBB occur in response to increased oxygen and nutrient demand, specifically through regulation of influx and efflux BBB transporters that alter microvessel permeability. We further hypothesize that although these responses are initially adaptive, these changes in BBB transporters can have long-term consequences that disrupt the brain’s microenvironment and alter synaptic plasticity leading to cognitive impairment. PMID:23541562

Locomotor adaptability in persons with unilateral transtibial amputation.

Science.gov (United States)

Darter, Benjamin J; Bastian, Amy J; Wolf, Erik J; Husson, Elizabeth M; Labrecque, Bethany A; Hendershot, Brad D

2017-01-01

Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb.

[Pregnancy in the context of general adaptation syndrome].

Science.gov (United States)

Gur'ianov, V A; Pyregov, A V; Tolmachev, G N; Volodin, A V

2007-01-01

Based on their own findings and the data available in the literature on pregnancy including that complicated by gestosis, the authors consider these conditions in the context of Selye's general adaptation syndrome. They identify its basic links (the autonomic nervous and cardiovascular systems) the function of which is affected by all the physiological and pathophysiological processes involved in its development. There is a high likelihood of baseline impaired adaption processes in these links, which may lead to an inability to accommodate (dysadaptation) by the moment of delivery. The paper gives the current interpretation of functional disorders, called Zangemeister'a triad in 1913, from the present-day points of view of the evaluation of pregnancy as the systemic inflammatory response syndrome and, probably, adaptation disease. Based on the results of analyzing the data available in the literature, the authors indicate physiologically the basic trends in the modulation of impaired development processes of the general adaptation syndrome towards the completion of pregnancy and surgical delivery.

[Problems in the individual adaptation of working women].

Science.gov (United States)

Grebeneva, O V; Balaeva, E A

2008-01-01

The mechanisms of development of dysadaptive changes were revealed in factory workers in relation to congenital personality traits and the schemes of individual adaptation strategies were defined. At the same time increased anxiety leading to the accelerated rates of aging preceded impaired adaptive processes. The differences in the female adaptive patterns were determined by both the degree of emotional stability and the baseline energy capacities of the cardiorespiratory system and the involvement of a mental component in adaptation.

Extracellular superoxide dismutase deficiency impairs wound healing in advanced age by reducing neovascularization and fibroblast function.

Science.gov (United States)

Fujiwara, Toshihiro; Duscher, Dominik; Rustad, Kristine C; Kosaraju, Revanth; Rodrigues, Melanie; Whittam, Alexander J; Januszyk, Michael; Maan, Zeshaan N; Gurtner, Geoffrey C

2016-03-01

Advanced age is characterized by impairments in wound healing, and evidence is accumulating that this may be due in part to a concomitant increase in oxidative stress. Extended exposure to reactive oxygen species (ROS) is thought to lead to cellular dysfunction and organismal death via the destructive oxidation of intra-cellular proteins, lipids and nucleic acids. Extracellular superoxide dismutase (ecSOD/SOD3) is a prime antioxidant enzyme in the extracellular space that eliminates ROS. Here, we demonstrate that reduced SOD3 levels contribute to healing impairments in aged mice. These impairments include delayed wound closure, reduced neovascularization, impaired fibroblast proliferation and increased neutrophil recruitment. We further establish that SOD3 KO and aged fibroblasts both display reduced production of TGF-β1, leading to decreased differentiation of fibroblasts into myofibroblasts. Taken together, these results suggest that wound healing impairments in ageing are associated with increased levels of ROS, decreased SOD3 expression and impaired extracellular oxidative stress regulation. Our results identify SOD3 as a possible target to correct age-related cellular dysfunction in wound healing. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Science.gov (United States)

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

2017-01-01

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

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.

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....... However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated...... from the vastus lateralis of young and elderly donors. Mitochondrial respiratory functions were addressed by high-resolution respirometry, and ROS production was analyzed by in situ staining with the redox-sensitive dye dihydroethidium. We found that aged human skeletal muscles contain fully functional...

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

Science.gov (United States)

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

2016-08-01

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

TELEGRAM: contribution in assistive technology indication for individuals with hearing impairment.

Science.gov (United States)

Jacob, Regina Tangerino de Souza; Lopes, Natália Barreto Frederigue; Cruz, Aline Duarte da; Alves, Tacianne Kriscia Machado; Santos, Larissa Germiniani Dos; Angelo, Thais Corina Said de; Mondelli, Maria Fernanda Capoani Garcia; Moret, Adriane Lima Mortari

2017-02-23

The objective of the study was to translate and culturally adapt to Portuguese the TELEGRAM instrument and to evaluate its effectiveness in adults with hearing impairment using hearing aids. The TELEGRAM was translated into the Portuguese language, reviewed for grammatical and idiomatic equivalences (reverse translations) and linguistic and cultural adaptations. After translation, the TELEGRAM was applied to 20 individuals with hearing impairment. A descriptive analysis of the results was performed. After the grammatical and idiomatic equivalence, the replacement of one term/item was suggested, which was modified and adapted to the Brazilian context. In general, the questions of the instrument were considered easy to understand. Among the categories assessed, individuals with hearing loss had greater difficulty using the telephone and in activities such as attending church gatherings, parties, or in situations of noisy environments, distance and reverberation. The TELEGRAM translated into Brazilian Portuguese proved to be an easily applicable tool in population studies and effective to assess which are the main situations where individuals with hearing impairment have greater difficulty in communication, reinforcing the importance of hearing rehabilitation and assistive technology to minimize these difficulties.

Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress and activation of crucial mitogen-activated protein kinases in pancreatic tumour AR42J cells.

Science.gov (United States)

Santofimia-Castaño, Patricia; Izquierdo-Alvarez, Alicia; Plaza-Davila, María; Martinez-Ruiz, Antonio; Fernandez-Bermejo, Miguel; Mateos-Rodriguez, Jose M; Salido, Gines M; Gonzalez, Antonio

2018-01-01

Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. However, evidence suggests that this compound could exert deleterious actions on cell physiology. In this study, we have analyzed the effect of ebselen on rat pancreatic AR42J cells. Cytosolic free-Ca 2+ concentration ([Ca 2+ ] c ), cellular oxidative status, setting of endoplasmic reticulum stress, and phosphorylation of major mitogen-activated protein kinases were analyzed. Our results show that ebselen evoked a concentration-dependent increase in [Ca 2+ ] c . The compound induced an increase in the generation of reactive oxygen species in the mitochondria. We also observed an increase in global cysteine oxidation in the presence of ebselen. In the presence of ebselen an impairment of cholecystokinin-evoked amylase release was noted. Moreover, involvement of the unfolded protein response markers, ER chaperone and signaling regulator GRP78/BiP, eukaryotic translation initiation factor 2α and X-box binding protein 1 was detected. Finally, increases in the phosphorylation of SAPK/JNK, p38 MAPK, and p44/42 MAPK in the presence of ebselen were also observed. Our results provide evidences for an impairment of cellular oxidative state and enzyme secretion, the induction of endoplasmic reticulum stress and the activation of crucial mitogen-activated protein kinases in the presence of ebselen. As a consequence ebselen exerts a potential toxic effect on AR42J cells. © 2017 Wiley Periodicals, Inc.

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.

Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice.

Science.gov (United States)

Javadi-Paydar, Mehrak; Zakeri, Marjan; Norouzi, Abbas; Rastegar, Hossein; Mirazi, Naser; Dehpour, Ahmad Reza

2012-01-06

Granisetron, a serotonin 5-HT(3) receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750 mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750 mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory. This article is part of a Special Issue entitled The Cognitive Neuroscience. Copyright © 2011 Elsevier B.V. All rights reserved.

An Adaptive Fault-Tolerant Communication Scheme for Body Sensor Networks

Directory of Open Access Journals (Sweden)

Zichuan Xu

2010-10-01

Full Text Available A high degree of reliability for critical data transmission is required in body sensor networks (BSNs. However, BSNs are usually vulnerable to channel impairments due to body fading effect and RF interference, which may potentially cause data transmission to be unreliable. In this paper, an adaptive and flexible fault-tolerant communication scheme for BSNs, namely AFTCS, is proposed. AFTCS adopts a channel bandwidth reservation strategy to provide reliable data transmission when channel impairments occur. In order to fulfill the reliability requirements of critical sensors, fault-tolerant priority and queue are employed to adaptively adjust the channel bandwidth allocation. Simulation results show that AFTCS can alleviate the effect of channel impairments, while yielding lower packet loss rate and latency for critical sensors at runtime.

Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress

Science.gov (United States)

Greaney, Jody L; DuPont, Jennifer J; Lennon-Edwards, Shannon L; Sanders, Paul W; Edwards, David G; Farquhar, William B

2012-01-01

Animal studies have reported dietary salt-induced reductions in vascular function independent of increases in blood pressure (BP). The purpose of this study was to determine if short-term dietary sodium loading impairs cutaneous microvascular function in normotensive adults with salt resistance. Following a control run-in diet, 12 normotensive adults (31 ± 2 years) were randomized to a 7 day low-sodium (LS; 20 mmol day−1) and 7 day high-sodium (HS; 350 mmol day−1) diet (controlled feeding study). Salt resistance, defined as a ≤5 mmHg change in 24 h mean BP determined while on the LS and HS diets, was confirmed in all subjects undergoing study (LS: 84 ± 1 mmHg vs. HS: 85 ± 2 mmHg; P > 0.05). On the last day of each diet, subjects were instrumented with two microdialysis fibres for the local delivery of Ringer solution and 20 mm ascorbic acid (AA). Laser Doppler flowmetry was used to measure red blood cell flux during local heating-induced vasodilatation (42°C). After the established plateau, 10 mm l-NAME was perfused to quantify NO-dependent vasodilatation. All data were expressed as a percentage of maximal cutaneous vascular conductance (CVC) at each site (28 mm sodium nitroprusside; 43°C). Sodium excretion increased during the HS diet (P sodium loading impairs cutaneous microvascular function independent of BP in normotensive adults and suggest a role for oxidative stress. PMID:22907057

Adaptive Processes in Hearing

DEFF Research Database (Denmark)

Santurette, Sébastien; Christensen-Dalsgaard, Jakob; Tranebjærg, Lisbeth

2018-01-01

, and is essential to achieve successful speech communication, correct orientation in our full environment, and eventually survival. These adaptive processes may differ in individuals with hearing loss, whose auditory system may cope via ‘‘readapting’’ itself over a longer time scale to the changes in sensory input...... induced by hearing impairment and the compensation provided by hearing devices. These devices themselves are now able to adapt to the listener’s individual environment, attentional state, and behavior. These topics related to auditory adaptation, in the broad sense of the term, were central to the 6th...... International Symposium on Auditory and Audiological Research held in Nyborg, Denmark, in August 2017. The symposium addressed adaptive processes in hearing from different angles, together with a wide variety of other auditory and audiological topics. The papers in this special issue result from some...

Association of Oxidative Stress with Psychiatric Disorders.

Science.gov (United States)

Hassan, Waseem; Noreen, Hamsa; Castro-Gomes, Vitor; Mohammadzai, Imdadullah; da Rocha, Joao Batista Teixeira; Landeira-Fernandez, J

2016-01-01

When concentrations of both reactive oxygen species and reactive nitrogen species exceed the antioxidative capability of an organism, the cells undergo oxidative impairment. Impairments in membrane integrity and lipid and protein oxidation, protein mutilation, DNA damage, and neuronal dysfunction are some of the fundamental consequences of oxidative stress. The purpose of this work was to review the associations between oxidative stress and psychological disorders. The search terms were the following: "oxidative stress and affective disorders," "free radicals and neurodegenerative disorders," "oxidative stress and psychological disorders," "oxidative stress, free radicals, and psychiatric disorders," and "association of oxidative stress." These search terms were used in conjunction with each of the diagnostic categories of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders and World Health Organization's International Statistical Classification of Diseases and Related Health Problems. Genetic, pharmacological, biochemical, and preclinical therapeutic studies, case reports, and clinical trials were selected to explore the molecular aspects of psychological disorders that are associated with oxidative stress. We identified a broad spectrum of 83 degenerative syndromes and psychiatric disorders that were associated with oxidative stress. The multi-dimensional information identified herein supports the role of oxidative stress in various psychiatric disorders. We discuss the results from the perspective of developing novel therapeutic interventions.

Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1

Directory of Open Access Journals (Sweden)

Dan He

2018-05-01

Full Text Available Disruption of endothelial monolayer integrity is the primary instigating factor for many cardiovascular diseases. High density lipoprotein (HDL oxidized by heme enzyme myeloperoxidase (MPO is dysfunctional in promoting endothelial repair. Apolipoprotein A-1 mimetic 4F with its pleiotropic benefits has been proven effective in many in vivo models. In this study we investigated whether 4F promotes endothelial repair and restores the impaired function of oxidized HDL (Cl/NO2-HDL in promoting re-endothelialization. We demonstrate that 4F and Cl/NO2-HDL act on scavenger receptor type I (SR-B1 using human aorta endothelial cells (HAEC and SR-B1 (-/- mouse aortic endothelial cells. Wound healing, transwell migration, lamellipodia formation and single cell migration assay experiments show that 4F treatment is associated with a recovery of endothelial cell migration and associated with significantly increased endothelial nitric oxide synthase (eNOS activity, Akt phosphorylation and SR-B1 expression. 4F increases NO generation and diminishes oxidative stress. In vivo, 4F can stimulate cell proliferation and re-endothelialization in the carotid artery after treatment with Cl/NO2-HDL in a carotid artery electric injury model but fails to do so in SR-B1(-/- mice. These findings demonstrate that 4F promotes endothelial cell migration and has a potential therapeutic benefit against early endothelial injury in cardiovascular diseases.

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

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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.

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

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Mumtaz, Sidra; Khan, Laiq

2017-01-01

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

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

Science.gov (United States)

Khan, Laiq

2017-01-01

The hybrid power system (HPS) is an emerging power generation scheme due to the plentiful availability of renewable energy sources. Renewable energy sources are characterized as highly intermittent in nature due to meteorological conditions, while the domestic load also behaves in a quite uncertain manner. In this scenario, to maintain the balance between generation and load, the development of an intelligent and adaptive control algorithm has preoccupied power engineers and researchers. This paper proposes a Hermite wavelet embedded NeuroFuzzy indirect adaptive MPPT (maximum power point tracking) control of photovoltaic (PV) systems to extract maximum power and a Hermite wavelet incorporated NeuroFuzzy indirect adaptive control of Solid Oxide Fuel Cells (SOFC) to obtain a swift response in a grid-connected hybrid power system. A comprehensive simulation testbed for a grid-connected hybrid power system (wind turbine, PV cells, SOFC, electrolyzer, battery storage system, supercapacitor (SC), micro-turbine (MT) and domestic load) is developed in Matlab/Simulink. The robustness and superiority of the proposed indirect adaptive control paradigm are evaluated through simulation results in a grid-connected hybrid power system testbed by comparison with a conventional PI (proportional and integral) control system. The simulation results verify the effectiveness of the proposed control paradigm. PMID:28329015

Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension.

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Malenfant, Simon; Potus, François; Fournier, Frédéric; Breuils-Bonnet, Sandra; Pflieger, Aude; Bourassa, Sylvie; Tremblay, Ève; Nehmé, Benjamin; Droit, Arnaud; Bonnet, Sébastien; Provencher, Steeve

2015-05-01

Exercise limitation comes from a close interaction between cardiovascular and skeletal muscle impairments. To better understand the implication of possible peripheral oxidative metabolism dysfunction, we studied the proteomic signature of skeletal muscle in pulmonary arterial hypertension (PAH). Eight idiopathic PAH patients and eight matched healthy sedentary subjects were evaluated for exercise capacity, skeletal muscle proteomic profile, metabolism, and mitochondrial function. Skeletal muscle proteins were extracted, and fractioned peptides were tagged using an iTRAQ protocol. Proteomic analyses have documented a total of 9 downregulated proteins in PAH skeletal muscles and 10 upregulated proteins compared to healthy subjects. Most of the downregulated proteins were related to mitochondrial structure and function. Focusing on skeletal muscle metabolism and mitochondrial health, PAH patients presented a decreased expression of oxidative enzymes (pyruvate dehydrogenase, p metabolism in PAH skeletal muscles. We provide evidences that impaired mitochondrial and metabolic functions found in the lungs and the right ventricle are also present in skeletal muscles of patients. • Proteomic and metabolic analysis show abnormal oxidative metabolism in PAH skeletal muscle. • EM of PAH patients reveals abnormal mitochondrial structure and distribution. • Abnormal mitochondrial health and function contribute to exercise impairments of PAH. • PAH may be considered a vascular affliction of heart and lungs with major impact on peripheral muscles.

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

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

2017-11-01

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

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

International Nuclear Information System (INIS)

Lei Ming; Hua Xiangdong; Xiao Ming; Ding Jiong; Han Qunying; Hu Gang

2008-01-01

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

Blast induces oxidative stress, inflammation, neuronal loss and subsequent short-term memory impairment in rats.

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Cho, H J; Sajja, V S S S; Vandevord, P J; Lee, Y W

2013-12-03

Molecular and cellular mechanisms of brain injury after exposure to blast overpressure (BOP) are not clearly known. The present study hypothesizes that pro-oxidative and pro-inflammatory pathways in the brain may be responsible for neuronal loss and behavioral deficits following BOP exposure. Male Sprague-Dawley rats were anesthetized and exposed to calibrated BOP of 129.23±3.01kPa while controls received only anesthesia. In situ dihydroethidium fluorescence staining revealed that BOP significantly increased the production of reactive oxygen species in the brain. In addition, real-time reverse transcriptase-polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assay demonstrated a significant up-regulation of mRNA and protein expressions of pro-inflammatory mediators, such as interferon-γ and monocyte chemoattractant protein-1, in brains collected from BOP-exposed animals compared with the controls. Furthermore, immunoreactivity of neuronal nuclei in brains indicated that fewer neurons were present following BOP exposure. Moreover, novel object recognition paradigm showed a significant impairment in the short-term memory at 2weeks following BOP exposure. These results suggest that pro-oxidative and pro-inflammatory environments in the brain could play a potential role in BOP-induced neuronal loss and behavioral deficits. It may provide a foundation for defining a molecular and cellular basis of the pathophysiology of blast-induced neurotrauma (BINT). It will also contribute to the development of new therapeutic approaches selectively targeting these pathways, which have great potential in the diagnosis and therapy of BINT. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

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

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

2010-02-01

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

Low overhead and nonlinear-tolerant adaptive zero-guard-interval CO-OFDM.

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Wang, Wei; Zhuge, Qunbi; Gao, Yuliang; Qiu, Meng; Morsy-Osman, Mohamed; Chagnon, Mathieu; Xu, Xian; Plant, David V

2014-07-28

We propose an adaptive channel estimation (CE) method for zero-guard-interval (ZGI) coherent optical (CO)-OFDM systems, and demonstrate its performance in a single channel 28 Gbaud polarization-division multiplexed ZGI CO-OFDM experiment with only 1% OFDM processing overhead. We systematically investigate its robustness against various transmission impairments including residual chromatic dispersion, polarization-mode dispersion, state of polarization rotation, sampling frequency offset and fiber nonlinearity. Both experimental and numerical results show that the adaptive CE-aided ZGI CO-OFDM is highly robust against these transmission impairments in fiber optical transmission systems.

Test Anxiety, Computer-Adaptive Testing and the Common Core

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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…

Periconception onset diabetes is associated with embryopathy and fetal growth retardation, reproductive tract hyperglycosylation and impaired immune adaptation to pregnancy.

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Brown, Hannah M; Green, Ella S; Tan, Tiffany C Y; Gonzalez, Macarena B; Rumbold, Alice R; Hull, M Louise; Norman, Robert J; Packer, Nicolle H; Robertson, Sarah A; Thompson, Jeremy G

2018-02-01

Diabetes has been linked with impaired fertility but the underlying mechanisms are not well defined. Here we use a streptozotocin-induced diabetes mouse model to investigate the cellular and biochemical changes in conceptus and maternal tissues that accompany hyperglycaemia. We report that streptozotocin treatment before conception induces profound intra-cellular protein β-O-glycosylation (O-GlcNAc) in the oviduct and uterine epithelium, prominent in early pregnancy. Diabetic mice have impaired blastocyst development and reduced embryo implantation rates, and delayed mid-gestation growth and development. Peri-conception changes are accompanied by increased expression of pro-inflammatory cytokine Trail, and a trend towards increased Il1a, Tnf and Ifng in the uterus, and changes in local T-cell dynamics that skew the adaptive immune response to pregnancy, resulting in 60% fewer anti-inflammatory regulatory T-cells within the uterus-draining lymph nodes. Activation of the heat shock chaperones, a mechanism for stress deflection, was evident in the reproductive tract. Additionally, we show that the embryo exhibits elevated hyper-O-GlcNAcylation of both cytoplasmic and nuclear proteins, associated with activation of DNA damage (ɣH2AX) pathways. These results advance understanding of the impact of peri-conception diabetes, and provide a foundation for designing interventions to support healthy conception without propagation of disease legacy to offspring.

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

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Takashi Kitano

2017-01-01

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

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

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Tao Zeng

2018-04-01

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

Impact of Nitric Oxide Bioavailability on the Progressive Cerebral and Peripheral Circulatory Impairments During Aging and Alzheimer's Disease

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Massimo Venturelli

2018-03-01

Full Text Available Advanced aging, vascular dysfunction, and nitric oxide (NO bioavailability are recognized risk factors for Alzheimer's disease (AD. However, the contribution of AD, per se, to this putative pathophysiological mechanism is still unclear. To better answer this point, we quantified cortical perfusion with arterial spin labeling (PVC-CBF, measured ultrasound internal carotid (ICA, and femoral (FA artery blood flow in a group of patients with similar age (~78 years but different cognitive impairment (i.e., mild cognitive impairment MCI, mild AD-AD1, moderate AD-AD2, and severe AD-AD3 and compared them to young and healthy old (aged-matched controls. NO-metabolites and passive leg-movement (PLM induced hyperemia were used to assess systemic vascular function. Ninety-eight individuals were recruited for this study. PVC-CBF, ICA, and FA blood flow were markedly (range of 9–17% and significantly (all p < 0.05 reduced across the spectrum from YG to OLD, MCI, AD1, AD2, AD3 subjects. Similarly, plasma level of nitrates and the values of PLM were significantly reduced (range of 8–26%; p < 0.05 among the six groups. Significant correlations were retrieved between plasma nitrates, PLM and PVC-CBF, CA, and FA blood flow. This integrative and comprehensive approach to vascular changes in aging and AD showed progressive changes in NO bioavailability and cortical, extracranial, and peripheral circulation in patients with AD and suggested that they are directly associated with AD and not to aging. Moreover, these results suggest that AD-related impairments of circulation are progressive and not confined to the brain. The link between cardiovascular and the central nervous systems degenerative processes in patients at different severity of AD is likely related to the depletion of NO.

Impaired skeletal muscle substrate oxidation in glucose-intolerant men improves after weight loss

NARCIS (Netherlands)

Corpeleijn, E.; Mensink, M.; Kooi, M.E.; Roekaerts, P.M.H.J.; Saris, W.H.M.; Blaak, E.E.

2008-01-01

Objective: An impaired fatty acid handling in skeletal muscle may be involved in the development of insulin resistance and diabetes mellitus type 2 (DM2). We investigated muscle fatty acid metabolism in glucose-intolerant men (impaired glucose tolerance (IGT)), a prediabetic state, relative to

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

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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.

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

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Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

2014-01-01

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

Motor ability and adaptive function in children with attention deficit hyperactivity disorder

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Hui-Yi Wang

2011-10-01

Full Text Available Attention deficit hyperactivity disorder (ADHD is a common neuropsychiatric disorder. Previous studies have reported that children with ADHD exhibit deficits of adaptive function and insufficient motor ability. The objective of this study was to investigate the association between adaptive function and motor ability in children with ADHD compared with a group of normal children. The study group included 25 children with ADHD (19 boys and 6 girls, aged from 4.6 years to 8.6 years (mean±standard deviation, 6.5±1.2. A group of 24 children without ADHD (normal children were selected to match the children with ADHD on age and gender. The Movement Assessment Battery for Children, which includes three subtests, was used to assess the motor ability of the children of both groups. The Chinese version of Adaptive Behavior Scales, which consists of 12 life domains, was used to assess adaptive function of the children with ADHD. Compared with the normal children, children with ADHD exhibited poorer motor ability on all the three subtests of motor assessment. In the ADHD group, nine (36% children had significant motor impairments and seven (28% were borderline cases. A total of 10 (40% children with ADHD had definite adaptive problems in one or more adaptive domains. With statistically controlling of IQ for the ADHD group, those children with impaired motor ability had significantly poorer behaviors in the adaptive domain of home living (p=0.035. Moreover, children with ADHD who had severely impaired manual dexterity performed worse than the control group in the adaptive domains of home living (r=−0.47, p=0.018, socialization (r=−0.49, p=0.013, and self-direction (r=−0.41, p=0.040. In addition, children with poorer ball skills had worse home living behavior (r=−0.56, p=0.003. Children who had more impaired balance exhibited poorer performance in social behavior (r=−0.41, p=0.040. This study found significant correlation between motor ability and

Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation.

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Cotter, David G; Schugar, Rebecca C; Wentz, Anna E; d'Avignon, D André; Crawford, Peter A

2013-02-15

During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1(+/-) mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states.

Oxidative Stress Associated with Neuronal Apoptosis in Experimental Models of Epilepsy

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Marisela Méndez-Armenta

2014-01-01

Full Text Available Epilepsy is considered one of the most common neurological disorders worldwide. Oxidative stress produced by free radicals may play a role in the initiation and progression of epilepsy; the changes in the mitochondrial and the oxidative stress state can lead mechanism associated with neuronal death pathway. Bioenergetics state failure and impaired mitochondrial function include excessive free radical production with impaired synthesis of antioxidants. This review summarizes evidence that suggest what is the role of oxidative stress on induction of apoptosis in experimental models of epilepsy.

Phenylethanoid glycosides of Pedicularis muscicola Maxim ameliorate high altitude-induced memory impairment.

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Zhou, Baozhu; Li, Maoxing; Cao, Xinyuan; Zhang, Quanlong; Liu, Yantong; Ma, Qiang; Qiu, Yan; Luan, Fei; Wang, Xianmin

2016-04-01

Exposure to hypobaric hypoxia causes oxidative stress, neuronal degeneration and apoptosis that leads to memory impairment. Though oxidative stress contributes to neuronal degeneration and apoptosis in hypobaric hypoxia, the ability for phenylethanoid glycosides of Pedicularis muscicola Maxim (PhGs) to reverse high altitude memory impairment has not been studied. Rats were supplemented with PhGs orally for a week. After the fourth day of drug administration, rats were exposed to a 7500 m altitude simulation in a specially designed animal decompression chamber for 3 days. Spatial memory was assessed by the 8-arm radial maze test before and after exposure to hypobaric hypoxia. Histological assessment of neuronal degeneration was performed by hematoxylin-eosin (HE) staining. Changes in oxidative stress markers and changes in the expression of the apoptotic marker, caspase-3, were assessed in the hippocampus. Our results demonstrated that after exposure to hypobaric hypoxia, PhGs ameliorated high altitude memory impairment, as shown by the decreased values obtained for reference memory error (RME), working memory error (WME), and total error (TE). Meanwhile, administration of PhGs decreased hippocampal reactive oxygen species levels and consequent lipid peroxidation by elevating reduced glutathione levels and enhancing the free radical scavenging enzyme system. There was also a decrease in the number of pyknotic neurons and a reduction in caspase-3 expression in the hippocampus. These findings suggest that PhGs may be used therapeutically to ameliorate high altitude memory impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

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Reeg, Sandra

2015-01-01

Abstract Significance: A constant accumulation of oxidized proteins takes place during aging. Oxidation of proteins leads to a partial unfolding and, therefore, to aggregation. Protein aggregates impair the activity of cellular proteolytic systems (proteasomes, lysosomes), resulting in further accumulation of oxidized proteins. In addition, the accumulation of highly crosslinked protein aggregates leads to further oxidant formation, damage to macromolecules, and, finally, to apoptotic cell death. Furthermore, protein oxidation seems to play a role in the development of various age-related diseases, for example, neurodegenerative diseases. Recent Advances: The highly oxidized lipofuscin accumulates during aging. Lipofuscin formation might cause impaired lysosomal and proteasomal degradation, metal ion accumulation, increased reactive oxygen species formation, and apoptosis. Critical Issues: It is still unclear to which extent protein oxidation is involved in the progression of aging and in the development of some age-related diseases. Future Directions: An extensive knowledge of the effects of protein oxidation on the aging process and its contribution to the development of age-related diseases could enable further strategies to reduce age-related impairments. Strategies aimed at lowering aggregate formation might be a straightforward intervention to reduce age-related malfunctions of organs. Antioxid. Redox Signal. 23, 239–255. PMID:25178482

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

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Fang-Fang Wang

2017-12-01

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

Graceful degradation of cooperative adaptive cruise control

NARCIS (Netherlands)

Ploeg, J.; Semsar-Kazerooni, E.; Lijster, G.; Wouw, N. van de; Nijmeijer, H.

2015-01-01

Cooperative adaptive cruise control (CACC) employs wireless intervehicle communication, in addition to onboard sensors, to obtain string-stable vehicle-following behavior at small intervehicle distances. As a consequence, however, CACC is vulnerable to communication impairments such as latency and

Revisiting nicotine's role in the ageing brain and cognitive impairment

DEFF Research Database (Denmark)

Majdi, Alireza; Kamari, Farzin; Vafaee, Manouchehr Seyedi

2017-01-01

Brain ageing is a complex process which in its pathologic form is associated with learning and memory dysfunction or cognitive impairment. During ageing, changes in cholinergic innervations and reduced acetylcholinergic tonus may trigger a series of molecular pathways participating in oxidative...... in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment....

