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Sample records for metabolic activity decreasing

  1. Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

    Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

    2015-02-01

    Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

  2. Metabolic consequences of decreased nitric oxide synthesis in the hearth

    Pechanova, O.; Bernatova, I.; Pelouch, V.

    1998-01-01

    The aim of the present study was to determine long-term effect of NO-synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) on concentrations of cyclic nucleotides, nucleic acids and of collagenous proteins in the left ventricle. Male Wistar rats were investigated. NO-synthase activity in the homogenates of left ventricle was determined by measuring the formation of 3 H]-L-citrulline from [ 3 H]-L-arginine. Cyclic GMP and cAMP concentrations were determined by using radioimmunoassay procedures and commercial cGMP and cAMP 125 I scintillation proximity assay systems.Significantly more remarkable decrease of NO-synthase activity was recorded in the group with higher dose (40 mg/kg/day) of L-NAME. The changes in metabolic parameters corresponded well with the dose-depend decrease of NO-synthase activity. (authors)

  3. Decreased spontaneous activity in AMPK alpha 2 muscle specific kinase dead mice is not caused by changes in brain dopamine metabolism

    Møller, Lisbeth Liliendal Valbjørn; Sylow, Lykke; Gøtzsche, Casper René

    2016-01-01

    was tested in an open field test. Furthermore, we investigated maximal running capacity and voluntary running over a period of 19 days. AMPK α2 KD mice ran 30% less in daily distance compared to WT. Furthermore, AMPK α2 KD mice showed significantly decreased locomotor activity in the open field test compared...... through alterations of the brain dopamine levels specifically in the striatal region. To test this hypothesis, transgenic mice overexpressing an inactivatable dominant negative α2 AMPK construct (AMPK α2 KD) in muscles and littermate wildtype (WT) mice were tested. AMPK α2 KD mice have impaired running...... capacity and display reduced voluntary wheel running activity. Striatal content of dopamine and its metabolites were measured under basal physiological conditions and after cocaine-induced dopamine efflux from the ventral striatum by in vivo microdialysis. Moreover, cocaine-induced locomotor activity...

  4. High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium

    Zhongyan Lu

    2018-03-01

    Full Text Available Background/Aims: In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. Methods: RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive. In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. Results: The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. Conclusions: These results indicated that the

  5. High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium.

    Lu, Zhongyan; Shen, Hong; Shen, Zanming

    2018-01-01

    In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive). In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. These results indicated that the alterations of cellular metabolism promote the alterations in cellular

  6. Prokaryote metabolism activity

    Biederman, Lori

    2017-01-01

    I wrote this activity to emphasize that prokaryotic organisms can carry out 6 different types of metabolisms (as presented in Freeman’s Biological Science textbook) and this contrasts to eukaryotes, which can only use 2 metabolism pathways (photoautotroph and heterotroph).    For in class materials I remove the  red box (upper right corner) and print slides 3-10, place them back-to-back and laminate them.  The students get a key (slide 2) and a two-sided organism sheet...

  7. Obese individuals with more components of the metabolic syndrome and/or prediabetes demonstrate decreased activation of reward-related brain centers in response to food cues in both the fed and fasting states: a preliminary fMRI study.

    Farr, O M; Mantzoros, C S

    2017-03-01

    It remains unknown whether obese individuals with more components of the metabolic syndrome and/or prediabetes demonstrate altered activation of brain centers in response to food cues. We examined obese individuals with prediabetes (n=26) vs obese individuals without prediabetes (n=11) using fMRI. We also performed regression analyses on the basis of the number of MetS components per subject. Obese individuals with prediabetes have decreased activation of the reward-related putamen in the fasting state and decreased activation of the salience- and reward-related insula after eating. Obese individuals with more components of MetS demonstrate decreased activation of the putamen while fasting. All these activations remain significant when corrected for BMI, waist circumference (WC), HbA1c and gender. Decreased activation in the reward-related central nervous system areas among the obese is more pronounced in subjects with prediabetes and MetS. Prospective studies are needed to quantify their contributions to the development of prediabetes/MetS and to study whether they may predispose to the exacerbation of obesity and the development of comorbidities over time.

  8. Low doses of alcohol substantially decrease glucose metabolism in the human brain.

    Volkow, Nora D; Wang, Gene-Jack; Franceschi, Dinko; Fowler, Joanna S; Thanos, Panayotis Peter K; Maynard, Laurence; Gatley, S John; Wong, Christopher; Veech, Richard L; Kunos, George; Kai Li, Ting

    2006-01-01

    Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that blood-borne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain.

  9. Impaired Glucose Metabolism Despite Decreased Insulin Resistance After Renal Transplantation

    Manfred Hecking

    2012-06-01

    Full Text Available The pathophysiology underlying new-onset diabetes after transplantation (NODAT is unresolved. We obtained demographics and laboratory data from all 1064 renal transplant recipients followed at our outpatient clinic in 2009/2010, randomly assigned 307 patients without previously diagnosed diabetes to a routine 2-hour oral glucose tolerance test (OGTT, and compared the metabolic results to a large, unrelated cross-sectional cohort of non-transplanted subjects. Among renal transplant recipients, 11% had a history of NODAT, and 12% had type 1 and type 2 diabetes. 42% of all OGTTs were abnormal (9% diabetic, predominantly in older patients who received tacrolimus. Compared to non-transplanted subjects, basal glucose was lower and HbA1c higher in renal transplant patients. Compared to non-transplanted subjects, insulin secretion was inferior, and insulin sensitivity improved at ≥6 months, as well as 3 months post-transplantation:(The Figure shows linear spline interpolation; all p for overall difference between non-Tx and Tx patients <0.02, using likelihood ratio testing. Our results indicate that impaired insulin secretion is the predominant problem after renal transplantation, suggesting benefit for therapeutic regimens that preserve beta cell function after renal transplantation. The mechanism of increased insulin sensitivity might be pathophysiologically similar to pancreatogenic diabetes.fx1

  10. Decreased occipital lobe metabolism by FDG-PET/CT

    Solnes, Lilja; Nalluri, Abhinav; Cohen, Jesse; Jones, Krystyna M.; Zan, Elcin; Javadi, Mehrbod S.; Venkatesan, Arun

    2017-01-01

    Objective: To compare brain metabolism patterns on fluorodeoxyglucose (FDG)-PET/CT in anti–NMDA receptor and other definite autoimmune encephalitis (AE) and to assess how these patterns differ between anti–NMDA receptor neurologic disability groups. Methods: Retrospective review of clinical data and initial dedicated brain FDG-PET/CT studies for neurology inpatients with definite AE, per published consensus criteria, treated at a single academic medical center over a 10-year period. Z-score maps of FDG-PET/CT were made using 3-dimensional stereotactic surface projections in comparison to age group–matched controls. Brain region mean Z scores with magnitudes ≥2.00 were interpreted as significant. Comparisons were made between anti–NMDA receptor and other definite AE patients as well as among patients with anti–NMDA receptor based on modified Rankin Scale (mRS) scores at the time of FDG-PET/CT. Results: The medial occipital lobes were markedly hypometabolic in 6 of 8 patients with anti–NMDA receptor encephalitis and as a group (Z = −4.02, interquartile range [IQR] 2.14) relative to those with definite AE (Z = −2.32, 1.46; p = 0.004). Among patients with anti–NMDA receptor encephalitis, the lateral and medial occipital lobes were markedly hypometabolic for patients with mRS 4–5 (lateral occipital lobe Z = −3.69, IQR 1; medial occipital lobe Z = −4.08, 1) compared with those with mRS 0–3 (lateral occipital lobe Z = −0.83, 2; p occipital lobe Z = −1.07, 2; p = 0.001). Conclusions: Marked medial occipital lobe hypometabolism by dedicated brain FDG-PET/CT may serve as an early biomarker for discriminating anti–NMDA receptor encephalitis from other AE. Resolution of lateral and medial occipital hypometabolism may correlate with improved neurologic status in anti–NMDA receptor encephalitis. PMID:29159205

  11. Pulmonary metabolism of foreign compounds: Its role in metabolic activation

    Cohen, G.M.

    1990-01-01

    The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity

  12. Increased physical activity decreases periodontitis risk in men

    Merchant, Anwar T.; Pitiphat, Waranuch; Rimm, Eric B.; Joshipura, Kaumudi

    2003-01-01

    Background: Increased physical activity improves insulin sensitivity and glucose metabolism, and may therefore affect incidence of periodontitis. Methods: We studied the association of physical activity, walking and periodontitis in 39,461 male, US based, health professionals, 40-75 years old at baseline, more than half of whom were dentists, being followed up continuously since 1986. Participants were free of periodontitis, coronary heart disease and stroke at the start of follow-up. Physical activity and periodontitis were measured by validated questionnaires (expressed in metabolic equivalents - METs); the first report of professionally diagnosed periodontitis was considered a case. Results: Periodontitis risk decreased by 3% for every 10-MET increase in average physical activity after adjustment for age, smoking, diabetes, BMI, alcohol consumption and total calories (RR = 0.97; 95% CI: 0.95-0.99). The inverse trend remained significant in the categorical analysis. Compared to men in the lowest quintile of physical activity, those in the highest quintile had a 13% lower risk of periodontitis (RR = 0.87; 95% CI: 0.76-1.01, p-value, test for trend = 0.02). In a sub-sample of men with radiographs (n = 137) the physically active had less average bone loss (β = -0.29, p-value = 0.03) after multivariate adjustment compared to those inactive. Conclusions: In this large-scale prospective study, we found an inverse, linear association between sustained physical activity and periodontitis independent of known risk factors. The benefits of a physically active lifestyle may extend to periodontal health

  13. Statistical probabilistic mapping in the individual brain space: decreased metabolism in epilepsy with FDG PET

    Oh, Jung Su; Lee, Jae Sung; Kim, Yu Kyeong; Chung, June Key; Lee, Myung Chul; Lee, Dong Soo

    2005-01-01

    In the statistical probabilistic mapping, commonly, differences between two or more groups of subjects are statistically analyzed following spatial normalization. However, to our best knowledge, there is few study which performed the statistical mapping in the individual brain space rather than in the stereotaxic brain space, i.e., template space. Therefore, in the current study, a new method for mapping the statistical results in the template space onto individual brain space has been developed. Four young subjects with epilepsy and their age-matched thirty normal healthy subjects were recruited. Both FDG PET and T1 structural MRI was scanned in these groups. Statistical analysis on the decreased FDG metabolism in epilepsy was performed on the SPM with two sample t-test (p < 0.001, intensity threshold 100). To map the statistical results onto individual space, inverse deformation was performed as follows. With SPM deformation toolbox, DCT (discrete cosine transform) basis-encoded deformation fields between individual T1 images and T1 MNI template were obtained. Afterward, inverse of those fields, i.e., inverse deformation fields were obtained. Since both PET and T1 images have been already normalized in the same MNI space, inversely deformed results in PET is on the individual brain MRI space. By applying inverse deformation field on the statistical results of the PET, the statistical map of decreased metabolism in individual spaces were obtained. With statistical results in the template space, localization of decreased metabolism was in the inferior temporal lobe, which was slightly inferior to the hippocampus. The statistical results in the individual space were commonly located in the hippocampus, where the activation should be decreased according to a priori knowledge of neuroscience. With our newly developed statistical mapping on the individual spaces, the localization of the brain functional mapping became more appropriate in the sense of neuroscience

  14. Statistical probabilistic mapping in the individual brain space: decreased metabolism in epilepsy with FDG PET

    Oh, Jung Su; Lee, Jae Sung; Kim, Yu Kyeong; Chung, June Key; Lee, Myung Chul; Lee, Dong Soo [Seoul National University Hospital, Seoul (Korea, Republic of)

    2005-07-01

    In the statistical probabilistic mapping, commonly, differences between two or more groups of subjects are statistically analyzed following spatial normalization. However, to our best knowledge, there is few study which performed the statistical mapping in the individual brain space rather than in the stereotaxic brain space, i.e., template space. Therefore, in the current study, a new method for mapping the statistical results in the template space onto individual brain space has been developed. Four young subjects with epilepsy and their age-matched thirty normal healthy subjects were recruited. Both FDG PET and T1 structural MRI was scanned in these groups. Statistical analysis on the decreased FDG metabolism in epilepsy was performed on the SPM with two sample t-test (p < 0.001, intensity threshold 100). To map the statistical results onto individual space, inverse deformation was performed as follows. With SPM deformation toolbox, DCT (discrete cosine transform) basis-encoded deformation fields between individual T1 images and T1 MNI template were obtained. Afterward, inverse of those fields, i.e., inverse deformation fields were obtained. Since both PET and T1 images have been already normalized in the same MNI space, inversely deformed results in PET is on the individual brain MRI space. By applying inverse deformation field on the statistical results of the PET, the statistical map of decreased metabolism in individual spaces were obtained. With statistical results in the template space, localization of decreased metabolism was in the inferior temporal lobe, which was slightly inferior to the hippocampus. The statistical results in the individual space were commonly located in the hippocampus, where the activation should be decreased according to a priori knowledge of neuroscience. With our newly developed statistical mapping on the individual spaces, the localization of the brain functional mapping became more appropriate in the sense of neuroscience.

  15. Decreased active vasodilator sensitivity in aged skin.

    Kenney, W L; Morgan, A L; Farquhar, W B; Brooks, E M; Pierzga, J M; Derr, J A

    1997-04-01

    Older men and women respond to local and reflex-mediated heat stress with an attenuated increase in cutaneous vascular conductance (CVC). This study was performed to test the hypothesis that an augmented or sustained noradrenergic vasoconstriction (VC) may play a role in this age-related difference. Fifteen young (22 +/- 1 yr) and 15 older (66 +/- 1 yr) men exercised at 50% peak oxygen uptake in a 36 degrees C environment. Skin perfusion was monitored at two sites on the right forearm by laser-Doppler flowmetry: one site pretreated with bretylium tosylate (BT) to block the local release of norepinephrine and thus VC and an adjacent control site. Blockade of reflex VC was verified during whole body cooling using a water-perfused suit. CVC (perfusion divided by mean arterial pressure) at each site was reported as a percentage of the maximal CVC (%CVCmax) induced at the end of each experiment by prolonged local heating at 42 degrees C. Neither age nor BT affected the %CVCmax (75-86%) attained at high core temperatures. During the early rise phase of CVC, the %CVCmax-change in esophageal temperature (delta T(es)) curve was shifted to the right in the older men (effective delta T(es) associated with 50% CVC response for young, 0.22 +/- 0.04 and 0.39 +/- 0.04 degrees C and for older, 0.73 +/- 0.04 and 0.85 +/- 0.04 degrees C at control and BT sites, respectively). BT had no interactive effect on this age difference, suggesting a lack of involvement of the VC system in the attenuated CVC response of individuals over the age of 60 yr. Additionally, increases in skin vascular conductance were quantitatively compared by measuring increases in total forearm vascular conductance (FVC, restricted to the forearm skin under these conditions). After the initial approximately 0.2 degrees C increase in T(es), FVC was 40-50% lower in the older men (P < 0.01) for the remainder of the exercise. Decreased active vasodilator sensitivity to increasing core temperature, coupled with

  16. Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism

    Murugaiyan, Jayaseelan; Rockstroh, Maxie; Wagner, Juliane [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Baumann, Sven [Department of Metabolomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Schorsch, Katrin [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Trump, Saskia; Lehmann, Irina [Department of Environmental Immunology, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Bergen, Martin von [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Department of Environmental Immunology, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Aalborg (Denmark); Tomm, Janina M., E-mail: Janina.tomm@ufz.de [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany)

    2013-06-15

    There is a clear evidence that environmental pollutants, such as benzo[a]pyrene (B[a]P), can have detrimental effects on the immune system, whereas the underlying mechanisms still remain elusive. Jurkat T cells share many properties with native T lymphocytes and therefore are an appropriate model to analyze the effects of environmental pollutants on T cells and their activation. Since environmental compounds frequently occur at low, not acute toxic concentrations, we analyzed the effects of two subtoxic concentrations, 50 nM and 5 μM, on non- and activated cells. B[a]P interferes directly with the stimulation process as proven by an altered IL-2 secretion. Furthermore, B[a]P exposure results in significant proteomic changes as shown by DIGE analysis. Pathway analysis revealed an involvement of the AhR independent Nrf2 pathway in the altered processes observed in unstimulated and stimulated cells. A participation of the Nrf2 pathway in the change of IL-2 secretion was confirmed by exposing cells to the Nrf2 activator tBHQ. tBHQ and 5 μM B[a]P caused similar alterations of IL-2 secretion and glutamine/glutamate metabolism. Moreover, the proteome changes in unstimulated cells point towards a modified regulation of the cytoskeleton and cellular stress response, which was proven by western blotting. Additionally, there is a strong evidence for alterations in metabolic pathways caused by B[a]P exposure in stimulated cells. Especially the glutamine/glutamate metabolism was indicated by proteome pathway analysis and validated by metabolite measurements. The detrimental effects were slightly enhanced in stimulated cells, suggesting that stimulated cells are more vulnerable to the environmental pollutant model compound B[a]P. - Highlights: • B[a]P affects the proteome of Jurkat T cells also at low concentrations. • Exposure to B[a]P (50 nM, 5 μM) did not change Jurkat T cell viability. • Both B[a]P concentrations altered the IL-2 secretion of stimulated cells.

  17. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  18. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  19. Sedentary activity associated with metabolic syndrome independent of physical activity

    Bankoski, Andrea; Harris, Tamara B; McClain, James J

    2011-01-01

    This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults.......This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults....

  20. Physical activity as a metabolic stressor.

    Coyle, E F

    2000-08-01

    Both physical activity and diet stimulate processes that, over time, alter the morphologic composition and biochemical function of the body. Physical activity provides stimuli that promote very specific and varied adaptations according to the type, intensity, and duration of exercise performed. There is further interest in the extent to which diet or supplementation can enhance the positive stimuli. Prolonged walking at low intensity presents little metabolic, hormonal, or cardiovascular stress, and the greatest perturbation from rest appears to be from increased fat oxidation and plasma free fatty acid mobilization resulting from a combination of increased lipolysis and decreased reesterification. More intense jogging or running largely stimulates increased oxidation of glycogen and triacylglycerol, both of which are stored directly within the muscle fibers. Furthermore, these intramuscular stores of carbohydrate and fat appear to be the primary substrates for the enhanced oxidative and performance ability derived from endurance training-induced increases in muscle mitochondrial density. Weightlifting that produces fatigue in brief periods (ie, in 15-90 s and after 15 repetitive contractions) elicits a high degree of motor unit recruitment and muscle fiber stimulation. This is a remarkably potent stimulus for altering protein synthesis in muscle and increasing neuromuscular function. The metabolic stress of physical activity can be measured by substrate turnover and depletion, cardiovascular response, hormonal perturbation, accumulation of metabolites, or even the extent to which the synthesis and degradation of specific proteins are altered, either acutely or by chronic exercise training.

  1. VISCOSITY DICTATES METABOLIC ACTIVITY of Vibrio ruber

    Maja eBoric

    2012-07-01

    Full Text Available Little is known about metabolic activity of bacteria, when viscosity of their environment changes. In this work, bacterial metabolic activity in media with viscosity ranging from 0.8 to 29.4 mPas was studied. Viscosities up to 2.4 mPas did not affect metabolic activity of Vibrio ruber. On the other hand, at 29.4 mPas respiration rate and total dehydrogenase activity increased 8 and 4-fold, respectively. The activity of glucose-6-phosphate dehydrogenase increased up to 13-fold at higher viscosities. However, intensified metabolic activity did not result in faster growth rate. Increased viscosity delayed the onset as well as the duration of biosynthesis of prodigiosin. As an adaptation to viscous environment V. ruber increased metabolic flux through the pentose phosphate pathway and reduced synthesis of a secondary metabolite. In addition, V. ruber was able to modify the viscosity of its environment.

  2. Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice

    Lin, Ai-Ling; Pulliam, Daniel A; Deepa, Sathyaseelan S; Halloran, Jonathan J; Hussong, Stacy A; Burbank, Raquel R; Bresnen, Andrew; Liu, Yuhong; Podlutskaya, Natalia; Soundararajan, Anuradha; Muir, Eric; Duong, Timothy Q; Bokov, Alex F; Viscomi, Carlo; Zeviani, Massimo; Richardson, Arlan G; Van Remmen, Holly; Fox, Peter T; Galvan, Veronica

    2013-01-01

    Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders. PMID:23838831

  3. Clinical correlates of decreased anteroposterior metabolic gradients in positron emission tomography (PET) of schizophrenic patients

    DeLisi, L.E.; Buchsbaum, M.S.; Holcomb, H.H.

    1985-01-01

    The finding in schizophrenic patients of a reversal of the normal frontal to posterior pattern of brain metabolic activity with positron emission tomography (PET) is of interest, but its relevance to psychopathology is unknown. Using PET, the authors studied 21 patients with chronic schizophrenia and 21 age- and sex-matched control subjects. Although eight of the 21 patients and only one of the control subjects showed a relatively lower anteroposterior metabolic gradient, no clinical correlates of this finding were noted. In addition, cerebral atrophy, as determined by CAT scan, was not associated with this aberrant metabolic pattern

  4. Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

    Jialin Xu

    Full Text Available AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD, regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting. METHODS AND RESULTS: Male C57BL/6 (WT and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36 and Fatty acid transport protein (FATP 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

  5. Experimental sources of variation in avian energetics: estimated basal metabolic rate decreases with successive measurements.

    Jacobs, Paul J; McKechnie, Andrew E

    2014-01-01

    Basal metabolic rate (BMR) is one of the most widely used metabolic variables in endotherm ecological and evolutionary physiology. Surprisingly few studies have investigated how BMR is influenced by experimental and analytical variables over and above the standardized conditions required for minimum normothermic resting metabolism. We tested whether avian BMR is affected by habituation to the conditions experienced during laboratory gas exchange measurements by measuring BMR five times in succession in budgerigars (Melopsittacus undulatus) housed under constant temperature and photoperiod. Both the magnitude and the variability of BMR decreased significantly with repeated measurements, from 0.410 ± 0.092 W (n = 9) during the first measurement to 0.285 ± 0.042 W (n = 9) during the fifth measurement. Thus, estimated BMR decreased by ∼30% within individuals solely on account of the number of times they had previously experienced the experimental conditions. The most likely explanation for these results is an attenuation with repeated exposure of the acute stress response induced by birds being handled and placed in respirometry chambers. Our data suggest that habituation to experimental conditions is potentially an important determinant of observed BMR, and this source of variation needs to be taken into account in future studies of metabolic variation among individuals, populations, and species.

  6. Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

    Dam, Gitte; Keiding, Susanne; Munk, Ole Lajord

    2013-01-01

    Studies have shown decreased cerebral oxygen metabolism (CMRO(2)) and blood flow (CBF) in patients with cirrhosis with hepatic encephalopathy (HE). It remains unclear, however, whether these disturbances are associated with HE or with cirrhosis itself and how they may relate to arterial blood...... associated with HE rather than the liver disease as such. The changes in CMRO(2) and CBF could not be linked to blood ammonia concentration or CMRA....

  7. Sixteen weeks of resistance training can decrease the risk of metabolic syndrome in healthy postmenopausal women

    Conceição MS

    2013-09-01

    Full Text Available Miguel Soares Conceição,1 Valéria Bonganha,1 Felipe Cassaro Vechin,2 Ricardo Paes de Barros Berton,1 Manoel Emílio Lixandrão,1 Felipe Romano Damas Nogueira,1 Giovana Vergínia de Souza,1 Mara Patricia Traina Chacon-Mikahil,1 Cleiton Augusto Libardi2 1Exercise Physiology Laboratory, School of Physical Education, State University of Campinas, Campinas, 2Laboratory of Neuromuscular Adaptation to Strength Training, School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil Background: The postmenopausal phase has been considered an aggravating factor for developing metabolic syndrome. Notwithstanding, no studies have as yet investigated the effects of resistance training on metabolic syndrome in postmenopausal women. Thus, the purpose of this study was to verify whether resistance training could reduce the risk of metabolic syndrome in postmenopausal women. Methods: Twenty postmenopausal women were randomly assigned to a resistance training protocol (n = 10, 53.40 ± 3.95 years, 64.58 ± 9.22 kg or a control group (n = 10, 53.0 ± 5.7 years, 64.03 ± 5.03 kg. In the resistance training protocol, ten exercises were performed, with 3 × 8–10 maximal repetitions three times per week, and the load was increased every week. Two-way analysis of variance was used to evaluate specific metabolic syndrome Z-score, high density lipoprotein cholesterol, fasting blood glucose, triglycerides, waist circumference, blood pressure, strength, and body composition. The level of statistical significance was set at P < 0.05. Results: The main results demonstrated a significant decrease of metabolic syndrome Z-score when the postmenopausal women performed resistance training (P = 0.0162. Moreover, we observed decreases in fasting blood glucose for the resistance training group (P = 0.001, and also significant improvements in lean body mass (P = 0.042, 2.46%, reduction of body fat percentage (P = 0.001, −6.75% and noticeable increases in

  8. Industry as a metabolic activity.

    Smart, B

    1992-02-01

    The concept of "industrial economic metabolism" can provide a bridge to better understanding between environmentalists and industry. In nature each individual or species reacts to natural stimuli, competing with others for resources, extending its domain until it loses comparative advantage and comes to equilibrium with an adjacent competitor. Those species that succeed over time flourish; those that do not, diminish or disappear. Nature's rule book has no moral or ethical ingredient beyond self-interest. Corporate metabolisms are remarkably similar to those of nature. They too react to stimuli, collect and use resources, and grow or perish based on how effectively they compete. Corporate management recognizes and responds naturally and efficiently to cost and price signals. Through them it selects resources and converts them into useful products. The efficiency with which this is done is measured by profit, the lifeblood of the corporation and its means of growth. Profit thus provides a discipline on corporate behavior, encouraging efficient performers, and, by its absence, weeding out others. Unfettered by influences other than economics, the path to corporate success is unlikely to be a compassionate one. The dilemma of the manager is that to do what is socially "right" often conflicts with what must be done to survive and prosper. Fortunately, corporations' behavior can be altered by society when their purely economic role comes into conflict with other human values. The environment and the economy are not separate systems but intertwined to form a complex natural and social setting. The human-designed economic system depends on natural resource inputs, and in turn its metabolic wastes can overload the ecological system, threatening the long-term survivability of both. Increasing concern for the environment now gives the farsighted manager new latitude. There are competitive benefits in some pollution prevention. But there are not sufficiently strong forces to

  9. Test accuracy of metabolic indicators in predicting decreased fertility in dairy cows

    Lomander, H; Gustafsson, H; Svensson, C

    2012-01-01

    Negative energy balance is a known risk factor for decreased fertility in dairy cows. This study evaluated the accuracy of plasma concentrations of nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and insulin-like growth factor 1 (IGF-1)—factors related to negative energy balance...... was low when metabolic indicators measured as single values in early lactation were used to predict fertility in dairy cows, but accuracy was influenced by cow-level factors such as parity. The prevalence of the target condition (in this case, decreased fertility) also influences test usefulness......—in predicting decreased fertility. One plasma sample per cow was collected from 480 cows in 12 herds during the period from d 4 to 21 in milk and analyzed for NEFA, BHBA, and IGF-1. For each cow, data on breed, parity, calving date, gynecological examinations, and insemination dates were obtained. Milk samples...

  10. AMPK Activation Affects Glutamate Metabolism in Astrocytes

    Voss, Caroline Marie; Pajęcka, Kamilla; Stridh, Malin H

    2015-01-01

    acid (TCA) cycle was studied using high-performance liquid chromatography analysis supplemented with gas chromatography-mass spectrometry technology. It was found that AMPK activation had profound effects on the pathways involved in glutamate metabolism since the entrance of the glutamate carbon...... on glutamate metabolism in astrocytes was studied using primary cultures of these cells from mouse cerebral cortex during incubation in media containing 2.5 mM glucose and 100 µM [U-(13)C]glutamate. The metabolism of glutamate including a detailed analysis of its metabolic pathways involving the tricarboxylic...... skeleton into the TCA cycle was reduced. On the other hand, glutamate uptake into the astrocytes as well as its conversion to glutamine catalyzed by glutamine synthetase was not affected by AMPK activation. Interestingly, synthesis and release of citrate, which are hallmarks of astrocytic function, were...

  11. A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats.

    French, William W; Dridi, Sami; Shouse, Stephanie A; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I

    2017-06-08

    A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake ( p diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 ( p protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

  12. Regulation of Metabolic Activity by p53

    Jessica Flöter

    2017-05-01

    Full Text Available Metabolic reprogramming in cancer cells is controlled by the activation of multiple oncogenic signalling pathways in order to promote macromolecule biosynthesis during rapid proliferation. Cancer cells also need to adapt their metabolism to survive and multiply under the metabolically compromised conditions provided by the tumour microenvironment. The tumour suppressor p53 interacts with the metabolic network at multiple nodes, mostly to reduce anabolic metabolism and promote preservation of cellular energy under conditions of nutrient restriction. Inactivation of this tumour suppressor by deletion or mutation is a frequent event in human cancer. While loss of p53 function lifts an important barrier to cancer development by deleting cell cycle and apoptosis checkpoints, it also removes a crucial regulatory mechanism and can render cancer cells highly sensitive to metabolic perturbation. In this review, we will summarise the major concepts of metabolic regulation by p53 and explore how this knowledge can be used to selectively target p53 deficient cancer cells in the context of the tumour microenvironment.

  13. The effect of decreased developer activity on patient exposure

    Burns, C.B.; Turner, G.W.

    1983-01-01

    Overexposing and underdeveloping a radiographic image is not a common practice, but it has been observed to occur as a result of poor processing protocols. This study discovered that, as a result of decreased developer activity, the patient exposure could be three times as great as it would be under normal conditions

  14. DNA damage and decrease of cellular oxidase activity in piglet ...

    DNA damage and decrease of cellular oxidase activity in piglet sertoli cells exposed to gossypol. Ming Zhang, Hui Yuan, Zuping He, Liyun Yuan, Jine Yi, Sijun Deng, Li Zhu, Chengzhi Guo, Yin Lu, Jing Wu, Lixin Wen, Qiang Wei, Liqun Xue ...

  15. Metabolic benefits of physical activity

    Špela Volčanšek

    2014-10-01

    Full Text Available Physical activity is the most beneficial intervention in prevention and treatment of chronic diseases. Life style, which has become mostly sedentary, leads to growing incidence in obesity, what could cause the first so far reduction in life expectancy in developed countries.Physical activity reduces the chronic low-grade inflammation, which plays an important role in the pathogenesis of type 2 diabetes, cardiovascular disease and certain types of cancer. Regular physical activity exerts two anti-inflammatory effects: reduction of visceral fat, which produces the majority of pro-inflammatory cytokines, and production of myokines. It has been proposed that cytokines and other peptides that are produced by muscle fibers should be classified as myokines that exert autocrine, paracrine and endocrine effects. Myokines induce muscle hypertrophy and myogenesis, stimulate fat oxidation, improve insulin sensitivity and have an anti-inflammatory effect.  Therefore, skeletal muscle has been identified as a secretory organ and this provides the basis for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, gut, bones and brain. Physical inactivity leads to an altered myokine profile, associating sedentary life style with some chronic diseases.Physical activity is recommended as a tool for weight management and prevention of weight gain, for weight loss and for prevention of weight regain. High quality studies have confirmed the important impact of exercise on improving blood glucose control in diabetic patients, and on preventing or delaying the onset of type 2 diabetes in predisposed populations. Prescribing specific exercise tailored to individual's needs is an intervention strategy for health improvement. Physical fitness counteracts the detrimental effects of obesity reducing morbidity and mortality.

  16. Decreased antitoxic activities among children with clinical episodes of malaria

    Jakobsen, P H; McKay, V; N'Jie, R

    1998-01-01

    Healthy Gambian children, children with clinical Plasmodium falciparum malaria, and children with asymptomatic P. falciparum infections were studied to investigate whether antitoxic activities may contribute to protection against malarial symptoms. Markers of inflammatory reactions, soluble tumor...... necrosis factor receptor I, and C-reactive protein were found in high concentrations in children with symptomatic P. falciparum malaria compared with levels in children with asymptomatic P. falciparum infections or in healthy children, indicating that inflammatory reactions are induced only in children...... decreased capacity to block induction of LAL activation by P. falciparum exoantigen. The decreased blocking activity was restored in the following dry season, when the children had no clinical malaria. Symptomatic children also had the highest immunoglobulin G (IgG) reactivities to conserved P. falciparum...

  17. A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats

    William W. French

    2017-06-01

    Full Text Available A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa and lean control (Fa/fa rats were randomly assigned to either a high-protein (40% energy or moderate-protein (20% energy diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8, lean 40% protein (L40; n = 10, obese 20% protein (O20; n = 8, and obese 40% protein (O40; n = 10. At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake (p < 0.05 compared to O20. O40 rats had lower liver weight (p < 0.05 compared to O20. However, O40 rats had higher orexin (p < 0.05 levels compared to L20, L40 and O20. Rats in the L40 and O40 groups had less liver and muscle lipid deposition compared to L20 and L40 diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1 phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ mRNA expression compared to O20 (p < 0.05, with no difference in 5′ AMP-activated protein kinase (AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4EBP1, protein kinase B (Akt or p70 ribosomal S6 kinase (p70S6K phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

  18. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-01

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  19. Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

    Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

    2014-01-01

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  20. Community-based primary prevention programs decrease the rate of metabolic syndrome among socioeconomically disadvantaged women.

    Gilstrap, Lauren Gray; Malhotra, Rajeev; Peltier-Saxe, Donna; Slicas, Donna; Pineda, Eliana; Culhane-Hermann, Catherine; Cook, Nakela; Fernandez-Golarz, Carina; Wood, Malissa

    2013-04-01

    Metabolic Syndrome (MetSyn) is one of the strongest predictors of type 2 diabetes (DM2) and cardiovascular disease (CVD). It is associated with a 4- to 10-fold increased risk of DM2 and a 2- to 3-fold increased risk of CVD. Low income and minority women have some of the highest rates of MetSyn. This study examines the effect of a unique, community based, primary prevention program on the rates of MetSyn and health habits. Sixty-four low income and minority women were enrolled in the HAPPY (Health Awareness and Primary Prevention in Your neighborhood) Heart Program in an eastern suburb of Boston. Over these 2 years, patients were evaluated by an interdisciplinary medical team: their primary physician, cardiologist, nutritionist, physical therapist, and health coach. The rate of MetSyn was measured at baseline, year 1, and year 2. Comparisons were made either using the paired t test for normally distributed variables or the Wilcoxon Sign test for non-normal variables. The rate of MetSyn fell from 64.7% at baseline to 34.9% at year 1 (p=0.01) and 28.2% at year 2 (p<0.001). This was driven by increases in high-density lipoprotein (HDL-C) (p<0.001) and decreases in blood pressure (p=0.05). Fasting blood glucose trended down, but the hemoglobin A1c (HbA1c) reached significance (decreasing from 6 to 5.8, p<0.01). Nutrition and exercise habits trended toward improvement. There were significant decreases in anxiety (p<0.001), depression (p=0.006) and stress (p=0.002). This lifestyle intervention program is effective at decreasing MetSyn in a socioeconomically disadvantaged, largely minority, female population. This program also decreases anxiety, stress, and depression among participants.

  1. Some human activities to decrease public radiation dose

    Pan Ziqiang; Guo Minqiang

    1994-01-01

    The necessity of studying the variations in radiation levels from the balance viewpoint is discussed. Some human activities may increase, while others may decrease, radiation dose to population. In 1988, China's investigation showed that travel by air caused a raise of population collective dose by 3.6 x 10 1 man·Sv, while travel by ship, train and vehicle lead to a drop of 5.36 x 10 2 man·Sv, and that dwellings of coal cinder brick decreased collective dose by 3.5 x 10 3 man·Sv, while buildings of reinforced concrete structure increased collective dose by 3.7 x 10 3 man·Sv. It is inadequate to only study those activities which may increase radiation levels

  2. Generalized decrease in brain glucose metabolism during fasting in humans studied by PET

    Redies, C.; Hoffer, L.J.; Beil, C.

    1989-01-01

    In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged

  3. Mineral water 222 Rn activity decrease due to consumption habits

    Cipriani, Moacir; Taddei, Maria Helena Tirollo; Silva, Nivaldo Carlos da

    2001-01-01

    Mineral waters from the Pocos de Caldas Plateau springs, an elevated region with high natural radioactivity, in the State of Minas Gerais, Brazil, have significant 222 Rn concentration on site. The highest concentration in the waters are from: Fonte Villela - Aguas da Prata (∼ 1000 Bql -1 ); Fonte Grande Hotel - Pocinhos do Rio Verde (∼ 400 Brq -1 ) and Fonte CNEN Lab - Pocos de Caldas (∼ 290 Bql -1 ). These waters are used by the population as drinking water and due to consumption habits, can lead to internal doses above accepted limits for the public. This work deals with the decrease of 222 Rn activity in mineral waters fro two different popular consumption habits, and with the adult effective dose equivalent reduction due to water consumption habits. It has been found that the estimated dose based on the biokinetic Crawford-Brown model, can be one fourth of dose based on 222 Rn activity on site. (author)

  4. Active Intervention Can Decrease Burnout In Ed Nurses.

    Wei, Rong; Ji, Hong; Li, Jianxin; Zhang, Liyao

    2017-03-01

    The aim of this study was to evaluate whether active intervention can decrease job burnout and improve performance among ED nurses. This study was carried out in the emergency departments of 3 hospitals randomly selected from 8 comprehensive high-level hospitals in Jinan, China. A total of 102 nurses were enrolled and randomly divided into control and intervention groups. For 6 months, nurses in intervention groups were treated with ordinary treatment plus comprehensive management, whereas nurses in the control group were treated with ordinary management, respectively. Questionnaires were sent and collected at baseline and at the end of the study. The Student t test was used to evaluate the effect of comprehensive management in decreasing burnout. All ED nurses showed symptoms of job burnout at different levels. Our data indicated that comprehensive management significantly decreased emotional exhaustion and depersonalization (P burnout in ED nurses and contribute to relieving work-related stress and may further protect against potential mental health problems. Copyright © 2016 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

  5. Why does serotonergic activity drastically decrease during REM sleep?

    Sato, Kohji

    2013-10-01

    Here, I postulate two hypotheses that can explain the missing link between sleep and the serotonergic system in terms of spine homeostasis and memory consolidation. As dendritic spines contain many kinds of serotonin receptors, and the activation of serotonin receptors generally increases the number of spines in the cortex and hippocampus, I postulate that serotonin neurons are down-regulated during sleep to decrease spine number, which consequently maintains the total spine number at a constant level. Furthermore, since synaptic consolidation during REM sleep needs long-term potentiation (LTP), and serotonin is reported to inhibit LTP in the cortex, I postulate that serotonergic activity must drastically decrease during REM sleep to induce LTP and do memory consolidation. Until now, why serotonergic neurons show these dramatic changes in the sleep-wake cycle remains unexplained; however, making these hypotheses, I can confer physiological meanings on these dramatic changes of serotonergic neurons in terms of spine homeostasis and memory consolidation. Copyright © 2013. Published by Elsevier Ltd.

  6. Metabolism

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  7. Adaptative increase of ornithine production and decrease of ammonia metabolism in rat colonocytes after hyperproteic diet ingestion.

    Mouillé, Béatrice; Robert, Véronique; Blachier, François

    2004-08-01

    Chronic high-protein consumption leads to increased concentrations of NH(4)(+)/NH(3) in the colon lumen. We asked whether this increase has consequences on colonic epithelial cell metabolism. Rats were fed isocaloric diets containing 20 (P20) or 58% (P58) casein as the protein source for 7 days. NH(4)(+)/NH(3) concentration in the colonic lumen and in the colonic vein blood as well as ammonia metabolism by isolated surface colonic epithelial cells was determined. After 2 days of consumption of the P58 diet, marked increases of luminal and colonic vein blood NH(4)(+)/NH(3) concentrations were recorded when compared with the values obtained in the P20 group. Colonocytes recovered from the P58 group were characterized at that time and thereafter by an increased capacity for l-ornithine and urea production through arginase (P diet consumption, however, the ammonia metabolism into l-citrulline was found lower (P < 0.01) when compared with the values measured in the colonocytes recovered from the P20 group despite any decrease in the related enzymatic activities (i.e., carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase). This decrease was found to coincide with a return of blood NH(4)(+)/NH(3) concentration in colonic portal blood to values close to the one recorded in the P20 group. In response to increased NH(4)(+)/NH(3) concentration in the colon, the increased capacity of the colonocytes to synthesize l-ornithine is likely to correspond to an elevated l-ornithine requirement for the elimination of excessive blood ammonia in the liver urea cycle. Moreover, in the presence of NH(4)Cl, colonocytes diminished their synthesis capacity of l-citrulline from l-ornithine, allowing a lower cellular utilization of this latter amino acid. These results are discussed in relationship with an adaptative process that would be related to both interorgan metabolism and to the role of the colonic epithelium as a first line of defense toward luminal NH(4)(+)/NH(3

  8. Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children : The ABCD Study

    Vrijkotte, Tanja G M; van den Born, Bert-Jan H; Hoekstra, Christine M C A; Gademan, Maaike G J; van Eijsden, Manon; de Rooij, Susanne R; Twickler, Marcel T B

    2015-01-01

    BACKGROUND: In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system

  9. Exercise training decreases store-operated Ca2+entry associated with metabolic syndrome and coronary atherosclerosis.

    Edwards, Jason M; Neeb, Zachary P; Alloosh, Mouhamad A; Long, Xin; Bratz, Ian N; Peller, Cassandra R; Byrd, James P; Kumar, Sanjay; Obukhov, Alexander G; Sturek, Michael

    2010-02-01

    Stenting attenuates restenosis, but accelerated coronary artery disease (CAD) adjacent to the stent (peri-stent CAD) remains a concern in metabolic syndrome (MetS). Smooth muscle cell proliferation, a major mechanism of CAD, is mediated partly by myoplasmic Ca2+ dysregulation and store-operated Ca2+ entry (SOCE) via canonical transient receptor potential 1 (TRPC1) channels is proposed to play a key role. Exercise is known to prevent Ca2+ dysregulation in CAD. We tested the hypothesis that MetS increases SOCE and peri-stent CAD and exercise attenuates these events. Groups (n = 9 pigs each) were (i) healthy lean Ossabaw swine fed standard chow, (ii) excess calorie atherogenic diet fed (MetS), and (iii) aerobically exercise trained starting after 50 weeks of development of MetS (XMetS). Bare metal stents were placed after 54 weeks on diets, and CAD and SOCE were assessed 4 weeks later. Coronary cells were dispersed proximal to the stent (peri-stent) and from non-stent segments, and fura-2 fluorescence was used to assess SOCE, which was verified by Ni2+ blockade and insensitivity to nifedipine. XMetS pigs had increased physical work capacity and decreased LDL/HDL (P molecular expression of TRPC1, STIM1, and Orai1 in MetS.

  10. Metabolic activation of 2-methylfuran by rat microsomal systems

    Ravindranath, V.; Boyd, M.R.

    1985-01-01

    2-Methylfuran (2-MF), a constituent of cigarette smoke and coffee, causes necrosis of liver, lungs, and kidneys in rodents. 2-MF is metabolically activated by mixed-function oxidases to acetylacrolein, a reactive metabolite that binds covalently to microsomal protein. The hepatic microsomal metabolism of 2-MF to reactive metabolite required the presence of NADPH and oxygen and was dependent on incubation time and substrate concentration. The microsomal metabolism of 2-MF was inducible by pretreatment of rats with phenobarbital and was inhibited by piperonyl butoxide and N-octyl imidazole, which indicates that the metabolism of 2-MF may be mediated by cytochrome P-450. Acetylacrolein was a potent inhibitor of mixed-function oxidase and completely inhibited the microsomal metabolism of 2-MF, indicating that 2-MF is a suicide substrate for the enzyme. The sulfhydryl nucleophile cysteine was a better trapping agent of the reactive metabolite of 2-MF than N-acetylcysteine or glutathione. Lysine decreased the covalent binding of 2-MF metabolites, presumably by reacting with the aldehyde group of acetylacrolein. In addition, in the presence of NADPH, 2-MF was bioactivated by both pulmonary and renal cortical microsomes to reactive metabolites that were covalently bound to microsomal proteins

  11. Assessment of myocardial metabolism with iodine-123 heptadecanoic acid: effect of decreased fatty acid oxidation on deiodination

    Luethy, P.C.; Chatelain, P.; Papageorgiou, I.; Schubiger, A.; Lerch, R.A.

    1988-01-01

    Terminally radioiodinated fatty acid analogs are of potential use for the noninvasive delineation of regional alterations of fatty acid metabolism by gamma imaging. Since radioactivity from extracted iodine-123 heptadecanoic acid [( 123I]HDA) is released from the myocardium in form of free radioiodide (123I-) the present study was performed to determine whether deiodination of [123I]HDA is related to free fatty acid metabolism. Myocardial production of free radioiodide was measured in rat hearts in vitro and in vivo both under control conditions and after inhibition of fatty acid oxidation. In isolated rat hearts perfused at constant flow with a medium containing [123I]HDA, release of 123I- was markedly reduced during cardioplegia and pharmacologic inhibition of mitochondrial fatty acid transfer with POCA by 67% (p less than 0.005) and 72% (p less than 0.005), respectively. In fasted rats in vivo, 1 min after i.v. injection of [123I]HDA, 51 +/- 5% of myocardial radioactivity was recovered in the aqueous phase, containing free iodide, of myocardial lipid extracts. Aqueous activity was significantly decreased in fed (20 +/- 2%; p less than 0.002) and POCA pretreated (30 +/- 3.7%; p less than 0.05) animals exhibiting reduced oxidation of [14C]palmitate. Thus, deiodination of [123I]HDA was consistently reduced during inhibition of fatty acid oxidation in vitro and in vivo. The results apply to the interpretation of myocardial clearance curves of terminally radioiodinated fatty acid analogs

  12. Metabolic assessments during extra-vehicular activity

    Osipov, Yu. Yu.; Spichkov, A. N.; Filipenkov, S. N.

    Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha'(ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO 2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

  13. Decreased dopamine activity predicts relapse in methamphetamine abusers

    Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-20

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  14. Decreased dopamine activity predicts relapse in methamphetamine abusers

    Wang, G.J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-01

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and ( 11 C)raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  15. Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia

    Meguro, K.; Doi, C.; Yamaguchi, T.; Sasaki, H.; Matsui, H.; Yamada, K.; Kinomura, S.; Tohoku Univ.; Itoh, M.

    1991-01-01

    Cerebral glucose metabolism of 18 patients with multi-infarct dementia (MID) and 10 age-matched normal subjects were examined with positron emission tomography and the 18 -F-fluoro-deoxy-glucose technique. MID patients had significantly lower glucose metabolsim in all the grey matter regions measured and were also characterized by more individuality in metabolic pattern. MID patients were also evaluated as to intelligence quotient (IQ). A positive correlation between IQ as shown by the Tanaka-Binet test and glucose metabolism for the entire grey matter was found. The clinical applicability of this test for predicting cerebral metabolism is discussed. (orig.)

  16. PPARβ/δ modulates ethanol-induced hepatic effects by decreasing pyridoxal kinase activity

    Goudarzi, Maryam; Koga, Takayuki; Khozoie, Combiz; Mak, Tytus D.; Kang, Boo-Hyon; Jr, Albert J. Fornace; Peters, Jeffrey M.

    2013-01-01

    Because of the significant morbidity and lethality caused by alcoholic liver disease (ALD), there remains a need to elucidate the regulatory mechanisms that can be targeted to prevent and treat ALD. Toward this goal, minimally invasive biomarker discovery represents an outstanding approach for these purposes. The mechanisms underlying ALD include hepatic lipid accumulation. As the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) has been shown to inhibit steatosis, the present study examined the role of PPARβ/δ in ALD coupling metabolomic, biochemical and molecular biological analyses. Wild-type and Pparβ/δ-null mice were fed either a control or 4% ethanol diet and examined after 4–7 months of treatment. Ethanol fed Pparβ/δ-null mice exhibited steatosis after short-term treatment compared to controls, the latter effect appeared to be due to increased activity of sterol regulatory element binding protein 1c (SREBP1c). The wild-type and Pparβ/δ-null mice fed the control diet showed clear differences in their urinary metabolomic profiles. In particular, metabolites associated with arginine and proline metabolism, and glycerolipid metabolism, were markedly different between genotypes suggesting a constitutive role for PPARβ/δ in the metabolism of these amino acids. Interestingly, urinary excretion of taurine was present in ethanol-fed wild-type mice but markedly lower in similarly treated Pparβ/δ-null mice. Evidence suggests that PPARβ/δ modulates pyridoxal kinase activity by altering K m , consistent with the observed decreased in urinary taurine excretion. These data collectively suggest that PPARβ/δ prevents ethanol-induced hepatic effects by inhibiting hepatic lipogenesis, modulation of amino acid metabolism, and altering pyridoxal kinase activity

  17. Nucleons II: cryopreservation and metabolic activity.

    Reyes, R; Flores-Alonso, J C; Rodríguez-Hernández, H M; Merchant-Larios, H M; Delgado, N M

    2001-01-01

    The establishment of intracytoplasmatic sperm injection (ICSI) as a routine procedure in assisted fertilization has been used in the treatment of male infertility. The major technical problem that has arisen with the use of immotile sperm for ICSI has been differentiating between live and dead cells. Nucleons from human, pig, hamster, mouse, rat, and bull have been able to induce their chromatin decondensation by the action of heparin/GSH. Cryopreservation is deleterious to sperm function, killing more than 50% of the spermatozoa during the process. Nucleon cryostorage was performed at 5 and -5 degrees C and analyzed for total area (mu2), perimeter (mu), width (mu), and length (mu), using Metamorph Imaging System software. On the other hand, fluorescein diacetate (FDA) is hydrolyzed by intracellular estereases to produce fluorescein, which exhibits green fluorescence when excited by blue light. This fact is a striking result since the presence of this metabolic activity opens the possibility to select the nucleons for ICSI. In the present study, the authors decided to search for a suitable metabolic test, which might reflect the metabolism and viability of these chromatin structures. This is a simple cryostorage technique that after months of cryopreservation, allow the use of nucleons for ICSI with suitable fertilization and pregnancies rates.