Proteomic analysis of endothelial cold-adaptation

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Zieger Michael AJ

2011-12-01

Full Text Available Abstract Background Understanding how human cells in tissue culture adapt to hypothermia may aid in developing new clinical procedures for improved ischemic and hypothermic protection. Human coronary artery endothelial cells grown to confluence at 37°C and then transferred to 25°C become resistant over time to oxidative stress and injury induced by 0°C storage and rewarming. This protection correlates with an increase in intracellular glutathione at 25°C. To help understand the molecular basis of endothelial cold-adaptation, isolated proteins from cold-adapted (25°C/72 h and pre-adapted cells were analyzed by quantitative proteomic methods and differentially expressed proteins were categorized using the DAVID Bioinformatics Resource. Results Cells adapted to 25°C expressed changes in the abundance of 219 unique proteins representing a broad range of categories such as translation, glycolysis, biosynthetic (anabolic processes, NAD, cytoskeletal organization, RNA processing, oxidoreductase activity, response-to-stress and cell redox homeostasis. The number of proteins that decreased significantly with cold-adaptation exceeded the number that increased by 2:1. Almost half of the decreases were associated with protein metabolic processes and a third were related to anabolic processes including protein, DNA and fatty acid synthesis. Changes consistent with the suppression of cytoskeletal dynamics provided further evidence that cold-adapted cells are in an energy conserving state. Among the specific changes were increases in the abundance and activity of redox proteins glutathione S-transferase, thioredoxin and thioredoxin reductase, which correlated with a decrease in oxidative stress, an increase in protein glutathionylation, and a recovery of reduced protein thiols during rewarming from 0°C. Increases in S-adenosylhomocysteine hydrolase and nicotinamide phosphoribosyltransferase implicate a central role for the methionine

High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production

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Ruggiero, Christine; Ehrenshaft, Marilyn; Cleland, Ellen

2011-01-01

Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases. PMID:21386058

Blocked muscle fat oxidation during exercise in neutral lipid storage disease

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Laforêt, Pascal; Ørngreen, Mette; Preisler, Nicolai

2012-01-01

To determine whether impaired exercise capacity in neutral lipid storage disease with myopathy is solely caused by muscle weakness or whether a defect in energy metabolism (blocked fat oxidation) may also play a role.......To determine whether impaired exercise capacity in neutral lipid storage disease with myopathy is solely caused by muscle weakness or whether a defect in energy metabolism (blocked fat oxidation) may also play a role....

Effects of fat adaptation on glucose kinetics and substrate oxidation during low-intensity exercise.

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Pagan, J D; Geor, R J; Harris, P A; Hoekstra, K; Gardner, S; Hudson, C; Prince, A

2002-09-01

This study was designed to determine the effects of fat adaptation on carbohydrate and fat oxidation in conditioned horses during low-intensity exercise. Five mature Arabians were studied. The study was conducted as a crossover design with 2 dietary periods, each of 10 week's duration: a) a control (CON) diet, and b) a fat-supplemented (FAT) diet. The total amount of digestible energy (DE) supplied by the fat in the CON and FAT diets was 7% and 29%, respectively. During each period, the horses completed exercise tests at the beginning of the period (Week 0) and after 5 and 10 weeks on the diet. Tests consisted of 90 min of exercise at a speed calculated to elicit 35% VO2max on a treadmill inclined to 3 degrees. Oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) were measured at 15-min intervals. For determination of glucose kinetics, a stable isotope ([6-6-d2] glucose) technique was used. Compared to the CON diet, FAT diet consumption for 5-10 weeks was associated with an altered metabolic response to low-intensity exercise, as evidenced by a more than 30% reduction in the production and utilisation of glucose; a decrease in RER; a decrease in the estimated rate of whole-body carbohydrate utilisation; and an increase in the whole-body rate of lipid oxidation during exercise.

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

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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…

Hyperglycaemia and diabetes impair gap junctional communication among astrocytes.

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Gandhi, Gautam K; Ball, Kelly K; Cruz, Nancy F; Dienel, Gerald A

2010-03-15

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.

L-carnitine prevents memory impairment induced by chronic REM-sleep deprivation.

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Alzoubi, Karem H; Rababa'h, Abeer M; Owaisi, Amani; Khabour, Omar F

2017-05-01

Sleep deprivation (SD) negatively impacts memory, which was related to oxidative stress induced damage. L-carnitine is a naturally occurring compound, synthesized endogenously in mammalian species and known to possess antioxidant properties. In this study, the effect of L-carnitine on learning and memory impairment induced by rapid eye movement sleep (REM-sleep) deprivation was investigated. REM-sleep deprivation was induced using modified multiple platform model (8h/day, for 6 weeks). Simultaneously, L-carnitine was administered (300mg/kg/day) intraperitoneally for 6 weeks. Thereafter, the radial arm water maze (RAWM) was used to assess spatial learning and memory. Additionally, the hippocampus levels of antioxidant biomarkers/enzymes: reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS) were assessed. The results showed that chronic REM-sleep deprivation impaired both short- and long-term memory (Psleep deprivation induced reduction in the hippocampus ratio of GSH/GSSG, activity of catalase, GPx, and SOD. No change was observed in TBARS among tested groups (P>0.05). In conclusion, chronic REM-sleep deprivation induced memory impairment, and treatment with L-carnitine prevented this impairment through normalizing antioxidant mechanisms in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

Placental adaptations to micronutrient dysregulation in the programming of chronic disease.

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Hofstee, Pierre; McKeating, Daniel; Perkins, Anthony V; Cuffe, James S M

2018-04-21

Poor nutrition during pregnancy is known to impair foetal development and increase the risk of chronic disease in offspring. Both macronutrients and micronutrients are required for a healthy pregnancy although significantly less is understood about the role of micronutrients in the programming of chronic disease. This is despite the fact that modern calorie rich diets are often also deficient in key micronutrients. The importance of micronutrients in gestational disorders is clearly understood but how they impact long term disease in humans requires further investigation. In contrast, animal studies have demonstrated how diets high or low in specific micronutrients influence offspring physiology. Many of these studies highlight the importance of the placenta in determining disease risk. This review will explore the effects of individual vitamins, minerals and trace elements on offspring disease outcomes and discuss several key placental adaptations that are affected by multiple micronutrients. These placental adaptations include micronutrient induced dysregulation of oxidative stress, altered methyl donor availability and its impact on epigenetic mechanisms as well as endocrine dysfunction. Critical gaps in our current knowledge and the relative importance of different micronutrients at different gestational ages will also be highlighted. Finally, this review will discuss the need for further studies to characterise the micronutrient status of Australian women of reproductive age and correlate micronutrient status to placental adaptations, pregnancy complications and offspring disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

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Nattaporn Phunchago

2015-01-01

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

Carbohydrate intake and glycemic index affect substrate oxidation during a controlled weight cycle in healthy men.

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Kahlhöfer, J; Lagerpusch, M; Enderle, J; Eggeling, B; Braun, W; Pape, D; Müller, M J; Bosy-Westphal, A

2014-09-01

Because both, glycemic index (GI) and carbohydrate content of the diet increase insulin levels and could thus impair fat oxidation, we hypothesized that refeeding a low GI, moderate-carbohydrate diet facilitates weight maintenance. Healthy men (n=32, age 26.0±3.9 years; BMI 23.4±2.0 kg/m(2)) followed 1 week of controlled overfeeding, 3 weeks of caloric restriction and 2 weeks of hypercaloric refeeding (+50, -50 and +50% energy requirement) with low vs high GI (41 vs 74) and moderate vs high CHO intake (50% vs 65% energy). We measured adaptation of fasting macronutrient oxidation and the capacity to supress fat oxidation during an oral glucose tolerance test. Changes in fat mass were measured by quantitative magnetic resonance. During overfeeding, participants gained 1.9±1.2 kg body weight, followed by a weight loss of -6.3±0.6 kg and weight regain of 2.8±1.0 kg. Subjects with 65% CHO gained more body weight compared with 50% CHO diet (Pfat oxidation when compared with a low-GI diet (Pfat oxidation was associated with regain in fat mass (r=0.43, Pcarbohydrate content affect substrate oxidation and thus the regain in body weight in healthy men. These results argue in favor of a lower glycemic load diet for weight maintenance after weight loss.

The New DSM-5 Impairment Criterion: A Challenge to Early Autism Spectrum Disorder Diagnosis?

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Zander, Eric; Bölte, Sven

2015-01-01

The possible effect of the DSM-5 impairment criterion on diagnosing autism spectrum disorder (ASD) in young children was examined in 127 children aged 20-47 months with a DSM-IV-TR clinical consensus diagnosis of ASD. The composite score of the Vineland Adaptive Behavior Scales (VABS) served as a proxy for the DSM-5 impairment criterion. When…

Oxidant/antioxidant balance in animal nutrition and health: the role of protein oxidation

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Pietro eCeli

2015-10-01

Full Text Available This review examines the role that oxidative stress, and protein oxidation in particular, plays in nutrition, metabolism and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functional modifications. Protein oxidation seems to be involved in pathological conditions such as respiratory diseases and parasitic infection; however some studies also suggest that protein oxidation plays a crucial role in the regulation of important physiological functions such as reproduction, nutrition, metabolism, lactation, gut health and neonatal physiology. As the characterization of the mechanisms by which oxidative stress may influence metabolism and health is attracting considerable scientific interest, the aim of this review is to present veterinary scientists and clinicians with various aspects of oxidative damage to proteins.

Oxygen Consumption and Usage During Physical Exercise: The Balance Between Oxidative Stress and ROS-Dependent Adaptive Signaling

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Zhao, Zhongfu; Koltai, Erika; Ohno, Hideki; Atalay, Mustafa

2013-01-01

Abstract The complexity of human DNA has been affected by aerobic metabolism, including endurance exercise and oxygen toxicity. Aerobic endurance exercise could play an important role in the evolution of Homo sapiens, and oxygen was not important just for survival, but it was crucial to redox-mediated adaptation. The metabolic challenge during physical exercise results in an elevated generation of reactive oxygen species (ROS) that are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which at moderate levels generate physiological responses. Several factors of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1α activation could result in decreased oxidative challenge, either by upregulation of antioxidant enzymes and/or by an increased number of mitochondria that allows lower levels of respiratory activity for the same degree of ATP generation. Endogenous thiol antioxidants glutathione and thioredoxin are modulated with high oxygen consumption and ROS generation during physical exercise, controlling cellular function through redox-sensitive signaling and protein–protein interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by ROS-mediated activation of hypoxia-inducible factor 1α. Moreover, the exercise-associated ROS production could be important to DNA methylation and post-translation modifications of histone residues, which create heritable adaptive conditions based on epigenetic features of chromosomes. Accumulating data indicate that exercise with moderate intensity has systemic and complex health-promoting effects, which undoubtedly involve regulation of redox homeostasis and signaling. Antioxid. Redox Signal. 18, 1208–1246. PMID:22978553

Neuroprotective effects of the polyphenolic antioxidant agent, Curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat.

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Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Kazeminejad, Behrang

2010-10-01

Aging is the major risk factor for neurodegenerative diseases and oxidative stress is involved in the pathophysiology of these diseases. In this study, the possible antioxidant and neuroprotective properties of the polyphenolic antioxidant compound, Curcumin against homocysteine (Hcy) neurotoxicity was investigated. Curcumin (5 and 50mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intrahippocampal injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests were studied 24h after the last Curcumin or its vehicle injection. We detected Malondialdehyde (MDA) and Super oxide anion (SOA) in rats' hippocampi. Results indicated that Hcy could induce lipid peroxidation and increase MDA and SOA levels in rats' hippocampi. Additionally, Hcy impaired memory retention in passive avoidance learning test. However, Curcumin treatment decreased MDA and SOA levels significantly as well as improved learning and memory in rats. Histopathological analysis also indicated that Hcy could decrease hippocampus cell count and Curcumin inhibited this toxic effect. These results suggest that Hcy may induce lipid peroxidation in rats' hippocampi and polyphenol treatment (Curcumin) improved learning and memory deficits by protecting the nervous system against Hcy toxicity. (c) 2010 Elsevier Inc. All rights reserved.

The adaptive evolution of the mammalian mitochondrial genome

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O'Brien Stephen J

2008-03-01

Full Text Available Abstract Background The mitochondria produce up to 95% of a eukaryotic cell's energy through oxidative phosphorylation. The proteins involved in this vital process are under high functional constraints. However, metabolic requirements vary across species, potentially modifying selective pressures. We evaluate the adaptive evolution of 12 protein-coding mitochondrial genes in 41 placental mammalian species by assessing amino acid sequence variation and exploring the functional implications of observed variation in secondary and tertiary protein structures. Results Wide variation in the properties of amino acids were observed at functionally important regions of cytochrome b in species with more-specialized metabolic requirements (such as adaptation to low energy diet or large body size, such as in elephant, dugong, sloth, and pangolin, and adaptation to unusual oxygen requirements, for example diving in cetaceans, flying in bats, and living at high altitudes in alpacas. Signatures of adaptive variation in the NADH dehydrogenase complex were restricted to the loop regions of the transmembrane units which likely function as protons pumps. Evidence of adaptive variation in the cytochrome c oxidase complex was observed mostly at the interface between the mitochondrial and nuclear-encoded subunits, perhaps evidence of co-evolution. The ATP8 subunit, which has an important role in the assembly of F0, exhibited the highest signal of adaptive variation. ATP6, which has an essential role in rotor performance, showed a high adaptive variation in predicted loop areas. Conclusion Our study provides insight into the adaptive evolution of the mtDNA genome in mammals and its implications for the molecular mechanism of oxidative phosphorylation. We present a framework for future experimental characterization of the impact of specific mutations in the function, physiology, and interactions of the mtDNA encoded proteins involved in oxidative phosphorylation.

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

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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.

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

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Lozano-Juste, Jorge; León, José

2010-01-01

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

Impaired Cleavage of Preproinsulin Signal Peptide Linked to Autosomal-Dominant Diabetes

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Liu, Ming; Lara-Lemus, Roberto; Shan, Shu-ou; Wright, Jordan; Haataja, Leena; Barbetti, Fabrizio; Guo, Huan; Larkin, Dennis; Arvan, Peter

2012-01-01

Recently, missense mutations upstream of preproinsulin’s signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. We find that whereas preproinsulin-A(SP23)S is efficiently cleaved, producing authentic proinsulin and insulin, preproinsulin-A(SP24)D is inefficiently cleaved at an improper site, producing two subpopulations of molecules. Both show impaired oxidative folding and are retained in the endoplasmic reticulum (ER). Preproinsulin-A(SP24)D also blocks ER exit of coexpressed wild-type proinsulin, accounting for its dominant-negative behavior. Upon increased expression of ER–oxidoreductin-1, preproinsulin-A(SP24)D remains blocked but oxidative folding of wild-type proinsulin improves, accelerating its ER export and increasing wild-type insulin production. We conclude that the efficiency of SP cleavage is linked to the oxidation of (pre)proinsulin. In turn, impaired (pre)proinsulin oxidation affects ER export of the mutant as well as that of coexpressed wild-type proinsulin. Improving oxidative folding of wild-type proinsulin may provide a feasible way to rescue insulin production in patients with MIDY. PMID:22357960

Time in Redox Adaptation Processes: From Evolution to Hormesis

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Mireille M. J. P. E. Sthijns

2016-09-01

Full Text Available Life on Earth has to adapt to the ever changing environment. For example, due to introduction of oxygen in the atmosphere, an antioxidant network evolved to cope with the exposure to oxygen. The adaptive mechanisms of the antioxidant network, specifically the glutathione (GSH system, are reviewed with a special focus on the time. The quickest adaptive response to oxidative stress is direct enzyme modification, increasing the GSH levels or activating the GSH-dependent protective enzymes. After several hours, a hormetic response is seen at the transcriptional level by up-regulating Nrf2-mediated expression of enzymes involved in GSH synthesis. In the long run, adaptations occur at the epigenetic and genomic level; for example, the ability to synthesize GSH by phototrophic bacteria. Apparently, in an adaptive hormetic response not only the dose or the compound, but also time, should be considered. This is essential for targeted interventions aimed to prevent diseases by successfully coping with changes in the environment e.g., oxidative stress.

Oxidant/Antioxidant Balance in Animal Nutrition and Health: The Role of Protein Oxidation.

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Celi, Pietro; Gabai, Gianfranco

2015-01-01

This review examines the role that oxidative stress (OS), and protein oxidation in particular, plays in nutrition, metabolism, and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functional modifications. Protein oxidation seems to be involved in pathological conditions, such as respiratory diseases and parasitic infection; however, some studies also suggest that protein oxidation plays a crucial role in the regulation of important physiological functions, such as reproduction, nutrition, metabolism, lactation, gut health, and neonatal physiology. As the characterization of the mechanisms by which OS may influence metabolism and health is attracting considerable scientific interest, the aim of this review is to present veterinary scientists and clinicians with various aspects of oxidative damage to proteins.

Increased asymmetric dimethylarginine in severe falciparum malaria: association with impaired nitric oxide bioavailability and fatal outcome.

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Tsin W Yeo

2010-04-01

Full Text Available Asymmetrical dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase (NOS, is a predictor of mortality in critical illness. Severe malaria (SM is associated with decreased NO bioavailability, but the contribution of ADMA to the pathogenesis of impaired NO bioavailability and adverse outcomes in malaria is unknown. In adults with and without falciparum malaria, we tested the hypotheses that plasma ADMA would be: 1 increased in proportion to disease severity, 2 associated with impaired vascular and pulmonary NO bioavailability and 3 independently associated with increased mortality. We assessed plasma dimethylarginines, exhaled NO concentrations and endothelial function in 49 patients with SM, 78 with moderately severe malaria (MSM and 19 healthy controls (HC. Repeat ADMA and endothelial function measurements were performed in patients with SM. Multivariable regression was used to assess the effect of ADMA on mortality and NO bioavailability. Plasma ADMA was increased in SM patients (0.85 microM; 95% CI 0.74-0.96 compared to those with MSM (0.54 microM; 95%CI 0.5-0.56 and HCs (0.64 microM; 95%CI 0.58-0.70; p<0.001. ADMA was an independent predictor of mortality in SM patients with each micromolar elevation increasing the odds of death 18 fold (95% CI 2.0-181; p = 0.01. ADMA was independently associated with decreased exhaled NO (r(s = -0.31 and endothelial function (r(s = -0.32 in all malaria patients, and with reduced exhaled NO (r(s = -0.72 in those with SM. ADMA is increased in SM and associated with decreased vascular and pulmonary NO bioavailability. Inhibition of NOS by ADMA may contribute to increased mortality in severe malaria.

Toll-like receptor 4 (TLR4) impairs nitric oxide contributing to Angiotensin II-induced cavernosal dysfunction.

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Nunes, Kenia P; Bomfim, Gisele F; Toque, Haroldo A; Szasz, Theodora; Clinton Webb, R

2017-12-15

Angiotensin II (AngII), a corpus cavernosum (CC) constrictor peptide, modulates Toll like receptor (TLR) expression, a key element of the innate immune system, contributing to impaired vascular function in pathological conditions. However, it is unknown whether TLR4 is involved in AngII-induced erectile dysfunction. In this study, we investigated whether TLR4 plays a role in cavernosal dysfunction caused by AngII upregulation. Cavernosal smooth muscle cells (CSMC) from C57/BL6 mice were treated with AngII (0.1μM) or bacterial LPS (50ng/ml) for 12-24h and TLR4 expression was assessed. Mice were infused with AngII (90ng/min, 28days) and treated with anti-TLR4 antibody (0.1mg/daily, i.p.) for the last 14days of the treatment. CC tissue was used for functional studies and for Western blotting. Nitric Oxide Synthase (NOS) activity was measured by conversion of [ 3 H]-l-arginine to [ 3 H]-l-citrulline, systemic TNF-α levels by ELISA, and reactive oxygen species (ROS) by immunofluorescence. We report upregulation of TLR4 in CSMC following AngII or LPS stimulation. In AngII-infused mice, chronic treatment with anti-TLR4 antibody (28±2.1%) attenuates adrenergic CC contraction, which also ameliorates nitrergic (68.90±0.21 vs. 51.07±0.63, 8Hz, AngII-infused mice treated vs. non-treated). Decreased endothelial NOS expression, reduced NOS activity, and augmented levels of TNF-α, and ROS were found following AngII-infusion. These alterations were prevented, or at least decreased by anti-TLR4 antibody treatment. Inhibition of TLR4 ameliorates AngII-impaired cavernosal relaxation, decreases TNF-α levels, and restores NO bioavailability, demonstrating that TLR4 partly mediates AngII-induced cavernosal dysfunction. Copyright © 2017. Published by Elsevier Inc.

Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses.

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Thakur, Tarun; Gulati, Kavita; Rai, Nishant; Ray, Arunabha

2017-09-01

The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses. Copyright © 2017. Published by Elsevier B.V.

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

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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…

Catalase expression impairs oxidative stress-mediated signalling in Trypanosoma cruzi.

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Freire, Anna Cláudia Guimarães; Alves, Ceres Luciana; Goes, Grazielle Ribeiro; Resende, Bruno Carvalho; Moretti, Nilmar Silvio; Nunes, Vinícius Santana; Aguiar, Pedro Henrique Nascimento; Tahara, Erich Birelli; Franco, Glória Regina; Macedo, Andréa Mara; Pena, Sérgio Danilo Junho; Gadelha, Fernanda Ramos; Guarneri, Alessandra Aparecida; Schenkman, Sergio; Vieira, Leda Quercia; Machado, Carlos Renato

2017-09-01

Trypanosoma cruzi is exposed to oxidative stresses during its life cycle, and amongst the strategies employed by this parasite to deal with these situations sits a peculiar trypanothione-dependent antioxidant system. Remarkably, T. cruzi's antioxidant repertoire does not include catalase. In an attempt to shed light on what are the reasons by which this parasite lacks this enzyme, a T. cruzi cell line stably expressing catalase showed an increased resistance to hydrogen peroxide (H2O2) when compared with wild-type cells. Interestingly, preconditioning carried out with low concentrations of H2O2 led untransfected parasites to be as much resistant to this oxidant as cells expressing catalase, but did not induce the same level of increased resistance in the latter ones. Also, presence of catalase decreased trypanothione reductase and increased superoxide dismutase levels in T. cruzi, resulting in higher levels of residual H2O2 after challenge with this oxidant. Although expression of catalase contributed to elevated proliferation rates of T. cruzi in Rhodnius prolixus, it failed to induce a significant increase of parasite virulence in mice. Altogether, these results indicate that the absence of a gene encoding catalase in T. cruzi has played an important role in allowing this parasite to develop a shrill capacity to sense and overcome oxidative stress.

Oxidative status and the severity of clinical symptoms in patients with post-traumatic stress disorder.

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Borovac Štefanović, Leda; Kalinić, Dubravka; Mimica, Ninoslav; Beer Ljubić, Blanka; Aladrović, Jasna; Mandelsamen Perica, Marina; Curić, Maja; Grošić, Petra Folnegović; Delaš, Ivančica

2015-01-01

The aim of this study was to measure the parameters of oxidative stress in the blood of patients with post-traumatic stress disorder. The study included 80 male war veterans who participated actively in the Homeland war in Croatia. Volunteers were divided into two groups: 50 veterans diagnosed with post-traumatic stress disorder and 30 without diagnosis. The self-assessment Hospital Anxiety and Depression Scale and the Beck Depression Inventory were used to detect the severity of depression and anxiety in the post-traumatic stress disorder patients. Catalytic concentrations of superoxide dismutase and glutathione peroxidase in erythrocytes and the concentration of malondialdehyde in serum were measured spectrophotometrically. Although the catalytic concentrations of erythrocyte superoxide dismutase and erythrocyte glutathione peroxidase were within the reference range for both groups, the values obtained for the post-traumatic stress disorder group were significantly lower (Ppost-traumatic stress disorder may indicate a weaker response to oxidative stress due to impaired enzyme activity and/or decreased synthesis. Conversely, no significant changes in serum malondialdehyde concentrations suggest a compensated balance and adaptive response to (oxidative) stress. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

[Hemodynamics, the autonomic nervous system and water metabolism as criteria for developing the general adaptation syndrome in pregnant women].

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Gur'ianov, V A; Shepetovskaia, N L; Pivovarova, G M; Tolmachev, G N; Volodin, A V

2007-01-01

By taking into account the fact that the autonomic nervous and cardiovascular systems (ANS and CVS) are the major links of development of the general adaptation syndrome in pregnancy, which are affected by all the processes involved in the development of the syndrome, the author analyzed the state of these systems in healthy non-pregnant and pregnant women (HNPW and HPW) and in pregnant women with gestosis. HNPW were found to have already a prerequisite for impairing pregnancy adaptive processes as ANS and CVS dysfunction. In HPW, these impairments were more pronounced. In the pregnant women, impaired adaptive processes manifested themselves as excess sympathicotonia in 72% and parasympathicotonia in 23% of cases despite the treatment performed, which was accompanied by hypokinetic hemodynamics in 53 and 50%, respectively. In hyper- and eukinetic hemodynamics, there were no physiologically required decreases in total peripheral vascular resistance while in hypokinetic hemodynamics, there was its pathological increase. Such disorders enhance the significance of abdominal compartment syndrome, aortocaval compression, ischemia-reperfusion, hydrodynamic and membranogenic (capillary leakage) factors of impaired water metabolism, which contributes to adaptation derangement. Based on the findings, the authors have created a developmental modulation algorithm for the general adaptation syndrome by completed pregnancy and surgical delivery.

Adaptive developmental assessment of young children with cognitive and/or functional impairments

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Visser, L.; Ruiter, S.A.J.; Timmerman, M.E.; Van der Meulen, B.F.; Ruijssenaars, A.J.J.M.

2011-01-01

The instrument being developed aims to give additional and more refined information about the developmental course of a child with a cognitive and / or functional impairment than is possible with existing tests. It will help tune interventions to the developmental course and potentials of a child.

Selection of metastatic breast cancer cells based on adaptability of their metabolic state.

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Balraj Singh

Full Text Available A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis

Selection of Metastatic Breast Cancer Cells Based on Adaptability of Their Metabolic State

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Singh, Balraj; Tai, Karen; Madan, Simran; Raythatha, Milan R.; Cady, Amanda M.; Braunlin, Megan; Irving, LaTashia R.; Bajaj, Ankur; Lucci, Anthony

2012-01-01

A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind) variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis and then primary

Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: associations and a hypothesis.

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Domínguez, R O; Pagano, M A; Marschoff, E R; González, S E; Repetto, M G; Serra, J A

2014-01-01

Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear. Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and β-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations. Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

The cerebellum does more than sensory prediction error-based learning in sensorimotor adaptation tasks.

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Butcher, Peter A; Ivry, Richard B; Kuo, Sheng-Han; Rydz, David; Krakauer, John W; Taylor, Jordan A

2017-09-01

Individuals with damage to the cerebellum perform poorly in sensorimotor adaptation paradigms. This deficit has been attributed to impairment in sensory prediction error-based updating of an internal forward model, a form of implicit learning. These individuals can, however, successfully counter a perturbation when instructed with an explicit aiming strategy. This successful use of an instructed aiming strategy presents a paradox: In adaptation tasks, why do individuals with cerebellar damage not come up with an aiming solution on their own to compensate for their implicit learning deficit? To explore this question, we employed a variant of a visuomotor rotation task in which, before executing a movement on each trial, the participants verbally reported their intended aiming location. Compared with healthy control participants, participants with spinocerebellar ataxia displayed impairments in both implicit learning and aiming. This was observed when the visuomotor rotation was introduced abruptly ( experiment 1 ) or gradually ( experiment 2 ). This dual deficit does not appear to be related to the increased movement variance associated with ataxia: Healthy undergraduates showed little change in implicit learning or aiming when their movement feedback was artificially manipulated to produce similar levels of variability ( experiment 3 ). Taken together the results indicate that a consequence of cerebellar dysfunction is not only impaired sensory prediction error-based learning but also a difficulty in developing and/or maintaining an aiming solution in response to a visuomotor perturbation. We suggest that this dual deficit can be explained by the cerebellum forming part of a network that learns and maintains action-outcome associations across trials. NEW & NOTEWORTHY Individuals with cerebellar pathology are impaired in sensorimotor adaptation. This deficit has been attributed to an impairment in error-based learning, specifically, from a deficit in using sensory

Resilience in Parents of Young Adults with Visual Impairments

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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…

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

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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.

Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

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Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

2016-10-01

Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

Exercise-Induced Oxidative Stress Responses in the Pediatric Population

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Alexandra Avloniti

2017-01-01

Full Text Available Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty.

Nrf2 and regulation of the antioxidant system in the Antarctic silverfish, Pleuragramma antarctica: Adaptation to environmental changes of pro-oxidant pressure.

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Giuliani, Maria Elisa; Benedetti, Maura; Nigro, Marco; Regoli, Francesco

2017-08-01

Despite the key importance of Nrf2-Keap1 in regulating antioxidant system in vertebrates, this system is still poorly investigated in marine species. The present study focused on the Antarctic silverfish Pleuragramma antarctica which, during the final phases of embryo development in platelet ice, is challenged by a sudden enhancement of environmental oxidative conditions associated to ice melting. Partial coding sequences were identified for Nrf2, its repressor Keap1 and for typical Nrf2-target antioxidant genes, like catalase, glutathione peroxidase isoform 1 and Cu/Zn-dependent superoxide dismutase. Compared to temperate homologues, the protein sequences showed an elevated conservation of amino acids essential for catalytic functions, while a few specific substitutions in non-essential regions may represent a molecular adaptation to improve flexibility and accessibility to active site at cold temperatures. The role of the Nrf2-Keap1 pathway in modulating the activation of antioxidant defences was demonstrated at both transcriptional and functional levels with a clear temporal increase of antioxidant protection in embryos before the hatching. Such findings confirm the importance of Nrf2 and highlight regulation of antioxidants as an adaptive strategy in P. antarctica to protect the early life stages toward the environmental changes of pro-oxidant pressure. Copyright © 2017 Elsevier Ltd. All rights reserved.

An adaptive orienting theory of error processing.

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Wessel, Jan R

2018-03-01

The ability to detect and correct action errors is paramount to safe and efficient goal-directed behaviors. Existing work on the neural underpinnings of error processing and post-error behavioral adaptations has led to the development of several mechanistic theories of error processing. These theories can be roughly grouped into adaptive and maladaptive theories. While adaptive theories propose that errors trigger a cascade of processes that will result in improved behavior after error commission, maladaptive theories hold that error commission momentarily impairs behavior. Neither group of theories can account for all available data, as different empirical studies find both impaired and improved post-error behavior. This article attempts a synthesis between the predictions made by prominent adaptive and maladaptive theories. Specifically, it is proposed that errors invoke a nonspecific cascade of processing that will rapidly interrupt and inhibit ongoing behavior and cognition, as well as orient attention toward the source of the error. It is proposed that this cascade follows all unexpected action outcomes, not just errors. In the case of errors, this cascade is followed by error-specific, controlled processing, which is specifically aimed at (re)tuning the existing task set. This theory combines existing predictions from maladaptive orienting and bottleneck theories with specific neural mechanisms from the wider field of cognitive control, including from error-specific theories of adaptive post-error processing. The article aims to describe the proposed framework and its implications for post-error slowing and post-error accuracy, propose mechanistic neural circuitry for post-error processing, and derive specific hypotheses for future empirical investigations. © 2017 Society for Psychophysiological Research.

Diabetic Cardiovascular Disease Induced by Oxidative Stress

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Yosuke Kayama

2015-10-01

Full Text Available Cardiovascular disease (CVD is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM. DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD, cardiac hypertrophy, and heart failure (HF. HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS. ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

Intellectual Estimates of Hearing-Impaired Children: A Comparison of Three Measures

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Ritter, David R.

1976-01-01

The Arthur Adaptation of the Leiter International Performance Scale, Raven's Coloured Progressive Matrices, and Wechsler Intelligence Scale for Children-Performance Section were administered to 31 children with mild to moderate hearing impairments. A comparison of test results indicated moderate convergent validity among the measures. (Author)

Oxidative stress induces senescence in human mesenchymal stem cells

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Brandl, Anita [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Meyer, Matthias; Bechmann, Volker [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Nerlich, Michael [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Angele, Peter, E-mail: Peter.Angele@klinik.uni-regensburg.de [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany)

2011-07-01

Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.

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

DEFF Research Database (Denmark)

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

2015-01-01

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

Acquisition of tolerance against oxidative damage in Saccharomyces cerevisiae

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Eleutherio Elis CA

2001-07-01

Full Text Available Abstract Background Living cells constantly sense and adapt to redox shifts by the induction of genes whose products act to maintain the cellular redox environment. In the eukaryote Saccharomyces cerevisiae, while stationary cells possess a degree of constitutive resistance towards oxidants, treatment of exponential phase cultures with sub-lethal stresses can lead to the transient induction of protection against subsequent lethal oxidant conditions. The sensors of oxidative stress and the corresponding transcription factors that activate gene expression under these conditions have not yet been completely identified. Results We report the role of SOD1, SOD2 and TPS1 genes (which encode the cytoplasmic Cu/Zn-superoxide dismutase, the mitochondrial Mn-isoform and trehalose-6-phosphate synthase, respectively in the development of resistance to oxidative stress. In all experimental conditions, the cultures were divided into two parts, one was immediately submitted to severe stress (namely: exposure to H2O2, heat shock or ethanol stress while the other was initially adapted to 40°C for 60 min. The deficiency in trehalose synthesis did not impair the acquisition of tolerance to H2O2, but this disaccharide played an essential role in tolerance against heat and ethanol stresses. We also verified that the presence of only one Sodp isoform was sufficient to improve cellular resistance to 5 mM H2O2. On the other hand, while the lack of Sod2p caused high cell sensitivity to ethanol and heat shock, the absence of Sod1p seemed to be beneficial to the process of acquisition of tolerance to these adverse conditions. The increase in oxidation-dependent fluorescence of crude extracts of sod1 mutant cells upon incubation at 40°C was approximately 2-fold higher than in sod2 and control strain extracts. Furthermore, in Western blots, we observed that sod mutants showed a different pattern of Hsp104p and Hsp26p expression also different from that in their control

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

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Subbuswamy K. Prabu

2011-05-01

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

Smart-system of distance learning of visually impaired people based on approaches of artificial intelligence

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Samigulina, Galina A.; Shayakhmetova, Assem S.

2016-11-01

Research objective is the creation of intellectual innovative technology and information Smart-system of distance learning for visually impaired people. The organization of the available environment for receiving quality education for visually impaired people, their social adaptation in society are important and topical issues of modern education.The proposed Smart-system of distance learning for visually impaired people can significantly improve the efficiency and quality of education of this category of people. The scientific novelty of proposed Smart-system is using intelligent and statistical methods of processing multi-dimensional data, and taking into account psycho-physiological characteristics of perception and awareness learning information by visually impaired people.

Near-infrared spectroscopy and skeletal muscle oxidative function in vivo in health and disease: a review from an exercise physiology perspective

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Grassi, Bruno; Quaresima, Valentina

2016-09-01

In most daily activities related to work or leisure, the energy for muscle work substantially comes from oxidative metabolism. Functional limitations or impairments of this metabolism can significantly affect exercise tolerance and performance. As a method for the functional evaluation of skeletal muscle oxidative metabolism, near-infrared spectroscopy (NIRS) has important strengths but also several limitations, some of which have been overcome by recent technological developments. Skeletal muscle fractional O2 extraction, the main variable which can be noninvasively evaluated by NIRS, is the result of the dynamic balance between O2 utilization and O2 delivery; it can yield relevant information on key physiological and pathophysiological mechanisms, relevant in the evaluation of exercise performance and exercise tolerance in healthy subjects (in normal and in altered environmental conditions) and in patients. In the right hands, NIRS can offer insights into the physiological and pathophysiological adaptations to conditions of increased O2 needs that involve, in an integrated manner, different organs and systems of the body. In terms of patient evaluation, NIRS allows determination of the evolution of the functional impairments, to identify their correlations with clinical symptoms, to evaluate the effects of therapeutic or rehabilitative interventions, and to gain pathophysiological and diagnostic insights.

Near-infrared spectroscopy and skeletal muscle oxidative function in vivo in health and disease: a review from an exercise physiology perspective.

Science.gov (United States)

Grassi, Bruno; Quaresima, Valentina

2016-09-01

In most daily activities related to work or leisure, the energy for muscle work substantially comes from oxidative metabolism. Functional limitations or impairments of this metabolism can significantly affect exercise tolerance and performance. As a method for the functional evaluation of skeletal muscle oxidative metabolism, near-infrared spectroscopy (NIRS) has important strengths but also several limitations, some of which have been overcome by recent technological developments. Skeletal muscle fractional O2 extraction, the main variable which can be noninvasively evaluated by NIRS, is the result of the dynamic balance between O2 utilization and O2 delivery; it can yield relevant information on key physiological and pathophysiological mechanisms, relevant in the evaluation of exercise performance and exercise tolerance in healthy subjects (in normal and in altered environmental conditions) and in patients. In the right hands, NIRS can offer insights into the physiological and pathophysiological adaptations to conditions of increased O2 needs that involve, in an integrated manner, different organs and systems of the body. In terms of patient evaluation, NIRS allows determination of the evolution of the functional impairments, to identify their correlations with clinical symptoms, to evaluate the effects of therapeutic or rehabilitative interventions, and to gain pathophysiological and diagnostic insights.

Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

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Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

2017-08-01

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration

PGC-1α-mediated adaptations in skeletal muscle

DEFF Research Database (Denmark)

Olesen, Jesper; Kiilerich, Kristian; Pilegaard, Henriette

2010-01-01

multiple pathways and functions underline the potential importance of PGC-1alpha in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1alpha-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle...... involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1alpha transcription and potentially PGC-1alpha activity through post-translational modifications, and concomitant PGC-1alpha-mediated gene regulation is suggested...... to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1alpha-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise...

Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease.

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Sil, Susmita; Ghosh, Tusharkanti; Gupta, Pritha; Ghosh, Rupsa; Kabir, Syed N; Roy, Avishek

2016-12-01

The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.

RELATIONSHIP BETWEEN LIFE BUILDING SKILLS AND SOCIAL ADJUSTMENT OF STUDENTS WITH HEARING IMPAIRMENT: IMPLICATIONS FOR COUNSELING

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Samuel O. ADENIYI

2017-10-01

Full Text Available Introduction Hearing impairment contributes greatly to social and psychological deficits of the affected individuals, which can affect their interpersonal relation. The inability to hear and communicate effectively results in adjustment problem that leads to social isolation. Objectives: The objective of this study is to examine the relationship between life building skills and social adjustment of students with hearing impairment. Methods: The study employed descriptive survey research design. The samples consisted of 150 students with hearing impairment purposively selected from two inclusive schools in Lagos state, Nigeria. The samples comprised of 65 boys and 85 girls with age range between 15 and 18 years in the Senior Secondary School. The instruments used for data collection were Life building skills inventory (adapted with reliability of 0.80 and Social adjustment scale (Self developed. The instruments consisted of two sections namely: A&B. Section A of Life building skills contained bio- data of the respondents, while B contained 3 subscales: Self-efficacy inventory adapted from Schwarzer and Jerusalem 1995 with reliability of 0.85, Decision-making inventory adapted from Rowe 1997 with reliability of 0.75, Assertiveness inventory adapted from Aberti and Emmons 1995 with reliability of 0.80. The self-constructed Social Adjustment scale contained 10 items probing questions with reliability of 0.69. Data collected was analysed using Pearson Product Moment Correlation and Multiple Regression. Results: The results revealed relative contributions of some life building skills to social adjustment of students with hearing impairment. There were joint contributions of the independent variables to dependent variable, while decision-making contributed mostly. Conclusion: This study examined relationship between life building skills and social adjustment of students with hearing impairment with a bid to provide adequate counseling services. It was

Interaction between sexual steroids and immune response in affecting oxidative status of birds

NARCIS (Netherlands)

Casagrande, Stefania; Costantini, David; Groothuis, Ton G. G.

One hypothesis explaining the honesty of secondary sexual traits regulated by testosterone (T) is that T can impair the balance between pro-oxidant compounds and antioxidant defences, favouring a status of oxidative stress that only good quality individuals can sustain (oxidative handicap

Subthalamic nucleus stimulation impairs emotional conflict adaptation in Parkinson's disease.

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Irmen, Friederike; Huebl, Julius; Schroll, Henning; Brücke, Christof; Schneider, Gerd-Helge; Hamker, Fred H; Kühn, Andrea A

2017-10-01

The subthalamic nucleus (STN) occupies a strategic position in the motor network, slowing down responses in situations with conflicting perceptual input. Recent evidence suggests a role of the STN in emotion processing through strong connections with emotion recognition structures. As deep brain stimulation (DBS) of the STN in patients with Parkinson's disease (PD) inhibits monitoring of perceptual and value-based conflict, STN DBS may also interfere with emotional conflict processing. To assess a possible interference of STN DBS with emotional conflict processing, we used an emotional Stroop paradigm. Subjects categorized face stimuli according to their emotional expression while ignoring emotionally congruent or incongruent superimposed word labels. Eleven PD patients ON and OFF STN DBS and eleven age-matched healthy subjects conducted the task. We found conflict-induced response slowing in healthy controls and PD patients OFF DBS, but not ON DBS, suggesting STN DBS to decrease adaptation to within-trial conflict. OFF DBS, patients showed more conflict-induced slowing for negative conflict stimuli, which was diminished by STN DBS. Computational modelling of STN influence on conflict adaptation disclosed DBS to interfere via increased baseline activity. © The Author (2017). Published by Oxford University Press.

Mechanism of 1, 1-d2 propene oxidation over oxide catalysts

International Nuclear Information System (INIS)

Portefaix, J.L.; Figueras, F.; Forissier, M.

1980-01-01

CD 2 CHCH 3 was oxidized over bismuth molybdate, tin-antimony mixed oxides and supported molybdenum and vanadium oxide catalysts. The deuterium retention is high ( > 90%) in the recovered propene. Percentage retentions of deuterium in the acrolein agree with literature data when bismuth molybdate is used as catalyst. On Sb-Sn-O and supported Mo and V oxides, no isotope effect is noticed for the abstraction of the second hydrogen from the olefin. The slow step of the reaction may therefore be different for the oxidation of propene on Bi-Mo-O and Sb-Sn-O. The ethanal produced by oxidation of CD 2 CHCH 3 contains only minor amounts of deuterium, whatever the catalyst used. It is suggested that partial oxidation of propene to acrolein and C-C bond rupture are parallel reactions which involve different intermediates. Possible mechanisms adapted from organic chemistry are presented to explain these findings. 4 tables

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

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Bruno Pereira Carreira

2014-10-01

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

[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.

Impaired exercise performance and skeletal muscle mitochondrial function in rats with secondary carnitine deficiency

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Jamal BOUITBIR

2016-08-01

Full Text Available Purpose: The effects of carnitine depletion upon exercise performance and skeletal muscle mitochondrial function remain largely unexplored. We therefore investigated the effect of N-trimethyl-hydrazine-3-propionate (THP, a carnitine analogue inhibiting carnitine biosynthesis and renal carnitine reabsorption, on physical performance and skeletal muscle mitochondrial function in rats.Methods: Male Sprague Dawley rats were treated daily with water (control rats; n=12 or with 20 mg/100 g body weight THP (n=12 via oral gavage for 3 weeks. Following treatment, half of the animals of each group performed an exercise test until exhaustion.Results: Distance covered and exercise performance were lower in THP-treated compared to control rats. In the oxidative soleus muscle, carnitine depletion caused atrophy (-24% and impaired function of complex II and IV of the mitochondrial electron transport chain. The free radical leak (ROS production relative to oxygen consumption was increased and the cellular glutathione pool decreased. Moreover, mRNA expression of markers of mitochondrial biogenesis and mitochondrial DNA were decreased in THP-treated compared to control rats. In comparison, in the glycolytic gastrocnemius muscle, carnitine depletion was associated with impaired function of complex IV and increased free radical leak, whilst muscle weight and cellular glutathione pool were maintained. Markers of mitochondrial proliferation and mitochondrial DNA were unaffected.Conclusions: Carnitine deficiency is associated with impaired exercise capacity in rats treated with THP. THP-induced carnitine deficiency is associated with impaired function of the electron transport chain in oxidative and glycolytic muscle as well as with atrophy and decreased mitochondrial DNA in oxidative muscle.

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

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Alexandra C. Sevastre-Berghian

2017-01-01

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

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

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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.

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)

Ando, Hitoshi; Natsume, Atsushi; Iwami, Kenichiro; Ohka, Fumiharu; Kuchimaru, Takahiro; Kizaka-Kondoh, Shinae; Ito, Kengo; Saito, Kiyoshi; Sugita, Sachi; Hoshino, Tsuneyoshi; Wakabayashi, Toshihiko

2013-01-01

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

A Rare Case of Intermittent Claudication Associated with Impaired Arterial Vasodilation

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J. J. Posthuma

2017-01-01

Full Text Available Exercise-related intermittent claudication is marked by reduced blood flow to extremities caused by either stenosis or impaired vascular function. Although intermittent claudication is common in the elderly, it rarely occurs in the young and middle-aged individuals. Here, we report a case of exercise-related claudication in a 41-year-old woman, in the absence of overt vascular pathology. Using a series of imaging and functional tests, we established that her complaints were due to impaired arterial vasodilation, possibly due to a defect in nitrous oxide-mediated dilation. The symptoms were reversible upon administration of a calcium antagonist, showing reversibility of the vascular impairment. Identification of reversible vascular “stiffness” merits consideration in young and otherwise healthy subjects with claudication of unknown origin.

Coordinated balancing of muscle oxidative metabolism through PGC-1{alpha} increases metabolic flexibility and preserves insulin sensitivity

Energy Technology Data Exchange (ETDEWEB)

Summermatter, Serge [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Troxler, Heinz [Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University Children' s Hospital, University of Zurich, Steinwiesstrasse 75, CH-8032 Zurich (Switzerland); Santos, Gesa [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland); Handschin, Christoph, E-mail: christoph.handschin@unibas.ch [Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel (Switzerland)

2011-04-29

Highlights: {yields} PGC-1{alpha} enhances muscle oxidative capacity. {yields} PGC-1{alpha} promotes concomitantly positive and negative regulators of lipid oxidation. {yields} Regulator abundance enhances metabolic flexibility and balances oxidative metabolism. {yields} Balanced oxidation prevents detrimental acylcarnitine and ROS generation. {yields} Absence of detrimental metabolites preserves insulin sensitivity -- Abstract: The peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) enhances oxidative metabolism in skeletal muscle. Excessive lipid oxidation and electron transport chain activity can, however, lead to the accumulation of harmful metabolites and impair glucose homeostasis. Here, we investigated the effect of over-expression of PGC-1{alpha} on metabolic control and generation of insulin desensitizing agents in extensor digitorum longus (EDL), a muscle that exhibits low levels of PGC-1{alpha} in the untrained state and minimally relies on oxidative metabolism. We demonstrate that PGC-1{alpha} induces a strictly balanced substrate oxidation in EDL by concomitantly promoting the transcription of activators and inhibitors of lipid oxidation. Moreover, we show that PGC-1{alpha} enhances the potential to uncouple oxidative phosphorylation. Thereby, PGC-1{alpha} boosts elevated, yet tightly regulated oxidative metabolism devoid of side products that are detrimental for glucose homeostasis. Accordingly, PI3K activity, an early phase marker for insulin resistance, is preserved in EDL muscle. Our findings suggest that PGC-1{alpha} coordinately coactivates the simultaneous transcription of gene clusters implicated in the positive and negative regulation of oxidative metabolism and thereby increases metabolic flexibility. Thus, in mice fed a normal chow diet, over-expression of PGC-1{alpha} does not alter insulin sensitivity and the metabolic adaptations elicited by PGC-1{alpha} mimic the beneficial effects of endurance training

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

International Nuclear Information System (INIS)

Summermatter, Serge; Troxler, Heinz; Santos, Gesa; Handschin, Christoph

2011-01-01

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.

From linking of metal-oxide building blocks in a dynamic library to giant clusters with unique properties and towards adaptive chemistry.

Science.gov (United States)

Müller, Achim; Gouzerh, Pierre

2012-11-21

Following Nature's lessons, today chemists can cross the boundary of the small molecule world to construct multifunctional and highly complex molecular nano-objects up to protein size and even cell-like nanosystems showing responsive sensing. Impressive examples emerge from studies of the solutions of some oxoanions of the early transition metals especially under reducing conditions which enable the controlled linking of metal-oxide building blocks. The latter are available from constitutional dynamic libraries, thus providing the option to generate multifunctional unique nanoscale molecular systems with exquisite architectures, which even opens the way towards adaptive and evolutive (Darwinian) chemistry. The present review presents the first comprehensive report of current knowledge (including synthesis aspects not discussed before) regarding the related giant metal-oxide clusters mainly of the type {Mo(57)M'(6)} (M' = Fe(III), V(IV)) (torus structure), {M(72)M'(30)} (M = Mo, M' = V(IV), Cr(III), Fe(III), Mo(V)), {M(72)Mo(60)} (M = Mo, W) (Keplerates), {Mo(154)}, {Mo(176)}, {Mo(248)} ("big wheels"), and {Mo(368)} ("blue lemon") - all having the important transferable pentagonal {(M)M(5)} groups in common. These discoveries expanded the frontiers of inorganic chemistry to the mesoscopic world, while there is probably no collection of discrete inorganic compounds which offers such a versatile chemistry and the option to study new phenomena of interdisciplinary interest. The variety of different properties of the sphere- and wheel-type metal-oxide-based clusters can directly be related to their unique architectures: The spherical Keplerate-type capsules having 20 crown-ether-type pores and tunable internal functionalities allow the investigation of confined matter as well as that of sphere-surface-supramolecular and encapsulation chemistry - including related new aspects of the biologically important hydrophobic effects - but also of nanoscale ion transport and

Cannabis-induced impairment of learning and memory: effect of different nootropic drugs

Science.gov (United States)

Abdel-Salam, Omar M.E.; Salem, Neveen A.; El-Sayed El-Shamarka, Marwa; Al-Said Ahmed, Noha; Seid Hussein, Jihan; El-Khyat, Zakaria A.

2013-01-01

Cannabis sativa preparations are the most commonly used illicit drugs worldwide. The present study aimed to investigate the effect of Cannabis sativa extract in the working memory version of the Morris water maze (MWM; Morris, 1984[43]) test and determine the effect of standard memory enhancing drugs. Cannabis sativa was given at doses of 5, 10 or 20 mg/kg (expressed as Δ9-tetrahydrocannabinol) alone or co-administered with donepezil (1 mg/kg), piracetam (150 mg/ kg), vinpocetine (1.5 mg/kg) or ginkgo biloba (25 mg/kg) once daily subcutaneously (s.c.) for one month. Mice were examined three times weekly for their ability to locate a submerged platform. Mice were euthanized 30 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, glucose and brain monoamines were determined. Cannabis resulted in a significant increase in the time taken to locate the platform and enhanced the memory impairment produced by scopolamine. This effect of cannabis decreased by memory enhancing drugs with piracetam resulting in the most-shorter latency compared with the cannabis. Biochemically, cannabis altered the oxidative status of the brain with decreased MDA, increased GSH, but decreased nitric oxide and glucose. In cannabis-treated rats, the level of GSH in brain was increased after vinpocetine and donepezil and was markedly elevated after Ginkgo biloba. Piracetam restored the decrease in glucose and nitric oxide by cannabis. Cannabis caused dose-dependent increases of brain serotonin, noradrenaline and dopamine. After cannabis treatment, noradrenaline is restored to its normal value by donepezil, vinpocetine or Ginkgo biloba, but increased by piracetam. The level of dopamine was significantly reduced by piracetam, vinpocetine or Ginkgo biloba. These data indicate that cannabis administration is associated with impaired memory performance which is likely to involve decreased brain glucose

Association of Sympathovagal Imbalance With Cognitive Impairment in Type 2 Diabetes in Adults.

Science.gov (United States)

Auroprajna, Pal; Naik, Basanta Manjari; Sahoo, Jaya Prakash; Keerthi, Gorantla Shravya; Pavanya, Manohar; Pal, Gopal Krushna

2018-02-01

Sympathovagal imbalance (SVI) has been reported to be associated with metabolic derangements in type 2 diabetes. We investigated the association of SVI with cognitive impairment in patients with type 2 diabetes. Patients with a new diagnosis of type 2 diabetes (n=43) and age-matched healthy control subjects (n=43) were recruited for the study. Body mass index and blood pressure measurements were recorded. SVI was assessed by spectral analysis of heart rate variability (HRV), and cognitive function was assessed by recording the positive wave that appears in 300 milliseconds from application of stimulus in event-related potential tracing (P300). Insulin resistance was determined by the homeostatic model assessment of insulin resistance (HOMA-IR) formula using blood glucose and insulin data, and oxidative stress was assessed by estimation of malondialdehyde. Association of various factors with cognitive impairment was evaluated by Pearson correlation analysis, and independent contributions of these factors to cognitive impairment were assessed by multiple regression analysis. P300 latency was significantly prolonged in the diabetes group compared with the control group. Ratio of low-frequency to high-frequency power (LF-HF ratio) of HRV, the marker of SVI was found to be significantly correlated and linked with P300. Malondialdehyde and HOMA-IR were correlated with LF-HF ratio. Treatment-naïve patients with type 2 diabetes have SVI and considerable cognitive impairment. Insulin resistance and oxidative stress contribute to cognitive impairment, and SVI could be the physiologic link to cognitive impairment in treatment-naïve patients with type 2 diabetes. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Interactions between concentric form-from-structure and face perception revealed by visual masking but not adaptation

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Feczko, Eric; Shulman, Gordon L.; Petersen, Steven E.; Pruett, John R.

2014-01-01

Findings from diverse subfields of vision research suggest a potential link between high-level aspects of face perception and concentric form-from-structure perception. To explore this relationship, typical adults performed two adaptation experiments and two masking experiments to test whether concentric, but not nonconcentric, Glass patterns (a type of form-from-structure stimulus) utilize a processing mechanism shared by face perception. For the adaptation experiments, subjects were presented with an adaptor for 5 or 20 s, prior to discriminating a target. In the masking experiments, subjects saw a mask, then a target, and then a second mask. Measures of discriminability and bias were derived and repeated measures analysis of variance tested for pattern-specific masking and adaptation effects. Results from Experiment 1 show no Glass pattern-specific effect of adaptation to faces; results from Experiment 2 show concentric Glass pattern masking, but not adaptation, may impair upright/inverted face discrimination; results from Experiment 3 show concentric and radial Glass pattern masking impaired subsequent upright/inverted face discrimination more than translational Glass pattern masking; and results from Experiment 4 show concentric and radial Glass pattern masking impaired subsequent face gender discrimination more than translational Glass pattern masking. Taken together, these findings demonstrate interactions between concentric form-from-structure and face processing, suggesting a possible common processing pathway. PMID:24563526

Three transcription regulators of the Nss family mediate the adaptive response induced by nitrate, nitric oxide or nitrous oxide in Wolinella succinogenes.

Science.gov (United States)

Kern, Melanie; Simon, Jörg

2016-09-01

Sensing potential nitrogen-containing respiratory substrates such as nitrate, nitrite, hydroxylamine, nitric oxide (NO) or nitrous oxide (N2 O) in the environment and subsequent upregulation of corresponding catabolic enzymes is essential for many microbial cells. The molecular mechanisms of such adaptive responses are, however, highly diverse in different species. Here, induction of periplasmic nitrate reductase (Nap), cytochrome c nitrite reductase (Nrf) and cytochrome c N2 O reductase (cNos) was investigated in cells of the Epsilonproteobacterium Wolinella succinogenes grown either by fumarate, nitrate or N2 O respiration. Furthermore, fumarate respiration in the presence of various nitrogen compounds or NO-releasing chemicals was examined. Upregulation of each of the Nap, Nrf and cNos enzyme systems was found in response to the presence of nitrate, NO-releasers or N2 O, and the cells were shown to employ three transcription regulators of the Crp-Fnr superfamily (homologues of Campylobacter jejuni NssR), designated NssA, NssB and NssC, to mediate the upregulation of Nap, Nrf and cNos. Analysis of single nss mutants revealed that NssA controls production of the Nap and Nrf systems in fumarate-grown cells, while NssB was required to induce the Nap, Nrf and cNos systems specifically in response to NO-generators. NssC was indispensable for cNos production under any tested condition. The data indicate dedicated signal transduction routes responsive to nitrate, NO and N2 O and imply the presence of an N2 O-sensing mechanism. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Hippocampal Dysfunction Provoked by Mercury Chloride Exposure: Evaluation of Cognitive Impairment, Oxidative Stress, Tissue Injury and Nature of Cell Death

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Walessa Alana Bragança Aragão

2018-01-01

Full Text Available Mercury (Hg is a highly toxic metal, which can be found in its inorganic form in the environment. This form presents lower liposolubility and lower absorption in the body. In order to elucidate the possible toxicity of inorganic Hg in the hippocampus, we investigated the potential of low doses of mercury chloride (HgCl2 to promote hippocampal dysfunction by employing a chronic exposure model. For this, 56 rats were exposed to HgCl2 (0.375 mg/kg/day via the oral route for 45 days. After the exposure period, the animals were submitted to the cognitive test of fear memory. The hippocampus was collected for the measurement of total Hg levels, analysis of oxidative stress, and evaluation of cytotoxicity, apoptosis, and tissue injury. It was observed that chronic exposure to inorganic Hg promotes an increase in mercury levels in this region and damage to short- and long-term memory. Furthermore, we found that this exposure model provoked oxidative stress, which led to cytotoxicity and cell death by apoptosis, affecting astrocytes and neurons in the hippocampus. Our study demonstrated that inorganic Hg, even with its low liposolubility, is able to produce deleterious effects in the central nervous system, resulting in cognitive impairment and hippocampal damage when administered for a long time at low doses in rats.

Deficiency of adaptive immunity does not interfere with Wallerian degeneration.

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Christopher R Cashman

Full Text Available Following injury, distal axons undergo the process of Wallerian degeneration, and then cell debris is cleared to create a permissive environment for axon regeneration. The innate and adaptive immune systems are believed to be critical for facilitating the clearance of myelin and axonal debris during this process. However, immunodeficient animal models are regularly used in transplantation studies investigating cell therapies to modulate the degenerative/regenerative response. Given the importance of the immune system in preparing a permissive environment for regeneration by clearing debris, animals lacking, in part or in full, a functional immune system may have an impaired ability to regenerate due to poor myelin clearance, and may, thus, be poor hosts to study modulators of regeneration and degeneration. To study this hypothesis, three different mouse models with impaired adaptive immunity were compared to wild type animals in their ability to degenerate axons and clear myelin debris one week following sciatic nerve transection. Immunofluorescent staining for axons and quantitation of axon density with nerve histomorphometry of the distal stump showed no consistent discrepancy between immunodeficient and wild type animals, suggesting axons tended to degenerate equally between the two groups. Debris clearance was assessed by macrophage density and relative myelin basic protein expression within the denervated nerve stump, and no consistent impairment of debris clearance was found. These data suggested deficiency of the adaptive immune system does not have a substantial effect on axon degeneration one week following axonal injury.

Hydrogen-enriched water restoration of impaired calcium propagation by arsenic in primary keratinocytes

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Yu, Wei-Tai; Chiu, Yi-Ching; Lee, Chih-Hung; Yoshioka, Tohru; Yu, Hsin-Su

2013-11-01

Endemic contamination of artesian water for drinking by arsenic is known to cause several human cancers, including cancers of the skin, bladder, and lungs. In skin, multiple arsenic-induced Bowen's disease (As-BD) can develop into invasive cancers after decades of arsenic exposure. The characteristic histological features of As-BD include full-layer epidermal dysplasia, apoptosis, and abnormal proliferation. Calcium propagation is an essential cellular event contributing to keratinocyte differentiation, proliferation, and apoptosis, all of which occur in As-BD. This study investigated how arsenic interferes calcium propagation of skin keratinocytes through ROS production and whether hydrogen-enriched water would restore arsenic-impaired calcium propagation. Arsenic was found to induce oxidative stress and inhibit ATP- and thapsigaragin-induced calcium propagation. Pretreatment of arsenic-treated keratinocytes by hydrogen-enriched water or beta-mercaptoethanol with potent anti-oxidative effects partially restored the propagation of calcium by ATP and by thapsigaragin. It was concluded that arsenic may impair calcium propagation, likely through oxidative stress and interactions with thiol groups in membrane proteins.

[Evaluation of peruvian money test in screening of cognitive impairment among older adults].

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Oscanoa, Teodoro J; Cieza, Edwin; Parodi, José F; Paredes, Napoleón

2016-03-01

Objectives To evaluate the Peruvian adaptation of the money test (Eurotest) for identifying cognitive impairment among >60-year-old adults. Materials and methods This is a phase I study of diagnostic test, with a convenience sampling and calculation of the test´s sensitivity and specificity, based on a pretest prevalence of 50%. The criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) and Global Deterioration Scale (GDS) were used for the operational definition of patients with cognitive impairment. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cut-off value. Results The study evaluated 42 cases and 42 controls; there was no significant difference between age (77.88 ± 6.01 years vs. 6.49 76.14 ± years) and years of education (13.69 ± 3.70 years vs. 8.17 ± 4.71 years). The Peruvian version of the Eurotest has a sensitivity of 90.5% and specificity of 83.3% with cut-off value of 24. Conclusions The Peruvian adapted version of the Eurotest, called prueba de la moneda peruana could be useful in screening for cognitive impairment among older adults.