  18. High Glucose-Induced PC12 Cell Death by Increasing Glutamate Production and Decreasing Methyl Group Metabolism

    Minjiang Chen

    2016-01-01

    Full Text Available Objective. High glucose- (HG- induced neuronal cell death is responsible for the development of diabetic neuropathy. However, the effect of HG on metabolism in neuronal cells is still unclear. Materials and Methods. The neural-crest derived PC12 cells were cultured for 72 h in the HG (75 mM or control (25 mM groups. We used NMR-based metabolomics to examine both intracellular and extracellular metabolic changes in HG-treated PC12 cells. Results. We found that the reduction in intracellular lactate may be due to excreting more lactate into the extracellular medium under HG condition. HG also induced the changes of other energy-related metabolites, such as an increased succinate and creatine phosphate. Our results also reveal that the synthesis of glutamate from the branched-chain amino acids (isoleucine and valine may be enhanced under HG. Increased levels of intracellular alanine, phenylalanine, myoinositol, and choline were observed in HG-treated PC12 cells. In addition, HG-induced decreases in intracellular dimethylamine, dimethylglycine, and 3-methylhistidine may indicate a downregulation of methyl group metabolism. Conclusions. Our metabolomic results suggest that HG-induced neuronal cell death may be attributed to a series of metabolic changes, involving energy metabolism, amino acids metabolism, osmoregulation and membrane metabolism, and methyl group metabolism.

  19. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health

    Luigi Fontana

    2016-07-01

    Full Text Available Protein-restricted (PR, high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.

  20. Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.

    Wang, Chao-Yung; Shie, Shian-Sen; Wen, Ming-Shien; Hung, Kuo-Chun; Hsieh, I-Chang; Yeh, Ta-Sen; Wu, Delon

    2015-12-15

    A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to β-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4. Copyright © 2015, American Association for the Advancement of Science.

  1. Alteration In Bones Metabolism In Active Rheumatoid Arthritis

    Salem, E.S.

    2013-01-01

    The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Osteocalcin (OC) is synthesized by osteoblasts and is considered to be a marker of bone formation and helps in corporating calcium into bone tissue. Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease characterized by bone complication including bone pain, erosion and osteoporosis. The aim of the present study is to evaluate some factors responsible in bone metabolism termed OC, vitamin D (vit. D), oncostatin M (OSM), ionized calcium and alkaline phosphatase. Fifty pre-menopausal female patients with active RA and twenty healthy controls of the same age were included in the present study. Radioimmunoassay (RIA) was used to estimate serum OC and active vitamin D. The quantitative determination of ionized calcium and alkaline phosphatase were carried out colorimetrically. OSM was measured by ELISA and serum levels of OC and active vitamin D were significantly decreased in RA patients as compared to those of the control group. On the other hand, the levels of serum OSM, ionized calcium and alkaline phosphatase were significantly increased in the RA patients as compared to their healthy control subjects. The results of this study indicated that early investigation and therapy of disturbances of bone metabolism in active RA are necessary for better prognosis and exhibited the importance of OC as a diagnostic tool of alterations of bone metabolism in RA patients.

  2. Physical activity, BMI and metabolic risk in Portuguese adolescents

    Fernanda Karina dos Santos

    2016-03-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2016v18n1p103   It has been reported, in the last decades, a significant decrease in physical activity (PA levels, with a consequent increase in obesity and metabolic risk factors among youth. The aims of this study were to describe PA levels, the prevalence of overweight/obesity and metabolic risk factors, and to examine the association between PA and body mass index (BMI with metabolic risk among Portuguese youth. The sample comprises 212 Portuguese adolescents (12-16 years old. Height and weight were measured. PA was estimated with the Bouchard questionnaire (3 days recall, as well as with the use of a pedometer (used for 5 consecutive days. Metabolic risk factors comprised fasting glucose, triglycerides, HDL-cholesterol, systolic blood pressure and waist circumference. Subjects were classified as normal weight, overweight or obese according to BMI; the maturational status was indirectly estimated with the maturity offset procedure. A continuous metabolic risk score was computed (zMR and PA values were divided into tertiles. Qui-square test, t-test and ANOVA were used in statistical analyses. SPSS 18.0 and WinPepi softwares were used and p<0.05. A moderate to high prevalence of overweight/obesity and HDL-cholesterol was found, as well as a high prevalence of high blood pressure and low to moderate PA levels among Portuguese youth. The relationship between BMI and zMR showed that obese adolescents have higher zMR when compared to normal weight or overweight adolescents. This finding suggests that increased levels of PA and reduction in the prevalence of overweight/obesity may have a positive role against the development of metabolic risk factors.

  3. Fibroblast activation protein (FAP) as a novel metabolic target

    Sánchez-Garrido, Miguel Angel; Habegger, Kirk M; Clemmensen, Christoffer

    2016-01-01

    to block FAP enzymatic activity. RESULTS: TB administration to diet-induced obese (DIO) animals led to profound decreases in body weight, reduced food consumption and adiposity, increased energy expenditure, improved glucose tolerance and insulin sensitivity, and lowered cholesterol levels. Total...... (TB), we explored the impact of FAP inhibition on metabolic regulation in mice. METHODS: To address this question we evaluated the pharmacology of TB in various mouse models including those deficient in FGF21, GLP1 and GIP signaling. We also studied the ability of FAP to process FGF21 in vitro and TB...... and intact plasma FGF21 were observed to be elevated in TB-treated DIO mice but not lean animals where the metabolic impact of TB was significantly attenuated. Furthermore, and in stark contrast to naïve DIO mice, the administration of TB to obese FGF21 knockout animals demonstrated no appreciable effect...

  4. Effects of vasoactive and metabolic active substances (measurement of RCBF)

    Herrschaft, H.

    1986-09-29

    Methods, principles, normal values, reproducibility and clinical indications of rCBF-measurements, using the intraartrial 133-Xenon-clearance-technique, are presented. The effect of vaso- and metabolically active drugs on cerebral blood flow was examined in 215 patients, suffering from cerebral ischemia. Significant increase of rCBF was ascertained after intravenous injection of centrophenoxine, pyrithioxine, extractum sanguis deproteinatus, piracetam and solutions of low molecular dextran. All the other drugs tested proved to be either without any effect or caused decrease of rCBF. In 130 patients with obstructive disease of internal carotid artery after surgery at an interval of 6 - 8 weeks and 1 year a significant increase of CBF could be stated. The rank of psychological tests and quantitative EEF-investigations relating to evidence of efficacy of metabolically active drugs is discussed critically. Therapeutic efficacy and clinical relevance of vaso- and metabolically active drugs in cerebral ischemia of man are to be substantiated only by double-blind controlled studies.

  5. Effects of vasoactive and metabolic active substances (measurement of RCBF)

    Herrschaft, H.

    1986-01-01

    Methods, principles, normal values, reproducibility and clinical indications of rCBF-measurements, using the intraartrial 133-Xenon-clearance-technique, are presented. The effect of vaso- and metabolically active drugs on cerebral blood flow was examined in 215 patients, suffering from cerebral ischemia. Significant increase of rCBF was ascertained after intravenous injection of centrophenoxine, pyrithioxine, extractum sanguis deproteinatus, piracetam and solutions of low molecular dextran. All the other drugs tested proved to be either without any effect or caused decrease of rCBF. In 130 patients with obstructive disease of internal carotid artery after surgery at an interval of 6 - 8 weeks and 1 year a significant increase of CBF could be stated. The rank of psychological tests and quantitative EEF-investigations relating to evidence of efficacy of metabolically active drugs is discussed critically. Therapeutic efficacy and clinical relevance of vaso- and metabolically active drugs in cerebral ischemia of man are to be substantiated only by double-blind controlled studies. (orig.) [de

  6. Salinity Inhibits Rice Seed Germination by Reducing α-Amylase Activity via Decreased Bioactive Gibberellin Content

    Li Liu

    2018-03-01

    Full Text Available Seed germination plays important roles in the establishment of seedlings and their subsequent growth; however, seed germination is inhibited by salinity, and the inhibitory mechanism remains elusive. Our results indicate that NaCl treatment inhibits rice seed germination by decreasing the contents of bioactive gibberellins (GAs, such as GA1 and GA4, and that this inhibition can be rescued by exogenous bioactive GA application. To explore the mechanism of bioactive GA deficiency, the effect of NaCl on GA metabolic gene expression was investigated, revealing that expression of both GA biosynthetic genes and GA-inactivated genes was up-regulated by NaCl treatment. These results suggest that NaCl-induced bioactive GA deficiency is caused by up-regulated expression of GA-inactivated genes, and the up-regulated expression of GA biosynthetic genes might be a consequence of negative feedback regulation of the bioactive GA deficiency. Moreover, we provide evidence that NaCl-induced bioactive GA deficiency inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression. Additionally, exogenous bioactive GA rescues NaCl-inhibited seed germination by enhancing α-amylase activity. Thus, NaCl treatment reduces bioactive GA content through promotion of bioactive GA inactivation, which in turn inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression.

  7. Adolescent Metabolic Syndrome Risk Is Increased with Higher Infancy Weight Gain and Decreased with Longer Breast Feeding

    Kim Khuc

    2012-01-01

    Full Text Available Background. Prevalence of the metabolic syndrome is increasing in pediatric age groups worldwide. Meeting the criteria for the metabolic syndrome puts children at risk for later cardiovascular and metabolic disease. Methods. Using linear regression, we examined the association between infant weight gain from birth to 3 months and risk for the metabolic syndrome among 16- to 17-year-old Chilean adolescents (n=357, accounting for the extent of breastfeeding in infancy and known covariates including gender, birth weight, and socioeconomic status. Results. Participants were approximately half male (51%, born at 40 weeks of gestation weighing 3.5 kg, and 48% were exclusively breastfed for ≥90 days. Factors independently associated with increased risk of metabolic syndrome in adolescence were faster weight gain in the first 3 months of life (B=0.16, P<0.05 and male gender (B=0.24, P<0.05. Breastfeeding as the sole source of milk for ≥90 days was associated with significantly decreased risk of metabolic syndrome (B=−0.16. Conclusion. This study adds to current knowledge about early infant growth and breastfeeding and their long-term health effects.

  8. Mutagenicity of vinyl chloride after metabolic activation

    Rannug, U; Johansson, A; Ramel, C; Wachtmeister, C A

    1974-01-01

    Vinyl chloride has recently been shown to cause a malignant liver tumor disease in man after occupational exposure in PVC plants. This actualizes the problem of whether such hazards could be avoided or at least diminished in the future by a screening for mutagenicity of chemicals used in industries. The basis for such a screening procedure is the close correlation between carcinogenic and mutagenic effects of chemicals. Experiments with Salmonella bacteria showed that the carcinogenic hazard of vinyl chloride could have been traced by means of mutagenicity tests. The data indicate that vinyl chloride is not mutagenic per se but becomes mutagenic after a metabolic activation in the liver. 24 references, 1 figure, 4 tables.

  9. Physical activity effects on bone metabolism.

    Smith, E L; Gilligan, C

    1991-01-01

    The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.

  10. NFKB activity decreased in BALB/c mice with high fat diet and fructose

    Nur'aini, Farida Dewi; Rahayu, Sri; Rifa'i, Muhaimin

    2017-05-01

    Excessive consumption of fat and fructose leads to obesity due to lipid accumulation. The excessive lipid causes hypertrophy in the adipocytes which lead to cell death. Consequently, dead adipocytes will produce adipokines, which cause macrophages and lymphocytes to infiltrate into the adipose tissue, elevating pro-inflammatory cytokines, thus triggering the production of pro-inflammatory cytokines through NFκB activity. Elicited soybeans extract (ESE) with bacteria and light contain Glyceollin and Isoflavones, which inhibit the activation of NFKB and reduce plasma cholesterol levels by upregulating cholesterol metabolism. This study aimed to analyze the effect of ESE against the relative number of CD4+ NFκB+ cells in BALB/c mice spleen after administrated by high-fat diet food and fructose (HFD) for 20 weeks. Mice were given orally with ESE after administrated by HFD at dose 78 mg/kgBW (D1), 104 mg/kgBW (D2), and 130 mg/kgBW (D3) for 4 weeks. This study also used positive control (HFD mice model without ESE treatment) and normal mice. Identification of NFKB activation was conducted using Flowcytometry analytical methods. Our result indicated that ESE could decrease significantly activation of NFκB in CD4 cell compare than positive control. The optimum dose that can decrease the relative number of CD4+ NFκB+ cells is dose 3.

  11. Physically active lifestyle does not decrease the risk of fattening.

    Klaas R Westerterp

    Full Text Available BACKGROUND: Increasing age is associated with declining physical activity and a gain in fat mass. The objective was to observe the consequence of the age-associated reduction in physical activity for the maintenance of energy balance as reflected in the fat store of the body. METHODOLOGY/PRINCIPAL FINDINGS: Young adults were observed over an average time interval of more than 10 years. Physical activity was measured over two-week periods with doubly labeled water and doubly labeled water validated triaxial accelerometers, and body fat gain was measured with isotope dilution. There was a significant association between the change in physical activity and the change in body fat, where a high initial activity level was predictive for a higher fat gain. CONCLUSION/SIGNIFICANCE: The change from a physically active to a more sedentary routine does not induce an equivalent reduction of energy intake and requires cognitive restriction to maintain energy balance.

  12. Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

    Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun

    2007-01-01

    Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8±0.75 y, 5 IGAs: male, 22.6±2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA

  13. Insulin-induced decrease in protein phosphorylation in rat adipocytes not explained by decreased A-kinase activity

    Egan, J.J.; Greenberg, A.S.; Chang, M.K.; Londos, C.

    1987-01-01

    In isolated rat adipocytes, insulin inhibits lipolysis to a greater extent than would be predicted by the decrease in (-/+)cAMP activity ratio of cAMP-dependent protein kinase [A-kinase], from which it was speculated that insulin promotes the dephosphorylation of hormone-sensitive lipase. They have examined the phosphorylation state of cellular proteins under conditions of varying A-kinase activities in the presence and absence of insulin. Protein phosphorylation was determined by SDS-PAGE electrophoresis of extracts from 32 P-loaded cells; glycerol and A-kinase activity ratios were measured in the cytosolic extracts from control, non-radioactive cells. Increased protein phosphorylation in general occurred over the same range of A-kinase activity ratios, 0.1-0.3, associated with increased glycerol release. The insulin-induced decrease in lipolysis was associated with a decrease in the 32 P content of several proteins, an effect not explained by the modest reduction in A-kinase activity by insulin. This effect of insulin on protein phosphorylation was lost as the A-kinase activity ratios exceeded 0.5. The results suggest that insulin promotes the dephosphorylation of those adipocyte proteins which are subject to phosphorylation by A-kinase

  14. Metabolism

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  15. Decrease in gamma-band activity tracks sequence learning

    Madhavan, Radhika; Millman, Daniel; Tang, Hanlin; Crone, Nathan E.; Lenz, Fredrick A.; Tierney, Travis S.; Madsen, Joseph R.; Kreiman, Gabriel; Anderson, William S.

    2015-01-01

    Learning novel sequences constitutes an example of declarative memory formation, involving conscious recall of temporal events. Performance in sequence learning tasks improves with repetition and involves forming temporal associations over scales of seconds to minutes. To further understand the neural circuits underlying declarative sequence learning over trials, we tracked changes in intracranial field potentials (IFPs) recorded from 1142 electrodes implanted throughout temporal and frontal cortical areas in 14 human subjects, while they learned the temporal-order of multiple sequences of images over trials through repeated recall. We observed an increase in power in the gamma frequency band (30–100 Hz) in the recall phase, particularly in areas within the temporal lobe including the parahippocampal gyrus. The degree of this gamma power enhancement decreased over trials with improved sequence recall. Modulation of gamma power was directly correlated with the improvement in recall performance. When presenting new sequences, gamma power was reset to high values and decreased again after learning. These observations suggest that signals in the gamma frequency band may play a more prominent role during the early steps of the learning process rather than during the maintenance of memory traces. PMID:25653598

  16. Stereotypic wheel running decreases cortical activity in mice

    Fisher, Simon P.; Cui, Nanyi; McKillop, Laura E.; Gemignani, Jessica; Bannerman, David M.; Oliver, Peter L.; Peirson, Stuart N.; Vyazovskiy, Vladyslav V.

    2016-01-01

    Prolonged wakefulness is thought to gradually increase ‘sleep need' and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours. PMID:27748455

  17. Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative metabolism in sensorimotor regions after stroke.

    Ferris, Jennifer K; Peters, Sue; Brown, Katlyn E; Tourigny, Katherine; Boyd, Lara A

    2018-05-01

    Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

  18. Home-based exercise may not decrease the insulin resistance in individuals with metabolic syndrome.

    Chen, Chiao-Nan; Chuang, Lee-Ming; Korivi, Mallikarjuna; Wu, Ying-Tai

    2015-01-01

    This study investigated the differences in exercise self-efficacy, compliance, and effectiveness of home-based exercise in individuals with and without metabolic syndrome (MetS). One hundred and ten individuals at risk for diabetes participated in this study. Subjects were categorized into individuals with MetS and individuals without MetS. Metabolic risk factors and exercise self-efficacy were evaluated for all subjects before and after 3 months of home-based exercise. Univariate analysis of variance was used to compare the effectiveness of a home-based exercise program between individuals with and without MetS. The home-based exercise program improved body mass index and lipid profile in individuals at risk for diabetes, regardless of MetS status at baseline. Individuals without MetS had higher exercise self-efficacy at baseline and performed greater exercise volume compared with individuals with MetS during the intervention. The increased exercise volume in individuals without MetS may contribute to their better control of insulin resistance than individuals with MetS. Furthermore, baseline exercise self-efficacy was correlated with exercise volume executed by subjects at home. We conclude that home-based exercise programs are beneficial for individuals at risk for diabetes. However, more intensive and/or supervised exercise intervention may be needed for those with MetS.

  19. Decreased Prolidase Activity in Patients with Posttraumatic Stress Disorder.

    Demir, Süleyman; Bulut, Mahmut; Atli, Abdullah; Kaplan, İbrahim; Kaya, Mehmet Cemal; Bez, Yasin; Özdemir, Pınar Güzel; Sır, Aytekin

    2016-07-01

    Many neurochemical systems have been implicated in the development of Posttraumatic Stress Disorder (PTSD). The prolidase enzyme is a cytosolic exopeptidase that detaches proline or hydroxyproline from the carboxyl terminal position of dipeptides. Prolidase has important biological effects, and to date, its role in the etiology of PTSD has not been studied. In the present study, we aimed to evaluate prolidase activity in patients with PTSD. The study group consisted of patients who were diagnosed with PTSD after the earthquake that occurred in the province of Van in Turkey in 2011 (n=25); the first control group consisted of patients who experienced the earthquake but did not show PTSD symptoms (n=26) and the second control group consisted of patients who have never been exposed to a traumatic event (n=25). Prolidase activities in the patients and the control groups were determined by the ELISA method using commercial kits. Prolidase activity in the patient group was significantly lower when compared to the control groups. Prolidase activity was also significantly lower in the traumatized healthy subjects compared to the other healthy group (pactivity may have neuroprotective effects in patients with PTSD.

  20. Regular sports activities decrease the risk of venous thrombosis

    van Stralen, K. J.; le Cessie, S.; Rosendaal, F. R.; Doggen, C. J. M.

    2007-01-01

    BACKGROUND: Stasis of the blood has been postulated as a major cause of venous thrombosis. However, little is known about the effect of stimulating the blood flow in order to prevent venous thrombosis through, for example, sports activities. OBJECTIVES: In a large population-based case-control study

  1. Immune activation is associated with decreased thymic function in ...

    Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIVpositive treatment-naive individuals has thus far not been ...

  2. Physical Activity and Sedentary Behavior Associated with Components of Metabolic Syndrome among People in Rural China.

    Jing Xiao

    Full Text Available Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China.The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed.Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15-40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15-30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids.Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also, recommendations are

  3. Physical Activity and Sedentary Behavior Associated with Components of Metabolic Syndrome among People in Rural China.

    Xiao, Jing; Shen, Chong; Chu, Min J; Gao, Yue X; Xu, Guang F; Huang, Jian P; Xu, Qiong Q; Cai, Hui

    2016-01-01

    Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China. The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed. Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15-40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15-30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids. Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also, recommendations are developed to reduce

  4. Prevalence of metabolic syndrome and its relationship with physical activity in suburban Beijing, China.

    Zhang, Wei-Hong; Xue, Peng; Yao, Meng-Ying; Chang, Hai-Min; Wu, Yan; Zhang, Lei

    2013-01-01

    The present study aimed to estimate the up-to-date prevalence of metabolic syndrome and its relationship with physical activity among suburban adults in Beijing, China. A cross-sectional survey in a representative sample of 19,003 suburban adults aged 18-76 years was carried out in 2007-2008. Data was collected via questionnaires and blood pressure, anthropometric, and laboratory measurements. Of the residents aged 18-76 years in suburban Beijing, 25.9% (27.3% in men and 25.1% in women), 21.3% (19.4% in men and 22.9% in women), and 25.3% (24.2% in men and 26.1% in women) had 1 component, 2 components, and 3 or more components of metabolic syndrome, respectively. The age-standardized prevalence of metabolic syndrome and its components, including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting plasma glucose, decreased across categories with increasing physical activity. After adjusting for age, sex, education level, smoking, and alcohol consumption, residents were more likely to have metabolic syndrome across categories with decreasing physical activity; a similar relationship also applied to components of metabolic syndrome. A high prevalence of metabolic syndrome and its components is commonly present in suburban Beijing. Increasing physical activity can reduce the relative risk of metabolic syndrome and it components.

  5. Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat.

    Lasram, Mohamed Montassar; Bouzid, Kahena; Douib, Ines Bini; Annabi, Alya; El Elj, Naziha; El Fazaa, Saloua; Abdelmoula, Jaouida; Gharbi, Najoua

    2015-04-01

    Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-β. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.

  6. Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation.

    Santacruz, Lucia; Arciniegas, Antonio Jose Luis; Darrabie, Marcus; Mantilla, Jose G; Baron, Rebecca M; Bowles, Dawn E; Mishra, Rajashree; Jacobs, Danny O

    2017-08-01

    Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF-1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF-1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  7. Physical activity may decrease the likelihood of children developing constipation.

    Seidenfaden, Sandra; Ormarsson, Orri Thor; Lund, Sigrun H; Bjornsson, Einar S

    2018-01-01

    Childhood constipation is common. We evaluated children diagnosed with constipation, who were referred to an Icelandic paediatric emergency department, and determined the effect of lifestyle factors on its aetiology. The parents of children who were diagnosed with constipation and participated in a phase IIB clinical trial on laxative suppositories answered an online questionnaire about their children's lifestyle and constipation in March-April 2013. The parents of nonconstipated children that visited the paediatric department of Landspitali University Hospital or an Icelandic outpatient clinic answered the same questionnaire. We analysed responses regarding 190 children aged one year to 18 years: 60 with constipation and 130 without. We found that 40% of the constipated children had recurrent symptoms, 27% had to seek medical attention more than once and 33% received medication per rectum. The 47 of 130 control group subjects aged 10-18 were much more likely to exercise more than three times a week (72%) and for more than a hour (62%) than the 26 of 60 constipated children of the same age (42% and 35%, respectively). Constipation risk factors varied with age and many children diagnosed with constipation had recurrent symptoms. Physical activity may affect the likelihood of developing constipation in older children. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  8. Linking neuronal brain activity to the glucose metabolism

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-01-01

    Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regul...

  9. Metavanadate causes cellular accumulation of copper and decreased lysyl oxidase activity

    Cui, Changtai T.; Uriu-Adams, Janet Y.; Tchaparian, Eskouhie H.; Keen, Carl L.; Rucker, Robert B.

    2004-01-01

    Selected indices of copper metabolism in weanling rats and fibroblast cultures were progressively altered in response to increased levels of sodium metavanadate. In diets, vanadium was added in amounts ranging from 0 to 80 μg V/g of diet, that is, 0-1.6 μmol V/g of diet. In fibroblast cultures, vanadium ranged from 0 to 400 nmol V/ml. The inhibition of P-ATPase-7A activity by metavanadate, important to copper egress from cells, was a primary focus. In skin, and tendon, the copper concentration was increased in response to increased dietary levels of metavanadate, whereas lysyl oxidase activity, a secreted cuproprotein, was reduced. The reduction in lysyl oxidase activity was also accompanied by reduced redox cycling potential of isolated fractions of lysyl oxidase, presumably due to reduced lysyltyrosyl quinone (LTQ) formation at the active site of lysyl oxidase. In contrast, liver copper concentrations and plasma ceruloplasmin activity were not affected by metavanadate exposure. However, semicarbazide-sensitive benzylamine oxidase (SCBO) activity, which was taken as an indirect measure of vascular adhesive protein-1 (VAP-1), was increased. In cultured fibroblasts, cellular copper was also increased and lysyl oxidase decreased in response to metavanadate. Moreover, the steady-state levels of atp7a and lysyl oxidase mRNAs were not affected by addition of metavanadate to culture medium up to 200 nmol/ml. Taken together, these data suggest that pathways involving copper egress and lysyl oxidase activation are particularly sensitive to metavanadate exposure through processes that are predominately posttranslational

  10. Decreased occipital lobe metabolism by FDG-PET/CT: An anti-NMDA receptor encephalitis biomarker.

    Probasco, John C; Solnes, Lilja; Nalluri, Abhinav; Cohen, Jesse; Jones, Krystyna M; Zan, Elcin; Javadi, Mehrbod S; Venkatesan, Arun

    2018-01-01

    To compare brain metabolism patterns on fluorodeoxyglucose (FDG)-PET/CT in anti-NMDA receptor and other definite autoimmune encephalitis (AE) and to assess how these patterns differ between anti-NMDA receptor neurologic disability groups. Retrospective review of clinical data and initial dedicated brain FDG-PET/CT studies for neurology inpatients with definite AE, per published consensus criteria, treated at a single academic medical center over a 10-year period. Z-score maps of FDG-PET/CT were made using 3-dimensional stereotactic surface projections in comparison to age group-matched controls. Brain region mean Z scores with magnitudes ≥2.00 were interpreted as significant. Comparisons were made between anti-NMDA receptor and other definite AE patients as well as among patients with anti-NMDA receptor based on modified Rankin Scale (mRS) scores at the time of FDG-PET/CT. The medial occipital lobes were markedly hypometabolic in 6 of 8 patients with anti-NMDA receptor encephalitis and as a group (Z = -4.02, interquartile range [IQR] 2.14) relative to those with definite AE (Z = -2.32, 1.46; p = 0.004). Among patients with anti-NMDA receptor encephalitis, the lateral and medial occipital lobes were markedly hypometabolic for patients with mRS 4-5 (lateral occipital lobe Z = -3.69, IQR 1; medial occipital lobe Z = -4.08, 1) compared with those with mRS 0-3 (lateral occipital lobe Z = -0.83, 2; p occipital lobe Z = -1.07, 2; p = 0.001). Marked medial occipital lobe hypometabolism by dedicated brain FDG-PET/CT may serve as an early biomarker for discriminating anti-NMDA receptor encephalitis from other AE. Resolution of lateral and medial occipital hypometabolism may correlate with improved neurologic status in anti-NMDA receptor encephalitis.

  11. Metabolism features in the active rheumatoid disease

    Cossermelli, W; Carvalho, N; Papaleo Netto, M [Sao Paulo Univ. (Brazil). Centro de Medicina Nuclear

    1974-02-01

    The /sup 131/I-labelled albumin metabolism was studied in fourteen female patients with rheumatoid arthritis. The half-life of distribution was increased while the turnover half-life and turnover rate was within normal limits. These results led to assume that synthesis and catabolism may not change this disease, not being the responsible mechanism of hypoalbuminemia. Hypoalbuminemia would appear as compensatory mechanism in view of other protein alterations, as hypergammaglobulinemia, without changes of stabilizing and metabolic properties of albumin, perhaps due to albumin molecular alterations.

  12. Metabolism features in the active rheumatoid disease

    Cossermelli, W.; Carvalho, N.; Papaleo Netto, M.

    1974-01-01

    It was studied the 131 I-labelled albumin metabolism in fourteen female patients with rheumatoid arthritis. The half-life of distribution was increased while the turnover half-life and turnover rate was within normal limits. These results led to assume that synthesis and catabolism may not change this disease, not being the responsible mechanism of hypoalbuminemia. Hypoalbuminemia would appear as compensatory mechanism in view of other protein alterations, as hypergammaglobulinemia, without changes of stabilizing and metabolic properties of albumin, perhaps due to albumin molecular alterations [pt

  13. Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

    Kersten, A.H.

    2008-01-01

    Plasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that

  14. Association of Objectively Measured Physical Activity and Metabolic Syndrome Among US Adults With Osteoarthritis.

    Liu, Shao-Hsien; Waring, Molly E; Eaton, Charles B; Lapane, Kate L

    2015-10-01

    To investigate the association between objectively measured physical activity and metabolic syndrome among adults with osteoarthritis (OA). Using cross-sectional data from the 2003-2006 National Health and Nutrition Examination Survey, we identified 566 adults with OA with available accelerometer data assessed using Actigraph AM-7164 and measurements necessary to determine metabolic syndrome by the Adult Treatment Panel III. Analysis of variance was conducted to examine the association between continuous variables in each activity level and metabolic syndrome components. Logistic models estimated the relationship of quartile of daily minutes of different physical activity levels to odds of metabolic syndrome adjusted for socioeconomic and health factors. Among persons with OA, most were women average age of 62.1 years and average disease duration of 12.9 years. Half of adults with OA had metabolic syndrome (51.0%; 95% confidence interval [95% CI] 44.2%-57.8%), and only 9.6% engaged in the recommended 150 minutes per week of moderate/vigorous physical activity. Total sedentary time was associated with higher rates of metabolic syndrome and its components, while light and objectively measured moderate/vigorous physical activity was inversely associated with metabolic syndrome and its components. Higher levels of light activity were associated with lower prevalence of metabolic syndrome (quartile 4 versus quartile 1: adjusted odds ratio 0.45, 95% CI 0.24-0.84, P for linear trend physical activity, especially in light intensity, is more likely to be associated with decreasing prevalence of metabolic syndrome among persons with OA. © 2015, American College of Rheumatology.

  15. Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study.

    Tanja G M Vrijkotte

    Full Text Available In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5-6 years.Cross-sectional data from an apparently healthy population (within the ABCD study were collected at age 5-6 years in 1540 children. Heart rate (HR, respiratory sinus arrhythmia (RSA; parasympathetic activity and pre-ejection period (PEP; sympathetic activity were assessed during rest. Metabolic components were waist-height ratio (WHtR, systolic blood pressure (SBP, fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed.In analysis adjusted for child's physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01, higher SBP (p<0.001 and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01. Lower PEP was only associated with higher SBP (p <0.05. Of all children, 5.6% had 3 or more (out of 5 adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001.This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5-6 years.

  16. Adhesive ability and biofilm metabolic activity of Listeria ...

    SWEET

    2012-07-31

    Jul 31, 2012 ... monocytogenes strains were able to adhere to abiotic materials with different degrees. In fact, cold stressed strains ... packaging. Biofilms allow .... reduction of a tetrazolium salt by metabolically active cells to a colored water ...

  17. the prevalence of metabolic syndrome among active sportsmen

    User

    ABSTRACT. This study sought to establish the prevalence of the metabolic syndrome (MetS) among active .... Table 1: General characteristic of the studied population stratified by exercise. Parameters ..... Prolonged adaptation to fat- rich diet ...

  18. Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

    Warren, Emily Booth; Aicher, Aidan Edward; Fessel, Joshua Patrick; Konradi, Christine

    2017-01-01

    Mitochondrial DNA (mtDNA), the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD) patients who had developed L-DOPA Induced Dyskinesia (LID), compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr) treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

  19. Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

    Emily Booth Warren

    Full Text Available Mitochondrial DNA (mtDNA, the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD patients who had developed L-DOPA Induced Dyskinesia (LID, compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

  20. LECITHIN: CHOLESTEROL ACYLTRANSFERASE ACTIVITY IS DECREASED IN TYPE 2 DIABETES MELLITUS

    A. Ghanei

    2007-09-01

    Full Text Available Lecithin cholesterol acyltransferase (LCAT plays a major role in the removal of free cholesterol from tissues via assisting HDL-C maturation, and its activity has been proposed as the main indicator of HDL-C function. The aim of the study was to measure LCAT activity in type 2 diabetic patients and to elucidate whether LCAT is associated with metabolic control, and insulin resistance. A case-control study was conducted in Imam Khomeini Hospital during 2006, recruiting 45 type 2 diabetes mellitus patients and 45 healthy subjects. Cases and controls were matched regarding gender, age and body mass index (BMI. FBS, lipid profile, LCAT activity, HbA1C, insulin were measured and insulin resistance (HOMA-IRwas calculated for both patients and controls. The studied variables were then compared between the two groups, and the association of LCAT activity with any of the variables was examined. Twenty-five subjects were female and 20 male both among patients and controls. Mean age of diabetics was 49.9 yrs (range, 40-64, and of controls 51.1 yrs (range, 39-64. FBS, HbA1C, HOMA-IR and TG in patients were significantly higher than controls, and HDL-C in controls was significantly higher than patients. LCAT activity of patients (73 9.1 µmol/L/h was significantly lower than that in controls (88 4.5 µmol/L/h (p<0.001. LCAT activity had significant inverse correlations with HbA1C and duration of diabetes. After multilinear regression analysis in patients, LCAT activity was only correlated with HbA1C level (ß= -0.9, p<0.001. LCAT activity had no significant association with HDL-C and HOMA-IR in any of the groups."nLCAT activity is significantly decreased in patients with type 2 diabetes compared with healthy controls, and has an inverse correlation with the magnitude of hyperglycemia.

  1. Activating transcription factor 3 regulates immune and metabolic homeostasis.

    Rynes, Jan; Donohoe, Colin D; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek; Uhlirova, Mirka

    2012-10-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.

  2. Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21

    Kemin Yan

    2018-03-01

    Full Text Available Objective: Ileal transposition (IT surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21 is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with the FGF21 signaling pathway in diabetic Goto-Kakizaki (GK rats.Methods: Ten-week-old male GK rats were subjected to IT surgery with translocation of a 10 cm ileal segment to the proximal jejunum (IT group or sham surgery without the ileum transposition (Sham-IT group. Rats in the no surgery group did not receive any surgical intervention. Six weeks later, body weight, fat mass, fasting blood glucose (FBG, and serum levels of FGF21 and leptin were measured. The expression of the FGF21 signaling pathway and white adipose tissue (WAT browning-related genes in the WAT and liver were evaluated by real-time reverse transcription polymerase chain reaction (RT-qPCR and western blot.Results: IT surgery significantly decreased the body weights and FBG levels and increased the insulin sensitivity of GK rats. The total WAT mass of the IT rats showed a 41.5% reduction compared with the Sham-IT rats, and serum levels of FGF21 and leptin of the IT rats decreased by 26.3 and 61.7%, respectively (all P < 0.05. The mRNA levels of fibroblast growth factor receptor 1 (FGFR1 and its co-receptor β klotho (KLB in the perirenal WAT (pWAT of the IT rats were 1.4- and 2.4-fold that of the Sham-IT rats, respectively, and the FGFR1 protein levels were 1.7-fold of the Sham-IT rats (all P < 0.05. In accordance with the pWAT, the protein levels of FGFR1 and KLB in the epididymal WAT (eWAT of the IT rats notably increased to 3.0- and 3.9-fold of the Sham-IT rats (P < 0.05. Furthermore, uncoupling protein 1 (UCP1 protein levels in the eWAT and pWAT of the IT rats also increased to 2.2- and 2.3-fold of the Sham-IT rats (P < 0.05. However, the protein levels of FGFR1 and KLB in the

  3. Tetragonia tetragonioides (Pall.) Kuntze protects estrogen-deficient rats against disturbances of energy and glucose metabolism and decreases proinflammatory cytokines.

    Ryuk, Jin Ah; Ko, Byoung-Seob; Lee, Hye Won; Kim, Da Sol; Kang, Suna; Lee, Yong Hyen; Park, Sunmin

    2017-03-01

    JGTT groups were associated with enhanced β-cell proliferation and suppressed apoptosis, which was related to the decreased TNF-α and interleukin-1β expressions. In conclusion, JGTT did not improve menopausal symptoms better than TTK itself. TTK itself prevented the OVX-induced impairments in energy, lipid, and glucose metabolism, similar to the positive control, without changing serum 17β-estradiol levels and potentiating insulin signaling and decreasing proinflammatory cytokines. TTK may be a useful intervention to alleviate some menopausal symptoms similar to selective estrogen receptor modulators and should be investigated with further human study. Impact statement Menopause decreases the quality of life in middle-aged women and herbal remedies are sometimes used as alternatives for hormone replacement therapy, which may have detrimental side effects. Although several herbal extracts have been studied, no remedies improve all the menopausal symptoms. In this study, the 70% ethanol extract of Tetragonia tetragonioides (Pall.) Kuntze (TTK) reduced the symptoms of hot flushes and improved energy, glucose, and lipid metabolism in estrogen-deficient animals without increasing serum 17β-estradiol levels. This extract acts like a selective estrogen receptor modulator and it may be a useful intervention for alleviating menopausal symptoms. This is the first study to show that the 70% ethanol extract of TTK has the potential to treat menopause-associated symptoms and metabolic disturbances. It may be a useful intervention for alleviating the symptoms of menopause in women if its efficacy can be confirmed in human studies.

  4. Peroxisome Proliferators-Activated Receptor (PPAR Modulators and Metabolic Disorders

    Min-Chul Cho

    2008-01-01

    Full Text Available Overweight and obesity lead to an increased risk for metabolic disorders such as impaired glucose regulation/insulin resistance, dyslipidemia, and hypertension. Several molecular drug targets with potential to prevent or treat metabolic disorders have been revealed. Interestingly, the activation of peroxisome proliferator-activated receptor (PPAR, which belongs to the nuclear receptor superfamily, has many beneficial clinical effects. PPAR directly modulates gene expression by binding to a specific ligand. All PPAR subtypes (α,γ, and σ are involved in glucose metabolism, lipid metabolism, and energy balance. PPAR agonists play an important role in therapeutic aspects of metabolic disorders. However, undesired effects of the existing PPAR agonists have been reported. A great deal of recent research has focused on the discovery of new PPAR modulators with more beneficial effects and more safety without producing undesired side effects. Herein, we briefly review the roles of PPAR in metabolic disorders, the effects of PPAR modulators in metabolic disorders, and the technologies with which to discover new PPAR modulators.

  5. Physical activity enhances metabolic fitness independently of cardiorespiratory fitness in marathon runners

    Laye, M J; Nielsen, M B; Hansen, L S

    2015-01-01

    High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consisten......High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run...... consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI). Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg) (similar-VO2max......). The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max). Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior...

  6. Diminished neuronal metabolic activity in Alzheimer's disease. Review article

    Salehi, A.; Swaab, D. F.

    1999-01-01

    An increasing number of studies have appeared in the literature suggesting that Alzheimer's disease (AD) is a hypometabolic brain disorder. Decreased metabolism in AD has been revealed by a variety of in vivo and postmortem methods and techniques including positron emission tomography and glucose

  7. Metabolic Syndrome Remodels Electrical Activity of the Sinoatrial Node and Produces Arrhythmias in Rats

    Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

    2013-01-01

    In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats. PMID:24250786

  8. Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes.

    Xinwei Li

    Full Text Available The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic acid and BML-275 (an AMPKα inhibitor. Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.

  9. Educational level and decreases in leisure time physical activity: predictors from the longitudinal GLOBE study

    M. Droomers (Mariël); C.Th.M. Schrijvers (Carola); J.P. Mackenbach (Johan)

    2001-01-01

    textabstractSTUDY OBJECTIVE: This study describes educational differences in decreases in leisure time physical activity among an adult, physically active population and additionally attempts to identify predictors of these differences from information on health status

  10. Resistance Training Combined With Diet Decreases Body Fat While Preserving Lean Mass Independent of Resting Metabolic Rate: A Randomized Trial.

    Miller, Todd; Mull, Stephanie; Aragon, Alan Albert; Krieger, James; Schoenfeld, Brad Jon

    2018-01-01

    The purpose of this study was to determine the effects of resistance training only (RT; n = 10), dietary intervention only (DIET; n = 10), resistance training plus diet (RT+DIET; n = 10), and control (CON; n = 10) on body composition and resting metabolic rate (RMR) in a cohort of 40 premenopausal female volunteers. Subjects in DIET and RT+DIET were provided with daily macronutrient and calorie goals based on DXA and RMR tests, with protein maintained at 3.1 g/kg/day. Subjects in the RT and RT+DIET groups performed a supervised progressive RT program consisting of exercises for all the major muscle groups of the body. Results showed a significant month-by-group interaction for change in fat mass with no significant linear trend for control. The three treatment groups all showed significant linear decreases in fat mass, but the slope of the decrease became progressively steeper from the RT, to DIET, to RT+DIET. A significant linear increase for lean mass was seen for resistance training only. There was a nonsignificant increase in RMR in all groups from Month 0 to Month 4 but no significant month by group interaction. In conclusion, significant reductions in fat mass were achieved by all experimental groups, but results were maximized by RT+DIET. Only the RT group showed significant increases in lean mass.

  11. Impact of body mass decrease of patients with metabolic syndrome on cardiovascular risk factors and reproductive function

    Ol'ga Borisovna Kalinkina

    2015-06-01

    Full Text Available The obesity pandemia linked metabolic syndrome (MS connected with it acquires not only medical, but also increasing social importance. This state has unfavorable action on human organism and is the serious diseases risk factor. Special importance MS available in the women of childbearing age. There are described some literature data about the special features of MS pathogenesis in women and the possibilities of its correction with sibutramine and by the combined medication Reduxin® (sibutramine + cellulose microcrystalline. Our own data of the experience of treatment by the Reduxin® 53 women in reproductive age with MS are cited, opsomenorrhea and with a formation of polycystic ovarian syndrome. Patients took the medication during 12 weeks. Mean body weight loss was 13% and 27 patients had weight loss more than 5% at the end the period of observation. Circle of waist was also the decreased on the average on 6±2 cm. 43 women had a normalization of rhythm, duration and intensity of menstrual hemorrhages. Remaining patients it was required the designation of gestagen in the cyclic regime. An improvement of the blood lipid profile was detect: the average value of atherogenic index triglycerides/ high density lipoproteins cholesterol was improved to 35,8%. The maximum decrease of the cardiovascular disease risk factors was marked in the patients, who had weight loss more than 10%.

  12. Linking neuronal brain activity to the glucose metabolism.

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-08-29

    Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

  13. Nuclear 82-kDa choline acetyltransferase decreases amyloidogenic APP metabolism in neurons from APP/PS1 transgenic mice.

    Albers, Shawn; Inthathirath, Fatima; Gill, Sandeep K; Winick-Ng, Warren; Jaworski, Ewa; Wong, Daisy Y L; Gros, Robert; Rylett, R Jane

    2014-09-01

    Alzheimer disease (AD) is associated with increased amyloidogenic processing of amyloid precursor protein (APP) to β-amyloid peptides (Aβ), cholinergic neuron loss with decreased choline acetyltransferase (ChAT) activity, and cognitive dysfunction. Both 69-kDa ChAT and 82-kDa ChAT are expressed in cholinergic neurons in human brain and spinal cord with 82-kDa ChAT localized predominantly to neuronal nuclei, suggesting potential alternative functional roles for the enzyme. By gene microarray analysis, we found that 82-kDa ChAT-expressing IMR32 neural cells have altered expression of genes involved in diverse cellular functions. Importantly, genes for several proteins that regulate APP processing along amyloidogenic and non-amyloidogenic pathways are differentially expressed in 82-kDa ChAT-containing cells. The predicted net effect based on observed changes in expression patterns of these genes would be decreased amyloidogenic APP processing with decreased Aβ production. This functional outcome was verified experimentally as a significant decrease in BACE1 protein levels and activity and a concomitant reduction in the release of endogenous Aβ1-42 from neurons cultured from brains of AD-model APP/PS1 transgenic mice. The expression of 82-kDa ChAT in neurons increased levels of GGA3, which is involved in trafficking BACE1 to lysosomes for degradation. shRNA-induced decreases in GGA3 protein levels attenuated the 82-kDa ChAT-mediated decreases in BACE1 protein and activity and Aβ1-42 release. Evidence that 82-kDa ChAT can enhance GGA3 gene expression is shown by enhanced GGA3 gene promoter activity in SN56 neural cells expressing this ChAT protein. These studies indicate a novel relationship between cholinergic neurons and APP processing, with 82-kDa ChAT acting as a negative regulator of Aβ production. This decreased formation of Aβ could result in protection for cholinergic neurons, as well as protection of other cells in the vicinity that are sensitive to

  14. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study

    Hevia, David; Gonzalez-Menendez, Pedro; Fernandez-Fernandez, Mario; Cueto, Sergio; Mayo, Juan C.

    2017-01-01

    The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the “Warburg effect” only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type. PMID:28933733

  15. Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study.

    Hevia, David; Gonzalez-Menendez, Pedro; Fernandez-Fernandez, Mario; Cueto, Sergio; Rodriguez-Gonzalez, Pablo; Garcia-Alonso, Jose I; Mayo, Juan C; Sainz, Rosa M

    2017-07-26

    The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/ SLC2A ) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the "Warburg effect" only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13 C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13 C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13 C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13 C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type.

  16. STAT3 Activities and Energy Metabolism: Dangerous Liaisons

    Camporeale, Annalisa, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Demaria, Marco [Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945 (United States); Monteleone, Emanuele [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Giorgi, Carlotta [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Wieckowski, Mariusz R. [Nencki Institute of Experimental Biology, Department of Biochemistry, Pasteur Str. 3, Warsaw 02-093 (Poland); Pinton, Paolo [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Poli, Valeria, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy)

    2014-07-31

    STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3{sup C/C}) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3{sup C/C} MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3{sup C/C} MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms.

  17. STAT3 Activities and Energy Metabolism: Dangerous Liaisons

    Camporeale, Annalisa; Demaria, Marco; Monteleone, Emanuele; Giorgi, Carlotta; Wieckowski, Mariusz R.; Pinton, Paolo; Poli, Valeria

    2014-01-01

    STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3 C/C ) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3 C/C MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3 C/C MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms

  18. Long-term interdisciplinary therapy decreases symptoms of binge eating disorder and prevalence of metabolic syndrome in adults with obesity.

    Leite, Paula Bresciani; Dâmaso, Ana Raimunda; Poli, Vanessa Schoenardie; Sanches, Ricardo Badan; Silva, Stephan Garcia Andrade; Fidalgo, João Pedro Novo; Nascimento, Maythe Amaral; de Oliveira, Camila Aparecida Machado; Caranti, Danielle Arisa

    2017-04-01

    Obesity-associated comorbidities greatly impact the quality and expectancy of life. Binge eating disorder (BED) is the most prevalent eating disorder and it is an important risk factor for obesity and metabolic syndrome (MetS). For these reasons, we aimed to assess the effect of an interdisciplinary therapy on the symptoms of BED and the prevalence of MetS in obese adults. It was hypothesized that the interdisciplinary therapy would decrease symptoms of BED and markers of MetS. Twenty-four volunteers (BMI 34.80±3.17 kg/m 2 ; 41.21±6.28 years old) completed a 32-week intervention. Biochemical characteristics, body composition, the degree of symptoms of binge eating, and macronutrients, and sodium consumption pre- and post-treatment were determined. The prevalence of MetS dropped from 75% to 45.8%, post-therapy. Among the markers of MetS, waist circumference and systolic blood pressure decreased significantly, whereas high-density lipoprotein levels increased. Fasting plasma glucose, diastolic blood pressure, and triglycerides did not change. Based on binge-eating scale (BES) scores, before therapy, 33.3% of volunteers were classified as moderate bingers, and after therapy all volunteers were classified as having no BED symptoms. No difference in the prevalence of MetS between individuals classified as normal or moderate bingers was observed, but we found a positive post-therapy correlation between the BES score and body fat, gynoid fat and trunk fat. Sodium, fat, and carbohydrate consumption decreased. Protein intake did not change. In conclusion, the interdisciplinary approach was efficient in reducing symptoms of BED and MetS prevalence in this population. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Brain Metabolism Alterations Induced by Pregnancy Swimming Decreases Neurological Impairments Following Neonatal Hypoxia-Ischemia in Very Immature Rats

    Eduardo F. Sanches

    2018-06-01

    Full Text Available Introduction: Prematurity, through brain injury and altered development is a major cause of neurological impairments and can result in motor, cognitive and behavioral deficits later in life. Presently, there are no well-established effective therapies for preterm brain injury and the search for new strategies is needed. Intra-uterine environment plays a decisive role in brain maturation and interventions using the gestational window have been shown to influence long-term health in the offspring. In this study, we investigated whether pregnancy swimming can prevent the neurochemical metabolic alterations and damage that result from postnatal hypoxic-ischemic brain injury (HI in very immature rats.Methods: Female pregnant Wistar rats were divided into swimming (SW or sedentary (SE groups. Following a period of adaptation before mating, swimming was performed during the entire gestation. At postnatal day (PND3, rat pups from SW and SE dams had right common carotid artery occluded, followed by systemic hypoxia. At PND4 (24 h after HI, the early neurochemical profile was measured by 1H-magnetic resonance spectroscopy. Astrogliosis, apoptosis and neurotrophins protein expression were assessed in the cortex and hippocampus. From PND45, behavioral testing was performed. Diffusion tensor imaging and neurite orientation dispersion and density imaging were used to evaluate brain microstructure and the levels of proteins were quantified.Results: Pregnancy swimming was able to prevent early metabolic changes induced by HI preserving the energetic balance, decreasing apoptotic cell death and astrogliosis as well as maintaining the levels of neurotrophins. At adult age, swimming preserved brain microstructure and improved the performance in the behavioral tests.Conclusion: Our study points out that swimming during gestation in rats could prevent prematurity related brain damage in progeny with high translational potential and possibly interesting cost

  20. Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes.