A zinc-resistant human epithelial cell line is impaired in cadmium and manganese import

International Nuclear Information System (INIS)

Rousselet, Estelle; Richaud, Pierre; Douki, Thierry; Chantegrel, Jocelyne Garcia; Favier, Alain; Bouron, Alexandre; Moulis, Jean-Marc

2008-01-01

A human epithelial cell line (HZR) growing with high zinc concentrations has been analyzed for its ability to sustain high cadmium concentrations. Exposure to up to 200 μM of cadmium acetate for 24 h hardly impacted viability, whereas most of parental HeLa cells were killed by less than 10 μM of cadmium. Upon challenge by 35 fold higher cadmium concentrations than HeLa cells, HZR cells did not display increased DNA damage, increased protein oxidation, or changed intracellular cadmium localization. Rather, the main cause of resistance against cadmium was by avoiding cadmium entry into cells, which differs from that against zinc as the latter accumulates inside cells. The zinc-resistant phenotype of these cells was shown to also impair extracellular manganese uptake. Manganese and cadmium competed for entry into HeLa cells. Probing formerly identified cadmium or manganese transport systems in different animal cells did not evidence any significant change between HeLa and HZR cells. These results reveal zinc adaptation influences manganese and cadmium cellular traffic and they highlight previously unknown connections among homeostasis of divalent metals

Investigating the effects of nitrous oxide sedation on frontal-parietal interactions.

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Ryu, Ji-Ho; Kim, Pil-Jong; Kim, Hong-Gee; Koo, Yong-Seo; Shin, Teo Jeon

2017-06-09

Although functional connectivity has received considerable attention in the study of consciousness, few studies have investigated functional connectivity limited to the sedated state where consciousness is maintained but impaired. The aim of the present study was to investigate changes in functional connectivity of the parietal-frontal network resulting from nitrous oxide-induced sedation, and to determine the neural correlates of cognitive impairment during consciousness transition states. Electroencephalography was acquired from healthy adult patients who underwent nitrous oxide inhalation to induce cognitive impairment, and was analyzed using Granger causality (GC). Periods of awake, sedation and recovery for GC between frontal and parietal areas in the delta, theta, alpha, beta, gamma and total frequency bands were obtained. The Friedman test with post-hoc analysis was conducted for GC values of each period for comparison. As a sedated state was induced by nitrous oxide inhalation, power in the low frequency band showed increased activity in frontal regions that was reversed with discontinuation of nitrous oxide. Feedback and feedforward connections analyzed in spectral GC were changed differently in accordance with EEG frequency bands in the sedated state by nitrous oxide administration. Calculated spectral GC of the theta, alpha, and beta frequency regions in the parietal-to-frontal direction was significantly decreased in the sedated state while spectral GC in the reverse direction did not show significant change. Frontal-parietal functional connectivity is significantly affected by nitrous oxide inhalation. Significantly decreased parietal-to-frontal interaction may induce a sedated state. Copyright © 2017 Elsevier B.V. All rights reserved.

Staged membrane oxidation reactor system

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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.

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

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

2017-11-23

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

Adapting the mini mental status to the context of the West-Indies.

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Godaert, Lidvine; Godard-Sebillotte, Claire; Bousquet, Lionel; Devouche, Emmanuel; Hugonot-Diener, Laurence; Nuissier, Joëlle; Triboulet, Frank; Fanon, Jean-Luc

2017-03-01

The mini mental state examination (MMSE) has become a benchmark for the screening and follow-up of cognitive impairment. The numerous translations of the MMS into other languages attest to its popularity. Clinical practice suggests that the consensual French version from the Greco (Groupe de réflexion sur les évaluations cognitives - Research working group for cognitive assessment) is not adapted to the West-Indies population because of the low socio-economic level and the widespread use of the Creole language among the elderly population. Modification of certain items by a multidisciplinary committee made it possible to adapt the instrument to the Creole culture. This procedure increases comprehension of the instrument, and should lead to improved detection of cognitive impairment in the West-Indies.

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

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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…

Genetics Home Reference: combined oxidative phosphorylation deficiency 1

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... a severe condition that primarily impairs neurological and liver function. Most people with combined oxidative phosphorylation deficiency 1 have severe brain dysfunction (encephalopathy) that worsens over time; they also have difficulty ...

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

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

2014-09-01

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

Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess.

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Samino, Sara; Vinaixa, Maria; Díaz, Marta; Beltran, Antoni; Rodríguez, Miguel A; Mallol, Roger; Heras, Mercedes; Cabre, Anna; Garcia, Lorena; Canela, Nuria; de Zegher, Francis; Correig, Xavier; Ibáñez, Lourdes; Yanes, Oscar

2015-06-23

Hyperinsulinaemic androgen excess (HIAE) in prepubertal and pubertal girls usually precedes a broader pathological phenotype in adulthood that is associated with anovulatory infertility, metabolic syndrome and type 2 diabetes. The metabolic derangements that determine these long-term health risks remain to be clarified. Here we use NMR and MS-based metabolomics to show that serum levels of methionine sulfoxide in HIAE girls are an indicator of the degree of oxidation of methionine-148 residue in apolipoprotein-A1. Oxidation of apo-A1 in methionine-148, in turn, leads to an impaired maturation of high-density lipoproteins (HDL) that is reflected in a decline of large HDL particles. Notably, such metabolic alterations occur in the absence of impaired glucose tolerance, hyperglycemia and hypertriglyceridemia, and were partially restored after 18 months of treatment with a low-dose combination of pioglitazone, metformin and flutamide.

Muscle Involvement in Preservation of Metabolic Flexibility by a Combination Treatment using n-3 PUFA, and Rosiglitazone in Dietary-Obese Mice

NARCIS (Netherlands)

Medrikova, D.; Schothorst, van E.M.; Bunschoten, J.E.; Flachs, P.; Kopecky, J.; Keijer, J.

2012-01-01

Impaired resistance to insulin, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. The hampered metabolic adaptability triggers a further damage of insulin signaling. Since skeletal muscle is the

Muscle Involvement in Preservation of Metabolic Flexibility by Treatment using n-3 PUFA or Rosiglitazone in Dietary-Obese Mice

NARCIS (Netherlands)

Medrikova, Dasa; Schothorst, van Evert; Bunschoten, Annelies; Flachs, Pavel; Kopecky, Jan; Keijer, Jaap

2012-01-01

Impaired resistance to insulin, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. The hampered metabolic adaptability triggers a further damage of insulin signaling. Since skeletal muscle is the

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

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Choi Youkyung

2011-02-01

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

Free recall behaviour in children with and without spelling impairment: the impact of working memory subcapacities.

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Malstädt, Nadine; Hasselhorn, Marcus; Lehmann, Martin

2012-11-01

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 spelling deficits. Video analyses revealed that recall behaviour was similar in impaired and unimpaired children, indicating that both groups applied similar learning activities. Group differences in number of recalled items were attributed to differences in working memory subcapacities between children with and without spelling impairment, especially with regard to central executive and phonological loop functioning. Copyright © 2012 John Wiley & Sons, Ltd.

Characteristic Symptoms and Adaptive Behaviors of Children with Autism

International Nuclear Information System (INIS)

Rauf, N. K.; Haq, A.; Aslam, N.; Anjum, U.

2014-01-01

Objective: To determine the characteristic symptoms and adaptive behaviors of children with autism, as well as the distribution of autism severity groups across gender. Study Design: Cross-sectional observational study. Place and Duration of Study: Special Education Schools of Rawalpindi and Islamabad, from September 2011 to January 2012. Methodology: Thirty nine children of either gender, aged 3 - 16 years and enrolled in special education schools, fulfilled the DSM-IV-TR criteria of autism. Among those, were identified as meeting the criteria of autism. The childhood autism rating scale-2 (CARS-2) was used to study the characteristics and severity of symptoms of autism. Later, adaptive behavior scale (school edition: 2) ABS-S: 2, was administered on children (n=21) to formulate the level of adaptive functioning. Results: There were 15 boys and 8 girls with mean age of 10.6 +- 2.97 years. They showed marked impairment in verbal communication (mean=3.17 +- 0.90) followed by relating to people (mean=2.75 +- 0.83) and general impression (mean=2.73 +- 0.7). Most of the children showed average to below average adaptive behaviors on number and time (n=19, 90.5%), independent functioning (n=17, 81.0%), self direction (n=17, 81.0%), physical development (n=13, 61.9%), responsibility (n=12, 57.1%) and socialization (n=13, 61.9%) as well as poor to very poor adaptive behaviors on prevocational skill (n=15, 71.4%), language development (n=13, 61.9%) and economic development (n=13, 61.9%). The frequency of boys with autism was more towards moderate to severely impaired spectrum, without gender differences in any symptom associated with autism. Conclusion: Comprehension of the presentation of characteristic symptoms of children with autism will be helpful in devising the indigenous intervention plans that are congruent with the level of adaptive functioning. (author)

Perceived competence and school adjustment of hearing impaired children in mainstream primary school settings.

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Hatamizadeh, N; Ghasemi, M; Saeedi, A; Kazemnejad, A

2008-11-01

Although educational main streaming of children with special needs formally began in Iran since 1992 there is little information whether hearing impaired children feel competent in regular schools. To determine the perceived competence and school adjustment of hearing impaired children in mainstream primary school settings, the self-perception profile was administered to 60 mainstreamed hard of hearing children and 60 classmates with normal hearing matched for gender by a single interviewer. The instrument comprised 28 items, 23 of which were similar to those of 'adapted test Image for children with cochlear implants' asking children about their feelings about their own cognitive, physical, socio-emotional and communication competence and school adjustment. The Cronbach alpha coefficient for the instrument was 0.93. Hard of hearing children rated their competence significantly poorer than their hearing classmates for all domains. Mean differences for the five domains ranged from 0.48 (for physical competence) to 0.90 (for school adjustment) on a scale of 1-4. There were no significant differences between girls' and boys' competence, in either the hearing or the hearing impaired groups. Classifying overall scores for perceived competence into four groups ('poor competence', 'low competence', 'moderate competence' and 'high competence'), 23.4% of hearing impaired children but none of the hearing classmates rated themselves as having low or poor competence. On the other hand 85% of hearing children and only 18.3% of hearing impaired children rated themselves as highly competent. We suggest that periodical assessments of mainstreamed children might help to identify those children who are having difficulty adapting to their environment.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes

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Christie, Joshua R.; Beekman, Madeleine

2017-01-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes—specifically their organization into host cells and their uniparental (maternal) inheritance—enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller’s ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes—despite their asexual mode of reproduction—can readily undergo adaptive evolution. PMID:28025277

Hepatic toxicity of dronedarone in mice: Role of mitochondrial β-oxidation

International Nuclear Information System (INIS)

Felser, Andrea; Stoller, Andrea; Morand, Réjane; Schnell, Dominik; Donzelli, Massimiliano; Terracciano, Luigi; Bouitbir, Jamal; Krähenbühl, Stephan

2014-01-01

Highlights: • Dronedarone is not hepatotoxic to mice up to 200 mg/kg/day. • At 400 mg/kg/day dronedarone decreases food intake and inhibits hepatic fatty acid metabolism. • Impaired hepatic fatty acid metabolism is associated with increased hepatocyte apoptosis and serum transaminases. • Mice with subclinical impairment of β-oxidation are slightly more susceptible to dronaderone than wild type mice. - Abstract: Dronedarone is an amiodarone-like antiarrhythmic drug associated with severe liver injury. Since dronedarone inhibits mitochondrial respiration and β-oxidation in vitro, mitochondrial toxicity may also explain dronedarone-associated hepatotoxicity in vivo. We therefore studied hepatotoxicity of dronedarone (200 mg/kg/day for 2 weeks or 400 mg/kg/day for 1 week by intragastric gavage) in heterozygous juvenile visceral steatosis (jvs +/− ) and wild-type mice. Jvs +/− mice have reduced carnitine stores and are sensitive for mitochondrial β-oxidation inhibitors. Treatment with dronedarone 200 mg/kg/day had no effect on body weight, serum transaminases and bilirubin, and hepatic mitochondrial function in both wild-type and jvs +/− mice. In contrast, dronedarone 400 mg/kg/day was associated with a 10–15% drop in body weight, and a 3–5-fold increase in transaminases and bilirubin in wild-type mice and, more accentuated, in jvs +/− mice. In vivo metabolism of intraperitoneal 14 C-palmitate was impaired in wild-type, and, more accentuated, in jvs +/− mice treated with 400 mg/kg/day dronedarone compared to vehicle-treated mice. Impaired β-oxidation was also found in isolated mitochondria ex vivo. A likely explanation for these findings was a reduced activity of carnitine palmitoyltransferase 1a in liver mitochondria from dronedarone-treated mice. In contrast, dronedarone did not affect the activity of the respiratory chain ex vivo. We conclude that dronedarone inhibits mitochondrial β-oxidation in and ex vivo, but not the respiratory chain

Encoding in the visual word form area: an fMRI adaptation study of words versus handwriting.

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Barton, Jason J S; Fox, Christopher J; Sekunova, Alla; Iaria, Giuseppe

2010-08-01

Written texts are not just words but complex multidimensional stimuli, including aspects such as case, font, and handwriting style, for example. Neuropsychological reports suggest that left fusiform lesions can impair the reading of text for word (lexical) content, being associated with alexia, whereas right-sided lesions may impair handwriting recognition. We used fMRI adaptation in 13 healthy participants to determine if repetition-suppression occurred for words but not handwriting in the left visual word form area (VWFA) and the reverse in the right fusiform gyrus. Contrary to these expectations, we found adaptation for handwriting but not for words in both the left VWFA and the right VWFA homologue. A trend to adaptation for words but not handwriting was seen only in the left middle temporal gyrus. An analysis of anterior and posterior subdivisions of the left VWFA also failed to show any adaptation for words. We conclude that the right and the left fusiform gyri show similar patterns of adaptation for handwriting, consistent with a predominantly perceptual contribution to text processing.

Psychosocial adaptation status and health-related quality of life among older Chinese adults with visual disorders.

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Wang, Chong-Wen; Chan, Cecilia L W

2009-09-01

To examine the association of psychosocial adaptation status with vision-specific health-related quality of life (HRQOL) and the role of psychosocial adaptation in the linkage between visual impairment and vision-specific HRQOL outcomes among older adults with visual disorders. In this cross-sectional study, older urban adults with visual problems (N = 167) were interviewed using a structured questionnaire to assess their self-reported visual function, general health, psychosocial adaptation status, and vision-specific HRQOL. Performance-based measure of visual function marked by distance visual acuity was clinically conducted by ophthalmologists. It was found in the study that psychosocial adaptation status was significantly associated with vision-specific HRQOL, including the domains of mental health symptoms due to vision and dependency on others due to vision. The results also showed that psychosocial adaptation status could buffer the effect of visual impairment on vision-specific HRQOL, including the domains of social function, mental health, and dependency. Psychosocial adaptation status is significantly associated with multiple domains of vision-specific HRQOL. The findings have significant implications for health education and psychosocial intervention for older adults with age-related vision loss.

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

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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.

Monoterpenol Oxidative Metabolism: Role in Plant Adaptation and Potential Applications

Science.gov (United States)

Ilc, Tina; Parage, Claire; Boachon, Benoît; Navrot, Nicolas; Werck-Reichhart, Danièle

2016-01-01

Plants use monoterpenols as precursors for the production of functionally and structurally diverse molecules, which are key players in interactions with other organisms such as pollinators, flower visitors, herbivores, fungal, or microbial pathogens. For humans, many of these monoterpenol derivatives are economically important because of their pharmaceutical, nutraceutical, flavor, or fragrance applications. The biosynthesis of these derivatives is to a large extent catalyzed by enzymes from the cytochrome P450 superfamily. Here we review the knowledge on monoterpenol oxidative metabolism in plants with special focus on recent elucidations of oxidation steps leading to diverse linalool and geraniol derivatives. We evaluate the common features between oxidation pathways of these two monoterpenols, such as involvement of the CYP76 family, and highlight the differences. Finally, we discuss the missing steps and other open questions in the biosynthesis of oxygenated monoterpenol derivatives. PMID:27200002

Chronic insomnia in workers poisoned by inorganic mercury: psychological and adaptive aspects

Directory of Open Access Journals (Sweden)

ROSSINI SUELI REGINA G.

2000-01-01

Full Text Available Insomnia is one of the symptoms of inorganic mercury poisoning (IMP. The objective of this study is to analyze the chief psychological aspects in the adjustment of workers with chronic insomnia associated with IMP. For this purpose the Preventive Clinical Interview and the Ryad Simon Operational Adaptive Diagnostic Scale (Escala Diagnóstica Adaptativa Operacionalizada-EDAO were utilized. Fifteen subjects with mean age of 40 years (10 males and 5 females were studied. Nine were diagnosed with High Adaptive Inefficacy, five with Moderate Inefficient Adaptation and only one with Mild Inefficient Adaptation. Impairment occurred in four adaptive sectors: affective relationship, social-cultural, productivity and organic. Adaptive efficiency indicated that in all the 15 subjects studied the adaptive solutions were frustrating and led to psychic suffering and/or environmental conflict confirming the severity of the involvement in chronic IMP.

Adaptation of anaerobic cultures of E scherichia coli  K‐12 in response to environmental trimethylamine‐N‐oxide

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Denby, Katie J.; Rolfe, Matthew D.; Crick, Ellen; Sanguinetti, Guido; Poole, Robert K.

2015-01-01

Summary Systematic analyses of transcriptional and metabolic changes occurring when E scherichia coli  K‐12 switches from fermentative growth to anaerobic respiratory growth with trimethylamine‐N‐oxide (TMAO) as the terminal electron acceptor revealed: (i) the induction of torCAD, but not genes encoding alternative TMAO reductases; (ii) transient expression of frmRAB, encoding formaldehyde dehydrogenase; and (iii) downregulation of copper resistance genes. Simultaneous inference of 167 transcription factor (TF) activities implied that transcriptional re‐programming was mediated by 20 TFs, including the transient inactivation of the two‐component system ArcBA; a prediction validated by direct measurement of phosphorylated ArcA. Induction of frmRAB, detection of dimethylamine in culture medium and formaldehyde production when cell‐free extracts were incubated with TMAO suggested the presence of TMAO demethylase activity. Accordingly, the viability of an frmRAB mutant was compromised upon exposure to TMAO. Downregulation of genes involved in copper resistance could be accounted for by TMAO inhibition of Cu(II) reduction. The simplest interpretation of the data is that during adaptation to the presence of environmental TMAO, anaerobic fermentative cultures of E . coli respond by activating the TorTSR regulatory system with consequent induction of TMAO reductase activity, resulting in net oxidation of menaquinone and inhibition of Cu(II) reduction, responses that are sensed by ArcBA and CusRS respectively. PMID:25471524

Neuronal-like differentiated SH-SY5Y cells adaptation to a mild and transient H2 O2 -induced oxidative stress.

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Akki, Rachid; Siracusa, Rosalba; Morabito, Rossana; Remigante, Alessia; Campolo, Michela; Errami, Mohammed; La Spada, Giuseppina; Cuzzocrea, Salvatore; Marino, Angela

2018-03-01

Preconditioning (PC) is a cell adaptive response to oxidative stress and, with regard to neurons, can be considered as a neuroprotective strategy. The aim of the present study was to verify how neuronal-like differentiated SH-SY5Y cells adapt to a mild and transient H 2 O 2 -induced oxidative stress and, hence, whether may be considered as more sensitive cell model to study PC pathways. A first screening allowed to define H 2 O 2 concentrations for PC (10μM-50μM), applied before damage(100μM H 2 O 2 ). Cell viability measured 24 hours after 100μM H 2 O 2 -induced damage was ameliorated by 24-hour pre-exposure to low-concentration H 2 O 2 (10μM-30μM) with cell size as well restored. Markers for apoptosis (Bcl-2 and Bad), inflammation (iNOS), and redox system (MnSOD) were also determined, showing that, in cells pre-exposed to 10μM H 2 O 2 and then submitted to 100μM H 2 O 2 , Bcl-2 levels were higher, Bad and iNOS levels were lower than those observed in damaged cells, and MnSOD levels were unchanged. Such findings show that (1) neuronal-like differentiated SH-SY5Y cells are a suitable model to investigate PC response and more sensitive to the effect of a mild and transient H 2 O 2 -induced oxidative stress with respect to other neuronal cells; (2) 10μM H 2 O 2 -induced PC is mediated by apoptotic and inflammatory pathways, unlike antioxidant system; (3) such neuroprotective strategy and underlying signals proven in neuronal-like differentiated SH-SY5Y cells may contribute to understand in vivo PC mechanisms and to define a window for pharmacological intervention, namely, related to ischemic brain damage. Neuronal-like differentiated SH-SY5Y cells are a suitable model to investigate PC, an endogenous neuroprotective response to a mild and transient H 2 O 2 -induced oxidative stress, elicited by 24-hour exposure to very low H 2 O 2 concentrations and mediated by both apoptotic and inflammatory pathways. This model reflects in vivo PC mechanisms occurring

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

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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

Speech perception at positive signal-to-noise ratios using adaptive adjustment of time compression.

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Schlueter, Anne; Brand, Thomas; Lemke, Ulrike; Nitzschner, Stefan; Kollmeier, Birger; Holube, Inga

2015-11-01

Positive signal-to-noise ratios (SNRs) characterize listening situations most relevant for hearing-impaired listeners in daily life and should therefore be considered when evaluating hearing aid algorithms. For this, a speech-in-noise test was developed and evaluated, in which the background noise is presented at fixed positive SNRs and the speech rate (i.e., the time compression of the speech material) is adaptively adjusted. In total, 29 younger and 12 older normal-hearing, as well as 24 older hearing-impaired listeners took part in repeated measurements. Younger normal-hearing and older hearing-impaired listeners conducted one of two adaptive methods which differed in adaptive procedure and step size. Analysis of the measurements with regard to list length and estimation strategy for thresholds resulted in a practical method measuring the time compression for 50% recognition. This method uses time-compression adjustment and step sizes according to Versfeld and Dreschler [(2002). J. Acoust. Soc. Am. 111, 401-408], with sentence scoring, lists of 30 sentences, and a maximum likelihood method for threshold estimation. Evaluation of the procedure showed that older participants obtained higher test-retest reliability compared to younger participants. Depending on the group of listeners, one or two lists are required for training prior to data collection.

Beyond Thiamine: Treatment for Cognitive Impairment in Korsakoff's Syndrome.

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Johnson, Justin M; Fox, Valerie

2018-03-27

Wernicke's encephalopathy is a condition whose treatment many consultation-liaison psychiatrists know quite well. Less clear, however, is the treatment of its dementia disorder descendent, the Korsakoff's syndrome (KS). This article seeks to review treatment options and provide recommendations for consultation-liaison psychiatrists treating cognitive impairment in KS. In this nonsystematic review, we reviewed PubMed, CINAHL Plus, and Google Scholar for published reports and studies regarding treatment of KS. The literature revealed case reports and placebo-controlled trials of various medications for treatment of KS, though the samples sizes were small and were mostly case reports. There is more attention devoted toward medications used in other dementia disorders, such as donepezil and memantine. The literature revealed more studies around behavioral interventions recommended for treatment of memory impairment in KS and they focused on cognitive remediation and environmental adaptation, such as the use of PDAs or alarms. There is no single, well-studied intervention proven effective as a primary treatment for cognitive impairment in KS. An approach of using environmental modifications in a well-structured living environment, combined with various cognitive interventions, such as pictorial associations, and perhaps a trial of donepezil or memantine, likely represents the best strategy for treating long-term cognitive impairment in KS. Published by Elsevier Inc.

Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice.

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Zhang, Hao; Xu, Hao; Weihrauch, Dorothee; Jones, Deron W; Jing, Xigang; Shi, Yang; Gourlay, David; Oldham, Keith T; Hillery, Cheryl A; Pritchard, Kirkwood A

2013-11-01

Activated leukocytes and polymorphonuclear neutrophils (PMN) release myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated, and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To determine whether MPO impairs EC function in sickle cell disease (SCD), control (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC). SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin). KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas. Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice more than 2-fold, to ∼60% of levels in AA mice. KYC inhibited MPO-dependent 3-ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO₂Tyr) in SCD livers. These data support the hypothesis that SCD increases release of MPO, which generates oxidants that impair EC function and injure livers. Inhibiting MPO is an effective strategy for decreasing oxidative stress and liver injury and restoring EC function in SCD.

Age-Related Sensory Impairments and Risk of Cognitive Impairment

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Fischer, Mary E; Cruickshanks, Karen J.; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara EK; Klein, Ronald; Tweed, Ted S.

2016-01-01

Background/Objectives To evaluate the associations of sensory impairments with the 10-year risk of cognitive impairment. Previous work has primarily focused on the relationship between a single sensory system and cognition. Design The Epidemiology of Hearing Loss Study (EHLS) is a longitudinal, population-based study of aging in the Beaver Dam, WI community. Baseline examinations were conducted in 1993 and follow-up exams have been conducted every 5 years. Setting General community Participants EHLS members without cognitive impairment at EHLS-2 (1998–2000). There were 1,884 participants (mean age = 66.7 years) with complete EHLS-2 sensory data and follow-up information. Measurements Cognitive impairment was a Mini-Mental State Examination score of impairment was a pure-tone average of hearing thresholds (0.5, 1, 2 and 4 kHz) of > 25 decibel Hearing Level in either ear. Visual impairment was Pelli-Robson contrast sensitivity of impairment was a San Diego Odor Identification Test score of impairment were independently associated with cognitive impairment risk [Hearing: Hazard Ratio (HR) = 1.90, 95% Confidence Interval (C.I.) = 1.11, 3.26; Vision: HR = 2.05, 95% C.I. = 1.24, 3.38; Olfaction: HR = 3.92, 95% C.I. = 2.45, 6.26]. However, 85% with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. Conclusion The relationship between sensory impairment and cognitive impairment was not unique to one sensory system suggesting sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. PMID:27611845

Text and images: relations in illustrated book for children with visual impairment

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Tássia Ruiz

2014-12-01

Full Text Available Exploratory, the paper presents and discusses the response of children with visual impairment on the illustrated children’s book, analyzing how to establish relationships and dialogue between text and image support in the book from the perspective of non- visual , mainly in concerns the cognitive feature and the specific conditions of visual impairment . This study is justified by the importance that access to different languages ( image and text , added to the literary function of fictional narrative can provide the Bantam player, as well as access to imaging and its meaning to the reader , there is still the possibility include children with visual impairment in the literary universe in a field whose intricate set of languages provides the reader with a multiplicity of meanings that can take children’s reader to find new ways to relate to the world . The method used here , interview - conversation ( SARAMAGO , 2001 , questions blind and low vision between 10 and 14 years Londrinense Institute of Education and Work for the Blind of Londrina / PR on the relationship between image and text children during reading two illustrated works adapted : forgotten Adelia Adelia and dreamy, both selected by the diversity of graphical features ( smooth textures , flocked , granular , etc. used in the translation of images for relief . The aim is to compare two aspects equivalences and differences between reading narratives that rely on graphics to convey its essential message and that can easily be understood only by the text in order to verify that an integration or fragmentation of languages that exist on integrating image text - in the context of visual impairment . Results indicate that the experience of reading is complexed in each book , unique to each turn of the page and predominantly verbal. However, typologies act as effective parameter for understanding the various relationships between image and text observed during the interview and awaken

Impairment of probabilistic reward-based learning in schizophrenia.

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Weiler, Julia A; Bellebaum, Christian; Brüne, Martin; Juckel, Georg; Daum, Irene

2009-09-01

Recent models assume that some symptoms of schizophrenia originate from defective reward processing mechanisms. Understanding the precise nature of reward-based learning impairments might thus make an important contribution to the understanding of schizophrenia and the development of treatment strategies. The present study investigated several features of probabilistic reward-based stimulus association learning, namely the acquisition of initial contingencies, reversal learning, generalization abilities, and the effects of reward magnitude. Compared to healthy controls, individuals with schizophrenia exhibited attenuated overall performance during acquisition, whereas learning rates across blocks were similar to the rates of controls. On the group level, persons with schizophrenia were, however, unable to learn the reversal of the initial reward contingencies. Exploratory analysis of only the subgroup of individuals with schizophrenia who showed significant learning during acquisition yielded deficits in reversal learning with low reward magnitudes only. There was further evidence of a mild generalization impairment of the persons with schizophrenia in an acquired equivalence task. In summary, although there was evidence of intact basic processing of reward magnitudes, individuals with schizophrenia were impaired at using this feedback for the adaptive guidance of behavior.

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

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Tokiko Ishida

Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

Hot Water Bathing Impairs Training Adaptation in Elite Teen Archers.

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Hung, Ta-Cheng; Liao, Yi-Hung; Tsai, Yung-Shen; Ferguson-Stegall, Lisa; Kuo, Chia-Hua; Chen, Chung-Yu

2018-04-30

Despite heat imposes considerable physiological stress to human body, hot water immersion remains as a popular relaxation modality for athletes. Here we examined the lingering effect of hot tub relaxation after training on performance-associated measures and dehydroepiandrosterone sulfate (DHEA-S) in junior archers. Ten national level archers, aged 16.6 ± 0.3 years (M = 8, F = 2), participated in a randomized counter-balanced crossover study after baseline measurements. In particular, half participants were assigned to the hot water immersion (HOT) group, whereas another halves were assigned to the untreated control (CON) group. Crossover trial was conducted following a 2-week washout period. During the HOT trial, participants immersed in hot water for 30 min at 40°C, 1 h after training, twice a week (every 3 days) for 2 weeks. Participants during CON trial sat at the same environment without hot water after training. Performance-associated measures and salivary DHEA-S were determined 3 days after the last HOT session. We found that the HOT intervention significantly decreased shooting performance (CON: -4%; HOT: -22%, P HOT: -16%, P HOT: -60%, P < 0.05) of archers, compared with untreated CON trial. No group differences were found in motor unit recruitment (root mean square electromyography, RMS EMG) of arm muscles during aiming, autonomic nervous activity (sympathetic and vagal powers of heart rate variability, HRV), and plasma cortisol levels after treatments. Our data suggest that physiological adaptation against heat exposure takes away the sources needed for normal training adaptation specific to shooting performance in archers.

The Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment

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Youhua Xu

2017-04-01

Full Text Available Progressive cognitive dysfunction is a central characteristic of diabetic encephalopathy (DE. With an aging population, the incidence of DE is rising and it has become a major threat that seriously affects public health. Studies within this decade have indicated the important role of risk factors such as oxidative stress and inflammation on the development of cognitive impairment. With the recognition of the two-way communication between gut and brain, recent investigation suggests that “microbiota-gut-brain axis” also plays a pivotal role in modulating both cognition function and endocrine stability. This review aims to systemically elucidate the underlying impact of diabetes on cognitive impairment.

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....

Behavioral training promotes multiple adaptive processes following acute hearing loss.

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Keating, Peter; Rosenior-Patten, Onayomi; Dahmen, Johannes C; Bell, Olivia; King, Andrew J

2016-03-23

The brain possesses a remarkable capacity to compensate for changes in inputs resulting from a range of sensory impairments. Developmental studies of sound localization have shown that adaptation to asymmetric hearing loss can be achieved either by reinterpreting altered spatial cues or by relying more on those cues that remain intact. Adaptation to monaural deprivation in adulthood is also possible, but appears to lack such flexibility. Here we show, however, that appropriate behavioral training enables monaurally-deprived adult humans to exploit both of these adaptive processes. Moreover, cortical recordings in ferrets reared with asymmetric hearing loss suggest that these forms of plasticity have distinct neural substrates. An ability to adapt to asymmetric hearing loss using multiple adaptive processes is therefore shared by different species and may persist throughout the lifespan. This highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders.

Skeletal muscle neuronal nitric oxide synthase micro protein is reduced in people with impaired glucose homeostasis and is not normalized by exercise training.

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Bradley, Scott J; Kingwell, Bronwyn A; Canny, Benedict J; McConell, Glenn K

2007-10-01

Skeletal muscle inducible nitric oxide synthase (NOS) protein is greatly elevated in people with type 2 diabetes mellitus, whereas endothelial NOS is at normal levels. Diabetic rat studies suggest that skeletal muscle neuronal NOS (nNOS) micro protein expression may be reduced in human insulin resistance. The aim of this study was to determine whether skeletal muscle nNOSmicro protein expression is reduced in people with impaired glucose homeostasis and whether exercise training increases nNOSmicro protein expression in these individuals because exercise training increases skeletal muscle nNOSmicro protein in rats. Seven people with type 2 diabetes mellitus or prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and 7 matched (sex, age, fitness, body mass index, blood pressure, lipid profile) healthy controls aged 36 to 60 years participated in this study. Vastus lateralis muscle biopsies for nNOSmicro protein determination were obtained, aerobic fitness was measured (peak pulmonary oxygen uptake [Vo(2) peak]), and glucose tolerance and insulin homeostasis were assessed before and after 1 and 4 weeks of cycling exercise training (60% Vo(2) peak, 50 minutes x 5 d wk(-1)). Skeletal muscle nNOSmicro protein was significantly lower (by 32%) in subjects with type 2 diabetes mellitus or prediabetes compared with that in controls before training (17.7 +/- 1.2 vs 26.2 +/- 3.4 arbitrary units, P glucose homeostasis have reduced skeletal muscle nNOSmicro protein content. However, because exercise training improves insulin sensitivity without influencing skeletal muscle nNOSmicro protein expression, it seems that changes in skeletal muscle nNOSmicro protein are not central to the control of insulin sensitivity in humans and therefore may be a consequence rather than a cause of diabetes.

Enzyme-treated Asparagus officinalis extract shows neuroprotective effects and attenuates cognitive impairment in senescence-accelerated mice.

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Sakurai, Takuya; Ito, Tomohiro; Wakame, Koji; Kitadate, Kentaro; Arai, Takashi; Ogasawara, Junetsu; Kizaki, Takako; Sato, Shogo; Ishibashi, Yoshinaga; Fujiwara, Tomonori; Akagawa, Kimio; Ishida, Hitoshi; Ohno, Hideki

2014-01-01

Increases in the number of patients with dementia involving Alzheimer's disease (AD) are seen as a grave public health problem. In neurodegenerative disorders involving AD, biological stresses, such as oxidative and inflammatory stress, induce neural cell damage. Asparagus (Asparagus officinalis) is a popular vegetable, and an extract prepared from this reportedly possesses various beneficial biological activities. In the present study, we investigated the effects of enzyme-treated asparagus extract (ETAS) on neuronal cells and early cognitive impairment of senescence-accelerated mouse prone 8 (SAMP8) mice. The expression of mRNAs for factors that exert cytoprotective and anti-apoptotic functions, such as heat-shock protein 70 and heme oxygenase-1, was upregulated in NG108-15 neuronal cells by treatment with ETAS. Moreover, when release of lactate dehydrogenase from damaged NG108-15 cells was increased for cells cultured in medium containing either the nitric oxide donor sodium nitroprusside or the hypoxia mimic reagent cobalt chloride, ETAS significantly attenuated this cell damage. Also, when contextual fear memory, which is considered to be a hippocampus-dependent memory, was significantly impaired in SAMP8 mice, ETAS attenuated the cognitive impairment. These results suggest that ETAS produces cytoprotective effects in neuronal cells and attenuates the effects on the cognitive impairment of SAMP8 mice.

Sleep deprivation specifically impairs short-term olfactory memory in Drosophila.

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Li, Xinjian; Yu, Feng; Guo, Aike

2009-11-01

Sleep is crucial to memory consolidation in humans and other animals; however, the effect of insufficient sleep on subsequent learning and memory remains largely elusive. Learning and memory after 1-day sleep deprivation (slpD) was evaluated using Pavlovian olfactory conditioning in Drosophila, and locomotor activity was measured using the Drosophila Activity Monitoring System in a 12:12 light-dark cycle. We found that slpD specifically impaired 1-h memory in wild type Canton-S flies, and this effect could persist for at least 2 h. However, alternative stresses (heat stress, oxidative stress, starvation, and rotation stress) did not result in a similar effect and left the flies' memory intact. Mechanistic studies demonstrated that flies with either silenced transmission of the mushroom body (MB) during slpD or down-regulated cAMP levels in the MB demonstrated no slpD-induced 1-h memory impairment. We found that slpD specifically impaired 1-h memory in Drosophila, and either silencing of MB transmission during slpD or down-regulation of the cAMP level in the MB protected the flies from slpD-induced impairment.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes.

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Christie, Joshua R; Beekman, Madeleine

2017-03-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes-specifically their organization into host cells and their uniparental (maternal) inheritance-enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller's ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes-despite their asexual mode of reproduction-can readily undergo adaptive evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

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).

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. Copyright © 2012 Elsevier Inc. All rights reserved.

Impaired intuition in patients with major depressive disorder.

Science.gov (United States)

Remmers, Carina; Topolinski, Sascha; Dietrich, Detlef E; Michalak, Johannes

2015-06-01

In daily life, many decisions of minor and major importance have to be made. Thereby, intuitive judgments serve as useful guides and help us to adapt to our environment. People with major depressive disorder (MDD) often have difficulties to come to decisions. Is their intuition impaired? Since this question has not been addressed until now, the present study explored intuition in MDD. Depressed patients (n = 29) and healthy control participants (n = 27) completed the Judgment of Semantic Coherence Task, a well-established paradigm used in basic cognitive research to measure intuition. Furthermore, participants' severity of depressive symptoms (BDI-II), negative affect (PANAS), and rumination (RSQ) were assessed. All participants were interviewed with the SCID. Depressed patients showed impaired intuition compared to healthy control participants. In the depressed sample, negative affect accounts for the association between rumination and impaired intuition. Results further reveal that negative affect overall mediates the depression-intuition relationship. Patients with diminished ability to concentrate or indecisiveness had lower intuition indices compared to patients who did not fulfil this diagnostic criterion of MDD. The study introduces the phenomenon of intuition into depression research. Additionally, these results extent findings from basic research showing that induced negative mood as well difficulties to down-regulate negative affect impair intuitive coherence judgments. Current results indicate that the negative affectivity of patients is the crucial mediator in the association between depression and impaired intuition. Limitations of the study as well as the potential etiological role of intuition in MDD are discussed. The finding that intuition is impaired in depressed patients extends our knowledge as to the cognitive profile of patients with MDD. Patients who suffer from indecisiveness have lower intuition indices compared to patients who do not

The age- and sex-specific decline of the 20s proteasome and the Nrf2/CncC signal transduction pathway in adaption and resistance to oxidative stress in Drosophila melanogaster.

Science.gov (United States)

Pomatto, Laura C D; Wong, Sarah; Carney, Caroline; Shen, Brenda; Tower, John; Davies, Kelvin J A

2017-04-01

Hallmarks of aging include loss of protein homeostasis and dysregulation of stress-adaptive pathways. Loss of adaptive homeostasis, increases accumulation of DNA, protein, and lipid damage. During acute stress, the Cnc-C ( Drosophila Nrf2 orthologue) transcriptionally-regulated 20S proteasome degrades damaged proteins in an ATP-independent manner. Exposure to very low, non-toxic, signaling concentrations of the redox-signaling agent hydrogen peroxide (H 2 O 2 ) cause adaptive increases in the de novo expression and proteolytic activity/capacity of the 20S proteasome in female D. melanogaster (fruit-flies). Female 20S proteasome induction was accompanied by increased tolerance to a subsequent normally toxic but sub-lethal amount of H 2 O 2 , and blocking adaptive increases in proteasome expression also prevented full adaptation. We find, however, that this adaptive response is both sex- and age-dependent. Both increased proteasome expression and activity, and increased oxidative-stress resistance, in female flies, were lost with age. In contrast, male flies exhibited no H 2 O 2 adaptation, irrespective of age. Furthermore, aging caused a generalized increase in basal 20S proteasome expression, but proteolytic activity and adaptation were both compromised. Finally, continual knockdown of Keep1 (the cytosolic inhibitor of Cnc-C) in adults resulted in older flies with greater stress resistance than their age-matched controls, but who still exhibited an age-associated loss of adaptive homeostasis.

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

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

International Nuclear Information System (INIS)

Muhsain, Siti Nur Fadzilah; Lang, Matti A.; Abu-Bakar, A'edah

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

Risk behaviors and sexual abuse among men and woman with visual or hearing impairments

Directory of Open Access Journals (Sweden)

Silvia Susana Robles Montijo

2017-06-01

Full Text Available The present study proposed a descriptive analysis of sociodemographic and family variables, as well as risky sexual behaviors and sexual abuse in a sample of young Mexicans with hearing or visual impairments, examining differences based on gender and type of disability of the participants. 128 young persons (64 hearing impaired and 64 visually impaired of whom, 53.2% were male and 86.6% were single, were included in the study. The instruments used were adapted linguistically to be answered by young people with hearing disabilities, and translated into Braille for visually impaired young people. The results show that participants maintain an active sex life with a risk profile that is characterized by the early onset of sexual intercourse, lack of planning their first sexual encounter, underuse of condoms and victimization of some form of sexual abuse. The risk was higher in women and among those with visual disabilities.

ADHD and Adaptability: The Roles of Cognitive, Behavioural, and Emotional Regulation

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Burns, Emma; Martin, Andrew J.

2014-01-01

Adaptability has been recently proposed as cognitive, behavioural, and emotional regulation assisting individuals to effectively respond to change, uncertainty and novelty. Given students with attention-deficit/hyperactivity disorder (ADHD) have known impairments with regulatory functions, they may be at particular disadvantage as they seek to…

Gender, depression and physical impairment: an epidemiologic perspective from Aleppo, Syria

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Rastam, Samer; Ward, Kenneth D.; Maziak, Wasim

2010-01-01

Objective Examine the association of physical impairment with gender, depression, and socio-demographics in the community in Aleppo, Syria. Method We conducted a cross-sectional, population-based study in Aleppo on adults aged 18–65 (N = 2,038). We used a computerized interviewer-administered structured questionnaire. Physical impairment was measured via an adapted 12-item World Health Organization, Health State Description Individual Questionnaire which includes both physical and emotional items. We used physical impairment items score to classify individuals into low, middle, and high physical impairment category. Self-report of physician-diagnosed depression and chronic diseases active in the past year and their current treatment status were obtained. Results Sample mean age (SD) was 35.3 (12.1) years, 55% were female, and 4.5% had depression. Female gender, low socioeconomic status (SES), and depression were associated with high physical impairment. Women had more impairment (OR = 3.35, 95% CI: 2.15–5.21) with little change after controlling for depression and chronic diseases, but significantly decreased after controlling for socio-demographics (OR = 1.51, 95% CI: 0.84–2.73). The association with low (vs. high) SES was prominent (OR = 2.48, 95% CI: 1.32–4.67) after controlling for all variables. Depression’s association (OR = 4.85, 95% CI: 1.93–12.15) lost significance after controlling for chronic diseases (OR = 2.81, 95% CI: 0.96–8.25), but further adjustment for socio-demographics had little effect. Conclusion Women and individuals of low SES appear more vulnerable to physical impairment in the community in Aleppo. Depression’s association with physical impairment may be mediated through co-existing chronic diseases. Public health planning regarding physical impairment in Syria should encompass these as putative risk factors. PMID:20195569

Individualized evaluation of cholinesterase inhibitors effects in dementia with adaptive cognitive testing

NARCIS (Netherlands)

Wouters, Hans; van Campen, Jos P. C. M.; Appels, Bregje A.; Beijnen, Jos H.; Zwinderman, Aeilko H.; van Gool, Willem A.; Schmand, Ben

2016-01-01

Computerized Adaptive Testing (CAT) of cognitive function, selects for every individual patient, only items of appropriate difficulty to estimate his or her level of cognitive impairment. Therefore, CAT has the potential to combine brevity with precision. We retrospectively examined the evaluation

Individualized evaluation of cholinesterase inhibitors effects in dementia with adaptive cognitive testing

NARCIS (Netherlands)

Wouters, Hans; Van Campen, Jos P C M; Appels, Bregje A; Beijnen, Jos H; Zwinderman, Aeilko H; Van Gool, Willem A; Schmand, Ben

2015-01-01

Computerized Adaptive Testing (CAT) of cognitive function, selects for every individual patient, only items of appropriate difficulty to estimate his or her level of cognitive impairment. Therefore, CAT has the potential to combine brevity with precision. We retrospectively examined the evaluation

Individualized evaluation of cholinesterase inhibitors effects in dementia with adaptive cognitive testing

NARCIS (Netherlands)

Wouters, H.; van Campen, J.P.C.M.; Appels, B.A.; Beijnen, J.H.; Zwinderman, A.H.; van Gool, W.A.; Schmand, B.

Computerized Adaptive Testing (CAT) of cognitive function, selects for every individual patient, only items of appropriate difficulty to estimate his or her level of cognitive impairment. Therefore, CAT has the potential to combine brevity with precision. We retrospectively examined the evaluation

Forecasting Sensorimotor Adaptability from Baseline Inter-Trial Correlations

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Beaton, K. H.; Bloomberg, J. J.

2016-01-01

One of the greatest challenges for sensorimotor adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. This information could guide individually customized countermeasures, which would enable more efficient use of crew time and provide better outcomes. The principal aim of this work is to look for baseline performance metrics that relate to locomotor adaptability. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations ("noise") in motor performance, as a predictor of individual adaptive capabilities.

Brain imaging for oxidative stress and mitochondrial dysfunction in neurodegenerative diseases

International Nuclear Information System (INIS)

Okazawa, H.; Tsujikawa, T.; Kiyono, Y.; Ikawa, M.; Yoneda, M.

2014-01-01

Oxidative stress, one of the most probable molecular mechanisms for neuronal impairment, is reported to occur in the affected brain regions of various neurodegenerative diseases. Recently, many studies showed evidence of a link between oxidative stress or mitochondrial damage and neuronal degeneration. Basic in vitro experiments and postmortem studies demonstrated that biomarkers for oxidative damage can be observed in the pathogenic regions of the brain and the affected neurons. Model animal studies also showed oxidative damage associated with neuronal degeneration. The molecular imaging method with positron emission tomography (PET) is expected to delineate oxidatively stressed microenvironments to elucidate pathophysiological changes of the in vivo brain; however, only a few studies have successfully demonstrated enhanced stress in patients. Radioisotope copper labeled diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) may be the most promising candidate for this oxidative stress imaging. The tracer is usually known as a hypoxic tissue imaging PET probe, but the accumulation mechanism is based on the electron rich environment induced by mitochondrial impairment and/or microsomal over-reduction, and thus it is considered to represent the oxidative stress state correlated with the degree of disease severity. In this review, Cu-ATSM PET is introduced in detail from the basics to practical methods in clinical studies, as well as recent clinical studies on cerebrovascular diseases and neurodegenerative diseases. Several other PET probes are also introduced from the point of view of neuronal oxidative stress imaging. These molecular imaging methods should be promising tools to reveal oxidative injuries in various brain diseases

Pharmacokinetics and Safety of Momelotinib in Subjects With Hepatic or Renal Impairment.

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Xin, Yan; Kawashima, Jun; Weng, Winnie; Kwan, Ellen; Tarnowski, Thomas; Silverman, Jeffrey A

2018-04-01

Momelotinib is a Janus kinase 1/2 inhibitor in clinical development for the treatment of myelofibrosis. Two phase 1 open-label, parallel-group, adaptive studies were conducted to evaluate the pharmacokinetics of a single 200-mg oral dose of momelotinib in subjects with hepatic or renal impairment compared with healthy matched control subjects with normal hepatic or renal function. Plasma pharmacokinetics of momelotinib and its major active metabolite, M21, were evaluated, and geometric least-squares mean ratios (GMRs) and associated 90% confidence intervals (CIs) for impaired versus each control group were calculated for plasma exposures (area under concentration-time curve from time 0 to ∞ [AUC ∞ ] and maximum concentration) of momelotinib and M21. There was no clinically significant difference in plasma exposures of momelotinib and M21 between subjects with moderate or severe renal impairment or moderate hepatic impairment and healthy control subjects. Compared with healthy control subjects, momelotinib AUC ∞ was increased (GMR, 197%; 90%CI, 129%-301%), and M21 AUC ∞ was decreased (GMR, 52%; 90%CI, 34%-79%) in subjects with severe hepatic impairment. The safety profile following a single dose of momelotinib was similar between subjects with hepatic or renal dysfunction and healthy control subjects. These pharmacokinetic and safety results indicate that dose adjustment is not necessary for momelotinib in patients with renal impairment or mild to moderate hepatic impairment. In patients with severe hepatic impairment, however, the dose of momelotinib should be reduced. © 2017, The American College of Clinical Pharmacology.

Both oophorectomy and obesity impaired solely hippocampal-dependent memory via increased hippocampal dysfunction.

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Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2018-04-17

Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.

Erectile dysfunction and diabetes: Association with the impairment of lipid metabolism and oxidative stress.

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Belba, Arben; Cortelazzo, Alessio; Andrea, Giansanti; Durante, Jacopo; Nigi, Laura; Dotta, Francesco; Timperio, Anna Maria; Zolla, Lello; Leoncini, Roberto; Guerranti, Roberto; Ponchietti, Roberto

2016-01-01

To test the hypothesis that exists an association of non-diabetic and diabetic patients suffering from erectile dysfunction (ED) with lipid metabolism and oxidative stress. Clinical and laboratory characteristics in non-diabetic (n = 30, middle age range: 41–55.5 years; n = 25, old age range: 55.5–73), diabetic ED patients (n = 30, age range: 55.5–75 years) and diabetic patients (n = 25, age range: 56–73.25), were investigated. Proteomic analysis was performed to identify differentially expressed plasma proteins and to evaluate their oxidative posttranslational modifications. A decreased level of high-density lipoproteins in all ED patients (P < 0.001, C.I. 0.046–0.10), was detected by routine laboratory tests. Proteomic analysis showed a significant decreased expression (P < 0.05) of 5 apolipoproteins (i.e. apolipoprotein H, apolipoprotein A4, apolipoprotein J, apolipoprotein E and apolipoprotein A1) and zinc-alpha-2-glycoprotein, 50% of which are more oxidized proteins. Exclusively for diabetic ED patients, oxidative posttranslational modifications for prealbumin, serum albumin, serum transferrin and haptoglobin markedly increased. Showing evidence for decreased expression of apolipoproteins in ED and the remarkable enhancement of oxidative posttranslational modifications in diabetes-associated ED, considering type 2 diabetes mellitus and age as independent risk factors involved in the ED pathogenesis, lipid metabolism and oxidative stress appear to exert a complex interplay in the disease.

[Disabled workers with motor impairments: data from an occupational health service].

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Schnitzler, A; D'Apolito, A C; Roche, N; Genêt, F; Ameille, J; Azouvi, P

2006-04-01

Mediclen is an occupational health service in charge of following-up 36,736 workers (divided among 1770 companies) in 3 cities of an area near Paris. The employment rate of disabled people among the French population is not well known (rough estimate 4.4%), and few studies have reported on the situation of workers with a motor impairment. The recent computerization of medical records allowed us to identify 195 workers considered disabled by the French administration (i.e. 0.55% of the 36,736 workers followed up in 2002). Among these, 26 had a motor impairment. Twenty-one neurological disabilities were central and 5 were peripheral or neuromuscular. The workers were 44-years-old. Only two workers had a severe handicap. Companies had to adapt workstations for half of the workers, with the advice of neurologists (7 of 10 advice given) and once a physical medicine doctor. The integration of people with motor impairments into the world of work is rare and difficult. This practical experience showed the difficulties people with motor impairment face. Close collaboration of physical medicine services with occupational health services is necessary to improve the integration of this population into the world of work.

"I do like the activities which I can do…" Leisure participation experiences of children with movement impairments.

Science.gov (United States)

Kanagasabai, Parimala S; Mulligan, Hilda; Hale, Leigh A; Mirfin-Veitch, Brigit

2018-07-01

To explore in depth the leisure participation experiences of children with movement impairments. We used Interpretative Phenomenological Analysis approach to interpret and understand the experiences of 22 children with movement impairments, aged between 6 and 12 years. Children expressed their views through flexible child-centred methods of data collection that allowed the children to draw, paint, use stickers, and demonstrate their leisure activities and equipment while communicating about their experiences. Children participated in leisure activities of their choice, and expressed positive experience of fun, challenge, independence and achievement. The choice of activities depended on a combination of the motor functioning of the individual child, inspiration and support from families, friends and health professionals, as well as the possibility of adaptations and availability of community programmes. At times children felt disappointed and avoided some activities due to associated negative experience such as injury, fear, non-inclusion and the difficulty they had experienced in adapting and performing certain activities. Families, therapists and community service providers such as disability organisations could enhance leisure participation experiences by suggesting and creating opportunities that could increase children's choices of leisure activities. Implications for rehabilitation Children's choice of activities, places and friends is important for positive experiences of fun, achievement, challenge, independence and motivation in leisure participation. Families and health professionals could assist children make appropriate choices for leisure activities that depends on factors such as motor abilities, adaptations and availability of activities in the community. In the community, widening the options for leisure activities such as non-competitive adaptive sports and indoor sports for children with variable levels of movement impairment could improve

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.

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Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

2014-01-01

The aging brain undergoes 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 (per)oxidation 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 portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and 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.

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

Science.gov (United States)

Ahmad, Mir Kaisar; Mahmood, Riaz

2016-03-01

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

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

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Heike Kotarsky

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

Streptococcus agalactiae impairs cerebral bioenergetics in experimentally infected silver catfish.

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Baldissera, Matheus D; Souza, Carine F; Parmeggiani, Belisa S; Santos, Roberto C V; Leipnitz, Guilhian; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Baldisserotto, Bernardo

2017-10-01

It is becoming evident that bacterial infectious diseases affect brain energy metabolism, where alterations of enzymatic complexes of the mitochondrial respiratory chain and creatine kinase (CK) lead to an impairment of cerebral bioenergetics which contribute to disease pathogenesis in the central nervous system (CNS). Based on this evidence, the aim of this study was to evaluate whether alterations in the activity of complex IV of the respiratory chain and CK contribute to impairment of cerebral bioenergetics during Streptococcus agalactiae infection in silver catfish (Rhamdia quelen). The activity of complex IV of the respiratory chain in brain increased, while the CK activity decreased in infected animals compared to uninfected animals. Brain histopathology revealed inflammatory demyelination, gliosis of the brain and intercellular edema in infected animals. Based on this evidence, S. agalactiae infection causes an impairment in cerebral bioenergetics through the augmentation of complex IV activity, which may be considered an adaptive response to maintain proper functioning of the electron respiratory chain, as well as to ensure ongoing electron flow through the electron transport chain. Moreover, inhibition of cerebral CK activity contributes to lower availability of ATP, contributing to impairment of cerebral energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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Bonanato Karina

2013-01-01

Full Text Available 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 examination for malocclusion was carried out in people with DS by two calibrated examiners. Inter and Intra examiner agreement was assessed by Intraclass Correlation Coefficient (ICC and ranged from 0.92 to 0.97 respectively. Total of 157 people with DS and their caregivers were able to compose the sample. They were selected from eight institutions for people with DS in five cities of southeastern Brazil. The mean age of people with DS was 20.7 [±13.1] and for caregivers was 53.1 [±13.7]. The mean instrument score was 18.6 [±9.0]. Internal reliability ranged from 0.49 to 0.80 and external reliability ranged from 0.78 to 0.88. Construct validity was verified by significant correlations identified between malocclusion and the total instrument; and caregivers’ educational level and the instrument (p Conclusions Initial validity tests indicated that the instrument related to the oral health for people with DS may be a valid instrument to this segment of the population in Brazil.

Social, occupational and cultural adaptation in Antarctica

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Nicolas, Michel; Bishop, Sheryl; Weiss, Karine; Gaudino, Marvin

2016-07-01

Life in isolated and confined environments (ICEs, e.g., polar stations, submarine or space missions), is subject to important constraints which can generate psychosociological impaired outcomes. This study investigated psychological, social, occupational and cultural variables which are among the most important determinants in adaptation to a one-year wintering in Antarctica with 13 international participants. Our findings confirm and give further insight into the role of social (Cohesiveness, Social Support) and occupational (Implementation / Preparedness, Counterproductive Activity, Decision Latitude and Psychological Job Demands) dimensions of adaptation to ICE environments. Relationships between various social and occupational dimensions studies reflected detrimental effects ranging from decrements in cohesiveness, social support and work performance which differed across professional status and multicultural factors. These psychosocial issues have important implications for pre-mission selection and training, monitoring and support of crews during the mission and post-mission readaptation. Operational recommendations are suggested to improve adaptation, success and well-being for long-term ICE missions, e.g., to Mars and beyond.

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

Science.gov (United States)

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

2009-01-01

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

Oxidative proteome alterations during skeletal muscle ageing

Directory of Open Access Journals (Sweden)

Sofia Lourenço dos Santos

2015-08-01

Full Text Available Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the ‘oxi-proteome’ or ‘carbonylome’, have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.

Neuropsychological Impairment in Detoxified Alcohol-Dependent Subjects with Preserved Psychosocial Functioning

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Catherine Martelli

2017-09-01

Full Text Available BackgroundChronic alcoholism and its related cognitive impairments are associated with increased social, relational, and professional deficits which have a variable overall impact on social integration. These impairments are known to have varying severities and have rarely been studied among healthy alcohol-dependent subjects with preserved psychosocial functioning. Thus, the objective of this study is to describe neuropsychological performance in this particular population.MethodTwenty-nine socially adjusted alcohol-dependent men, hospitalized for a first or second withdrawal and abstinent for 3 weeks minimum, were compared to 29 healthy non-alcoholic controls. All subjects underwent clinical and psychiatric examination, neuropsychological tests of memory (M, working memory (WM, and executive functions (EF. Comparisons were performed using Student’s t-tests or Mann–Whitney U tests.ResultsNo group differences were found on the Self-Reported Social Adjustment Scale (SAS-SR or in the Mini-Mental State Examination. Compared to controls, patients had greater episodic, spatial, and WM deficits as well as slightly altered executive functions. In contrast, their executive functions (spontaneous flexibility, criteria generation, rule maintenance, and inhibitory control were relatively preserved.ConclusionOur sample of socially and professionally integrated alcoholic patients shows fewer cognitive deficits than described in previous studies. Our results suggest that early on, alcohol-dependent subjects develop compensatory adaptation processes to preserve social function and adaptation. Minor cognitive impairments should be screened early in the disease to integrate cognitive interventions into the health-care plan to thus eventually prevent further socio-professional marginalization.

Autistic symptomatology and language ability in autism spectrum disorder and specific language impairment.

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Loucas, Tom; Charman, Tony; Pickles, Andrew; Simonoff, Emily; Chandler, Susie; Meldrum, David; Baird, Gillian

2008-11-01

Autism spectrum disorders (ASD) and specific language impairment (SLI) are common developmental disorders characterised by deficits in language and communication. The nature of the relationship between them continues to be a matter of debate. This study investigates whether the co-occurrence of ASD and language impairment is associated with differences in severity or pattern of autistic symptomatology or language profile. Participants (N = 97) were drawn from a total population cohort of 56,946 screened as part of study to ascertain the prevalence of ASD, aged 9 to 14 years. All children received an ICD-10 clinical diagnosis of ASD or No ASD. Children with nonverbal IQ > or =80 were divided into those with a language impairment (language score of 77 or less) and those without, creating three groups: children with ASD and a language impairment (ALI; N = 41), those with ASD and but no language impairment (ANL; N = 31) and those with language impairment but no ASD (SLI; N = 25). Children with ALI did not show more current autistic symptoms than those with ANL. Children with SLI were well below the threshold for ASD. Their social adaptation was higher than the ASD groups, but still nearly 2 SD below average. In ALI the combination of ASD and language impairment was associated with weaker functional communication and more severe receptive language difficulties than those found in SLI. Receptive and expressive language were equally impaired in ALI, whereas in SLI receptive language was stronger than expressive. Co-occurrence of ASD and language impairment is not associated with increased current autistic symptomatology but appears to be associated with greater impairment in receptive language and functional communication.

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

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

2015-07-01

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

Coping Strategies and Adaptation of Mothers of Children with Handicapping Conditions.

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Hooshyar, Nahid T.