    Chen, Hui; Zhang, Liang; Li, Xinwei; Li, Xiaobing; Sun, Guoquan; Yuan, Xue; Lei, Liancheng; Liu, Juxiong; Yin, Liheng; Deng, Qinghua; Wang, Jianguo; Liu, Zhaoxi; Yang, Wentao; Wang, Zhe; Zhang, Hui; Liu, Guowen

    2013-11-01

    Adiponectin (Ad) plays a crucial role in hepatic lipid metabolism. However, the regulating mechanism of hepatic lipid metabolism by Ad in dairy cows is unclear. Hepatocytes from a newborn female calf were cultured in vitro and treated with different concentrations of Ad and BML-275 (an AMPKα inhibitor). The results showed that Ad significantly increased the expression of two Ad receptors. Furthermore, the phosphorylation and activity of AMPKα, as well as the expression levels and transcriptional activity of peroxisome proliferator activated receptor-α (PPARα) and its target genes involved in lipid oxidation, showed a corresponding trend of upregulation. However, the expression levels and transcriptional activity of sterol regulatory element binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) decreased in a similar manner. When BML-275 was added, the p-AMPKα level as well as the expression and activity of PPARα and its target genes were significantly decreased. However, the expression levels of SREBP-1c, ChREBP and their target genes showed a trend of upregulation. Furthermore, the triglyceride (TG) content was significantly decreased in the Ad-treated groups. These results indicate that Ad activates the AMPK signaling pathway and mediates lipid metabolism in bovine hepatocytes cultured in vitro by promoting lipid oxidation, suppressing lipid synthesis and reducing hepatic lipid accumulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Natural Killer Cell Activity and Interleukin-12 in Metabolically Healthy versus Metabolically Unhealthy Overweight Individuals

    Kim, Minjoo; Kim, Minkyung; Yoo, Hye Jin; Lee, Jong Ho

    2017-01-01

    The purpose of this study was to determine whether the immune system is involved in the different metabolic circumstances in healthy and unhealthy overweight individuals. We examined the metabolic and immune characteristics of 117 overweight individuals. Subjects were classified as metabolically healthy overweight (MHO, n = 72) or metabolically unhealthy overweight (MUO, n = 45). The immune response was measured by circulating levels of natural killer (NK) cell activity and cytokines. Both groups were comparable with regards to age, sex distribution, smoking and drinking status, and body mass index. When compared to the MHO group, the MUO group showed higher systolic and diastolic blood pressure, serum levels of triglyceride, glucose, glucose-related markers, and lower levels of HDL cholesterol. Compared to the MHO group, the MUO group showed 39% lower interferon-γ levels (not significant) and 41% lower interleukin (IL)-12 levels (significant). The MUO group also showed lower NK cell activity at E:T ratios of 10:1, 5:1, 2.5:1, and 1.25:1 (all Ps < 0.05) than the MHO group. This study indicates that individuals displaying the MUO phenotype present an unfavorable immune system with lower NK cell activities under all assay conditions and lower serum levels of IL-12 than the activities and levels in similarly overweight MHO individuals. This result suggests that the immune system may be altered in overweight individuals who are at risk for overweight/obesity-related comorbidities. PMID:29238351

  2. Natural Killer Cell Activity and Interleukin-12 in Metabolically Healthy versus Metabolically Unhealthy Overweight Individuals

    Minjoo Kim

    2017-11-01

    Full Text Available The purpose of this study was to determine whether the immune system is involved in the different metabolic circumstances in healthy and unhealthy overweight individuals. We examined the metabolic and immune characteristics of 117 overweight individuals. Subjects were classified as metabolically healthy overweight (MHO, n = 72 or metabolically unhealthy overweight (MUO, n = 45. The immune response was measured by circulating levels of natural killer (NK cell activity and cytokines. Both groups were comparable with regards to age, sex distribution, smoking and drinking status, and body mass index. When compared to the MHO group, the MUO group showed higher systolic and diastolic blood pressure, serum levels of triglyceride, glucose, glucose-related markers, and lower levels of HDL cholesterol. Compared to the MHO group, the MUO group showed 39% lower interferon-γ levels (not significant and 41% lower interleukin (IL-12 levels (significant. The MUO group also showed lower NK cell activity at E:T ratios of 10:1, 5:1, 2.5:1, and 1.25:1 (all Ps < 0.05 than the MHO group. This study indicates that individuals displaying the MUO phenotype present an unfavorable immune system with lower NK cell activities under all assay conditions and lower serum levels of IL-12 than the activities and levels in similarly overweight MHO individuals. This result suggests that the immune system may be altered in overweight individuals who are at risk for overweight/obesity-related comorbidities.

  3. Metabolic-epigenetic crosstalk in macrophage activation

    Baardman, Jeroen; Licht, Iris; de Winther, Menno P. J.; van den Bossche, Jan

    2015-01-01

    Epigenetic enzymes are emerging as crucial controllers of macrophages, innate immune cells that determine the outcome of many inflammatory diseases. Recent studies demonstrate that the activity of particular chromatin-modifying enzymes is regulated by the availability of specific metabolites like

  4. Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity

    Thiesson, Helle; Jensen, Boye L; Bistrup, Claus

    2007-01-01

    Downregulation of the renal glucocorticoid-metabolizing enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) during liver cirrhosis may allow activation of the mineralocorticoid receptor (MR) by glucocorticoids and contribute to sodium retention. We tested this hypothesis in male Wistar...... rats with decompensated liver cirrhosis and ascites 7 wk after bile duct ligation (BDL). Renal 11beta-HSD-2 mRNA, protein, and activity were significantly decreased in decompensated rats. The urinary Na(+)/K(+) ratio was reduced by 40%. Renal epithelial sodium channel (ENaC) mRNA and immunostaining...... were only slightly affected. Complete metabolic studies, including fecal excretion, showed that the BDL rats had avid renal sodium retention. Treatment of the BDL rats with dexamethasone suppressed endogenous glucocorticoid production, normalized total sodium balance and renal sodium excretion...

  5. Effects of activation of endocannabinoid system on myocardial metabolism

    Agnieszka Polak

    2016-05-01

    Full Text Available Endocannabinoids exert their effect on the regulation of energy homeostasis via activation of specific receptors. They control food intake, secretion of insulin, lipids and glucose metabolism, lipid storage. Long chain fatty acids are the main myocardial energy substrate. However, the heart exerts enormous metabolic flexibility emphasized by its ability to utilzation not only fatty acids, but also glucose, lactate and ketone bodies. Endocannabinoids can directly act on the cardiomyocytes through the CB1 and CB2 receptors present in cardiomyocytes. It appears that direct activation of CB1 receptors promotes increased lipogenesis, pericardial steatosis and bioelectrical dysfunction of the heart. In contrast, stimulation of CB2 receptors exhibits cardioprotective properties, helping to maintain appropriate amount of ATP in cardiomyocytes. Furthermore, the effects of endocannabinoids at both the central nervous system and peripheral tissues, such as liver, pancreas, or adipose tissue, resulting indirectly in plasma availability of energy substrates and affects myocardial metabolism. To date, there is little evidence that describes effects of activation of the endocannabinoid system in the cardiovascular system under physiological conditions. In the present paper the impact of metabolic diseases, i. e. obesity and diabetes, as well as the cardiovascular diseases - hypertension, myocardial ischemia and myocardial infarction on the deregulation of the endocannabinoid system and its effect on the metabolism are described.

  6. Glucose metabolism regulates T cell activation, differentiation and functions

    Clovis Steve Palmer

    2015-01-01

    Full Text Available The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The Warburg effect originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

  7. Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy

    Claire M. Doskey

    2016-12-01

    Full Text Available Ascorbate (AscH− functions as a versatile reducing agent. At pharmacological doses (P-AscH−; [plasma AscH−] ≥≈20 mM, achievable through intravenous delivery, oxidation of P-AscH− can produce a high flux of H2O2 in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2O2. We hypothesize that sensitivity of tumor cells to P-AscH− compared to normal cells is due to their lower capacity to metabolize H2O2. Rate constants for removal of H2O2 (kcell and catalase activities were determined for 15 tumor and 10 normal cell lines of various tissue types. A differential in the capacity of cells to remove H2O2 was revealed, with the average kcell for normal cells being twice that of tumor cells. The ED50 (50% clonogenic survival of P-AscH− correlated directly with kcell and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH−.

  8. Physical Activity Enhances Metabolic Fitness Independently of Cardiorespiratory Fitness in Marathon Runners

    M. J. Laye

    2015-01-01

    Full Text Available High levels of cardiovascular fitness (CRF and physical activity (PA are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI. Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg (similar-VO2max. The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max. Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior in runners versus sedentary controls despite similar VO2max. Furthermore, performance (velocity at VO2max, running economy, improved exercise metabolism (lactate threshold, and skeletal muscle levels of mitochondrial proteins were superior in runners versus sedentary controls with similar VO2max. In conclusion subjects with a high amount of PA have more positive metabolic health parameters independent of CRF. PA is thus a good marker against metabolic diseases.

  9. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  10. Pedometer assessed physical activity of people with metabolic syndrome in Poland.

    Anna Owlasiuk

    2014-06-01

    Full Text Available introduction. Metabolic syndrome is a contemporary disease of civilization, an effect of lack of healthy behaviour, a consequence of lifestyle devoid of physical activity, eating poor quality food rich in calories and excessive stress. Apart from a proper diet, physical activity remains an important part of metabolic syndrome management. objective. The main objective of the work was to evaluate the physical activity of an adult population of patients with metabolic syndrome. materials and method. Adults aged 35–70 fulfilling the criteria of metabolic syndrome according to International Diabetes Federation (IDF were included. New Lifestyles NL-2000 pedometers were used to assess locomotive physical activity during an entire week. results. In the group of 100 subjects, as many as 61 people (61% represented low or sedentary activity, while nearly one fourth of the respondents – 23 (32% represented the negligible activity type. Average weekly physical activity of those in the study was 6,743 steps/day (in 100 individuals and ranged from 1,781–15,169. A great diversity was found in the study group, since the highest number of steps per day was 23,347 and the lowest – 409. No significant differences in the number of steps on weekdays and at weekends were observed (mean: 6,676/day and 6,913/day, espectively. A statistically significant negative correlation (r = -0.29 was observed between age and physical activity, between the average daily number of steps in the week and Waist Hip Ratio (WHR (r = 0.201, as well as between the average daily number of steps in the week and Body Mass Index (BMI (r = 0.226. conclusions. The majority of people with metabolic syndrome represent a low or sedentary activity type and decrease of physical activity corresponds to increasing age, BMI and WHR. No significant differences in physical activity are observed between working days and free days (weekends.

  11. Sleep deprivation decreases phase-shift responses of circadian rhythms to light in the mouse: role of serotonergic and metabolic signals.

    Challet, E; Turek, F W; Laute, M; Van Reeth, O

    2001-08-03

    The circadian pacemaker in the suprachiasmatic nuclei is primarily synchronized to the daily light-dark cycle. The phase-shifting and synchronizing effects of light can be modulated by non-photic factors, such as behavioral, metabolic or serotonergic cues. The present experiments examine the effects of sleep deprivation on the response of the circadian pacemaker to light and test the possible involvement of serotonergic and/or metabolic cues in mediating the effects of sleep deprivation. Photic phase-shifting of the locomotor activity rhythm was analyzed in mice transferred from a light-dark cycle to constant darkness, and sleep-deprived for 8 h from Zeitgeber Time 6 to Zeitgeber Time 14. Phase-delays in response to a 10-min light pulse at Zeitgeber Time 14 were reduced by 30% in sleep-deprived mice compared to control mice, while sleep deprivation without light exposure induced no significant phase-shifts. Stimulation of serotonin neurotransmission by fluoxetine (10 mg/kg), a serotonin reuptake inhibitor that decreases light-induced phase-delays in non-deprived mice, did not further reduce light-induced phase-delays in sleep-deprived mice. Impairment of serotonin neurotransmission with p-chloroamphetamine (three injections of 10 mg/kg), which did not increase light-induced phase-delays in non-deprived mice significantly, partially normalized light-induced phase-delays in sleep-deprived mice. Injections of glucose increased light-induced phase-delays in control and sleep-deprived mice. Chemical damage of the ventromedial hypothalamus by gold-thioglucose (600 mg/kg) prevented the reduction of light-induced phase-delays in sleep-deprived mice, without altering phase-delays in control mice. Taken together, the present results indicate that sleep deprivation can reduce the light-induced phase-shifts of the mouse suprachiasmatic pacemaker, due to serotonergic and metabolic changes associated with the loss of sleep.

  12. Metabolic activation of the bladder carcinogen 4-nitrobiphenyl (NBP)

    Swaminathan, S.

    1986-01-01

    The metabolism of NBP, a dog bladder carcinogen, was examined in vitro using rat liver tissues. NBP was metabolized by enzymes localized both in the microsomes and cytosol. The microsomal enzyme activity was inducible by Aroclor 1254 and phenobarbital. High pressure liquid chromatography analysis of the ethyl acetate extract of the reaction mixture, following incubation of [ 3 H]NBP with NADPH and microsomes, revealed four radioactive and UV absorbing peaks with retention times of 5, 8, 14 and 28 min. The peaks at 8, 14 and 28 min corresponded with 4-aminobiphenyl (ABP), NBP and azoxy biphenyl, respectively. The early eluting component with a retention time of 5 min has been tentatively identified as a ring hydroxylated derivative. In contrast to microsomal metabolism, cytosol-mediated metabolism yielded only one major metabolite identified as ABP. Cytosol-mediate reduction was inhibited by the xanthine oxidase inhibitor allopurinol. In vitro incubation of NBP with NADH and commercial preparations of xanthine oxidase also yielded ABP and the formation of the latter was blocked by allopurinol. Xanthine oxidase catalyzed also the binding of [ 3 H]NBP to DNA and proteins; the binding was inhibited by allopurinol. These data support the hypothesis that the nitro reduction step is involved in the activation of the bladder carcinogen NBP, and that the nitroreductases occur in both the microsomes and cytosol. The cytosolic activity is primarily due to xanthine oxidase

  13. Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats

    Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptos...

  14. Decreasing prevalence of the full metabolic syndrome but a persistently high prevalence of dyslipidemia among adult Arabs.

    Nasser M Al-Daghri

    Full Text Available A decade has passed since metabolic syndrome (MetS was documented to be highly prevalent in the kingdom of Saudi Arabia. No follow-up epidemiologic study was done. This study aims to fill this gap. In this cross-sectional, observational study, a total of 2850 randomly selected Saudi adults aged 18-55 years were recruited. Subjects' information was generated from a database of more than 10,000 Saudi citizens from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort, Saudi Arabia. Anthropometrics included body mass index (BMI, blood pressure, as well as waist and hip circumferences. Fasting blood glucose and lipid profile were determined using routine laboratory procedures. The definition of ATP-III (NHANES III was used for the diagnosis of the full MetS. The overall prevalence of complete MetS was 35.3% [Confidence-Interval (CI 33.5-37.01]. Age-adjusted prevalence according to the European standard population is 37.0%. Low HDL-cholesterol was the most prevalent of all MetS risk factors, affecting 88.6% (CI 87.5-89.7 and hypertriglyceridemia the second most prevalent, affecting 34% (CI 32.3-35.7 of the subjects. The prevalence of the full MetS decreased from previous estimates but remains high, while dyslipidemia remains extremely high, affecting almost 90% of middle-aged Arabs. Screening for dyslipidemia among Saudi adults is warranted, especially among those most at risk. Scientific inquiry into the molecular causes of these manifestations should be pursued as a first step in the discovery of etiologic therapies.

  15. Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

    Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

    2012-01-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

  16. Solar activity associated with an unusual series of microwave flux decreases

    Sawyer, C.

    1976-01-01

    East-limb passage of an activity complex in the spring of 1974 was accompanied by a remarkable series of microwave flux decreases. Within an interval of four days, two post-burst decreases and five 'absorption' events occurred, along with two oscillations. Hα patrol films and a spectrogram show a surge and flare sprays with an unusually large velocity of approach at the time of the first post-burst decrease. Two other 'absorption' events were loosely associated with prominence activations, but no outstanding Hα activity was seen at the time of the oscillations. These observations, along with published data, show that the flux decreases followed only flares that lay westward of the major microwave source; ejections from this location would likely have overlain the source while the region was near the east limb. Absorption by flare-ejected material is a plausible, though not exclusive, explanation of these events. (author)

  17. Increasing physical activity and decreasing sedentary activity in adolescent girls – The Incorporating More Physical Activity and Calcium in Teens (IMPACT study

    Hergenroeder Albert

    2008-08-01

    Full Text Available Abstract Background Lack of regular physical activity and consequent sub-optimal bone mass acquisition in youth has been implicated as a primary cause of adult-onset osteoporosis. IMPACT was a behavioral theory-based 1 1/2 year randomized controlled field study aimed at increasing bone accretion in middle school girls. The objective of this study was to determine the intervention effects of the IMPACT program upon key physical and sedentary activity endpoints among schools that participated in the IMPACT study. Endpoints examined included weight bearing physical activity (WBPA; moderate to vigorous physical activity (MVPA; vigorous physical activity (VPA; MET (metabolic equivalent – weighted WBPA and MVPA; sedentary activity; before/after-school physical activity; and weekend physical activity. Methods Primary data analysis using a pretest-posttest control group design was conducted utilizing mixed model analysis of covariance. Data gathered from the IMPACT cohort from 2000–2002 were analyzed to determine baseline versus follow-up differences in activity endpoints. Confounders investigated included ethnicity, body mass index, menarcheal status, participation in 7th grade PE/athletics, friend/familial support and neighborhood safety. Results Follow-up means were higher for participating intervention schools relative to control schools for all physical activity variables but were statistically significant only for the following variables: daily minutes of vigorous physical activity (mean difference between Intervention (I and Control (C = 6.00↑ minutes, 95% CI = 5.82–6.18, p = 0.05, daily after school activity minutes (mean difference between I and C = 8.95↑ minutes, 95% CI = 8.69–9.21, p = 0.04, and daily weekend activity minutes (mean difference between I and C = 19.00↑ minutes, 95% CI = 18.40–19.60, p = 0.05. The intervention significantly reduced duration of student daily TV/Video watching (mean difference between I and C = 12

  18. Glucose-6-phosphate dehydrogenase activity decreases during storage of leukoreduced red blood cells

    Peters, Anna L.; van Bruggen, Robin; de Korte, Dirk; van Noorden, Cornelis J. F.; Vlaar, Alexander P. J.

    2016-01-01

    During storage, the activity of the red blood cell (RBC) antioxidant system decreases. Glucose-6-phosphate dehydrogenase (G6PD) is essential for protection against oxidative stress by producing NADPH. G6PD function of RBC transfusion products is reported to remain stable during storage, but activity

  19. 5' adenosine monophosphate-activated protein kinase, metabolism and exercise.

    Aschenbach, William G; Sakamoto, Kei; Goodyear, Laurie J

    2004-01-01

    The 5' adenosine monophosphate-activated protein kinase (AMPK) is a member of a metabolite-sensing protein kinase family that functions as a metabolic 'fuel gauge' in skeletal muscle. AMPK is a ubiquitous heterotrimeric protein, consisting of an alpha catalytic, and beta and gamma regulatory subunits that exist in multiple isoforms and are all required for full enzymatic activity. During exercise, AMPK becomes activated in skeletal muscle in response to changes in cellular energy status (e.g. increased adenosine monophosphate [AMP]/adenosine triphosphate [ATP] and creatine/phosphocreatine ratios) in an intensity-dependent manner, and serves to inhibit ATP-consuming pathways, and activate pathways involved in carbohydrate and fatty-acid metabolism to restore ATP levels. Recent evidence shows that although AMPK plays this key metabolic role during acute bouts of exercise, it is also an important component of the adaptive response of skeletal muscles to endurance exercise training because of its ability to alter muscle fuel reserves and expression of several exercise-responsive genes. This review discusses the putative roles of AMPK in acute and chronic exercise responses, and suggests avenues for future AMPK research in exercise physiology and biochemistry.

  20. Enhancement of the Electrocatalytic Activity of Gold Nanoparticles via Anodic Treatment and the Decrease of the Enhanced Activity with Aging

    Jo, Kyung Min; Kang, Hyun Ju; Yang, Hae Sik

    2011-01-01

    We have recently shown that the electrocatalytic activity of Au nanoparticles (AuNPs) can be enhanced via NaBH 4 treatment and cathodic treatment and that the enhanced activity slowly decreases with aging. We have also demonstrated that the electrocatalytic activity of the AuNPs freshly prepared by electrochemical or chemical reduction slowly decreases with aging in both air and solution. Likewise, the electrocatalytic activity of anodically treated Au electrodes or AuNPs might change with aging. Herein, we report that the electrocatalytic activity of long-aged AuNPs can be enhanced via anodic treatment and that the enhanced electrocatalytic activity decreases with aging in air. The change in the electrocatalytic activity of AuNPs was evaluated by comparing cyclic voltammograms for the electrooxi-dation of hydrogen peroxide (H 2 O 2 ) and formic acid

  1. Effect of tributyltin (TBT) in the metabolic activity of TBT-resistant and sensitive estuarine bacteria.

    Cruz, Andreia; Oliveira, Vanessa; Baptista, Inês; Almeida, Adelaide; Cunha, Angela; Suzuki, Satoru; Mendo, Sónia

    2012-01-01

    The effect of tributyltin (TBT) on growth and metabolic activity of three estuarine bacteria with different TBT resistance profiles was investigated in an organic-rich culture medium (TSB) and in phosphate buffered saline (PBS) buffer. Exposure to TBT was assessed by determining its effect on growth (OD(600 nm) measurement), bacterial productivity (leucine incorporation), viability (CFU counts), aggregation and cell size (from Live/Dead analysis), ATP and NADH concentrations. TBT exposure resulted in decrease of bacterial density, cell size, and metabolic activity. In addition, cell aggregates were observed in the TBT-treated cultures. TBT strongly affected bacterial cell metabolism and seemed to exert an effect on its equilibrium, interfering with cell activity. Also, TBT toxicity was lower when cells were grown in TSB than in PBS, suggesting that a nutrient-rich growth medium can protect cells from TBT toxicity. This study contributes to our understanding of the TBT-resistant cell behavior reflected in its physiology and metabolic activity. This information is of utmost importance for further studies of TBT bioremediation. Copyright © 2010 Wiley Periodicals, Inc.

  2. Metabolic syndrome and cognitive decline: the role of physical activity

    M. Rinaldi

    2013-01-01

    Full Text Available Metabolic Syndrome (MetS is a cluster of conditions, each of which represents a risk factor for cardiovascular disease: central obesity, hyperglycemia, dyslipidemia and hypertension. Any of these conditions and MetS itself have been associated to Alzheimer's Disease and Vascular Dementia. In recent years there is a growing evidence for the role of physical activity in preventing metabolic diseases and cognitive decline. In our research we assessed the prevalence of MetS in a sample of 154 elderly people. Furthermore, we evaluated cognition (with Mini Mental State Examination, MMSE  and the physical activity level in every patient. We found a significant association between MetS, borderline cognitive impairment and sedentary lifestyle.

  3. Fluvoxamine alters the activity of energy metabolism enzymes in the brain

    Gabriela K. Ferreira

    2014-09-01

    Full Text Available Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.

  4. Correlations decrease with propagation of spiking activity in the mouse barrel cortex

    Gayathri Nattar Ranganathan

    2011-05-01

    Full Text Available Propagation of suprathreshold spiking activity through neuronal populations is important for the function of the central nervous system. Neural correlations have an impact on cortical function particularly on the signaling of information and propagation of spiking activity. Therefore we measured the change in correlations as suprathreshold spiking activity propagated between recurrent neuronal networks of the mammalian cerebral cortex. Using optical methods we recorded spiking activity from large samples of neurons from two neural populations simultaneously. The results indicate that correlations decreased as spiking activity propagated from layer 4 to layer 2/3 in the rodent barrel cortex.