Mothers' coping mechanisms and adaptations to having a handicapped child were analyzed through extensive structured interviews with mothers of eight preschool-aged Down syndrome children and a language impaired child. Three illustrative case studies are presented, and general conclusions are drawn. Mothers of Down syndrome children go through the…

Feasibility of the adaptive and automatic presentation of tasks (ADAPT system for rehabilitation of upper extremity function post-stroke

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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

THE DEVELOPMENT OF SCIENCE LEARNING MODULE FOR CHILDRENT WITH HEARING IMPAIRMENT

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Ahmad Marzuqi

2017-02-01

Full Text Available There are the absence of teaching materials in accordance with the characteristics and conditions of a hearing impairment children in terms of learning, especially science subjects. The characteristics of hearing impairment children is poor in their vocabularies, so that, the teaching materials emphasizing the visual aspect is necessary. This study used a Research and Development (R & D adapted by the Sugiyono model in order to produce teaching materials in the form of pictorial modules and to test their effectiveness. The result of the research showed that it was a very valid criteria with a score of 97% of the materials experts, 85% of media experts, and 93% of skilled practitioners. The score of the effectiveness of the modules was 75% with the effective criteria.

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

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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)

Role of NAD, Oxidative Stress, and Tryptophan Metabolism in Autism Spectrum Disorders

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Musthafa Mohamed Essa

2013-01-01

Full Text Available Autism spectrum disorder (ASD is a pervasive neuro-developmental disorder characterized by impaired social interaction, reduced/absent verbal and non-verbal communication, and repetitive behavior during early childhood. The etiology of this developmental disorder is poorly understood, and no biomarkers have been identified. Identification of novel biochemical markers related to autism would be advantageous for earlier clinical diagnosis and intervention. Studies suggest that oxidative stress-induced mechanisms and reduced antioxidant defense, mitochondrial dysfunction, and impaired energy metabolism (NAD + , NADH, ATP, pyruvate, and lactate, are major causes of ASD. This review provides renewed insight regarding current autism research related to oxidative stress, mitochondrial dysfunction, and altered tryptophan metabolism in ASD.

Noradrenergic Stimulation Impairs Memory Generalization in Women.

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Kluen, Lisa Marieke; Agorastos, Agorastos; Wiedemann, Klaus; Schwabe, Lars

2017-07-01

Memory generalization is essential for adaptive decision-making and action. Our ability to generalize across past experiences relies on medial-temporal lobe structures, known to be highly sensitive to stress. Recent evidence suggests that stressful events may indeed interfere with memory generalization. Yet, the mechanisms involved in this generalization impairment are unknown. We tested here whether a pharmacological elevation of major stress mediators-noradrenaline and glucocorticoids-is sufficient to disrupt memory generalization. In a double-blind, placebo-controlled design, healthy men and women received orally a placebo, hydrocortisone, the α2-adrenoceptor antagonist yohimbine that leads to increased noradrenergic stimulation, or both drugs, before they completed an associative learning task probing memory generalization. Drugs left learning performance intact. Yohimbine, however, led to a striking generalization impairment in women, but not in men. Hydrocortisone, in turn, had no effect on memory generalization, neither in men nor in women. The present findings indicate that increased noradrenergic activity, but not cortisol, is sufficient to disrupt memory generalization in a sex-specific manner, with relevant implications for stress-related mental disorders characterized by generalization deficits.

Intermittent Hypoxia Impairs Glucose Homeostasis in C57BL6/J Mice: Partial Improvement with Cessation of the Exposure

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Polak, Jan; Shimoda, Larissa A.; Drager, Luciano F.; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y.; Punjabi, Naresh M.

2013-01-01

Objectives: Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. Interventions: C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Results: Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Conclusions: Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism. Citation: Polak J; Shimoda LA; Drager LF; Undem C; McHugh H; Polotsky VY; Punjabi NM

Metabolic and endocrine adaptations to fasting in lean and obese individuals

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Wijngaarden, Marjolein A.

2015-01-01

In this thesis we examined several effects of fasting in lean and obese individuals. As expected, both the hormonal response as well as the metabolic shift from glucose towards lipid oxidation was impaired in obese individuals. At baseline, mitochondrial protein content in skeletal muscle of obese

Modeling of thermal expansion coefficient of perovskite oxide for solid oxide fuel cell cathode

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Heydari, F.; Maghsoudipour, A.; Alizadeh, M.; Khakpour, Z.; Javaheri, M.

2015-09-01

Artificial intelligence models have the capacity to eliminate the need for expensive experimental investigation in various areas of manufacturing processes, including the material science. This study investigates the applicability of adaptive neuro-fuzzy inference system (ANFIS) approach for modeling the performance parameters of thermal expansion coefficient (TEC) of perovskite oxide for solid oxide fuel cell cathode. Oxides (Ln = La, Nd, Sm and M = Fe, Ni, Mn) have been prepared and characterized to study the influence of the different cations on TEC. Experimental results have shown TEC decreases favorably with substitution of Nd3+ and Mn3+ ions in the lattice. Structural parameters of compounds have been determined by X-ray diffraction, and field emission scanning electron microscopy has been used for the morphological study. Comparison results indicated that the ANFIS technique could be employed successfully in modeling thermal expansion coefficient of perovskite oxide for solid oxide fuel cell cathode, and considerable savings in terms of cost and time could be obtained by using ANFIS technique.

Dysfunction of pulmonary surfactant mediated by phospholipid oxidation is cholesterol-dependent.

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Al-Saiedy, Mustafa; Pratt, Ryan; Lai, Patrick; Kerek, Evan; Joyce, Heidi; Prenner, Elmar; Green, Francis; Ling, Chang-Chun; Veldhuizen, Ruud; Ghandorah, Salim; Amrein, Matthias

2018-04-01

Pulmonary surfactant forms a cohesive film at the alveolar air-lung interface, lowering surface tension, and thus reducing the work of breathing and preventing atelectasis. Surfactant function becomes impaired during inflammation due to degradation of the surfactant lipids and proteins by free radicals. In this study, we examine the role of reactive nitrogen (RNS) and oxygen (ROS) species on surfactant function with and without physiological cholesterol levels (5-10%). Surface activity was assessed in vitro in a captive bubble surfactometer (CBS). Surfactant chemistry, monolayer fluidity and thermodynamic behavior were also recorded before and after oxidation. We report that physiologic amounts of cholesterol combined with oxidation results in severe impairment of surfactant function. We also show that surfactant polyunsaturated phospholipids are the most susceptible to oxidative alteration. Membrane thermodynamic experiments showed significant surfactant film stiffening after free radical exposure in the presence of cholesterol. These results point to a previously unappreciated role for cholesterol in amplifying defects in surface activity caused by oxidation of pulmonary surfactant, a finding that may have implications for treating several lung diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

Melatonin Attenuates Memory Impairment Induced by Klotho Gene Deficiency Via Interactive Signaling Between MT2 Receptor, ERK, and Nrf2-Related Antioxidant Potential

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Shin, Eun-Joo; Chung, Yoon Hee; Le, Hoang-Lan Thi; Jeong, Ji Hoon; Dang, Duy-Khanh; Nam, Yunsung; Wie, Myung Bok; Nah, Seung-Yeol; Nabeshima, Yo-Ichi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2015-01-01

Background: We demonstrated that oxidative stress plays a crucial role in cognitive impairment in klotho mutant mice, a genetic model of aging. Since down-regulation of melatonin due to aging is well documented, we used this genetic model to determine whether the antioxidant property of melatonin affects memory impairment. Methods: First, we examined the effects of melatonin on hippocampal oxidative parameters and the glutathione/oxidized glutathione (GSH/GSSG) ratio and memory dysfunction of klotho mutant mice. Second, we investigated whether a specific melatonin receptor is involved in the melatonin-mediated pharmacological response by application with melatonin receptor antagonists. Third, we examined phospho-extracellular-signal-regulated kinase (ERK) expression, nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, Nrf2 DNA binding activity, and glutamate-cysteine ligase (GCL) mRNA expression. Finally, we examined effects of the ERK inhibitor SL327 in response to antioxidant efficacy and memory enhancement mediated by melatonin. Results: Treatment with melatonin resulted in significant attenuations of oxidative damage, a decrease in the GSH/GSSG ratio, and a significant amelioration of memory impairment in this aging model. These effects of melatonin were significantly counteracted by the selective MT2 receptor antagonist 4-P-PDOT. Importantly, 4-P-PDOT or SL327 also counteracted melatonin-mediated attenuation in response to the decreases in phospho-ERK expression, Nrf2 nuclear translocation, Nrf2 DNA-binding activity, and GCL mRNA expression in the hippocampi of klotho mutant mice. SL327 also counteracted the up-regulation of the GSH/GSSG ratio and the memory enhancement mediated by melatonin in klotho mutant mice. Conclusions: Melatonin attenuates oxidative stress and the associated memory impairment induced by klotho deficiency via signaling interaction between the MT2 receptor and ERK- and Nrf2-related antioxidant potential. PMID

Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial improvement with cessation of the exposure.

Science.gov (United States)

Polak, Jan; Shimoda, Larissa A; Drager, Luciano F; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y; Punjabi, Naresh M

2013-10-01

Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism.

The process of production/adaptation of phonetics and phonology’s didactic material for visual deficient

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Edson Carlos Romualdo

2015-02-01

Full Text Available This paper describes the process of production and adaptation of phonetics and phonology teaching material for the visually impaired. The research was motivated by the lack of means to represent phonetic and phonological symbols to a visually impaired undergraduate student of the Language and Literature Course of Universidade Estadual de Maringá (UEM [Maringá State University], Brazil, due to the fact that these symbols are elementary for the professional development of future Portuguese teachers. Considering this shortcoming and in favor of educational inclusion, the intention was to find the best method to represent these symbols. Half-structured interviews were undertaken with special education professionals who work with the visually impaired, which insisted that the Braille method is the most efficient resource for teaching and learning for these students. The result of this research was the adaptation to the Braille system, by professionals of the Centro de Apoio Pedagógico (CAP [Center for Pedagogical Aid] in Maringá, of a book on phonetics and phonology, including symbols, organized for teachers’ formation.

Visuomotor adaptability in older adults with mild cognitive decline.

Science.gov (United States)

Schaffert, Jeffrey; Lee, Chi-Mei; Neill, Rebecca; Bo, Jin

2017-02-01

The current study examined the augmentation of error feedback on visuomotor adaptability in older adults with varying degrees of cognitive decline (assessed by the Montreal Cognitive Assessment; MoCA). Twenty-three participants performed a center-out computerized visuomotor adaptation task when the visual feedback of their hand movement error was presented in a regular (ratio=1:1) or enhanced (ratio=1:2) error feedback schedule. Results showed that older adults with lower scores on the MoCA had less adaptability than those with higher MoCA scores during the regular feedback schedule. However, participants demonstrated similar adaptability during the enhanced feedback schedule, regardless of their cognitive ability. Furthermore, individuals with lower MoCA scores showed larger after-effects in spatial control during the enhanced schedule compared to the regular schedule, whereas individuals with higher MoCA scores displayed the opposite pattern. Additional neuro-cognitive assessments revealed that spatial working memory and processing speed were positively related to motor adaptability during the regular scheduled but negatively related to adaptability during the enhanced schedule. We argue that individuals with mild cognitive decline employed different adaptation strategies when encountering enhanced visual feedback, suggesting older adults with mild cognitive impairment (MCI) may benefit from enhanced visual error feedback during sensorimotor adaptation. Copyright © 2016 Elsevier B.V. All rights reserved.

A framework for communication between visually impaired, hearing impaired and speech impaired using arduino

Science.gov (United States)

Sujatha, R.; Khandelwa, Prakhar; Gupta, Anusha; Anand, Nayan

2017-11-01

A long time ago our society accepted the notion of treating people with disabilities not as unviable and disabled but as differently-abled, recognizing their skills beyond their disabilities. The next step has to be taken by our scientific community, that is, to normalize lives of the people with disabilities and make it so as if they are no different to us. The primary step in this direction would be to normalize communication between people. People with an impaired speech or impaired vision or impaired hearing face difficulties while having a casual conversation with others. Any form of communication feels so strenuous that the impaired end up communicating just the important information and avoid a casual conversation. To normalize conversation between the impaired we need a simple and compact device which facilitates the conversation by providing the information in the desired form.

Obstructive sleep apnea-hypopnea syndrome and cognitive impairments in the elderly

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Song Shuling

2017-01-01

Full Text Available Obstructive sleep apnea-hypopnea syndrome (OSAHS is a common sleep-related breathing disorder that is associated with significant morbidity and mortality. It has received increasing attention that neurocognitive deficits occur with a high frequency in OSAHS. However, it is rarely known that OSAHS impacts on cognition in the elderly in whom an increased prevalence of OSAHS is present. In this review we consider recent studies in the association between OSAHS and cognitive impairments, with specific interest in the older population. Firstly, we elucidate the characteristics of OSAHS and OSAHS-related cognitive impairments in the older patients. Many studies have showed that the prevalence of OSAHS increases with age and it is higher in the elderly than other population. Moreover, OSAHS is associated with higher incidence of comorbidities and increased risk of clinical deterioration in the elderly, especially the neurocognitive impairments which even can develop dementia. Subsequently, we discuss the possible reasons of cognitive impairments that caused or aggravated by OSAHS in the elderly. The intermittent hypoxia (IH-related disturbances of homeostasis such as oxidative stress, inflammation, and age-related changes such as the changes of sleep architecture, the declined expression level of anti-aging gene, medical comorbidities and polypharmacy, may be both contribute to the increased risk of cognitive impairments in the older patients with OSAHS.

Indoor navigation by people with visual impairment using a digital sign system.

Directory of Open Access Journals (Sweden)

Gordon E Legge

Full Text Available There is a need for adaptive technology to enhance indoor wayfinding by visually-impaired people. To address this need, we have developed and tested a Digital Sign System. The hardware and software consist of digitally-encoded signs widely distributed throughout a building, a handheld sign-reader based on an infrared camera, image-processing software, and a talking digital map running on a mobile device. Four groups of subjects-blind, low vision, blindfolded sighted, and normally sighted controls-were evaluated on three navigation tasks. The results demonstrate that the technology can be used reliably in retrieving information from the signs during active mobility, in finding nearby points of interest, and following routes in a building from a starting location to a destination. The visually impaired subjects accurately and independently completed the navigation tasks, but took substantially longer than normally sighted controls. This fully functional prototype system demonstrates the feasibility of technology enabling independent indoor navigation by people with visual impairment.

Indoor navigation by people with visual impairment using a digital sign system.

Science.gov (United States)

Legge, Gordon E; Beckmann, Paul J; Tjan, Bosco S; Havey, Gary; Kramer, Kevin; Rolkosky, David; Gage, Rachel; Chen, Muzi; Puchakayala, Sravan; Rangarajan, Aravindhan

2013-01-01

There is a need for adaptive technology to enhance indoor wayfinding by visually-impaired people. To address this need, we have developed and tested a Digital Sign System. The hardware and software consist of digitally-encoded signs widely distributed throughout a building, a handheld sign-reader based on an infrared camera, image-processing software, and a talking digital map running on a mobile device. Four groups of subjects-blind, low vision, blindfolded sighted, and normally sighted controls-were evaluated on three navigation tasks. The results demonstrate that the technology can be used reliably in retrieving information from the signs during active mobility, in finding nearby points of interest, and following routes in a building from a starting location to a destination. The visually impaired subjects accurately and independently completed the navigation tasks, but took substantially longer than normally sighted controls. This fully functional prototype system demonstrates the feasibility of technology enabling independent indoor navigation by people with visual impairment.

20 CFR 416.998 - If you become disabled by another impairment(s).

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your...

20 CFR 404.1598 - If you become disabled by another impairment(s).

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which your last impairment(s) ends, we will find that your disability is...

Impairments in Dark Adaptation Are Associated with Age-Related Macular Degeneration Severity and Reticular Pseudodrusen.

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Flamendorf, Jason; Agrón, Elvira; Wong, Wai T; Thompson, Darby; Wiley, Henry E; Doss, E Lauren; Al-Holou, Shaza; Ferris, Frederick L; Chew, Emily Y; Cukras, Catherine

2015-10-01

We investigate whether ocular and person-based characteristics were associated with dark adaptation (DA). Cross-sectional, single-center, observational study. One hundred sixteen participants older than 50 years of age with a range of age-related macular degeneration (AMD) severity. Participants underwent best-corrected visual acuity (BCVA) testing, ophthalmoscopic examination, and multimodal imaging. Presence of reticular pseudodrusen (RPD) was assessed by masked grading of fundus images and was confirmed with optical coherence tomography. Eyes also were graded for AMD features (drusen, pigmentary changes, late AMD) to generate person-based AMD severity groups. One eye was designated the study eye for DA testing. Nonparametric statistical testing was performed on all comparisons. The primary outcome of this study was the rod intercept time (RIT), which is defined as the time for a participant's visual sensitivity to recover to a stimulus intensity of 5×10(-3) cd/m(2) (a decrease of 3 log units), or until a maximum test duration of 40 minutes was reached. A total of 116 study eyes from 116 participants (mean age, 75.4±9.4 years; 58% female) were analyzed. Increased RIT was associated significantly with increasing AMD severity, increasing age (r = 0.34; P = 0.0002), decreasing BCVA (r = -0.54; P < 0.0001), pseudophakia (P = 0.03), and decreasing subfoveal choroidal thickness (r = -0.27; P = 0.003). Study eyes with RPD (15/116 [13%]) had a significantly greater mean RIT compared with eyes without RPD in any AMD severity group (P < 0.02 for all comparisons), with 80% reaching the DA test ceiling. Impairments in DA increased with age, worse visual acuity, presence of RPD, AMD severity, and decreased subfoveal choroidal thickness. Analysis of covariance found the multivariate model that best fit the data included age, AMD group, and presence of RPD (R(2) = 0.56), with the presence of RPD conferring the largest parameter estimate. Copyright © 2015 American Academy of

Physiological responses to food deprivation in the house sparrow, a species not adapted to prolonged fasting.

Science.gov (United States)

Khalilieh, Anton; McCue, Marshall D; Pinshow, Berry

2012-09-01

Many wild birds fast during reproduction, molting, migration, or because of limited food availability. Species that are adapted to fasting sequentially oxidize endogenous fuels in three discrete phases. We hypothesized that species not adapted to long fasts have truncated, but otherwise similar, phases of fasting, sequential changes in fuel oxidization, and similar changes in blood metabolites to fasting-adapted species. We tested salient predictions in house sparrows (Passer domesticus biblicus), a subspecies that is unable to tolerate more than ~32 h of fasting. Our main hypothesis was that fasting sparrows sequentially oxidize substrates in the order carbohydrates, lipids, and protein. We dosed 24 house sparrows with [(13)C]glucose, palmitic acid, or glycine and measured (13)CO(2) in their breath while they fasted for 24 h. To ascertain whether blood metabolite levels reflect fasting-induced changes in metabolic fuels, we also measured glucose, triacylglycerides, and β-hydroxybutyrate in the birds' blood. The results of both breath (13)CO(2) and plasma metabolite analyses did not support our hypothesis; i.e., that sparrows have the same metabolic responses characteristic of fasting-adapted species, but on a shorter time scale. Contrary to our main prediction, we found that recently assimilated (13)C-tracers were oxidized continuously in different patterns with no definite peaks corresponding to the three phases of fasting and also that changes in plasma metabolite levels accurately tracked the changes found by breath analysis. Notably, the rate of recently assimilated [(13)C]glycine oxidization was significantly higher (P fast for longer than 32 h is likely related to their inability to accrue large lipid stores, separately oxidize different fuels, and/or spare protein during fasting.

Robust model predictive cooperative adaptive cruise control subject to V2V impairments

NARCIS (Netherlands)

Van Nunen, Ellen; Verhaegh, Jan; Silvas, Emilia; Semsar-Kazerooni, Elham; Van De Wouw, Nathan

2018-01-01

To improve traffic throughput, Cooperative Adaptive Cruise Control (CACC) has been proposed as a solution. The usage of Vehicle-to-Vehicle (V2V) communication enables short following distances, thereby increasing road capacity and fuel reduction (especially for trucks). Control designs for CACC use

Compensatory responses induced by oxidative stress in Alzheimer disease

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PAULA I MOREIRA

2006-01-01

Full Text Available Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques. In the first stage of development of the disease, amyloid-β deposition and hyperphosphorylated tau function as compensatory responses and downstream adaptations to ensure that neuronal cells do not succumb to oxidative damage. These findings suggest that Alzheimer disease is associated with a novel balance in oxidant homeostasis.

Diabetic beta-cells can achieve self-protection against oxidative stress through an adaptive up-regulation of their antioxidant defenses.

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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.

Hypertension-Induced Cerebral Small Vessel Disease Leading to Cognitive Impairment.

Science.gov (United States)

Liu, Yang; Dong, Yan-Hong; Lyu, Pei-Yuan; Chen, Wei-Hong; Li, Rui

2018-03-05

Alzheimer's disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease (CSVD) is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of "hypertension", "cerebral small vessel disease", "white matter lesions", "enlarged perivascular spaces", "lacunar infarcts", "cerebral microbleeds", and "cognitive impairment" in the database of PubMed. Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. In recent years, studies have demonstrated that hypertension-related changes (e.g., small vascular lesions, inflammatory reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy) can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure (BP) control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the numbers, volumes, and anatomical locations of CSVD and cognitive impairment.

Family adaptation to cerebral palsy in adolescents

DEFF Research Database (Denmark)

Guyard, Audrey; Michelsen, Susan I; Arnaud, Catherine

2017-01-01

modelled with structural equations. RESULTS: 31.8% of parents living with an adolescent with CP showed clinically significant high stress requiring professional assistance. The main stressors were the level of motor impairment and behavioural disorders in adolescent. A good family functioning was the best......BACKGROUND AND AIM: Factors promoting family adaptation to child's disability are poorly studied together. The aim of the study was to describe the family adaptation to disability and to identify determinants associated with using a global theoretical model. MATERIALS AND METHODS: 286 families...... of teenagers [13-17 years] with cerebral palsy (CP) from 4 European disability registers were included and visited at home. Face to face interviews were performed in order to measure parental distress, perceived impact in various dimensions of family life, family resources and stressors. Relationships were...

Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice1[S

Science.gov (United States)

Zhang, Hao; Xu, Hao; Weihrauch, Dorothee; Jones, Deron W.; Jing, Xigang; Shi, Yang; Gourlay, David; Oldham, Keith T.; Hillery, Cheryl A.; Pritchard, Kirkwood A.

2013-01-01

Activated leukocytes and polymorphonuclear neutrophils (PMN) release myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated, and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To determine whether MPO impairs EC function in sickle cell disease (SCD), control (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC). SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin). KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas. Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice more than 2-fold, to ∼60% of levels in AA mice. KYC inhibited MPO-dependent 3-ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO2Tyr) in SCD livers. These data support the hypothesis that SCD increases release of MPO, which generates oxidants that impair EC function and injure livers. Inhibiting MPO is an effective strategy for decreasing oxidative stress and liver injury and restoring EC function in SCD. PMID:23956444

20 CFR 220.184 - If the annuitant becomes disabled by another impairment(s).

Science.gov (United States)

2010-04-01

... impairment(s). 220.184 Section 220.184 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... Activity or Medical Improvement § 220.184 If the annuitant becomes disabled by another impairment(s). If a new severe impairment(s) begins in or before the month in which the last impairment(s) ends, the Board...

Cognitive Impairment in Chronic Kidney Disease: Vascular Milieu and the Potential Therapeutic Role of Exercise

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Ulf G. Bronas

2017-01-01

Full Text Available Chronic kidney disease (CKD is considered a model of accelerated aging. More specifically, CKD leads to reduced physical functioning and increased frailty, increased vascular dysfunction, vascular calcification and arterial stiffness, high levels of systemic inflammation, and oxidative stress, as well as increased cognitive impairment. Increasing evidence suggests that the cognitive impairment associated with CKD may be related to cerebral small vessel disease and overall impairment in white matter integrity. The triad of poor physical function, vascular dysfunction, and cognitive impairment places patients living with CKD at an increased risk for loss of independence, poor health-related quality of life, morbidity, and mortality. The purpose of this review is to discuss the available evidence of cerebrovascular-renal axis and its interconnection with early and accelerated cognitive impairment in patients with CKD and the plausible role of exercise as a therapeutic modality. Understanding the cerebrovascular-renal axis pathophysiological link and its interconnection with physical function is important for clinicians in order to minimize the risk of loss of independence and improve quality of life in patients with CKD.

Physiological complexity and system adaptability: evidence from postural control dynamics of older adults.

Science.gov (United States)

Manor, Brad; Costa, Madalena D; Hu, Kun; Newton, Elizabeth; Starobinets, Olga; Kang, Hyun Gu; Peng, C K; Novak, Vera; Lipsitz, Lewis A

2010-12-01

The degree of multiscale complexity in human behavioral regulation, such as that required for postural control, appears to decrease with advanced aging or disease. To help delineate causes and functional consequences of complexity loss, we examined the effects of visual and somatosensory impairment on the complexity of postural sway during quiet standing and its relationship to postural adaptation to cognitive dual tasking. Participants of the MOBILIZE Boston Study were classified into mutually exclusive groups: controls [intact vision and foot somatosensation, n = 299, 76 ± 5 (SD) yr old], visual impairment only (Postural sway (i.e., center-of-pressure) dynamics were assessed during quiet standing and cognitive dual tasking, and a complexity index was quantified using multiscale entropy analysis. Postural sway speed and area, which did not correlate with complexity, were also computed. During quiet standing, the complexity index (mean ± SD) was highest in controls (9.5 ± 1.2) and successively lower in the visual (9.1 ± 1.1), somatosensory (8.6 ± 1.6), and combined (7.8 ± 1.3) impairment groups (P = 0.001). Dual tasking resulted in increased sway speed and area but reduced complexity (P postural sway speed from quiet standing to dual-tasking conditions. Sensory impairments contributed to decreased postural sway complexity, which reflected reduced adaptive capacity of the postural control system. Relatively low baseline complexity may, therefore, indicate control systems that are more vulnerable to cognitive and other stressors.

Toll‐Like Receptor‐2 Mediates Adaptive Cardiac Hypertrophy in Response to Pressure Overload Through Interleukin‐1β Upregulation via Nuclear Factor κB Activation

Science.gov (United States)

Higashikuni, Yasutomi; Tanaka, Kimie; Kato, Megumi; Nureki, Osamu; Hirata, Yasunobu; Nagai, Ryozo; Komuro, Issei; Sata, Masataka

2013-01-01

Background Inflammation is induced in the heart during the development of cardiac hypertrophy. The initiating mechanisms and the role of inflammation in cardiac hypertrophy, however, remain unclear. Toll‐like receptor‐2 (TLR2) recognizes endogenous molecules that induce noninfectious inflammation. Here, we examined the role of TLR2‐mediated inflammation in cardiac hypertrophy. Methods and Results At 2 weeks after transverse aortic constriction, Tlr2−/− mice showed reduced cardiac hypertrophy and fibrosis with greater left ventricular dilatation and impaired systolic function compared with wild‐type mice, which indicated impaired cardiac adaptation in Tlr2−/− mice. Bone marrow transplantation experiment revealed that TLR2 expressed in the heart, but not in bone marrow–derived cells, is important for cardiac adaptive response to pressure overload. In vitro experiments demonstrated that TLR2 signaling can induce cardiomyocyte hypertrophy and fibroblast and vascular endothelial cell proliferation through nuclear factor–κB activation and interleukin‐1β upregulation. Systemic administration of a nuclear factor–κB inhibitor or anti–interleukin‐1β antibodies to wild‐type mice resulted in impaired adaptive cardiac hypertrophy after transverse aortic constriction. We also found that heat shock protein 70, which was increased in murine plasma after transverse aortic constriction, can activate TLR2 signaling in vitro and in vivo. Systemic administration of anti–heat shock protein 70 antibodies to wild‐type mice impaired adaptive cardiac hypertrophy after transverse aortic constriction. Conclusions Our results demonstrate that TLR2‐mediated inflammation induced by extracellularly released heat shock protein 70 is essential for adaptive cardiac hypertrophy in response to pressure overload. Thus, modulation of TLR2 signaling in the heart may provide a novel strategy for treating heart failure due to inadequate adaptation to hemodynamic

Participation of a preschooler with visual impairments on the playground: effects of musical adaptations and staff development.

Science.gov (United States)

Kern, P; Wolery PhD, M

2001-01-01

The purpose of this study was to evaluate the adaptations of a playground, and subsequently staff development, on the participation of a 3-year-old boy with congenital blindness. A single-subject design with three conditions (baseline, adaptations of the playground, and staff development) was used. The playground adaptation involved adding musical stations in strategic locations on the playground and connecting them with a "path" that provided auditory feedback. The staff training involved the music therapist providing individualized instruction to the staff who supervised the child. The child's participation was measured in terms of social interaction with peers or adults, play and engagement with materials, movement on the playground, and stereotypic behaviors. The playground adaptation resulted in no changes in the child's social interactions with peers or adults, increases in engagement, no change in movement on the playground, and a decrease in stereotypic responses. Staff training resulted in increased but variable interactions with adults and peers, in additional increases in engagement, less movement, and similar levels of stereotypic behavior. The findings suggest that musical adaptations of physical environments may he helpful but not sufficient for promoting desired outcomes.

The enhancing of Au-Ag-Te content in tellurium-bearing ore mineral by bio-oxidation-leaching

Science.gov (United States)

Kim, PyeongMan; Kim, HyunSoo; Myung, EunJi; Kim, YoonJung; Lee, YongBum; Park*, CheonYoung

2015-04-01

The purpose of this study is to enhance the content of valuable metals such as Au-Ag-Te in tellurium-bearing minerals by bio-oxidation-leaching. It was confirmed that pyrite, chalcopyrite, sphalerite and galena were produced together with tellurium-bearing minerals including hessite, sylvanite and tellurobismuthite from ore minerals and concentrates through microscopic observation and SEM/EDS analysis. In a bio-oxidation-leaching experiment, with regard to Au, Ag, Te, Cu and Fe, the changes in the amount of leaching and the content of leaching residues were compared and analyzed with each other depending on the adaptation of an indigenous microbe identified as Acidithiobacillus ferrooxidans. As a result of the experiment, the Au-Ag-Te content in tellurium-bearing ore mineral was enhanced in the order of physical oxidation leaching, physical/non-adaptive bio-oxidation-leaching and physical/adaptive biological leaching. It suggests that the bio-oxidation-leaching using microbes adapted in tellurium-bearing ore mineral can be used as a pre-treatment and a main process in a recovery process of valuable metals. "This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(NRF-2013R1A1A2004898)"

Control of bovine hepatic fatty acid oxidation

International Nuclear Information System (INIS)

Jesse, B.W.; Emery, R.S.; Thomas, J.W.