  5. Decreased medial prefrontal cortex activation during self-referential processing in bipolar mania.

    Herold, Dorrit; Usnich, Tatiana; Spengler, Stephanie; Sajonz, Bastian; Bauer, Michael; Bermpohl, Felix

    2017-09-01

    Patients with bipolar disorder in mania exhibit symptoms pointing towards altered self-referential processing, such as decreased self-focus, flight of ideas and high distractibility. In depression, the opposite pattern of symptoms has been connected to increased activation of medial prefrontal cortex (mPFC) during self-referential processing. In this study, we hypothesized that (1) patients with mania will exhibit decreased activation in the mPFC during self-referential processing and (2) will be more alexithymic and that levels of alexithymia will correlate negatively with mPFC activation. The neural response to standardized pictures was compared in 14 patients with bipolar I disorder in mania to 14 healthy controls using blood oxygen level dependent contrast magnetic resonance imaging. Participants were asked to indicate with button press during the scanning session for each picture whether the pictures personally related to them or not. Toronto alexithymia scale (TAS) scores were recorded from all participants. In the group analysis, patients with mania exhibited decreased activation in a predefined region of interest in the mPFC during self-referential processing compared to healthy controls. Patients with mania showed significantly higher levels of alexithymia, attributable to difficulties in identifying and describing emotions. Activation in the mPFC correlated negatively with levels of alexithymia. Results presented here should be replicated in a larger group, potentially including unmedicated patients. The finding of decreased mPFC activation during self-referential processing in mania may reflect decreased self-focus and high distractibility. Support for this view comes from the negative correlation between higher alexithymia scores and decreased mPFC activation. These findings represent an opposite clinical and neuroimaging pattern to findings in depression. Copyright © 2017. Published by Elsevier B.V.

  6. Prediction of residual metabolic activity after treatment in NSCLC patients

    Rios Velazquez, Emmanuel; Aerts, Hugo J.W.L.; Oberije, Cary; Ruysscher, Dirk De; Lambin, Philippe

    2010-01-01

    Purpose. Metabolic response assessment is often used as a surrogate of local failure and survival. Early identification of patients with residual metabolic activity is essential as this enables selection of patients who could potentially benefit from additional therapy. We report on the development of a pre-treatment prediction model for metabolic response using patient, tumor and treatment factors. Methods. One hundred and one patients with inoperable NSCLC (stage I-IV), treated with 3D conformal radical (chemo)-radiotherapy were retrospectively included in this study. All patients received a pre and post-radiotherapy fluorodeoxyglucose positron emission tomography-computed tomography FDG-PET-CT scan. The electronic medical record system and the medical patient charts were reviewed to obtain demographic, clinical, tumor and treatment data. Primary outcome measure was examined using a metabolic response assessment on a post-radiotherapy FDG-PET-CT scan. Radiotherapy was delivered in fractions of 1.8 Gy, twice a day, with a median prescribed dose of 60 Gy. Results. Overall survival was worse in patients with residual metabolic active areas compared with the patients with a complete metabolic response (p=0.0001). In univariate analysis, three variables were significantly associated with residual disease: larger primary gross tumor volume (GTVprimary, p=0.002), higher pre-treatment maximum standardized uptake value (SUV max , p=0.0005) in the primary tumor and shorter overall treatment time (OTT, p=0.046). A multivariate model including GTVprimary, SUV max , equivalent radiation dose at 2 Gy corrected for time (EQD2, T) and OTT yielded an area under the curve assessed by the leave-one-out cross validation of 0.71 (95% CI, 0.65-0.76). Conclusion. Our results confirmed the validity of metabolic response assessment as a surrogate of survival. We developed a multivariate model that is able to identify patients at risk of residual disease. These patients may benefit from

  7. Physical activity, body composition and metabolic syndrome in young adults.

    Minna K Salonen

    Full Text Available Low physical activity (PA is a major risk factor for cardiovascular and metabolic disorders in all age groups. We measured intensity and volume of PA and examined the associations between PA and the metabolic syndrome (MS, its components and body composition among young Finnish adults.The study comprises 991 men and women born 1985-86, who participated in a clinical study during the years 2009-11 which included assessments of metabolism, body composition and PA. Objectively measured (SenseWear Armband five-day PA data was available from 737 participants and was expressed in metabolic equivalents of task (MET.The prevalence of MS ranged between 8-10%. Higher total mean volume (MET-hours or intensity (MET were negatively associated with the risk of MS and separate components of MS, while the time spent at sedentary level of PA was positively associated with MS.MS was prevalent in approximately every tenth of the young adults at the age of 24 years. Higher total mean intensity and volume rates as well as longer duration spent at moderate and vigorous PA level had a beneficial impact on the risk of MS. Longer time spent at the sedentary level of PA increased the risk of MS.

  8. Tributyltin toxicity in abalone (Haliotis diversicolor supertexta) assessed by antioxidant enzyme activity, metabolic response, and histopathology.

    Zhou, Jin; Zhu, Xiao-shan; Cai, Zhong-hua

    2010-11-15

    A toxicity test was performed to investigate the possible harmful effects of tributyltin (TBT) on abalone (Haliotis diversicolor supertexta). Animals were exposed to TBT in a range of environmentally relevant concentrations (2, 10 and 50 ng/L) for 30 days under laboratory conditions. TBT-free conditions were used as control treatments. The activity of antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD), and malondialdehyde (MDA), along with levels of haemolymph metabolites, and hepatopancreas histopathology were analyzed. The results showed that TBT decreased SOD activity, and increased POD level and MDA production in a dose-dependent way, indicating that oxidative injury was induced by TBT. Haemolymph metabolite measurements showed that TBT increased alanine and glutamate levels, and decreased glucose content, which suggested perturbation of energy metabolism. Elevated levels of acetate and pyruvate in the haemolymph indicated partial alteration of lipid metabolism. A decrease in lactate and an increase in succinate, an intermediate of the tricarboxylic acid (TCA) cycle, indicated disturbance of amino acid metabolism. Hepatopancreas tissues also exhibited inflammatory responses characterized by histopathological changes such as cell swelling, granular degeneration, and inflammation. Taken together, these results demonstrated that TBT was a potential toxin with a variety of deleterious effects on abalone. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.

    Gong, Meng-Juan; Han, Bin; Wang, Shu-mei; Liang, Sheng-wang; Zou, Zhong-jie

    2016-05-10

    Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Relationships among nocturnal jaw muscle activities, decreased esophageal pH, and sleep positions.

    Miyawaki, Shouichi; Tanimoto, Yuko; Araki, Yoshiko; Katayama, Akira; Imai, Mikako; Takano-Yamamoto, Teruko

    2004-11-01

    The purpose of this study was to examine the relationships among nocturnal jaw muscle activities, decreased esophageal pH, and sleep positions. Twelve adult volunteers, including 4 bruxism patients, participated in this study. Portable pH monitoring, electromyography of the temporal muscle, and audio-video recordings were conducted during the night in the subjects' homes. Rhythmic masticatory muscle activity (RMMA) episodes were observed most frequently, with single short-burst episodes the second most frequent. The frequencies of RMMA, single short-burst, and clenching episodes were significantly higher during decreased esophageal pH episodes than those during other times. Both the electromyography and the decreased esophageal pH episodes were most frequently observed in the supine position. These results suggest that most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position.

  11. Rewiring yeast acetate metabolism through MPC1 loss of function leads to mitochondrial damage and decreases chronological lifespan

    Ivan Orlandi

    2014-11-01

    Full Text Available During growth on fermentable substrates, such as glucose, pyruvate, which is the end-product of glycolysis, can be used to generate acetyl-CoA in the cytosol via acetaldehyde and acetate, or in mitochondria by direct oxidative decarboxylation. In the latter case, the mitochondrial pyruvate carrier (MPC is responsible for pyruvate transport into mitochondrial matrix space. During chronological aging, yeast cells which lack the major structural subunit Mpc1 display a reduced lifespan accompanied by an age-dependent loss of autophagy. Here, we show that the impairment of pyruvate import into mitochondria linked to Mpc1 loss is compensated by a flux redirection of TCA cycle intermediates through the malic enzyme-dependent alternative route. In such a way, the TCA cycle operates in a “branched” fashion to generate pyruvate and is depleted of intermediates. Mutant cells cope with this depletion by increasing the activity of glyoxylate cycle and of the pathway which provides the nucleocytosolic acetyl-CoA. Moreover, cellular respiration decreases and ROS accumulate in the mitochondria which, in turn, undergo severe damage. These acquired traits in concert with the reduced autophagy restrict cell survival of the mpc1∆ mutant during chronological aging. Conversely, the activation of the carnitine shuttle by supplying acetyl-CoA to the mitochondria is sufficient to abrogate the short-lived phenotype of the mutant.

  12. Activity syndromes and metabolism in giant deep-sea isopods

    Wilson, Alexander D. M.; Szekeres, Petra; Violich, Mackellar; Gutowsky, Lee F. G.; Eliason, Erika J.; Cooke, Steven J.

    2017-03-01

    Despite growing interest, the behavioural ecology of deep-sea organisms is largely unknown. Much of this scarcity in knowledge can be attributed to deepwater animals being secretive or comparatively 'rare', as well as technical difficulties associated with accessing such remote habitats. Here we tested whether two species of giant marine isopod (Bathynomus giganteus, Booralana tricarinata) captured from 653 to 875 m in the Caribbean Sea near Eleuthera, The Bahamas, exhibited an activity behavioural syndrome across two environmental contexts (presence/absence of food stimulus) and further whether this syndrome carried over consistently between sexes. We also measured routine metabolic rate and oxygen consumption in response to a food stimulus in B. giganteus to assess whether these variables are related to individual differences in personality. We found that both species show an activity syndrome across environmental contexts, but the underlying mechanistic basis of this syndrome, particularly in B. giganteus, is unclear. Contrary to our initial predictions, neither B. giganteus nor B. tricarinata showed any differences between mean expression of behavioural traits between sexes. Both sexes of B. tricarinata showed strong evidence of an activity syndrome underlying movement and foraging ecology, whereas only male B. giganteus showed evidence of an activity syndrome. Generally, individuals that were more active and bolder, in a standard open arena test were also more active when a food stimulus was present. Interestingly, individual differences in metabolism were not related to individual differences in behaviour based on present data. Our study provides the first measurements of behavioural syndromes and metabolism in giant deep-sea isopods.

  13. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

    Nieves Baenas

    2016-02-01

    Full Text Available We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo, a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus.

  14. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A.; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E.

    2016-01-01

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus. PMID:26901196

  15. Soluble ectodomain of neuroligin 1 decreases synaptic activity by activating metabotropic glutamate receptor 2

    Gjørlund, Michelle D.; Carlsen, Eva Maria Meier; Kønig, Andreas Bay

    2017-01-01

    Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent ...

  16. Causes of decreased activity of daily life in elderly patients who need daily living care.

    Yoshino, Hiroshi; Sakurai, Takashi; Hasegawa, Kazuo; Yokono, Koichi

    2011-07-01

    The causes of decreased activity of daily life (ADL) in elderly patients include cerebrovascular diseases, bone fracture by falls, and dementia. The present study was conducted among elderly patients with decreased ADL who were hospitalized in nursing wards in order to investigate the causes of becoming early bedridden and to determine precautionary measures against decreased ADL. The study subjects were 224 elderly patients with decreased ADL (mean age: 83.3 ± 8.0 years) and 49 outpatients without decreased ADL (mean age: 76.8 ± 5.3 years). Current age, age at the start of ADL decrease, medical history and history of smoking were investigated. In the groups with decreased ADL, current age and the age of becoming bedridden in non-diabetic versus diabetic groups were 84.7 ± 7.9 versus 80.3 ± 7.5 and 82.7 ± 8.3 versus 77.6 ± 8.0 years, respectively, both showing significantly lower values in the diabetic group (P bedridden. Diabetic patients with smoking habit were significantly younger than diabetic and non-diabetic patients without smoking habit. Sex difference, smoking habit and presence of diabetes mellitus are independent risk factors of becoming early bedridden. Therefore, the major targets of medical care among elderly should be diabetic men with a smoking habit to lower the risks of decreased ADL. © 2011 Japan Geriatrics Society.

  17. Serum microRNA miR-206 is decreased in hyperthyroidism and mediates thyroid hormone regulation of lipid metabolism in HepG2 human hepatoblastoma cells.

    Zheng, Yingjuan; Zhao, Chao; Zhang, Naijian; Kang, Wenqin; Lu, Rongrong; Wu, Huadong; Geng, Yingxue; Zhao, Yaping; Xu, Xiaoyan

    2018-04-01

    The actions of thyroid hormone (TH) on lipid metabolism in the liver are associated with a number of genes involved in lipogenesis and lipid metabolism; however, the underlying mechanisms through which TH impacts on lipid metabolism remain to be elucidated. The present study aimed to investigate the effects of hyperthyroidism on the serum levels of the microRNA (miR) miR‑206 and the role of miR‑206 on TH‑regulated lipid metabolism in liver cells. Serum was obtained from 12 patients diagnosed with hyperthyroidism and 10 healthy control subjects. Human hepatoblastoma (HepG2) cells were used to study the effects of triiodothyronine (T3) and miR‑206 on lipid metabolism. Expression of miR‑206 in serum and cells was determined by reverse transcription‑quantitative polymerase chain reaction analysis. Lipid accumulation in HepG2 cells was assessed with Oil Red O staining. Suppression or overexpression of miR‑206 was performed via transfection with a miR‑206 mimic or miR‑206 inhibitor. Serum miR‑206 was significantly decreased in patients with hyperthyroidism compared with euthyroid controls. Treatment of HepG2 cells with T3 led to reduced total cholesterol (TC) and triglyceride (TG) content, accompanied by reduced miR‑206 expression. Inhibition of endogenous miR‑206 expression decreased intracellular TG and TC content in HepG2 cells. By contrast, overexpression of miR‑206 in HepG2 partially prevented the reduction in TG content induced by treatment with T3. In conclusion, serum miR‑206 expression is reduced in patients with hyperthyroidism. In addition, miR‑206 is involved in T3‑mediated regulation of lipid metabolism in HepG2 cells, indicating a role for miR‑206 in thyroid hormone‑induced disorders of lipid metabolism in the liver.

  18. Piracetam prevents scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities.

    Marisco, Patricia C; Carvalho, Fabiano B; Rosa, Michelle M; Girardi, Bruna A; Gutierres, Jessié M; Jaques, Jeandre A S; Salla, Ana P S; Pimentel, Víctor C; Schetinger, Maria Rosa C; Leal, Daniela B R; Mello, Carlos F; Rubin, Maribel A

    2013-08-01

    Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.

  19. Influence of metabolism on endocrine activities of bisphenol S.

    Skledar, Darja Gramec; Schmidt, Jan; Fic, Anja; Klopčič, Ivana; Trontelj, Jurij; Dolenc, Marija Sollner; Finel, Moshe; Mašič, Lucija Peterlin

    2016-08-01

    Bisphenol S (BPS; bis[4-hydroxyphenyl]sulfone) is commonly used as a replacement for bisphenol A in numerous consumer products. The main goal of this study was to examine the influence of different metabolic reactions that BPS undergoes on the endocrine activity. We demonstrate that hydroxylation of the aromatic ring of BPS, catalyzed mainly by the cytochrome P450 enzymes CYP3A4 and CYP2C9, is its major in-vitro phase I biotransformation. Nevertheless, coupled oxidative-conjugative reactions analyses revealed that glucuronidation and formation of BPS glucuronide is the predominant BPS metabolic pathway. BPS reactive metabolites that can be tracked as glutathione conjugates were not detected in the present study. Two in-vitro systems were used to evaluate the endocrine activity of BPS and its two main metabolites, BPS glucuronide and hydroxylated BPS 4-(4-hydroxy-benzenesulfonyl)-benzene-1,2-diol (BPSM1). In addition, we have tested two structural analogs of BPS, bis[4-(2-hydroxyetoxy)phenyl]sulfone (BHEPS) and 4,4-sulfonylbis(2-methylphenol) (dBPS). The test systems were yeast cells, for evaluating estrogenic and androgenic activities, and the GH3.TRE-Luc reporter cell line for measuring thyroid hormone activity. BPS and BPSM1 were weak agonists of the estrogen receptor, EC50 values of 8.4 × 10(-5) M and 6.7 × 10(-4) M, respectively. Additionally, BPSM1 exhibited weak antagonistic activity toward the thyroid hormone receptor, with an IC50 of 4.3 × 10(-5) M. In contrast to BPSM1, BPS glucuronide was inactive in these assays, inhibiting neither the estrogen nor the thyroid hormone receptors. Hence, glucuronidation appears to be the most important pathway for both BPS metabolism and detoxification. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Modelling decreased food chain accumulation of HOCs due to strong sorption to carbonaceous materials and metabolic transformation

    Moermond, C.T.A.; Traas, T.P.; Roessink, I.; Veltman, K.; Hendriks, A.J.; Koelmans, A.A.

    2007-01-01

    The predictive power of bioaccumulation models may be limited when they do not account for strong sorption of organic contaminants to carbonaceous materials (CM) such as black carbon, and when they do not include metabolic transformation. We tested a food web accumulation model, including sorption

  1. Histone deacetylase activity is decreased in peripheral blood monocytes in patients with COPD

    Chen Yanwei

    2012-03-01

    Full Text Available Abstract Background Histone deacetylase (HDAC is an enzyme that regulates chromatin structure and inflammatory gene expression. In patients with chronic obstructive pulmonary disease (COPD, while accumulating evidence indicates that the activity of HDAC is decreased in lung tissue alveolar macrophages, HDAC activity in peripheral inflammatory cells has not yet been evaluated in detail. Methods HDAC activities in peripheral blood mononuclear cells (PBMC were investigated in patients with stable COPD (n = 26, non-smoking controls (n = 13, and smoking controls (n = 10, respectively. HDAC activity was measured using an HDAC Activity/Inhibitor Screening Assay Kit. Serum interleukine-8 (CXCL8 levels were determined by ELISA techniques. Lung function test was carried out according to the ATS/ERS guidelines. Results Compared with healthy non-smokers, HDAC activity in the PBMCs of COPD patients was decreased by 40% (13.06 ± 5.95 vs. 21.39 ± 4.92 (μM/μg, p Moreover, serum CXCL8 levels in patients with COPD were significantly higher than that in controls and were negatively correlated to HDAC activities. Conclusion In patients with COPD, HDAC activity in the PBMCs is lower than that in healthy controls. The reduction of HDAC activity may be associated with smoking exposure through inflammatory pathways.

  2. Proliferation activity and radiosensitivity of CFU-S in their decreased compartments in continuously irradiated rats

    Kalina, I.; Vacek, A.; Brezani, P.

    1984-01-01

    Effects of the continuous irradiation (0.25 Gy/day) on proliferation activity and radiosensitivity (D 0 ) of CFU-S were studied in rats after accumulated doses of 1.75 Gy and 15 Gy, resp. The proliferation activity of CFU-S in continuously irradiated groups was increased 4 - 5 fold compared with the control group. D 0 values for CFU-S in their decreased compartments were not changed after long-term irradiation compared with the controls. (author)

  3. Educational level and decreases in leisure time physical activity: predictors from the longitudinal GLOBE study

    Droomers, Mariël; Schrijvers, Carola; Mackenbach, Johan

    2001-01-01

    STUDY OBJECTIVE—This study describes educational differences in decreases in leisure time physical activity among an adult, physically active population and additionally attempts to identify predictors of these differences from information on health status and individual and environmental factors.
DESIGN—Prospective population based study. Baseline measurement were carried out in 1991 and follow up in 1997.
SETTING—South eastern part of the Netherlands.
PARTICIPANTS—The study included 3793 su...

  4. Sympathetic nervous activity decreases during head-down bed rest but not during microgravity

    Christensen, Niels J; Heer, Martina; Ivanova, Krassimira

    2005-01-01

    We tested the hypothesis that sympathoadrenal activity in humans is low during spaceflight and that this effect can be simulated by head-down bed rest (HDBR). Platelet norepinephrine and epinephrine were measured as indexes of long-term changes in sympathoadrenal activity. Ten normal healthy......, and at least 2 wk after return to Earth. Because of the long half-life of platelet norepinephrine, data obtained early after landing would still reflect the microgravity state. Platelet norepinephrine decreased markedly during HDBR (P

  5. Recurrent forbush decreases and the relationship between active regions and M regions

    Shah, G.N.; Kaul, C.L.; Razdan, H.; Bemalkhedkar, M.M.

    1978-01-01

    Recurrent Forbush decreases and recurrent geomagnetic disturbances have been attributed to the solar M regions, which are sources of high-velocity solar plasma streams. A study of recurrent Forbush decreases for the period 1966--1975 has been made to examine any possible relationship of M regions with solar active regions. It is shown that at the onset of the recurrent Forbush decrease at the earth there is a high probability of encountering a class of active regions at the central meridian of the sun which give rise to flares of importance > or =2B/3N. These active regions are found to be long lasting and to have large areas as well as high Hα intensities. Other active regions, producing flares of lower importance, are distributed randomly on the sun with respect to the onset of a recurrent Forbush decrease. By using the quasi-radial hypervelocity approximation the base of the leading edge of the high-velocity stream at the onset of a recurrent Forbush decrease at the earth is traced to the solar longitude about 40 0 west of the central meridan. From these results it is deduced that M regions are located preferentially to the west of long-lasting magnetically complex active regions. Earlier studies of the identification of the M regions on the sun have been reexamined and shown to conform to this positional relationship. A possible mechanism of the development of an M region to the west of the long-lasting magnetically complex active region is also discussed

  6. Recurrent Forbush decreases and relationship between active regions and M-regions

    Shah, G.N.; Kaul, C.L.; Razdan, H.; Bemalkhedkar, M.M.

    1977-01-01

    Recurrent Forbush decreases and recurrent geomagnetic disturbances have been attributed to the solar M-regions, which are sources of high velocity solar plasma streams. A study of recurrent Forbush decreases for the period 1966-75 has been made to examine any possible relationship of M-regions with solar active regions. It is shown that at the onset of the recurrent Forbush decrease at earth, there is a high probability of encountering a class of active regions at central meridian of the sun which give rise to flares of importance >= 28/3N. These active regions are found to be long-lasting and to have large areas as well as high Hsub(α)-intensities. Other active regions, producing flares of only lower importance, are distributed randomly on the sun with respect to the onset of a recurrent Forbush decrease. Using the quasiradial hypervelocity approximation, the base of the leading edge of the high velocity stream, at the onset of a recurrent Forbush decrease at earth, is traced to the solar longitude about 40 deg West of the central meridian. From these results, it is deduced that M-regions are located preferentially to the West of long-lasting, magnetically complex active regions. Earlier studies of the identification of the M-regions on the sun have been re-examined and shown to conform to this positional relationship. A possible mechanism of the development of an M-region to the West of the long-lasting magnetically complex active region is also discussed. (author)

  7. Rapid decreases in preoptic aromatase activity and brain monoamine concentrations after engaging in male sexual behavior.

    Cornil, C A; Dalla, C; Papadopoulou-Daifoti, Z; Baillien, M; Dejace, C; Ball, G F; Balthazart, J

    2005-09-01

    In Japanese quail, as in rats, the expression of male sexual behavior over relatively long time periods (days to weeks) is dependent on the local production of estradiol in the preoptic area via the aromatization of testosterone. On a short-term basis (minutes to hours), central actions of dopamine as well as locally produced estrogens modulate behavioral expression. In rats, a view of and sexual interaction with a female increase dopamine release in the preoptic area. In quail, in vitro brain aromatase activity (AA) is rapidly modulated by calcium-dependent phosphorylations that are likely to occur in vivo as a result of changes in neurotransmitter activity. Furthermore, an acute estradiol injection rapidly stimulates copulation in quail, whereas a single injection of the aromatase inhibitor vorozole rapidly inhibits this behavior. We hypothesized that brain aromatase and dopaminergic activities are regulated in quail in association with the expression of male sexual behavior. Visual access as well as sexual interactions with a female produced a significant decrease in brain AA, which was maximal after 5 min. This expression of sexual behavior also resulted in a significant decrease in dopaminergic as well as serotonergic activity after 1 min, which returned to basal levels after 5 min. These results demonstrate for the first time that AA is rapidly modulated in vivo in parallel with changes in dopamine activity. Sexual interactions with the female decreased aromatase and dopamine activities. These data challenge established views about the causal relationships among dopamine, estrogen action, and male sexual behavior.

  8. [L-arginine metabolism enzyme activities in rat liver subcellular fractions under condition of protein deprivation].

    Kopyl'chuk, G P; Buchkovskaia, I M

    2014-01-01

    The features of arginase and NO-synthase pathways of arginine's metabolism have been studied in rat liver subcellular fractions under condition of protein deprivation. During the experimental period (28 days) albino male rats were kept on semi synthetic casein diet AIN-93. The protein deprivation conditions were designed as total absence of protein in the diet and consumption of the diet partially deprived with 1/2 of the casein amount compared to in the regular diet. Daily diet consumption was regulated according to the pair feeding approach. It has been shown that the changes of enzyme activities, involved in L-arginine metabolism, were characterized by 1.4-1.7 fold decrease in arginase activity, accompanied with unchanged NO-synthase activity in cytosol. In mitochondrial fraction the unchanged arginase activity was accompanied by 3-5 fold increase of NO-synthase activity. At the terminal stages of the experiment the monodirectional dynamics in the studied activities have been observed in the mitochondrial and cytosolfractions in both experimental groups. In the studied subcellular fractions arginase activity decreased (2.4-2.7 fold with no protein in the diet and 1.5 fold with partly supplied protein) and was accompanied by NO-synthase activity increase by 3.8 fold in cytosole fraction, by 7.2 fold in mitochondrial fraction in the group with no protein in the diet and by 2.2 and 3.5 fold in the group partialy supplied with protein respectively. The observed tendency is presumably caused by the switch of L-arginine metabolism from arginase into oxidizing NO-synthase parthway.

  9. Decrease in catalase activity of Folsomia candida fed a Bt rice diet

    Yuan Yiyang, E-mail: yuanyy@ioz.ac.cn [State Key Laboratory of Integrated Management of Pest and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101 (China); Graduate School, Chinese Academy of Sciences, Beijing 100039 (China); Ke Xin, E-mail: xinke@sibs.ac.cn [Shanghai Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 300 Fenglin Road, Shanghai 200032 (China); Chen Fajun, E-mail: fajunchen@njau.edu.cn [College of Plant Protection, Department of Entomology, Nanjing Agricultural University, Nanjing 210095 (China); Krogh, Paul Henning, E-mail: phk@dmu.dk [Department of Bioscience, University of Aarhus, P.O. Box 314, Vejlsoevej 25, DK-8600 Silkeborg (Denmark); Ge Feng, E-mail: gef@ioz.ac.cn [State Key Laboratory of Integrated Management of Pest and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101 (China)

    2011-12-15

    Here we report the effects of three Bt-rice varieties and their non-Bt conventional isolines on biological traits including survival, reproduction, and the activities of three antioxidant enzymes superoxide dismutase, catalase and peroxidase, in the Collembolan, Folsomia candida. The reproduction was significantly lower when fed Kemingdao and Huahui1 than those feeding on their non-GM near-isogenic varieties Xiushui and Minghui63 respectively, this can be explained by the differences of plant compositions depended on variety of rice. The catalase activity of F. candida was significantly lower when fed the Bt-rice variety Kemingdao compared to the near-isogenic non-Bt-rice variety Xiushui. This suggests that some Bt-rice varieties may impose environmental stress to collembolans. We emphasize that changes in activity of antioxidant enzymes of non-target organisms are important in understanding the ecological consequences for organisms inhabiting transgenic Bt-rice plantations. - Highlights: > We examine the effects of Bt-rice on Folsomia candida with laboratory test. > The reproduction of F. candida was decreased by two Bt-rice varieties. > Decreased reproduction caused by the differences of varieties or C/N ratio of rice. > The catalase activity was decreased by Bt-rice Kemingdao. > Some Bt-rice may impose environmental stress on NTOs. - The catalase of the collembolan (Folsomia candida) was decreased when fed Bt-rice, Kemingdao.

  10. Decreasing Sports Activity with Increasing Age? Findings from a 20-Year Longitudinal and Cohort Sequence Analysis

    Breuer, Christoph; Wicker, Pamela

    2009-01-01

    According to cross-sectional studies in sport science literature, decreasing sports activity with increasing age is generally assumed. In this paper, the validity of this assumption is checked by applying more effective methods of analysis, such as longitudinal and cohort sequence analyses. With the help of 20 years' worth of data records from the…

  11. Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions

    Muris, A.H.; Rolf, L.; Damoiseaux, J.; Koeman, E.; Hupperts, R.

    2014-01-01

    Background: Fingolimod is a disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod decreases annual relapse rates and gadolinium enhancing lesions on MRI as compared to either interferon beta (IFNβ) or placebo. The effect of

  12. Decrease in catalase activity of Folsomia candida fed a Bt rice diet

    Yuan Yiyang; Ke Xin; Chen Fajun; Krogh, Paul Henning; Ge Feng

    2011-01-01

    Here we report the effects of three Bt-rice varieties and their non-Bt conventional isolines on biological traits including survival, reproduction, and the activities of three antioxidant enzymes superoxide dismutase, catalase and peroxidase, in the Collembolan, Folsomia candida. The reproduction was significantly lower when fed Kemingdao and Huahui1 than those feeding on their non-GM near-isogenic varieties Xiushui and Minghui63 respectively, this can be explained by the differences of plant compositions depended on variety of rice. The catalase activity of F. candida was significantly lower when fed the Bt-rice variety Kemingdao compared to the near-isogenic non-Bt-rice variety Xiushui. This suggests that some Bt-rice varieties may impose environmental stress to collembolans. We emphasize that changes in activity of antioxidant enzymes of non-target organisms are important in understanding the ecological consequences for organisms inhabiting transgenic Bt-rice plantations. - Highlights: → We examine the effects of Bt-rice on Folsomia candida with laboratory test. → The reproduction of F. candida was decreased by two Bt-rice varieties. → Decreased reproduction caused by the differences of varieties or C/N ratio of rice. → The catalase activity was decreased by Bt-rice Kemingdao. → Some Bt-rice may impose environmental stress on NTOs. - The catalase of the collembolan (Folsomia candida) was decreased when fed Bt-rice, Kemingdao.

  13. Valsartan Decreases Platelet Activity and Arterial Thrombotic Events in Elderly Patients with Hypertension

    Fang Wu

    2015-01-01

    Conclusions: AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

  14. Simple glycolipids of microbes: Chemistry, biological activity and metabolic engineering

    Ahmad Mohammad Abdel-Mawgoud

    2018-03-01

    Full Text Available Glycosylated lipids (GLs are added-value lipid derivatives of great potential. Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents, they have diverse biological activities with promising biomedical and cosmeceutical applications. Glycolipids, especially those of microbial origin, have interesting antimicrobial, anticancer, antiparasitic as well as immunomodulatory activities. Nonetheless, GLs are hardly accessing the market because of their high cost of production. We believe that experience of metabolic engineering (ME of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications. This review presents chemical groups of bacterial and fungal GLs, their biological activities, their general biosynthetic pathways and an insight on ME strategies for their production.

  15. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models

    Hammami Ines

    2012-07-01

    Full Text Available Abstract Background The tumor microenvironment contains a vast array of pro- and anti-inflammatory cytokines that alter myelopoiesis and lead to the maturation of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs. Incubating bone marrow (BM precursors with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-6 (IL-6 generated a tumor-infiltrating MDSC-like population that impaired anti-tumor specific T-cell functions. This in vitro experimental approach was used to simulate MDSC maturation, and the cellular metabolic response was then monitored. A complementary experimental model that inhibited L-arginine (L-Arg metabolizing enzymes in MSC-1 cells, an immortalized cell line derived from primary MDSCs, was used to study the metabolic events related to immunosuppression. Results Exposure of BM cells to GM-CSF and IL-6 activated, within 24 h, L-Arg metabolizing enzymes which are responsible for the MDSCs immunosuppressive potential. This was accompanied by an increased uptake of L-glutamine (L-Gln and glucose, the latter being metabolized by anaerobic glycolysis. The up-regulation of nutrient uptake lead to the accumulation of TCA cycle intermediates and lactate as well as the endogenous synthesis of L-Arg and the production of energy-rich nucleotides. Moreover, inhibition of L-Arg metabolism in MSC-1 cells down-regulated central carbon metabolism activity, including glycolysis, glutaminolysis and TCA cycle activity, and led to a deterioration of cell bioenergetic status. The simultaneous increase of cell specific concentrations of ATP and a decrease in ATP-to-ADP ratio in BM-derived MDSCs suggested cells were metabolically active during maturation. Moreover, AMP-activated protein kinase (AMPK was activated during MDSC maturation in GM-CSF and IL-6–treated cultures, as revealed by the continuous increase of AMP-to-ATP ratios and the phosphorylation of AMPK. Likewise, AMPK activity was

  16. Neural correlates of skill acquisition: decreased cortical activity during a serial interception sequence learning task.

    Gobel, Eric W; Parrish, Todd B; Reber, Paul J

    2011-10-15

    Learning of complex motor skills requires learning of component movements as well as the sequential structure of their order and timing. Using a Serial Interception Sequence Learning (SISL) task, participants learned a sequence of precisely timed interception responses through training with a repeating sequence. Following initial implicit learning of the repeating sequence, functional MRI data were collected during performance of that known sequence and compared with activity evoked during novel sequences of actions, novel timing patterns, or both. Reduced activity was observed during the practiced sequence in a distributed bilateral network including extrastriate occipital, parietal, and premotor cortical regions. These reductions in evoked activity likely reflect improved efficiency in visuospatial processing, spatio-motor integration, motor planning, and motor execution for the trained sequence, which is likely supported by nondeclarative skill learning. In addition, the practiced sequence evoked increased activity in the left ventral striatum and medial prefrontal cortex, while the posterior cingulate was more active during periods of better performance. Many prior studies of perceptual-motor skill learning have found increased activity in motor areas of the frontal cortex (e.g., motor and premotor cortex, SMA) and striatal areas (e.g., the putamen). The change in activity observed here (i.e., decreased activity across a cortical network) may reflect skill learning that is predominantly expressed through more accurate performance rather than decreased reaction time. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Mean platelet volume is decreased in adults with active lupus disease

    Guillermo Delgado-García

    Full Text Available ABSTRACT Background: Only a few biomarkers are available for assessing disease activity in systemic lupus erythematosus (SLE. Mean platelet volume (MPV has been recently studied as an inflammatory biomarker. It is currently unclear whether MPV may also play a role as a biomarker of disease activity in adult patients with SLE. Objective: We investigated the association between MPV and disease activity in adult patients with SLE. Methods: In this retrospective study, we compared two groups of adult patients divided according to disease activity (36 per group. Subjects were age- and gender-matched. Results: MPV was significantly decreased with respect to those of inactive patients (7.16 ± 1.39 vs. 8.16 ± 1.50, p = 0.005. At a cutoff level of 8.32 fL, MPV has a sensitivity of 86% and a specificity of 41% for the detection of disease activity. A modest positive correlation was found between MPV and albumin (r = 0.407, p = 0.001, which in turn is inversely associated with disease activity. Conclusions: In summary, MPV is decreased in adult patients with active lupus disease, and positively correlated with albumin, another biomarker of disease activity. Prospective studies are needed to evaluate the prognostic value of this biomarker.

  18. Mean platelet volume is decreased in adults with active lupus disease.

    Delgado-García, Guillermo; Galarza-Delgado, Dionicio Ángel; Colunga-Pedraza, Iris; Borjas-Almaguer, Omar David; Mandujano-Cruz, Ilse; Benavides-Salgado, Daniel; Martínez-Granados, Rolando Jacob; Atilano-Díaz, Alexandro

    Only a few biomarkers are available for assessing disease activity in systemic lupus erythematosus (SLE). Mean platelet volume (MPV) has been recently studied as an inflammatory biomarker. It is currently unclear whether MPV may also play a role as a biomarker of disease activity in adult patients with SLE. We investigated the association between MPV and disease activity in adult patients with SLE. In this retrospective study, we compared two groups of adult patients divided according to disease activity (36 per group). Subjects were age- and gender-matched. MPV was significantly decreased with respect to those of inactive patients (7.16±1.39 vs. 8.16±1.50, p=0.005). At a cutoff level of 8.32fL, MPV has a sensitivity of 86% and a specificity of 41% for the detection of disease activity. A modest positive correlation was found between MPV and albumin (r=0.407, p=0.001), which in turn is inversely associated with disease activity. In summary, MPV is decreased in adult patients with active lupus disease, and positively correlated with albumin, another biomarker of disease activity. Prospective studies are needed to evaluate the prognostic value of this biomarker. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  19. N-3 fatty acids, neuronal activity and energy metabolism in the brain

    Harbeby Emilie

    2012-07-01

    Full Text Available The content of docosahexaenoic acid (DHA in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1 a lower brain glucose utilization, 2 a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3 a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.

  20. Azolla filiculoides Nitrogenase Activity Decrease Induced by Inoculation with Chlamydomonas sp. †

    Habte, Mitiku

    1986-01-01

    Experiments were conducted to determine the influence of Chlamydomonas sp. on nitrogen fixation (C2H2 → C2H4) in Azolla filiculoides and on the nitrogen fixation and growth of free-living Anabaena azollae 2B organisms. Inoculation of azolla medium with Chlamydomonas sp. was associated with decreased nitrogenase activity in A. filiculoides and with increases in the density of a fungal population identified as Acremonium sp. Subsequent inoculation of azolla medium with this fungus was also accompanied by a significant decrease in nitrogenase activity of A. filiculoides. However, the extent of depression of nitrogenase activity was significantly higher when azolla medium was inoculated with Chlamydomonas sp. than when it was inoculated with Acremonium sp. Inoculation of nitrogen-free Stanier medium with either Acremonium sp. or Chlamydomonas sp. did not adversely affect the growth or nitrogenase activity of free-living A. azollae. Decreased nitrogenase activity in A. filiculoides is apparently related to the adverse influence of the green alga and the fungus on the macrosymbiont. The mechanisms that might be involved are discussed. PMID:16347211

  1. The cell-free fetal DNA fraction in maternal blood decreases after physical activity

    Schlütter, Jacob Mørup; Hatt, Lotte; Bach, Cathrine

    2014-01-01

    of cycling with a pulse-rate of 150 beats per minute. The concentrations of cffDNA (DYS14) and cfDNA (RASSF1A) were assessed using quantitative real-time polymerase chain reaction. RESULTS: The fetal fraction decreased significantly in all participants after physical activity (p decrease varying......OBJECTIVE: If noninvasive prenatal testing using next generation sequencing is to be effective for pregnant women, a cell-free fetal DNA (cffDNA) fraction above 4% is essential unless the depth of sequencing is increased. This study's objective is to determine whether physical activity has...... from 1-17 percentage points. This was due to a significant increase in the concentration of cfDNA (p physical activity. CONCLUSION: When planning the timing of noninvasive...

  2. Adjuvant activity of peptidoglycan monomer and its metabolic products.

    Halassy, Beata; Krstanović, Marina; Frkanec, Ruza; Tomasić, Jelka

    2003-02-14

    Peptidoglycan monomer (PGM) is a natural compound of bacterial origin. It is a non-toxic, non-pyrogenic, water-soluble immunostimulator potentiating humoral immune response to ovalbumin (OVA) in mice. It is fast degraded and its metabolic products-the pentapeptide (PP) and the disaccharide (DS)-are excreted from the mammalian organism upon parenteral administration. The present study investigates: (a). whether PGM could influence the long-living memory generation; (b). whether metabolic products retain adjuvant properties of the parent compound and contribute to its adjuvanticity. We report now that mice immunised twice with OVA+PGM had significantly higher anti-OVA IgG levels upon challenge with antigen alone 6 months later in comparison to control group immunised with OVA only. PP and DS were prepared enzymatically in vitro as apyrogenic and chemically pure compounds. When mice were immunised with OVA plus PP and DS, respectively, the level of anti-OVA IgGs in sera was not higher than in mice immunised with OVA alone, while PGM raised the level of specific antibodies. Results implicate that the adjuvant active molecule, capable of enhancing long-living memory generation, is PGM itself, and none of its metabolic products.

  3. Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

    Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8{+-}0.75 y, 5 IGAs: male, 22.6{+-}2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA.

  4. Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity.

    Takayama, S; White, M F; Kahn, C R

    1988-03-05

    The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the function of the insulin receptor was examined in intact hepatoma cells (Fao) and in solubilized extracts purified by wheat germ agglutinin chromatography. Incubation of ortho[32P]phosphate-labeled Fao cells with TPA increased the phosphorylation of the insulin receptor 2-fold after 30 min. Analysis of tryptic phosphopeptides from the beta-subunit of the receptor by reverse-phase high performance liquid chromatography and determination of their phosphoamino acid composition suggested that TPA predominantly stimulated phosphorylation of serine residues in a single tryptic peptide. Incubation of the Fao cells with insulin (100 nM) for 1 min stimulated 4-fold the phosphorylation of the beta-subunit of the insulin receptor. Prior treatment of the cells with TPA inhibited the insulin-stimulated tyrosine phosphorylation by 50%. The receptors extracted with Triton X-100 from TPA-treated Fao cells and purified on immobilized wheat germ agglutinin retained the alteration in kinase activity and exhibited a 50% decrease in insulin-stimulated tyrosine autophosphorylation and phosphotransferase activity toward exogenous substrates. This was due primarily to a decrease in the Vmax for these reactions. TPA treatment also decreased the Km of the insulin receptor for ATP. Incubation of the insulin receptor purified from TPA-treated cells with alkaline phosphatase decreased the phosphate content of the beta-subunit to the control level and reversed the inhibition, suggesting that the serine phosphorylation of the beta-subunit was responsible for the decreased tyrosine kinase activity. Our results support the notion that the insulin receptor is a substrate for protein kinase C in the Fao cell and that the increase in serine phosphorylation of the beta-subunit of the receptor produced by TPA treatment inhibited tyrosine kinase activity in vivo and in vitro. These data suggest that protein kinase C may regulate the function

  5. In vivo enzyme activity in inborn errors of metabolism

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. (Clinical Research Centre, Harrow (England))

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  6. In vivo enzyme activity in inborn errors of metabolism

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D.

    1990-01-01

    Low-dose continuous infusions of [2H5]phenylalanine, [1-13C]propionate, and [1-13C]leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD

  7. Metabolic Syndrome and Physical Activity in Hemodialysis Patients

    derya atik

    2014-06-01

    Full Text Available Purpose: This descriptive study was carried out to reveal the level of physical activity in patients who receive hemodialysis due to chronic kidney failure and to identify its relationship with the prevalence of metabolic syndrome (MetS. Material and method: The study was conducted with 55 patients at the hemodialysis units of Alanya State Hospital and Private Alanya Anadolu Hospital between 10 and 30 June 2013. The study data were collected using the National Cholesterol Education Program, the Adult Treatment Panel III (NCEP-ATP III, a data collection form containing Metabolic Syndrome Diagnosis Criteria, and the International Physical Activity Questionnaire (IPAQ. The data were analyzed using arithmetic mean +/- standard deviation (SD, number and percentage distributions, independent sample t test, crosstabs, One Way Anova, and Pearson and #8217;s Correlation Analysis. Conclusion and suggestions: It was found that 41.8% of the patients were between 50 and 65 years of age, the majority of them were male (58.2%, hemodialysis had been administered to 69.1% of them for at least 36 months, and 50.9% of them met three and more of the MetS criteria. There was no statistically significant relationship between MetS and physical activity levels, but the length of physical activity was longer in those who did not meet the MetS diagnosis criteria (p>0.05. An increase in sedentary time raised the MetS criteria (p<0.05. Conclusion: Nearly 1/2 of the patients were at risk of MetS. Physical activity level being statistically ineffective on MetS can be associated with low physical activity level and longer sedentary time. It can be said that being completely sedentary increases BMI and therefore MetS. The study can be repeated on different samples and the results can be compared. [J Contemp Med 2014; 4(2.000: 69-75

  8. Decreased electrophysiological activity represents the conscious state of emptiness in meditation

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful “thoughtless emptiness (TE),” a “focused attention,” and an “open monitoring” task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness. PMID:24596562

  9. Age-related decrease in physical activity and functional fitness among elderly men and women.

    Milanović, Zoran; Pantelić, Saša; Trajković, Nebojša; Sporiš, Goran; Kostić, Radmila; James, Nic

    2013-01-01

    To determine differences in physical activity level and functional fitness between young elderly (60-69 years) and old elderly (70-80 years) people with the hypothesis that an age-related decline would be found. A total of 1288 participants' level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg) and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg). Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test. Significant differences (P men. Similar results were found for the women, except no significant differences were found for the chair sit and reach and the 2-minute step test. From the viewpoint of energy consumption estimated by the International Physical Activity Questionnaire, moderate physical activity is dominant. In addition, with aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P physical activity level and functional fitness was equal for both men and women and was due to the aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body-fat percentage, flexibility, agility, and endurance.

  10. Decreased activation and subsyndromal manic symptoms predict lower remission rates in bipolar depression.

    Caldieraro, Marco Antonio; Walsh, Samantha; Deckersbach, Thilo; Bobo, William V; Gao, Keming; Ketter, Terence A; Shelton, Richard C; Reilly-Harrington, Noreen A; Tohen, Mauricio; Calabrese, Joseph R; Thase, Michael E; Kocsis, James H; Sylvia, Louisa G; Nierenberg, Andrew A

    2017-11-01

    Activation encompasses energy and activity and is a central feature of bipolar disorder. However, the impact of activation on treatment response of bipolar depression requires further exploration. The aims of this study were to assess the association of decreased activation and sustained remission in bipolar depression and test for factors that could affect this association. We assessed participants with Diagnostic and Statistical Manual of Mental Disorders (4th ed) bipolar depression ( n = 303) included in a comparative effectiveness study of lithium- and quetiapine-based treatments (the Bipolar CHOICE study). Activation was evaluated using items from the Bipolar Inventory of Symptoms Scale. The selection of these items was based on a dimension of energy and interest symptoms associated with poorer treatment response in major depression. Decreased activation was associated with lower remission rates in the raw analyses and in a logistic regression model adjusted for baseline severity and subsyndromal manic symptoms (odds ratio = 0.899; p = 0.015). The manic features also predicted lower remission (odds ratio = 0.934; p bipolar depression. Patients with these features may require specific treatment approaches, but new studies are necessary to identify treatments that could improve outcomes in this population.

  11. Decreased sialidase activity in alveolar macrophages of guinea pigs exposed to coal mine dust.

    Terzidis-Trabelsi, H; Lefèvre, J P; Bignon, J; Lambré, C R

    1992-01-01

    The origin of immune dysfunctions that are observed in pneumoconiotic miners still remains unknown. There is evidence that the carbohydrate moiety of membrane glycoconjugates is of primary importance in many functions of immunocompetent cells. The glycosylation, and especially the sialylation level of membrane components of various lymphocyte and macrophage subsets, vary depending on the state of cellular differentiation and activation. Sialidases, which may regulate the amount of sialic acids exposed on the cell membrane, can thus be considered as immunoregulatory enzymes. In this report, the sialidase activity has been measured in alveolar macrophages (AM) and in cell-free bronchoalveolar lavage fluid (BALF) from guinea pigs exposed for 4 months to coal mine dust at a concentration of 300 mg/m3. The samples were collected by bronchoalveolar lavage 2 months after cessation of exposure. The sialidase activity in the cell-free fluid and in the purified alveolar macrophages showed a 10-fold decrease (p less than 0.001). Kinetic parameters of the enzyme such as Km and optimum pH did not change. This changed activity was specific for sialidase, as two other lysosomal glycosidases, beta-galactosidase and N-acetylglucosaminidase, showed unchanged activities. These results suggest the possibility that, by inducing a decreased sialidase activity, exposure to coal mine dust may lead to a modified expression of AM membrane-associated sialic acids giving rise to altered immune functions (i. e., phagocytosis, antigen processing, response to cytokines, etc.). PMID:1396442

  12. Activation of PPARα decreases bile acids in livers of female mice while maintaining bile flow and biliary bile acid excretion.

    Zhang, Youcai; Lickteig, Andrew J; Csanaky, Iván L; Klaassen, Curtis D

    2018-01-01

    Fibrates are hypolipidemic drugs that act as activators of peroxisome proliferator-activated receptor α (PPARα). In both humans and rodents, females were reported to be less responsive to fibrates than males. Previous studies on fibrates and PPARα usually involved male mice, but little has been done in females. The present study aimed to provide the first comprehensive analysis of the effects of clofibrate (CLOF) and PPARα on bile acid (BA) homeostasis in female mice. Study in WT male mice showed that a 4-day CLOF treatment increased liver weight, bile flow, and biliary BA excretion, but decreased total BAs in both serum and liver. In contrast, WT female mice were less susceptible to these CLOF-mediated responses observed in males. In WT female mice, CLOF decreased total BAs in the liver, but had little effect on the mRNAs of hepatic BA-related genes. Next, a comparative analysis between WT and PPARα-null female mice showed that lack of PPARα in female mice decreased total BAs in serum, but had little effect on total BAs in liver or bile. However, lack of PPARα in female mice increased mRNAs of BA synthetic enzymes (Cyp7a1, Cyp8b1, Cyp27a1, and Cyp7b1) and transporters (Ntcp, Oatp1a1, Oatp1b2, and Mrp3). Furthermore, the increase of Cyp7a1 in PPARα-null female mice was associated with an increase in liver Fxr-Shp-Lrh-1 signaling. In conclusion, female mice are resistant to CLOF-mediated effects on BA metabolism observed in males, which could be attributed to PPARα-mediated suppression in females on genes involved in BA synthesis and transport. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Effects of bagging on sugar metabolism and the activity of sugar ...