1986-01-01

Fatty acid oxidation by bovine liver slices and mitochondria was examined to determine potential regulatory sites of fatty acid oxidation. Conversion of 1-[ 14 C]palmitate to 14 CO 2 and total [ 14 C]acid-soluble metabolites was used to measure fatty acid oxidation. Oxidation of palmitate (1 mM) was linear in both liver slice weight and incubation time. Carnitine stimulated palmitate oxidation; 2 mM dl-carnitine produced maximal stimulation of palmitate oxidation to both CO 2 and acid-soluble metabolites. Propionate (10 mM) inhibited palmitate oxidation by bovine liver slices. Propionate (.5 to 10 mM) had no effect on palmitate oxidation by mitochondria, but malonyl Coenzyme A, the first committed intermediate of fatty acid synthesis, inhibited mitochondrial palmitate oxidation (inhibition constant = .3 μM). Liver mitochonndrial carnitine palmitoyltransferase exhibited Michaelis constants for palmitoyl Coenzyme A and l-carnitine of 11.5 μM and .59 mM, respectively. Long-chain fatty acid oxidation in bovine liver is regulated by mechanisms similar to those in rats but adapted to the unique digestive physiology of the bovine

Progress and Prospects in Human Genetic Research into Age-Related Hearing Impairment

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Yasue Uchida

2014-01-01

Full Text Available Age-related hearing impairment (ARHI is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed.

Oxidative Stress and Anesthesia in Diabetic Patients

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Peivandi Yazdi A

2014-04-01

Full Text Available Free radical and peroxide production lead to intracellular damage. On the other hand, free radicals are used by the human immune system to defend against pathogens. The aging process could be limited by oxidative stress in the short term. Chronic diseases like diabetes mellitus (DM are full-stress conditions in which remarkable metabolic functional destructions might happen. There is strong evidence regarding antioxidant impairment in diabetes. Performing a particular method for anesthesia in diabetic patients might prevent or modify excessive free radical formation and oxidative stress. It seems that prescribing antioxidant drugs could promote wound healing in diabetics.  

The effect of valinomycin in fibroblasts from patients with fatty acid oxidation disorders

International Nuclear Information System (INIS)

Ndukwe Erlingsson, Uzochi Chimdinma; Iacobazzi, Francesco; Liu, Aiping; Ardon, Orly; Pasquali, Marzia; Longo, Nicola

2013-01-01

Highlights: •Valinomycin can cause mitochondrial stress and stimulate fatty acid oxidation. •Cells with VLCAD deficiency fail to increase fatty acid oxidation in response to valinomycin. •Response to valinomycin can help in the diagnosis of VLCAD deficiency. -- Abstract: Disorders of the carnitine cycle and of the beta oxidation spiral impair the ability to obtain energy from fats at time of fasting and stress. This can result in hypoketotic hypoglycemia, cardiomyopathy, cardiac arrhythmia and other chronic medical problems. The in vitro study of fibroblasts from patients with these conditions is impaired by their limited oxidative capacity. Here we evaluate the capacity of valinomycin, a potassium ionophore that increases mitochondrial respiration, to increase the oxidation of fatty acids in cells from patients with inherited fatty acid oxidation defects. The addition of valinomycin to fibroblasts decreased the accumulation of the lipophilic cation tetraphenylphosphonium (TPP + ) at low concentrations due to the dissipation of the mitochondrial membrane potential. At higher doses, valinomycin increased TPP + accumulation due to the increased potassium permeability of the plasma membrane and subsequent cellular hyperpolarization. The incubation of normal fibroblasts with valinomycin increased [ 14 C]-palmitate oxidation (measured as [ 14 C]O 2 release) in a dose-dependent manner. By contrast, valinomycin failed to increase palmitate oxidation in fibroblasts from patients with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This was not observed in fibroblasts from patients heterozygous for this condition. These results indicate that valinomycin can increase fatty acid oxidation in normal fibroblasts and could be useful to differentiate heterozygotes from patients affected with VLCAD deficiency

Endurance Exercise in Hypoxia, Hyperoxia and Normoxia: Mitochondrial and Global Adaptations.

Science.gov (United States)

Przyklenk, Axel; Gutmann, Boris; Schiffer, Thorsten; Hollmann, Wildor; Strueder, Heiko K; Bloch, Wilhelm; Mierau, Andreas; Gehlert, Sebastian

2017-07-01

We hypothesized short-term endurance exercise (EN) in hypoxia (HY) to exert decreased mitochondrial adaptation, peak oxygen consumption (VO 2peak ) and peak power output (PPO) compared to EN in normoxia (NOR) and hyperoxia (PER). 11 male subjects performed repeated unipedal cycling EN in HY, PER, and NOR over 4 weeks in a cross-over design. VO 2peak , PPO, rate of perceived exertion (RPE) and blood lactate (Bla) were determined pre- and post-intervention to assess physiological demands and adaptation. Skeletal muscle biopsies were collected to determine molecular mitochondrial signaling and adaptation. Despite reduced exercise intensity (P0.05). Electron transport chain complexes tended to increase in all groups with the highest increase in HY (n.s.). EN-induced mitochondrial adaptability and exercise capacity neither decreased significantly in HY nor increased in PER compared to NOR. Despite decreased exercise intensity, short term EN under HY may not necessarily impair mitochondrial adaptation and exercise capacity while PER does not augment adaptation. HY might strengthen adaptive responses under circumstances when absolute training intensity has to be reduced. © Georg Thieme Verlag KG Stuttgart · New York.

Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice.

Science.gov (United States)

Bowen, T Scott; Aakerøy, Lars; Eisenkolb, Sophia; Kunth, Patricia; Bakkerud, Fredrik; Wohlwend, Martin; Ormbostad, Anne Marie; Fischer, Tina; Wisloff, Ulrik; Schuler, Gerhard; Steinshamn, Sigurd; Adams, Volker; Bronstad, Eivind

2017-05-01

Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease and emphysema. However, evidence on the extrapulmonary effects of smoke exposure that precede lung impairments remains unclear at present, as are data on nonpharmacological treatments such as exercise training. Three groups of mice, including control (n = 10), smoking (n = 10), and smoking with 6 wk of high-intensity interval treadmill running (n = 11), were exposed to 20 wk of fresh air or whole-body cigarette smoke. Exercise capacity (peak oxygen uptake) and lung destruction (histology) were subsequently measured, whereas the heart, peripheral endothelium (aorta), and respiratory (diaphragm) and limb (extensor digitorum longus and soleus) skeletal muscles were assessed for in vivo and in vitro function, in situ mitochondrial respiration, and molecular alterations. Smoking reduced body weight by 26% (P 0.05). Smoking impaired exercise capacity by 15% while inducing right ventricular dysfunction by ~20%, endothelial dysfunction by ~20%, and diaphragm muscle weakness by ~15% (all P exercise training (P smoking mice had normal limb muscle and mitochondrial function (cardiac and skeletal muscle fibers); however, diaphragm measures of oxidative stress and protein degradation were increased by 111% and 65%, respectively (P exercise training (P smoking reduced exercise capacity concomitant with functional impairments to the heart, peripheral endothelium, and respiratory muscle that preceded the development of overt emphysema. However, high-intensity exercise training was able to reverse these smoke-induced extrapulmonary impairments.

Oxidative stress biomarkers in Oreochromis niloticus as early ...

African Journals Online (AJOL)

2018-04-10

Apr 10, 2018 ... stress biomarkers and sub-cellular components are the most commonly used ..... metal ions usually occur in low concentrations in the aquatic environment and ..... injured cells from a reduced to an oxidized state (Gul et al.,. 2004). ... ions through their gills, impaired respiration may result from chronic and ...

Aspergillus fumigatus mitochondrial electron transport chain mediates oxidative stress homeostasis, hypoxia responses and fungal pathogenesis.

Science.gov (United States)

Grahl, Nora; Dinamarco, Taisa Magnani; Willger, Sven D; Goldman, Gustavo H; Cramer, Robert A

2012-04-01

We previously observed that hypoxia is an important component of host microenvironments during pulmonary fungal infections. However, mechanisms of fungal growth in these in vivo hypoxic conditions are poorly understood. Here, we report that mitochondrial respiration is active in hypoxia (1% oxygen) and critical for fungal pathogenesis. We generated Aspergillus fumigatus alternative oxidase (aoxA) and cytochrome C (cycA) null mutants and assessed their ability to tolerate hypoxia, macrophage killing and virulence. In contrast to ΔaoxA, ΔcycA was found to be significantly impaired in conidia germination, growth in normoxia and hypoxia, and displayed attenuated virulence. Intriguingly, loss of cycA results in increased levels of AoxA activity, which results in increased resistance to oxidative stress, macrophage killing and long-term persistence in murine lungs. Thus, our results demonstrate a previously unidentified role for fungal mitochondrial respiration in the pathogenesis of aspergillosis, and lay the foundation for future research into its role in hypoxia signalling and adaptation. © 2012 Blackwell Publishing Ltd.

Self-adapting metal-ceramic coating for biomass and waste incineration plants

Energy Technology Data Exchange (ETDEWEB)

Faulstich, Martin [Technische Univ. Muenchen (Germany); Fehr, Karl Thomas; Ye, Ya-Ping [Ludwig-Maximilians-Univ., Muenchen (Germany); Loeh, Ingrid; Mocker, Mario; Wolf, Gerhard [ATZ Entwicklungszentrum, Sulzbach-Rosenberg (Germany)

2010-07-01

Thermally sprayed coatings might become a reasonable alternative to cost-intensive cladding of heat exchangers in biomass and waste incineration. Shortcomings of these coatings might be overcome by a double-layer system, consisting of Alloy 625 covered with yttria-stabilized zirconia. Under appropriate conditions, re-crystallized zirconium oxide and chromium oxide form a dense, self-adapting and self-healing barrier against further infiltration of gaseous species. (orig.)

Studies on the effects of aspartame on memory and oxidative stress in brain of mice.

Science.gov (United States)

Abdel-Salam, O M E; Salem, N A; El-Shamarka, M E S; Hussein, J S; Ahmed, N A S; El-Nagar, M E S

2012-12-01

The dipeptide aspartame (N-L-alpha-aspartyl-Lphenylalanine, 1-methyl ester; alpha-APM) is one of the most widely used artificial sweeteners. The present study aimed to investigate the effect of repeated administration of aspartame in the working memory version of Morris water maze test, on oxidative stress and brain monoamines in brain of mice. Aspartame (0.625, 1.875 or 5.625 mg/kg) was administered once daily subcutaneously for 2 weeks and mice were examined four times a week for their ability to locate a submerged plate. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide levels (the concentrations of nitrite/nitrate) and glucose were determined in brain. Only at the highest dose of 5.625 mg/kg, did aspartame significantly impaired water maze performance. The mean time taken to find the escape platform (latency) over 2 weeks was significantly delayed by aspartame 5.625 mg/kg, compared with the saline-treated control group. Significant differences occurred only on the first trial to find the escape platform. Significant increase in brain MDA by 16.5% and nitric oxide by 16.2% and a decrease in GSH by 25.1% and glucose by 22.5% occurred after treatment with aspartame at 1.875 mg/kg. Aspartame administered at 5.625 mg/kg significantly increased brain MDA by 43.8%, nitric oxide by 18.6% and decreased GSH by 32.7% and glucose by 25.8%. Aspartame caused dose-dependent inhibition of brain serotonin, noradrenaline and dopamine. These findings suggest impaired memory performance and increased brain oxidative stress by repeated aspartame administration. The impaired memory performance is likely to involve increased oxidative stress as well as decreased brain glucose availability.

Family adaptation to cerebral palsy in adolescents: A European multicenter study.

Science.gov (United States)

Guyard, Audrey; Michelsen, Susan I; Arnaud, Catherine; Fauconnier, Jerome

2017-02-01

Factors promoting family adaptation to child's disability are poorly studied together. The aim of the study was to describe the family adaptation to disability and to identify determinants associated with using a global theoretical model. 286 families of teenagers [13-17 years] with cerebral palsy (CP) from 4 European disability registers were included and visited at home. Face to face interviews were performed in order to measure parental distress, perceived impact in various dimensions of family life, family resources and stressors. Relationships were modelled with structural equations. 31.8% of parents living with an adolescent with CP showed clinically significant high stress requiring professional assistance. The main stressors were the level of motor impairment and behavioural disorders in adolescent. A good family functioning was the best protective factor. Respite in care and a parents' positive attitude were significantly related to less parental distress. Material support, socioeconomical level, marital status or parental qualifications did not appear to be significant protector factors. Particular attention must be paid not only on physical condition but also on adolescent psychological problems to improve family adaptation. Families at risk of experiencing severe distress should be targeted early and proactive caregiver interventions on the whole family should be performed. Family is a dynamic system: facing disability, it tries to recover its balance with available resources and its perception of the situation. Literature highlights potential stressors and protecting factors that could affect the disabled child's family adaptation but few papers study a global model including most of these factors. This study validated a global theoretical model of family adaptation to disability at adolescence. It identified behaviour disorders and motor impairment level as main stressors, family functioning as the largest protecting factors, and equipment and

Cognitive properties of sedation agents: comparison of the effects of nitrous oxide and midazolam on memory and mood.

Science.gov (United States)

Thompson, J M; Neave, N; Moss, M C; Scholey, A B; Wesnes, K; Girdler, N M

1999-11-27

To compare the effects of nitrous oxide and midazolam on cognition and mood. A three-way, counterbalanced, cross-over study, using patients receiving conscious sedation for routine dental treatment. On each of three separate visits, patients performed a computerised test battery to determine baseline cognitive performance. Then, following administration of either midazolam, nitrous oxide, or no drug, patients re-performed the test battery. Finally, patients completed visual analogue scales assessing their subjective mood state. Relative to baseline performance, midazolam administration produced significantly slower reaction times compared with nitrous oxide and no-drug conditions. Furthermore, patients receiving midazolam were impaired in accuracy relative to the other conditions on many of the cognitive tasks, particularly those assessing the recall of information. Patient performance in nitrous oxide and control conditions did not significantly differ. These results could not be explained by differences in mood between the conditions, as subjective mood ratings during midazolam or nitrous oxide administration were very similar. It is important for clinicians to be aware that peri-operative recall of information is reduced in patients who have undergone midazolam sedation. This is an advantage for patients who are anxious, and do not wish to be aware of the operative treatment being performed. However, as the cognitive impairment is enduring, an adult escort and written post-operative instructions should be mandatory for midazolam sedation patients. In contrast, the use of nitrous oxide sedation does not significantly impair higher cognitive tasks and thus patients receiving nitrous oxide sedation can resume normal activities in the post-operative period.

Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats.

Science.gov (United States)

Ahmad, Mohammad Parwez; Hussain, Arshad; Siddiqui, Hefazat Hussain; Wahab, Shadma; Adak, Manoranjan

2015-03-01

Lipopolysaccharide (LPS) induced oxidative stress and impairment of normal physiological function generally categorized by increased anxiety and reduced mobility. Therefore, the present study was to find out the effect Methanolic extract of Asparagus racemosus (MEAR ) in lipopolysaccharide (LPS)-induced oxidative stress in rats . LPS-induced oxidative stress in rats was measured by locomotor activity by photoactometer test, anxiety with elevated plus maze test and also studied the oxidative stress markers, nitric oxide and cytokines. The obtained data shows that LPS markedly exhausted (pAsparagus racemosus Willd. is a functionally newer type of cerebroprotective agent.

The allosteric behavior of Fur mediates oxidative stress signal transduction in Helicobacter pylori

Directory of Open Access Journals (Sweden)

Simone ePelliciari

2015-08-01

Full Text Available The microaerophilic gastric pathogen Helicobacter pylori is exposed to oxidative stress originating from the aerobic environment, the oxidative burst of phagocytes and the formation of reactive oxygen species, catalyzed by iron excess. Accordingly, the expression of genes involved in oxidative stress defense have been repeatedly linked to the ferric uptake regulator Fur. Moreover, mutations in the Fur protein affect the resistance to metronidazole, likely due to loss-of-function in the regulation of genes involved in redox control. Although many advances in the molecular understanding of HpFur function were made, little is known about the mechanisms that enable Fur to mediate the responses to oxidative stress.Here we show that iron-inducible, apo-Fur repressed genes, such as pfr and hydA, are induced shortly after oxidative stress, while their oxidative induction is lost in a fur knockout strain. On the contrary, holo-Fur repressed genes, such as frpB1 and fecA1, vary modestly in response to oxidative stress. This indicates that the oxidative stress signal specifically targets apo-Fur repressed genes, rather than impairing indiscriminately the regulatory function of Fur. Footprinting analyses showed that the oxidative signal strongly impairs the binding affinity of Fur towards apo-operators, while the binding towards holo-operators is less affected. Further evidence is presented that a reduced state of Fur is needed to maintain apo-repression, while oxidative conditions shift the preferred binding architecture of Fur towards the holo-operator binding conformation, even in the absence of iron. Together the results demonstrate that the allosteric regulation of Fur enables transduction of oxidative stress signals in H. pylori, supporting the concept that apo-Fur repressed genes can be considered oxidation inducible Fur regulatory targets. These findings may have important implications in the study of H. pylori treatment and resistance to

Are Non-Intellectually Disabled Black Youth with ASD Less Impaired on Parent Report than Their White Peers?

Science.gov (United States)

Ratto, Allison B.; Anthony, Bruno J.; Kenworthy, Lauren; Armour, Anna Chelsea; Dudley, Katerina; Anthony, Laura Gutermuth

2016-01-01

There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social-emotional functioning. White and Black…

A review study on medicinal plants used in the treatment of learning and memory impairments

Institute of Scientific and Technical Information of China (English)

Nahid Jivad; Zahra Rabiei

2014-01-01

Alzheimer's disease (AD) is a progressive brain disorder that gradually impairs the person's memory and ability to learn, reasoning, judgment, communication and daily activities. AD is characterized clinically by cognitive impairment and pathologically by the deposition of β amyloid plaques and neurofibrillary tangles, and the degeneration of the cholinergic basal forebrain. During the progression of AD patients may produce changes in personality and behavior, such as anxiety, paranoia, confusion, hallucinations and also to experience delusions and fantasies. The first neurotransmitter defect discovered in AD involved acetylcholine as cholinergic function is required for short-term memory. Oxidative stress may underlie the progressive neurodegeneration characteristic of AD. Brain structures supporting memory are uniquely sensitive to oxidative stress due to their elevated demand for oxygen. The neurodegenerative process in AD may involveβ amyloid toxicity. Neurotoxicity of β amyloid appears to involve oxidative stress. Currently, there is no cure for this disease but in new treatments, reveals a new horizon on the biology of this disease. This paper reviews the effects of a number of commonly used types of herbal medicines for the treatment of AD. The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly.

A review study on medicinal plants used in the treatment of learning and memory impairments

Institute of Scientific and Technical Information of China (English)

Nahid; Jivad; Zahra; Rabiei

2014-01-01

Alzheimer′s disease(AD) is a progressive brain disorder thai gradual!) impairs the person’s memory and ability to learn,reasoning.judgment,communication and daily activities.All is characterized clinically by cognitive impairment and pathologically by the deposition of β amyloid plaques and neurofibrillary tangles,and the degeneration of the cholinergic basal forebrain.During the progression of AD patients may produce changes in personality and behavior,such as anxiety,paranoia,confusion,hallucinations and also to experience delusions and lanlasies.The first neurotransmitter defect discovered in Al) involved acetylcholine as cholinergic function is required for short—term memory.Oxidative stress may underlie the progressive neurodegeneration characteristic of AD.Brain structures supporting memory are uniquely sensitive to oxidative stress due to their elevated demand for oxygen.The neurodegenerative process in AD may involveβ amyloid toxicity.Neurotoxicity of β amyloid appears to involve oxidative stress.Currently,there is no cure for this disease but in new treatments,reveals a new horizon on the biology of this disease.This paper reviews the effects of a number of commonly used types of herbal medicines for the Irealment of AD.The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly.

Reduction of brain mitochondrial β-oxidation impairs complex I and V in chronic alcohol intake: the underlying mechanism for neurodegeneration.

Directory of Open Access Journals (Sweden)

James Haorah

Full Text Available Neuropathy and neurocognitive deficits are common among chronic alcohol users, which are believed to be associated with mitochondrial dysfunction in the brain. The specific type of brain mitochondrial respiratory chain complexes (mRCC that are adversely affected by alcohol abuse has not been studied. Thus, we examined the alterations of mRCC in freshly isolated mitochondria from mice brain that were pair-fed the ethanol (4% v/v and control liquid diets for 7-8 weeks. We observed that alcohol intake severely reduced the levels of complex I and V. A reduction in complex I was associated with a decrease in carnitine palmitoyltransferase 1 (cPT1 and cPT2 levels. The mitochondrial outer (cPT1 and inner (cPT2 membrane transporter enzymes are specialized in acylation of fatty acid from outer to inner membrane of mitochondria for ATP production. Thus, our results showed that alterations of cPT1 and cPT2 paralleled a decrease β-oxidation of palmitate and ATP production, suggesting that impairment of substrate entry step (complex I function can cause a negative impact on ATP production (complex V function. Disruption of cPT1/cPT2 was accompanied by an increase in cytochrome C leakage, while reduction of complex I and V paralleled a decrease in depolarization of mitochondrial membrane potential (ΔΨ, monitored by JC-1 fluorescence and ATP production in alcohol intake. We noted that acetyl-L-carnitine (ALC, a cofactor of cPT1 and cPT2 prevented the adverse effects of alcohol while coenzyme Q10 (CoQ10 was not very effective against alcohol insults. These results suggest that understanding the molecular, biochemical, and signaling mechanisms of the CNS mitochondrial β-oxidation such as ALC can mitigate alcohol related neurological disorders.

Reduction of brain mitochondrial β-oxidation impairs complex I and V in chronic alcohol intake: the underlying mechanism for neurodegeneration.

Science.gov (United States)

Haorah, James; Rump, Travis J; Xiong, Huangui

2013-01-01

Neuropathy and neurocognitive deficits are common among chronic alcohol users, which are believed to be associated with mitochondrial dysfunction in the brain. The specific type of brain mitochondrial respiratory chain complexes (mRCC) that are adversely affected by alcohol abuse has not been studied. Thus, we examined the alterations of mRCC in freshly isolated mitochondria from mice brain that were pair-fed the ethanol (4% v/v) and control liquid diets for 7-8 weeks. We observed that alcohol intake severely reduced the levels of complex I and V. A reduction in complex I was associated with a decrease in carnitine palmitoyltransferase 1 (cPT1) and cPT2 levels. The mitochondrial outer (cPT1) and inner (cPT2) membrane transporter enzymes are specialized in acylation of fatty acid from outer to inner membrane of mitochondria for ATP production. Thus, our results showed that alterations of cPT1 and cPT2 paralleled a decrease β-oxidation of palmitate and ATP production, suggesting that impairment of substrate entry step (complex I function) can cause a negative impact on ATP production (complex V function). Disruption of cPT1/cPT2 was accompanied by an increase in cytochrome C leakage, while reduction of complex I and V paralleled a decrease in depolarization of mitochondrial membrane potential (ΔΨ, monitored by JC-1 fluorescence) and ATP production in alcohol intake. We noted that acetyl-L-carnitine (ALC, a cofactor of cPT1 and cPT2) prevented the adverse effects of alcohol while coenzyme Q10 (CoQ10) was not very effective against alcohol insults. These results suggest that understanding the molecular, biochemical, and signaling mechanisms of the CNS mitochondrial β-oxidation such as ALC can mitigate alcohol related neurological disorders.

Measurement of the functional impact of adaptive seating technology in children with cerebral palsy

NARCIS (Netherlands)

Ryan, S.E.

2009-01-01

Many young children with cerebral palsy have motor impairments that affect their ability to sit and do activities unsupported. They often rely on special adaptive seating devices for postural control and stability. Healthcare practitioners generally accept that these products improve functioning in

Reduced lipid oxidation in myotubes established from obese and type 2 diabetic subjects

DEFF Research Database (Denmark)

Gaster, Michael

2009-01-01

To date, it is unknown whether reduced lipid oxidation of skeletal muscle of obese and obese type 2 diabetic (T2D) subjects partly is based on reduced oxidation of endogenous lipids. Palmitate (PA) accumulation, total oxidation and lipolysis were not different between myotubes established from lean...... both for endogenous and exogenous lipids. Thus myotubes established from obese and obese T2D subjects express a reduced complete oxidation of endogenous lipids. Two cardinal principles govern the reduced lipid oxidation in obese and diabetic myotubes; firstly, an impaired coupling between endogenous...... lipid and mitochondria in obese and obese diabetic myotubes and secondly, a mismatch between beta-oxidation and citric acid cycle in obese diabetic myotubes....

Cortical visual impairment

OpenAIRE

Koželj, Urša

2013-01-01

In this thesis we discuss cortical visual impairment, diagnosis that is in the developed world in first place, since 20 percent of children with blindness or low vision are diagnosed with it. The objectives of the thesis are to define cortical visual impairment and the definition of characters suggestive of the cortical visual impairment as well as to search for causes that affect the growing diagnosis of cortical visual impairment. There are a lot of signs of cortical visual impairment. ...

Restoration of nuclear-import failure caused by triple A syndrome and oxidative stress

International Nuclear Information System (INIS)

Kiriyama, Takao; Hirano, Makito; Asai, Hirohide; Ikeda, Masanori; Furiya, Yoshiko; Ueno, Satoshi

2008-01-01

Triple A syndrome is an autosomal recessive neurological disease, mimicking motor neuron disease, and is caused by mutant ALADIN, a nuclear-pore complex component. We recently discovered that the pathogenesis involved impaired nuclear import of DNA repair proteins, including DNA ligase I and the cerebellar ataxia causative protein aprataxin. Such impairment was overcome by fusing classical nuclear localization signal (NLS) and 137-aa downstream sequence of XRCC1, designated stretched NLS (stNLS). We report here that the minimum essential sequence of stNLS (mstNLS) is residues 239-276, downsized by more than 100 aa. mstNLS enabled efficient nuclear import of DNA repair proteins in patient fibroblasts, functioned under oxidative stress, and reduced oxidative-stress-induced cell death, more effectively than stNLS. The stress-tolerability of mstNLS was also exerted in control fibroblasts and neuroblastoma cells. These findings may help develop treatments for currently intractable triple A syndrome and other oxidative-stress-related neurological diseases, and contribute to nuclear compartmentalization study

Acute alcohol intoxication impairs segmental body alignment in upright standing.

Science.gov (United States)

Hafstrom, A; Patel, M; Modig, F; Magnusson, M; Fransson, P A

2014-01-01

Balance control when standing upright is a complex process requiring input from several partly independent mechanisms such as coordination, feedback and feedforward control, and adaptation. Acute alcohol intoxication from ethanol is recognized as a major contributor to accidental falls requiring medical care. This study aimed to investigate if intoxication at 0.06 and 0.10% blood alcohol concentration affected body alignment. Mean angular positions of the head, shoulder, hip, and knee were measured with 3D-motion analysis and compared with the ankle position in 25 healthy adults during standing with or without perturbations, and with eyes open or closed. Alcohol intoxication had significant effects on body alignment during perturbed and unperturbed stance, and on adaptation to perturbations. It induced a significantly more posterior alignment of the knees and shoulders, and a tendency for a more posterior and left deviated head alignment in perturbed stance than when sober. The impact of alcohol intoxication was most apparent on the knee alignment, where availability of visual information deteriorated the adaptation to perturbations. Thus, acute alcohol intoxication resulted in inadequate balance control strategies with increased postural rigidity and impaired adaptation to perturbations. These factors probably contribute to the increased risk of falling when intoxicated with alcohol.

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

DEFF Research Database (Denmark)

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

2008-01-01

BackgroundNitric oxide deficiency is involved in the development of hypertension, but the mechanisms are currently unclear. This study was conducted to further elucidate the role of neuronal nitric oxide synthase (nNOS) in blood pressure regulation and renin release in relation to different sodiu......-116; doi:10.1038/ajh.2007.16American Journal of Hypertension (2008) 21 111-116; doi:10.1038/ajh.2007.16....

Quality of life in patients with cognitive impairment: validation of the Quality of Life-Alzheimer's Disease scale in Portugal.

Science.gov (United States)

Bárrios, Helena; Verdelho, Ana; Narciso, Sofia; Gonçalves-Pereira, Manuel; Logsdon, Rebecca; de Mendonça, Alexandre

2013-07-01

Quality of Life-Alzheimer's Disease (QOL-AD) is a widely used scale for the study of quality of life in patients with dementia. The aim of this study is the transcultural adaptation and validation of the QOL-AD scale in Portugal. Translation and transcultural adaptation was performed according to state-of-the-art recommendations. For the validation study, 104 patient/caregiver pairs were enrolled. Patients had mild cognitive impairment or mild-to-moderate dementia (due to Alzheimer's disease or vascular dementia). Participants were recruited in a dementia outpatient clinic setting and a long-term care dementia ward. An additional comparison group of 22 patients without cognitive impairment, and their proxies, was recruited in a family practice outpatient clinic. Sociodemographic information on patients and caregivers was obtained. Acceptability, reliability, and construct validity were analyzed. Internal consistency of the Portuguese version of QOL-AD was good for both patient and caregiver report (Cronbach's α = 0.867 and 0.858, respectively). Construct validity was confirmed by the correlation of patient reported QOL-AD with patient geriatric depression scale scores (ρ = -0.702, p cognitive impairment than in the comparison group without cognitive impairment (p < 0.01). A Portuguese version of QOL-AD with consistent psychometric properties was obtained and is proposed as a useful tool for research and clinical purposes.

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

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...... of iron oxidizing bacterial in the highly oxic environments found in typical rapid sand filters. The neutrophilic FeOB were enriched by the Fe2+/O2 opposing gradient technique and quantified by MPN methodology. Diversity fingerprints of the enrichment cultures were obtained with a 16S rRNA targeted DGGE...

Concentration-related metabolic rate and behavioral thermoregulatory adaptations to serial administrations of nitrous oxide in rats

Science.gov (United States)

2018-01-01

Background Initial administration of ≥60% nitrous oxide (N2O) to rats evokes hypothermia, but after repeated administrations the gas instead evokes hyperthermia. This sign reversal is driven mainly by increased heat production. To determine whether rats will behaviorally oppose or assist the development of hyperthermia, we previously performed thermal gradient testing. Inhalation of N2O at ≥60% causes rats to select cooler ambient temperatures both during initial administrations and during subsequent administrations in which the hyperthermic state exists. Thus, an available behavioral response opposes (but does not completely prevent) the acquired hyperthermia that develops over repeated high-concentration N2O administrations. However, recreational and clinical uses of N2O span a wide range of concentrations. Therefore, we sought to determine the thermoregulatory adaptations to chronic N2O administration over a wide range of concentrations. Methods This study had two phases. In the first phase we adapted rats to twelve 3-h N2O administrations at either 0%, 15%, 30%, 45%, 60% or 75% N2O (n = 12 per group); outcomes were core temperature (via telemetry) and heat production (via respirometry). In the second phase, we used a thermal gradient (range 8°C—38°C) to assess each adapted group’s thermal preference, core temperature and locomotion on a single occasion during N2O inhalation at the assigned concentration. Results In phase 1, repeated N2O administrations led to dose related hyperthermic and hypermetabolic states during inhalation of ≥45% N2O compared to controls (≥ 30% N2O compared to baseline). In phase 2, rats in these groups selected cooler ambient temperatures during N2O inhalation but still developed some hyperthermia. However, a concentration-related increase of locomotion was evident in the gradient, and theoretical calculations and regression analyses both suggest that locomotion contributed to the residual hyperthermia. Conclusions Acquired

Secondhand smoke exposure induces acutely airway acidification and oxidative stress.

Science.gov (United States)

Kostikas, Konstantinos; Minas, Markos; Nikolaou, Eftychia; Papaioannou, Andriana I; Liakos, Panagiotis; Gougoura, Sofia; Gourgoulianis, Konstantinos I; Dinas, Petros C; Metsios, Giorgos S; Jamurtas, Athanasios Z; Flouris, Andreas D; Koutedakis, Yiannis

2013-02-01

Previous studies have shown that secondhand smoke induces lung function impairment and increases proinflammatory cytokines. The aim of the present study was to evaluate the acute effects of secondhand smoke on airway acidification and airway oxidative stress in never-smokers. In a randomized controlled cross-over trial, 18 young healthy never-smokers were assessed at baseline and 0, 30, 60, 120, 180 and 240 min after one-hour secondhand smoke exposure at bar/restaurant levels. Exhaled NO and CO measurements, exhaled breath condensate collection (for pH, H(2)O(2) and NO(2)(-)/NO(3)(-) measurements) and spirometry were performed at all time-points. Secondhand smoke exposure induced increases in serum cotinine and exhaled CO that persisted until 240 min. Exhaled breath condensate pH decreased immediately after exposure (p secondhand smoke induced airway acidification and increased airway oxidative stress, accompanied by significant impairment of lung function. Despite the reversal in EBC pH and lung function, airway oxidative stress remained increased 4 h after the exposure. Clinical trial registration number (EudraCT): 2009-013545-28. Copyright © 2012 Elsevier Ltd. All rights reserved.

Can an aversive, extinction-resistant memory trigger impairments in walking adaptability? An experimental study using adult rats.

Science.gov (United States)

Medeiros, Filipe Mello; de Carvalho Myskiw, Jociane; Baptista, Pedro Porto Alegre; Neves, Laura Tartari; Martins, Lucas Athaydes; Furini, Cristiane Regina Guerino; Izquierdo, Iván; Xavier, Léder Leal; Hollands, Kristen; Mestriner, Régis Gemerasca

2018-02-05

Cognitive demands can influence the adaptation of walking, a crucial skill to maintain body stability and prevent falls. Whilst previous research has shown emotional load tunes goal-directed movements, little attention has been given to this finding. This study sought to assess the effects of suffering an extinction-resistant memory on skilled walking performance in adult rats, as an indicator of walking adaptability. Thus, 36 Wistar rats were divided in a two-part experiment. In the first part (n=16), the aversive, extinction-resistance memory paradigm was established using a fear-conditioning chamber. In the second, rats (n=20) were assessed in a neutral room using the ladder rung walking test before and tree days after inducing an extinction-resistance memory. In addition, the elevated plus-maze test was used to control the influence of the anxiety-like status on gait adaptability. Our results revealed the shock group exhibited worse walking adaptability (lower skilled walking score), when compared to the sham group. Moreover, the immobility time in the ladder rung walking test was similar to the controls, suggesting that gait adaptability performance was not a consequence of the fear generalization. No anxiety-like behavior was observed in the plus maze test. Finally, correlation coefficients also showed the skilled walking performance score was positively correlated with the number of gait cycles and trial time in the ladder rung walking test and the total crossings in the plus maze. Overall, these preliminary findings provide evidence to hypothesize an aversive, extinction-resistant experience might change the emotional load, affecting the ability to adapt walking. Copyright © 2017. Published by Elsevier B.V.

Role of oxidative stress and DNA hydroxymethylation in the neurotoxicity of fine particulate matter

International Nuclear Information System (INIS)

Wei, Hongying; Feng, Yan; Liang, Fan; Cheng, Wei; Wu, Xiaomeng; Zhou, Ren; Wang, Yan

2017-01-01

Highlights: • Oxidative stress-mediated neurocytotoxicity and DNA hydroxymethylation abnormalities involved in neuronal pathology of PM 2.5 . • PM 2.5 particles and toxic compounds adsorbed on the particle caused different types of neurocytotoxicity. • DNA hydroxymethylation abnormalities participated in PM 2.5 -induced impairments in neurite outgrowth and synapse formation. - Abstract: Epidemiological studies have implicated fine particulate matter (PM 2.5 ) as a risk factor for neurodegenerative diseases and neurodevelopmental disorders. However, the underlying molecular mechanisms and the influences of different components remain largely elusive. Here, we extended our previous work to investigate the role of oxidative stress and DNA hydroxymethylation in neuronal pathology of PM 2.5 . We found PM 2.5 and its extracts (water-soluble extracts, organic extracts and carbon core component) differentially caused cell cycle arrest, cell apoptosis and the cell proliferation inhibition in neuronal cells. These effects were mechanistically related to each other and oxidative stress, suggesting PM 2.5 and toxic compounds adsorbed on the particles may cause different types of brain damages. In addition, PM 2.5 and its organic extracts increased global DNA hydroxymethylation and gene-specific DNA hydroxymethylation of neuronal genes, and subsequently interfered with their mRNA expression. The impairments in neuronal progression characterized with decreased length of neurite and reduced mRNA expression of neuronal markers and synaptic markers. The blocking effects of antioxidants demonstrated the involvement of oxidative stress-mediated hydroxymethylation abnormalities in PM 2.5 -induced defects in neurite outgrowth and synapse formation. Our results first revealed the role of oxidative stress-mediated abnormal DNA hydroxymethylation in neuronal impairments of PM 2.5 , and thoroughly evaluated the neurocytotoxicity of different components.

Oxidative stress resistance in Porphyromonas gingivalis

Science.gov (United States)

Henry, Leroy G; McKenzie, Rachelle ME; Robles, Antonette; Fletcher, Hansel M

2012-01-01

Porphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The harsh inflammatory condition of the periodontal pocket implies that this organism has properties that will facilitate its ability to respond and adapt to oxidative stress. Because the stress response in the pathogen is a major determinant of its virulence, a comprehensive understanding of its oxidative stress resistance strategy is vital. We discuss multiple mechanisms and systems that clearly work in synergy to defend and protect P. gingivalis against oxidative damage caused by reactive oxygen species. The involvement of multiple hypothetical proteins and/or proteins of unknown function in this process may imply other unique mechanisms and potential therapeutic targets. PMID:22439726

[The relationship between neuroendocrine dysfunction and free-radical oxidation in old age alcoholism].

Science.gov (United States)

Vinogradov, D B; Mingazov, A Kh; Izarovskaya, I V; Babin, K A; Sinitsky, A I

2015-01-01

to study the relationship between dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and free-radical oxidation in old age alcoholism. Authors examined 46 men and women, aged 60-80 years, with alcoholism. Contents of cortisol, lipid peroxidation products and the level of an oxidatively modified protein were measured. A decrease in blood cortisol content and correlations between its level and activity of free-radical oxidation were identified. The severity of neuroendocrine dysfunction in old patients was sex-related. It has been suggested that the impairment of HPA system activity may be a cause of oxidative stress and development of alcoholism.

Global transcriptional, physiological and metabolite analyses of Desulfovibrio vulgaris Hildenborough responses to salt adaptation

Energy Technology Data Exchange (ETDEWEB)

He, Z.; Zhou, A.; Baidoo, E.; He, Q.; Joachimiak, M. P.; Benke, P.; Phan, R.; Mukhopadhyay, A.; Hemme, C.L.; Huang, K.; Alm, E.J.; Fields, M.W.; Wall, J.; Stahl, D.; Hazen, T.C.; Keasling, J.D.; Arkin, A.P.; Zhou, J.

2009-12-01

The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by physiological, global transcriptional, and metabolite analyses. The growth of D. vulgaris was inhibited by high levels of NaCl, and the growth inhibition could be relieved by the addition of exogenous amino acids (e.g., glutamate, alanine, tryptophan) or yeast extract. Salt adaptation induced the expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). Genes involved in carbon metabolism, cell motility, and phage structures were repressed. Comparison of transcriptomic profiles of D. vulgaris responses to salt adaptation with those of salt shock (short-term NaCl exposure) showed some similarity as well as a significant difference. Metabolite assays showed that glutamate and alanine were accumulated under salt adaptation, suggesting that they may be used as osmoprotectants in D. vulgaris. A conceptual model is proposed to link the observed results to currently available knowledge for further understanding the mechanisms of D. vulgaris adaptation to elevated NaCl.

Saccadic gain adaptation is predicted by the statistics of natural fluctuations in oculomotor function

Directory of Open Access Journals (Sweden)

Mark V Albert

2012-12-01

Full Text Available Due to multiple factors such as fatigue, muscle strengthening, and neural plasticity, the responsiveness of the motor apparatus to neural commands changes over time. To enable precise movements the nervous system must adapt to compensate for these changes. Recent models of motor adaptation derive from assumptions about the way the motor apparatus changes. Characterizing these changes is difficult because motor adaptation happens at the same time, masking most of the effects of ongoing changes. Here, we analyze eye movements of monkeys with lesions to the posterior cerebellar vermis that impair adaptation. Their fluctuations better reveal the underlying changes of the motor system over time. When these measured, unadapted changes are used to derive optimal motor adaptation rules the prediction precision significantly improves. Among three models that similarly fit single-day adaptation results, the model that also matches the temporal correlations of the nonadapting saccades most accurately predicts multiple day adaptation. Saccadic gain adaptation is well matched to the natural statistics of fluctuations of the oculomotor plant.

Molecular basis for arsenic-Induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction

International Nuclear Information System (INIS)

Kumagai, Yoshito; Pi Jingbo

2004-01-01

Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed

The effect of valinomycin in fibroblasts from patients with fatty acid oxidation disorders

Energy Technology Data Exchange (ETDEWEB)

Ndukwe Erlingsson, Uzochi Chimdinma [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); Iacobazzi, Francesco [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); Department of Basic Medical Sciences, University of Bari, Piazza Giulio Cesare 11, Policlinico, I-70124 Bari (Italy); Liu, Aiping [ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (United States); Ardon, Orly; Pasquali, Marzia [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (United States); Department of Pathology, University of Utah, Salt Lake City, UT 84132 (United States); Longo, Nicola, E-mail: Nicola.Longo@hsc.utah.edu [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (United States); Department of Pathology, University of Utah, Salt Lake City, UT 84132 (United States)

2013-08-09

Highlights: •Valinomycin can cause mitochondrial stress and stimulate fatty acid oxidation. •Cells with VLCAD deficiency fail to increase fatty acid oxidation in response to valinomycin. •Response to valinomycin can help in the diagnosis of VLCAD deficiency. -- Abstract: Disorders of the carnitine cycle and of the beta oxidation spiral impair the ability to obtain energy from fats at time of fasting and stress. This can result in hypoketotic hypoglycemia, cardiomyopathy, cardiac arrhythmia and other chronic medical problems. The in vitro study of fibroblasts from patients with these conditions is impaired by their limited oxidative capacity. Here we evaluate the capacity of valinomycin, a potassium ionophore that increases mitochondrial respiration, to increase the oxidation of fatty acids in cells from patients with inherited fatty acid oxidation defects. The addition of valinomycin to fibroblasts decreased the accumulation of the lipophilic cation tetraphenylphosphonium (TPP{sup +}) at low concentrations due to the dissipation of the mitochondrial membrane potential. At higher doses, valinomycin increased TPP{sup +} accumulation due to the increased potassium permeability of the plasma membrane and subsequent cellular hyperpolarization. The incubation of normal fibroblasts with valinomycin increased [{sup 14}C]-palmitate oxidation (measured as [{sup 14}C]O{sub 2} release) in a dose-dependent manner. By contrast, valinomycin failed to increase palmitate oxidation in fibroblasts from patients with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This was not observed in fibroblasts from patients heterozygous for this condition. These results indicate that valinomycin can increase fatty acid oxidation in normal fibroblasts and could be useful to differentiate heterozygotes from patients affected with VLCAD deficiency.

N-acetylcysteine prevents spatial memory impairment induced by chronic early postnatal glutaric acid and lipopolysaccharide in rat pups.

Directory of Open Access Journals (Sweden)

Fernanda S Rodrigues

Full Text Available BACKGROUND AND AIMS: Glutaric aciduria type I (GA-I is characterized by accumulation of glutaric acid (GA and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC on theses markers. METHODS: Rat pups were injected with GA (5 umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life, and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period. LPS (2 mg/kg; E.coli 055 B5 or vehicle (saline 0.9% was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed. RESULTS: GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers. CONCLUSIONS: These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could

Can parenting practices predict externalizing behavior problems among children with hearing impairment?

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Pino, María J; Castillo, Rosa A; Raya, Antonio; Herruzo, Javier

2017-11-09

To identify possible differences in the level of externalizing behavior problems among children with and without hearing impairment and determine whether any relationship exists between this type of problem and parenting practices. The Behavior Assessment System for Children was used to evaluate externalizing variables in a sample of 118 boys and girls divided into two matched groups: 59 with hearing disorders and 59 normal-hearing controls. Significant between-group differences were found in hyperactivity, behavioral problems, and externalizing problems, but not in aggression. Significant differences were also found in various aspects of parenting styles. A model for predicting externalizing behavior problems was constructed, achieving a predicted explained variance of 50%. Significant differences do exist between adaptation levels in children with and without hearing impairment. Parenting style also plays an important role.

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

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

2017-05-01

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

Effective long term adaptation and metabolic state regulation of ski-racers

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A.S. Bakhareva

2016-06-01

Full Text Available Purpose: to scientifically substantiate effective mechanisms of organism’s bio-chemical adaptation of ski-racers in competition period with the help of lipid peroxidation indicators, oxidative modification of proteins and activity of hypothalamus pituitary adrenocortical system. Material: in the research 14 sportsmen of 18-25 years’ age (combined team of university with different level of sportsmanship participated. Assessment of free radical oxidation, anti-oxidant system, cortisol level was fulfilled with the help of indicators’ quantitative analysis by bio-chemical methods applied to blood serum samples. Results: it was found that in the basis of bio-chemical changes under intensive physical loads is increase of catabolic processes’ speed. Change of organism’s metabolic orientation of ski racers at optimal level results in working muscles’ energy supply improvement, increase of energy systems’ power and sports efficiency. Conclusions: Application of interval trainings at stages of preparation to special significant competitions results in expected adaptation and increase of sports efficiency. We also showed their effective role in ensuring long term reactions, conditioning high sports efficiency.

[The impact of personality traits on adolescents' adaptation and compliance to clear retainers].

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Xu, Fan; Tang, Guo-Hua

2017-02-01

The aim of this study was to evaluate the adolescents' adaptation and compliance to clear retainers, and to investigate their associations with personality traits. Fifty adolescents at the end of fixed orthodontic treatment were consecutively recruited. After debonding the fixed orthodontic appliances, clear retainers were used. Participants were asked to fill questionnaires 2 months after wearing the clear retainers. A questionnaire was designed to evaluate their adaptation and compliance for clear retianers. Eysenck personality questionnaire was used to assess the personality traits. Spearman rank correlation was used to analyze the associations between personality traits with the adaptation and compliance to clear retainers using SAS8.0 software package. Forty-two of 50 adolescents accomplished the questionnaires. 76% felt no mucous irritation, 95% felt no influence on socializing. However, 75% showed oral constraint, 71% felt impaired speech. Moreover, 40% adolescents wore the retainers less than 18 hours per day. 31% patients had their aligner lost. 83% patients did not brush their teeth after each meal. Neuroticism was positively associated with the effect of impaired chewing (r=0.32). Psychoticism was positively associated with the oral constraint (r=0.31) and facial muscular soreness (r=0.35), but negatively associated with the influence on emotion (r=-0.34). Extraversion was positively associated with the retainers' damage (r=0.31). Adolescents showed good adaptation for clear retainers, but unsatisfactory compliance. There are associations between adolescents' adaptation and compliance for clear retainers and personality traits. These results suggest that clinicians should pay more attention to the compliance of adolescents when using clear retainer. Personality traits could be a useful prediction to assess the compliance for clear aligners.

Quantification of oxidative stress phenotypes based on high-throughput growth profiling of protein kinase and phosphatase knockouts

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Altıntaş, Ali; Martini, Jacopo; Mortensen, Uffe Hasbro

2016-01-01

Cellular responses to oxidative stress are important for restoring redox balance and ensuring cell survival. Genetic defects in response factors can lead to impaired response to oxidative damage and contribute to disease and aging. In single cell organisms, such as yeasts, the integrity of the ox...

Improvement in grade of minerals using simultaneous Bio-oxidation of invisible gold concentrate and deep-sea manganese crust

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Myung, EunJi; Cho, Kang Hee; Kim, Hyun Soo; Park, Cheon Young

2016-04-01

Many sulfides of metal such as galena, sphalerite, chalcopyrite, and pyrite, are semiconductors. When two kinds of such minerals contact each other in an electrolyte, a galvanic couple, where the mineral of lower rest potential as anode, and that of higher rest potential as cathode forms. Manganese dioxide is also a semiconductor with much higher rest potential than all sulfides mentioned above, so that a galvanic couple in which both the minerals would dissolve simultaneously can form, when it contacts with any of the sulfides. The aim of this study was to investigate the improvement in grade of minerals using the simultaneous bio-oxidation of deep-sea manganese crust and invisible gold concentrate. The samples(deep-sea manganese crust and invisible gold concentrate) were characterized by chemical and XRD analysis. The primary components of the invisible gold concentrate was pyrite and quartz and the deep-sea manganese crust was amorphous material, as detected using XRD. The result of chemical analysis showed that Au, Ag, Te contents in the invisible gold concentrate 130.2, 954.1 and 1,043.6 mg/kg, respectively. and that Mn, Ni, Co contents in the deep-sea manganese crust 19,501.5, 151.9, 400.4 mg/kg, respectively. In order to increase the bacteria's tolerance of heavy metals, the bacteria using bio-oxidation experiments were repeatedly subcultured in an Cu adaptation-medium containing of 382.98 mg/l for 20 periods of 21 days. The improvement in grade of samples of in present adapted bacteria condition was greater than another conditions(control and in present non-adapted bacteria). The Au-Ag-Te contents in the invisible gold concentrate was enhanced in the order of physical oxidation, simultaneous/non-adaptive bio-oxidation, adaptive/bio-oxidation, simultaneous/adaptive bio-oxidation. If the bacteria is adapted to heavy metal ions and an optimization of conditions is found in future bio-oxidation-leaching processes. Acknowledgment : "This research was supported

Cerebellar inactivation impairs memory of learned prism gaze-reach calibrations.

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Norris, Scott A; Hathaway, Emily N; Taylor, Jordan A; Thach, W Thomas

2011-05-01

Three monkeys performed a visually guided reach-touch task with and without laterally displacing prisms. The prisms offset the normally aligned gaze/reach and subsequent touch. Naive monkeys showed adaptation, such that on repeated prism trials the gaze-reach angle widened and touches hit nearer the target. On the first subsequent no-prism trial the monkeys exhibited an aftereffect, such that the widened gaze-reach angle persisted and touches missed the target in the direction opposite that of initial prism-induced error. After 20-30 days of training, monkeys showed long-term learning and storage of the prism gaze-reach calibration: they switched between prism and no-prism and touched the target on the first trials without adaptation or aftereffect. Injections of lidocaine into posterolateral cerebellar cortex or muscimol or lidocaine into dentate nucleus temporarily inactivated these structures. Immediately after injections into cortex or dentate, reaches were displaced in the direction of prism-displaced gaze, but no-prism reaches were relatively unimpaired. There was little or no adaptation on the day of injection. On days after injection, there was no adaptation and both prism and no-prism reaches were horizontally, and often vertically, displaced. A single permanent lesion (kainic acid) in the lateral dentate nucleus of one monkey immediately impaired only the learned prism gaze-reach calibration and in subsequent days disrupted both learning and performance. This effect persisted for the 18 days of observation, with little or no adaptation.

Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4'-dipyridyl disulfide

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López-Mirabal, H Reynaldo; Thorsen, Michael; Kielland-Brandt, Morten C

2007-01-01

Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS is very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma-glutamyl-c......Dipyridyl disulfide (DPS) is a highly reactive thiol oxidant that functions as electron acceptor in thiol-disulfide exchange reactions. DPS is very toxic to yeasts, impairing growth at low micromolar concentrations. The genes TRX2 (thioredoxin), SOD1 (superoxide dismutase), GSH1 (gamma...... antioxidant pools of glutathione (GSH) and thioredoxin are required for resistance to DPS. We found that DPS-sensitive mutants display increases in the disulfide form of GSH (GSSG) during DPS exposure that roughly correlate with their more oxidizing GSH redox potential in the cytosol and their degree of DPS...

The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

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Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M; Tan, Huiling; Brown, Peter

2017-04-01

Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could

Chronic exposure to low frequency noise at moderate levels causes impaired balance in mice.

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Haruka Tamura

Full Text Available We are routinely exposed to low frequency noise (LFN; below 0.5 kHz at moderate levels of 60-70 dB sound pressure level (SPL generated from various sources in occupational and daily environments. LFN has been reported to affect balance in humans. However, there is limited information about the influence of chronic exposure to LFN at moderate levels for balance. In this study, we investigated whether chronic exposure to LFN at a moderate level of 70 dB SPL affects the vestibule, which is one of the organs responsible for balance in mice. Wild-type ICR mice were exposed for 1 month to LFN (0.1 kHz and high frequency noise (HFN; 16 kHz at 70 dB SPL at a distance of approximately 10-20 cm. Behavior analyses including rotarod, beam-crossing and footprint analyses showed impairments of balance in LFN-exposed mice but not in non-exposed mice or HFN-exposed mice. Immunohistochemical analysis showed a decreased number of vestibular hair cells and increased levels of oxidative stress in LFN-exposed mice compared to those in non-exposed mice. Our results suggest that chronic exposure to LFN at moderate levels causes impaired balance involving morphological impairments of the vestibule with enhanced levels of oxidative stress. Thus, the results of this study indicate the importance of considering the risk of chronic exposure to LFN at a moderate level for imbalance.

Book4All: A Tool to Make an e-Book More Accessible to Students with Vision/Visual-Impairments

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Calabrò, Antonello; Contini, Elia; Leporini, Barbara

Empowering people who are blind or otherwise visually impaired includes ensuring that products and electronic materials incorporate a broad range of accessibility features and work well with screen readers and other assistive technology devices. This is particularly important for students with vision impairments. Unfortunately, authors and publishers often do not include specific criteria when preparing the contents. Consequently, e-books can be inadequate for blind and low vision users, especially for students. In this paper we describe a semi-automatic tool developed to support operators who adapt e-documents for visually impaired students. The proposed tool can be used to convert a PDF e-book into a more suitable accessible and usable format readable on desktop computer or on mobile devices.

Tutoring math platform accessible for visually impaired people.

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Maćkowski, Michał Sebastian; Brzoza, Piotr Franciszek; Spinczyk, Dominik Roland

2018-04-01

There are many problems with teaching and assessing impaired students in higher education, especially in technical science, where the knowledge is represented mostly by structural information like: math formulae, charts, graphs, etc. Developing e-learning platform for distance education solves this problem only partially due to the lack of accessibility for the blind. The proposed method is based on the decomposition of the typical mathematical exercise into a sequence of elementary sub-exercises. This allows for interactive resolving of math exercises and assessment of the correctness of exercise solutions at every stage. The presented methods were prepared and evaluated by visually impaired people and students. The article presents the accessible interactive tutoring platform for math teaching and assessment, and experience in exploring it. The results of conducted research confirm good understanding of math formulae described according to elaborated rules. Regardless of the level of complexity of the math formulae the level of math formulae understanding is higher for alternative structural description. The proposed solution enables alternative descriptions of math formulae. Based on the research results, the tool for computer-aided interactive learning of mathematics adapted to the needs of the blind has been designed, implemented and deployed as a platform for on-site and online and distance learning. The designed solution can be very helpful in overcoming many barriers that occur while teaching impaired students. Copyright © 2017 Elsevier Ltd. All rights reserved.

Longitudinal Investigation of Adaptive Functioning following Conformal Irradiation for Pediatric Craniopharyngioma and Low-Grade Glioma

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Netson, Kelli L.; Conklin, Heather M.; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E.

2013-01-01

Purpose Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated. Methods and Materials Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity-modulated radiation therapy. The median age was 8.05 years (3.21 years –17.64 years) and 8.09 years (2.20 years–19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at pre-irradiation baseline, 6 months after treatment, and annually through 5 years. A total of 588 evaluations were completed during the follow-up period. Results Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (p craniopharyngioma. Children with LGG performed below population norms (p < .05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (p < .05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. Conclusions There was relative sparing of post-irradiation functional outcomes over time in this sample. Baseline differences in functional abilities prior to the initiation of irradiation suggested that other factors influence functional outcomes above and beyond the effects of irradiation. PMID:23245284

Cyclic Oxidation and Hot Corrosion of NiCrY-Coated Disk Superalloys

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Gabb, Timothy P.; Miller, Robert A.; Sudbrack, Chantal K.; Draper, Susan L.; Nesbitt, James A.; Rogers, Richard B.; Telesman, Ignacy; Ngo, Vanda; Healy, Jonathan

2016-01-01

Powder metallurgy disk superalloys have been designed for higher engine operating temperatures through improvement of their strength and creep resistance. Yet, increasing disk application temperatures to 704 degrees Centigrade and higher could enhance oxidation and activate hot corrosion in harmful environments. Protective coatings could be necessary to mitigate such attack. Cylindrical coated specimens of disk superalloys LSHR and ME3 were subjected to thermal cycling to produce cyclic oxidation in air at a maximum temperature of 760 degrees Centigrade. The effects of substrate roughness and coating thickness on coating integrity after cyclic oxidation were considered. Selected coated samples that had cyclic oxidation were then subjected to accelerated hot corrosion tests. This cyclic oxidation did not impair the coating's resistance to subsequent hot corrosion pitting attack.

Oxidative stress and CCN1 protein in human skin connective tissue aging

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Zhaoping Qin

2016-06-01

Full Text Available Reactive oxygen species (ROS is an important pathogenic factor involved in human aging. Human skin is a primary target of oxidative stress from ROS generated from both extrinsic and intrinsic sources, like ultraviolet irradiation (UV and endogenous oxidative metabolism. Oxidative stress causes the alterations of collagen-rich extracellular matrix (ECM, the hallmark of skin connective tissue aging. Age-related alteration of dermal collagenous ECM impairs skin structural integrity and creates a tissue microenvironment that promotes age-related skin diseases, such as poor wound healing and skin cancer. Here, we review recent advances in our understanding of oxidative stress and CCN1 protein (first member of CCN family proteins, a critical mediator of oxidative stress-induced skin connective tissue aging.

Crocin Improved Learning and Memory Impairments in Streptozotocin-Induced Diabetic Rats

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Esmaeal Tamaddonfard

2013-01-01

Full Text Available Objective(s: Crocin influences many biological functions including memory and learning. The present study was aimed to investigate the effects of crocin on learning and memory impairments in streptozotocine-induced diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (IP injection of streptozotocin (STZ, 45 mg/kg. Transfer latency (TL paradigm in elevated plus-maze (EPM was used as an index of learning and memory. Plasma levels of total antioxidant capacity (TAC and malondialdehyde (MDA, blood levels of glucose, and serum concentrations of insulin were measured. The number of hippocampal neurons was also counted. Results: STZ increased acquisition transfer latency (TL1 and retention transfer latency (TL2, and MDA, decreased transfer latency shortening (TLs and TCA, produced hyperglycemia and hypoinsulinemia, and reduced the number of neurons in the hippocampus. Learning and memory impairments and blood TCA, MDA, glucose, and insulin changes induced by streptozotocin were improved with long-term IP injection of crocin at doses of 15 and 30 mg/kg. Crocin prevented hippocampal neurons number loss in diabetic rats. Conclusion: The results indicate that oxidative stress, hyperglycemia, hypoinsulinemia, and reduction of hippocampal neurons may be involved in learning and memory impairments in STZ-induced diabetic rats. Antioxidant, antihyperglycemic, antihypoinsulinemic, and neuroprotective activities of crocin might be involved in improving learning and memory impairments.

Tetrahydrobiopterin in antenatal brain hypoxia-ischemia-induced motor impairments and cerebral palsy.

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Vasquez-Vivar, Jeannette; Shi, Zhongjie; Luo, Kehuan; Thirugnanam, Karthikeyan; Tan, Sidhartha

2017-10-01

Antenatal brain hypoxia-ischemia, which occurs in cerebral palsy, is considered a significant cause of motor impairments in children. The mechanisms by which antenatal hypoxia-ischemia causes brain injury and motor deficits still need to be elucidated. Tetrahydrobiopterin is an important enzyme cofactor that is necessary to produce neurotransmitters and to maintain the redox status of the brain. A genetic deficiency of this cofactor from mutations of biosynthetic or recycling enzymes is a well-recognized factor in the development of childhood neurological disorders characterized by motor impairments, developmental delay, and encephalopathy. Experimental hypoxia-ischemia causes a decline in the availability of tetrahydrobiopterin in the immature brain. This decline coincides with the loss of brain function, suggesting this occurrence contributes to neuronal dysfunction and motor impairments. One possible mechanism linking tetrahydrobiopterin deficiency, hypoxia-ischemia, and neuronal injury is oxidative injury. Evidence of the central role of the developmental biology of tetrahydrobiopterin in response to hypoxic ischemic brain injury, especially the development of motor deficits, is discussed. Copyright © 2017. Published by Elsevier B.V.