    To investigate the effects of bagging on sugar metabolism and the activity of sugar metabolism related enzymes in Qingzhong loquat fruit development, the contents of sucrose, glucose and soluble solids as well as the activities of sugar metabolism related enzymes were evaluated. The content of sucrose, glucose and ...

  14. Cytosolic Calcium Coordinates Mitochondrial Energy Metabolism with Presynaptic Activity

    Chouhan, Amit K.; Ivannikov, Maxim V.; Lu, Zhongmin; Sugimori, Mutsuyuki; Llinas, Rodolfo R.; Macleod, Gregory T.

    2012-01-01

    Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]m indicate an increased capacity for ATP production. Elevations in pHm were blocked by manipulations which blocked mitochondrial Ca2+ uptake, including replacement of extracellular Ca2+ with Sr2+, and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+ that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+ levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]c level (329±11nM) was slightly above the average Ca2+ affinity of the mitochondria (281±13nM). In summary, we show that when MNs fire at endogenous rates [Ca2+]c is driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+ stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]c levels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity in Drosophila MNs. PMID:22279208

  15. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women

    Katarina Melzer

    2016-07-01

    Full Text Available “Metabolic Equivalent” (MET represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O2/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry were measured in adolescent males (n = 50 and females (n = 50, women during pregnancy (gestation week 35–41, n = 46, women 24–53 weeks postpartum (n = 27, and active men (n = 30, and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h was significantly higher than that of adolescent females (1.11 kcal/kg × h, with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h and overweight (0.89 kcal/kg × h adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard.

  16. Decreased arachidonic acid content and metabolism in tissues of NZB/W F1 females fed a diet containing 0.45% dehydroisoandrosterone (DHA)

    Matsunaga, A.; Cottam, G.L.

    1987-01-01

    A diet containing 0.45% DHA fed to NZB/W mice, a model of systemic lupus erythematosus, delays the time of onset, improves survival and decreases the formation of antibodies to ds-DNA. Essential fatty acid-deficient diets or inclusion of eicosapentaenoic acid have similar beneficial effects and led them to investigate arachidonic acid metabolism in response to feeding DHA. The arachidonic acid content of plasma cholesteryl ester decreased from 37.4 +/- 2.2 to 28.2 +/- 1.3 mg%. In total liver phospholipid the value decreased from 18.1 +/- 0.52 to 13.7 +/- 1.3 mg%, in total kidney phospholipid the value decreased from 24.10 +/- 0.87 to 20.7 +/- 0.32 mg% and in resident peritoneal macrophages the value decreased from 15.4 +/- 4.6 to 3.6 +/- 1.4 mg%. The metabolism of exogenous [1- 14 C]arachidonic acid by resident peritoneal macrophages in response to Zymosan stimulation for 2 hr was examined by extraction of metabolites and separation by HPLC. Cells isolated from DHA-fed animals produced less PGE2 than controls, yet similar amounts of 6-keto PGF1α were produced. Arachidonic acid metabolites have significant effects on the immune system and may be a mechanism involved in the benefits obtained by inclusion of DHA in the diet

  17. Airway Peroxidases Catalyze Nitration of the β2-Agonist Salbutamol and Decrease Its Pharmacological Activity

    Reszka, Krzysztof J.; Sallans, Larry; Macha, Stephen; Brown, Kari; McGraw, Dennis W.; Kovacic, Melinda Butsch; Britigan, Bradley E.

    2011-01-01

    β2-Agonists are the most effective bronchodilators for the rapid relief of asthma symptoms, but for unclear reasons, their effectiveness may be decreased during severe exacerbations. Because peroxidase activity and nitrogen oxides are increased in the asthmatic airway, we examined whether salbutamol, a clinically important β2-agonist, is subject to potentially inactivating nitration. When salbutamol was exposed to myeloperoxidase, eosinophil peroxidase or lactoperoxidase in the presence of hy...

  18. Pokemon decreases the transcriptional activity of RARα in the absence of ligand.

    Yang, Yutao; Li, Yueting; Di, Fei; Cui, Jiajun; Wang, Yue; David Xu, Zhi-Qing

    2016-12-20

    Pokemon is a transcriptional repressor that belongs to the POZ and Krüppel (POK) protein family. In this study, we investigated the potential interaction between Pokemon and retinoic acid receptor alpha (RARα) and determined the role of Pokemon in regulation of RARα transcriptional activity in the absence of ligand. We found that Pokemon could directly interact with RARα. Moreover, we demonstrated that Pokemon could decrease the transcriptional activity of RARα in the absence of ligand. Furthermore, we showed that Pokemon could repress the transcriptional activity of RARα by increasing the recruitment of nuclear receptor co-repressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) to the retinoic acid response element (RARE) element. Taken together, these data suggest that Pokemon is a novel partner of RARα that acts as a co-repressor to regulate RARα transcriptional activity in the absence of ligand.

  19. Octulosonic acid derivatives from Roman chamomile (Chamaemelum nobile) with activities against inflammation and metabolic disorder.

    Zhao, Jianping; Khan, Shabana I; Wang, Mei; Vasquez, Yelkaira; Yang, Min Hye; Avula, Bharathi; Wang, Yan-Hong; Avonto, Cristina; Smillie, Troy J; Khan, Ikhlas A

    2014-03-28

    Six new octulosonic acid derivatives (1-6) were isolated from the flower heads of Roman chamomile (Chamaemelum nobile). Their structures were elucidated by means of spectroscopic interpretation. The biological activity of the isolated compounds was evaluated toward multiple targets related to inflammation and metabolic disorder such as NAG-1, NF-κB, iNOS, ROS, PPARα, PPARγ, and LXR. Similar to the action of NSAIDs, all the six compounds (1-6) increased NAG-1 activity 2-3-fold. They also decreased cellular oxidative stress by inhibiting ROS generation. Compounds 3, 5, and 6 activated PPARγ 1.6-2.1-fold, while PPARα was activated 1.4-fold by compounds 5 and 6 only. None of the compounds showed significant activity against iNOS or NF-κB. This is the first report of biological activity of octulosonic acid derivatives toward multiple pathways related to inflammation and metabolic disorder. The reported anti-inflammatory, hypoglycemic, antiedemic, and antioxidant activities of Roman chamomile could be partly explained as due to the presence of these constituents.

  20. Changes in Cholinesterase Activity in Blood of Adolescent with Metabolic Syndrome after Supplementation with Extract from Aronia melanocarpa

    Piotr Duchnowicz

    2018-01-01

    Full Text Available Obesity and metabolic syndrome (MetS are growing problems among children and adolescents. There are no reports of changes in the activity of butyrylcholinesterase (BChE in children and adolescents with metabolic syndrome especially after supplementation with extract from Aronia melanocarpa. Materials studied included plasma and erythrocytes isolated from peripheral blood of patients with MetS and healthy subjects. We have estimated the following parameters: acetylcholinesterase (AChE and butyrylcholinesterase (BChE activity, lipid peroxidation and lipids levels in plasma, and erythrocytes membrane. In patients with MetS, a significant increase in AChE and BChE activity, higher LDL-cholesterol and triacylglycerol levels, and lower HDL-cholesterol level were observed. Supplementation with A. melanocarpa extract resulted in mild but statistically significant reduction of total cholesterol, LDL-cholesterol, and triacylglycerol levels and caused an increase in HDL-cholesterol level and a decrease in lipid peroxidation in plasma patients with MetS. Additionally, a decrease in lipid peroxidation and cholesterol level and a decrease in AChE activity in the erythrocyte membranes after supplementation with A. melanocarpa were noted. Summarizing, an increase in AChE and BChE activity and disruption of lipid metabolism in patients with MetS were observed. After supplementation of MetS patients with A. melanocarpa extract, a decrease in AChE activity and oxidative stress was noted.

  1. Physical Activity Dimensions Associated with Impaired Glucose Metabolism

    Amadid, Hanan; Johansen, Nanna B.; Bjerregaard, Anne-Louise

    2017-01-01

    Purpose Physical activity (PA) is important in the prevention of Type 2 diabetes, yet little is known about the role of specific dimensions of PA, including sedentary time in subgroups at risk for impaired glucose metabolism (IGM). We applied a data-driven decision tool to identify dimensions of PA...... identified subgroups in which different activity dimensions were associated with IGM. Methodology and results from this study may suggest a preliminary step toward the goal of tailoring and targeting PA interventions aimed at Type 2 diabetes prevention....... associated with IGM across age, sex, and body mass index (BMI) groups. Methods This cross-sectional study included 1501 individuals (mean (SD) age, 65.6 (6.8) yr) at high risk for Type 2 diabetes from the ADDITION-PRO study. PA was measured by an individually calibrated combined accelerometer and heart rate...

  2. Metabolic Activity Interferometer: A Powerful Tool for Testing Antibiotics

    Rachel R. P. Machado

    2012-01-01

    Full Text Available It is demonstrated that the efficiency of antibiotics can be tested using an interferometric method. Two antibiotics were used as models to show that an interferometric method to monitor the metabolic activity of slowly growing bacteria can be a safer method to judge antimicrobial properties of substances than conventional methods. The susceptibility of Mycobacterium bovis to hexane extract of Pterodon emarginatus and to the well-known antibiotic rifampicin was tested with the interferometric method and with the conventional microplate method. The microplate method revealed a potential activity of hexane extract against M. bovis. However, the interferometric method showed that the action of this substance is rather limited. Also in the case of rifampicin, the interferometric method was able to detect resistant bacteria.

  3. Survey of the Relationship Between Activity Energy Expenditure Metabolic Equivalents and Barrier Factors of Physical Activity in the Elderly in Kashan

    Sadrollahi, Ali; Khalili, Zahra; Pour Nazari, Robab; Mohammadi, Majid; Ahmadi Khatir, Maryam; Mossadegh, Najima

    2016-01-01

    Background Physical activity in the elderly is influenced by aspects of aging that cause personal, mental, environmental, and social changes. Increases in factors that are barriers to activity cause physical energy expenditure to decrease. Objectives The aim of the present study was to survey the relationship between energy expenditure in metabolic equivalent units (MET) and factors that are barriers to physical activity in elderly people in Kashan, Iran Methods This is a descriptive analysis...

  4. Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation.

    Rayssiguier, Yves; Libako, Patrycja; Nowacki, Wojciech; Rock, Edmond

    2010-06-01

    Magnesium (Mg) intake is inadequate in the western diet and metabolic syndrome is highly prevalent in populations around the world. Epidemiological studies suggest that high Mg intake may reduce the risk but the possibility of confounding factors exists, given the strong association between Mg and other beneficial nutriments (vegetables, fibers, cereals). The concept that metabolic syndrome is an inflammatory condition may explain the role of Mg.Mg deficiency results in a stress effect and increased susceptibility to physiological damage produced by stress. Stress activates the hypothalamic-pituitary-adrenal axis (HPA) axis and the sympathetic nervous system. The activation of the renin-angiotensin-aldosterone system is a factor in the development of insulin resistance by increasing oxidative stress. In both humans and rats, aldosteronism results in an immunostimulatory state and leads to an inflammatory phenotype. Stress response induces the release of large quantities of excitatory amino acids and activates the nuclear factor NFkappaB, promoting translation of molecules involved in cell regulation, metabolism and apoptosis. The rise in neuropeptides is also well documented. Stress-induced HPA activation has been identified to play an important role in the preferential body fat accumulation but evidence that Mg is involved in body weight regulation is lacking. One of the earliest events in the acute response to stress is endothelial dysfunction. Endothelial cells actively contribute to inflammation by elaborating cytokines, synthesizing chemical mediators and expressing adhesion molecules. Experimental Mg deficiency in rats induces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, synthesis of inflammatory cytokines and acute phase proteins, extensive production of free radicals. An increase in extracellular Mg concentration decreases inflammatory effects, while reduction in extracellular Mg results in cell activation. The

  5. Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring?

    Danielsen, Inge; Granström, Charlotta; Rytter, Dorte

    2013-01-01

    It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring.......It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring....

  6. Correlates and geographic patterns of knowledge that physical activity decreases cancer risk.

    Ramírez, A Susana; Finney Rutten, Lila J; Vanderpool, Robin C; Moser, Richard P; Hesse, Bradford W

    2013-04-01

    While many lifestyle-related cancer risk factors including tobacco use, poor diet, and sun exposure are well recognized by the general public, the role of physical activity in decreasing cancer risk is less recognized. Studies have demonstrated gender-, race/ethnicity-, and age-based disparities in cancer risk factor knowledge; however, beliefs and geographic factors that may be related to knowledge are under-examined. In this study, we analyzed data from the 2008 Health Information National Trends Survey to determine correlates of knowledge of the relationship between physical activity and reduced cancer risk in the adult US population. We generated geographic information system maps to examine the geographic distribution of this knowledge. Results revealed that there is confusion among US adults about the relationship between physical activity and cancer risk: Respondents who believed that cancer is not preventable had significantly lower odds of knowing that physical activity reduces cancer risk (p physical activity reduces cancer risk (p physical activity guidelines were also significantly more likely to know that physical activity reduces cancer risk (p physical inactivity. Correlates of cancer risk factor knowledge point to opportunities for targeted interventions.

  7. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats.

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

    2016-02-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin's impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin's attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin's effect on cocaine seeking may be mediated by different mechanisms in male and females. PsycINFO Database Record (c) 2016 APA, all rights reserved.

  8. Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism

    McClain, Donald A.; Abuelgasim, Khadega A.; Nouraie, Mehdi; Salomon-Andonie, Juan; Niu, Xiaomei; Miasnikova, Galina; Polyakova, Lydia A.; Sergueeva, Adelina; Okhotin, Daniel J.; Cherqaoui, Rabia; Okhotin, David; Cox, James E.; Swierczek, Sabina; Song, Jihyun; Simon, M.Celeste; Huang, Jingyu; Simcox, Judith A.; Yoon, Donghoon; Prchal, Josef T.; Gordeuk, Victor R.

    2012-01-01

    In Chuvash polycythemia, a homozygous 598C>T mutation in the von Hippel-Lindau gene (VHL) leads to an R200W substitution in VHL protein, impaired degradation of α-subunits of hypoxia inducible factor (HIF)-1 and HIF-2, and augmented hypoxic responses during normoxia. Chronic hypoxia of high altitude is associated with decreased serum glucose and insulin concentrations. Other investigators reported that HIF-1 promotes cellular glucose uptake by increased expression of GLUT1 and increased glycolysis by increased expression of enzymes such as PDK. On the other hand, inactivation of Vhl in murine liver leads to hypoglycemia associated with a HIF-2-related decrease in the expression of the gluconeogenic enzymes genes Pepck, G6pc, and Glut2. We therefore hypothesized that glucose concentrations are decreased in individuals with Chuvash polycythemia. We found that 88 Chuvash VHLR200W homozygotes had lower random glucose and glycosylated hemoglobin A1c levels than 52 Chuvash subjects with wildtype VHL alleles. Serum metabolomics revealed higher glycerol and citrate levels in the VHLR200W homozygotes. We expanded these observations in VHLR200W homozygote mice and found that they had lower fasting glucose values and lower glucose excursions than wild-type control mice but no change in fasting insulin concentrations. Hepatic expression of Glut2 and G6pc but not Pdk2 was decreased and skeletal muscle expression of Glut1, Pdk1 and Pdk4 was increased. These results suggest that both decreased hepatic gluconeogenesis and increased skeletal uptake and glycolysis contribute to the decreased glucose concentrations. Further study is needed to determine whether pharmacologically manipulating HIF expression might be beneficial for treatment of diabetic patients. PMID:23015148

  9. Decrease in the cytosolic NADP+-dependent isocitrate dehydrogenase activity through porcine sperm capacitation.

    Katoh, Yuki; Tamba, Michiko; Matsuda, Manabu; Kikuchi, Kazuhiro; Okamura, Naomichi

    2018-02-26

    In order to understand the molecular mechanisms involved in the sperm capacitation, we have identified the proteins tyrosine-phosphorylated during the capacitation especially in conjunction with the regulation of the levels of reactive oxygen species (ROS) in sperm. In the present study, the effects of the tyrosine phosphorylation of cytosolic NADP + -dependent isocitrate dehydrogenase (IDPc) on its catalytic activity and on the levels of ROS in sperm have been studied. The tyrosine phosphorylated IDPc showed a significantly lowered enzymatic activity. The immunocytochemical analyses using the highly specific antisera against IDPc revealed that IDPc was mainly localized to the principal piece of the porcine sperm flagellum. As IDPc is one of the major NADPH regenerating enzymes in porcine sperm, it is strongly suggested that the decrease in IDPc activity is involved in the increased levels of ROS, which results in the induction of hyperactivated flagellar movement and capacitation. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Soluble CD206 plasma levels in rheumatoid arthritis reflect decrease in disease activity

    Heftdal, Line Dam; Stengaard-Pedersen, Kristian; Ørnbjerg, Lykke Midtbøll

    2017-01-01

    internalization and degradation. The soluble form has been suggested as a biomarker of M2A-macrophage activation. The aim of this study was to investigate sCD206 plasma levels in early RA patients initiating anti-TNFα treatment. Plasma levels of sCD206 were measured by ELISA in samples from 155 early RA patients...... from baseline after 6 months. In the ADA group, however, levels remained lower than baseline throughout the treatment period. In conclusion, initially, plasma sCD206 in early RA patients decreased in accordance with disease activity and initiation of DMARD treatment. Treatment with anti-TNFα preserved......Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and infiltration by activated macrophages. TNFα is a central mediator in this process. The mannose receptor, CD206, is a scavenger receptor expressed by M2A-macrophages and dendritic cells. It is involved in collagen...

  11. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Atorvastatin and fenofibrate increase apolipoprotein AV and decrease triglycerides by up-regulating peroxisome proliferator-activated receptor-α

    Huang, Xian-sheng; Zhao, Shui-ping; Bai, Lin; Hu, Min; Zhao, Wang; Zhang, Qian

    2009-01-01

    Background and purpose: Combining statin and fibrate in clinical practice provides a greater reduction of triglycerides than either drug given alone, but the mechanism for this effect is poorly understood. Apolipoprotein AV (apoAV) has been implicated in triglyceride metabolism. This study was designed to investigate the effect of the combination of statin and fibrate on apoAV and the underlying mechanism(s). Experimental approach: Hypertriglyceridaemia was induced in rats by giving them 10% fructose in drinking water for 2 weeks. They were then treated with atorvastatin, fenofibrate or the two agents combined for 4 weeks, and plasma triglyceride and apoAV measured. We also tested the effects of these two agents on triglycerides and apoAV in HepG2 cells in culture. Western blot and reverse transcription polymerase chain reaction was used to measure apoAV and peroxisome proliferator-activated receptor-α (PPARα) expression. Key results: The combination of atorvastatin and fenofibrate resulted in a greater decrease in plasma triglycerides and a greater increase in plasma and hepatic apoAV than either agent given alone. Hepatic expression of the PPARα was also more extensively up-regulated in rats treated with the combination. A similar, greater increase in apoAV and a greater decrease in triglycerides were observed following treatment of HepG2 cells pre-exposed to fructose), with the combination. Adding an inhibitor of PPARα (MK886) abolished the effects of atorvastatin on HepG2 cells. Conclusions and implications: A combination of atorvastatin and fenofibrate increased apoAV and decreased triglycerides through up-regulation of PPARα. PMID:19694729

  13. Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer's disease.

    Ewers, Michael

    2012-02-01

    The enzyme beta-secretase (BACE1) is essentially involved in the production of cerebral amyloidogenic pathology in Alzheimer\\'s disease (AD). The measurement of BACE1 activity in cerebrospinal fluid (CSF) has been reported, which may render CSF measurement of BACE1 a potential biomarker candidate of AD. In order to investigate whether BACE1 protein activity is correlated with regional brain atrophy in AD, we investigated the association between CSF levels of BACE1 and MRI-assessed hippocampus volume in patients with AD (n = 30). An increase in CSF-BACE1 activity was associated with decreased left and right hippocampus volume corrected for global head volume in the AD patients. Boot-strapped regression analysis showed that increased CSF levels of BACE1 activity were associated with increased CSF concentration of total tau but not amyloid-beta1-42 in AD. White matter hyperintensities did not influence the results. BACE1 activity and protein levels were significantly increased in AD compared to 19 elderly healthy controls. Thus, the CSF biomarker candidate of BACE1 activity was associated with hippocampus atrophy in AD in a robust manner and may reflect neurotoxic amyloid-beta-related processes.

  14. Decreased plasma ADAMTS-13 activity as a predictor of postoperative bleeding in cyanotic congenital heart disease

    Rosangela P.S. Soares

    2013-04-01

    Full Text Available OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity. The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years. The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001. An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081, was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029 and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004. Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group, preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79, 1.096 (95% CI 1.016 to 1.183, and 37.43 (95% CI 1.79 to 782.73. CONCLUSION: Low plasma ADAMTS-13

  15. Age-related decrease in physical activity and functional fitness among elderly men and women

    Milanović Z

    2013-05-01

    Full Text Available Zoran Milanovic,1 Saša Pantelic,1 Nebojša Trajkovic,1 Goran Sporiš,2 Radmila Kostic,1 Nic James31Faculty of Sport and Physical Education, University of Niš, Niš, Serbia; 2Faculty of Kinesiology, University of Zagreb, Zagreb, Croatia; 3London Sport Institute, Middlesex University, London, UKAim: To determine differences in physical activity level and functional fitness between young elderly (60–69 years and old elderly (70–80 years people with the hypothesis that an age-related decline would be found.Methods: A total of 1288 participants’ level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg. Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test.Results: Significant differences (P < 0.05 were found for all Senior Fitness tests between young elderly (60–69 years and old elderly (70–80 men. Similar results were found for the women, except no significant differences were found for the chair sit and reach and the 2-minute step test. From the viewpoint of energy consumption estimated by the International Physical Activity Questionnaire, moderate physical activity is dominant. In addition, with aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P < 0.05.Conclusions: This study found that the reduction in physical activity level and functional fitness was equal for both men and women and was due to the aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body

  16. Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity.

    Sullivan, Elinor L; Shearin, Jean; Koegler, Frank H; Cameron, Judy L

    2012-04-01

    The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone (P Physical activity increased during the 3rd mo of treatment (P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment (P = 0.02). Metabolic rate did not change (P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.

  17. Upregulating Nonneuronal Cholinergic Activity Decreases TNF Release from Lipopolysaccharide-Stimulated RAW264.7 Cells

    Yi Lv

    2014-01-01

    Full Text Available Nonneuronal cholinergic system plays a primary role in maintaining homeostasis. It has been proved that endogenous neuronal acetylcholine (ACh could play an anti-inflammatory role, and exogenous cholinergic agonists could weaken macrophages inflammatory response to lipopolysaccharide (LPS stimulation through activation of α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR. We assumed that nonneuronal cholinergic system existing in macrophages could modulate inflammation through autocrine ACh and expressed α7nAChR on the cells. Therefore, we explored whether LPS continuous stimulation could upregulate the nonneuronal cholinergic activity in macrophages and whether increasing autocrine ACh could decrease TNF release from the macrophages. The results showed that, in RAW264.7 cells incubated with LPS for 20 hours, the secretion of ACh was significantly decreased at 4 h and then gradually increased, accompanied with the enhancement of α7nAChR expression level. The release of TNF was greatly increased from RAW264.7 cells at 4 h and 8 h exposure to LPS; however, it was suppressed at 20 h. Upregulating choline acetyltransferase (ChAT expression through ChAT gene transfection could enhance ACh secretion and reduce TNF release from the infected RAW264. 7cells. The results indicated that LPS stimulation could modulate the activity of nonneuronal cholinergic system of RAW264.7 cells. Enhancing autocrine ACh production could attenuate TNF release from RAW264.7 cells.

  18. The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin.

    Yasini, Seyed Ali; Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

    2015-11-01

    The first aim of this study was to synthesize nanocellulose conjugated with aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation. In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000 μg mL(-1), at various conditions. Then, the quantity of adsorption and release was separately measured. Furthermore, both toxicity and antibacterial activity of NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this study, MD simulation clearly showed the adsorption after 50 picoseconds. The adsorption tests revealed that the increase of incubation time and NCABP concentration, at range of 50-200 μg mL(-1), led to increase of adsorption. Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP could adsorb enrofloxacin, up to 1000 μg mL(-1), in different types of meat. Moreover, the increase of incubation time and temperature did not release enrofloxacin, but the increase of pH increased release. This study showed that both toxicity and antibacterial activity of enrofloxacin were decreased when exposed together with NCABP. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Pouteria ramiflora extract inhibits salivary amylolytic activity and decreases glycemic level in mice

    NEIRE M. DE GOUVEIA

    2013-09-01

    Full Text Available In this study, extracts of plant species from the Cerrado biome were assessed in order to find potential inhibitors of human salivary alpha-amylase. The plants were collected and extracts were obtained from leaves, bark, and roots. We performed a preliminary phytochemical analysis and a screening for salivar alpha-amylase inhibitory activity. Only three botanical families (Sapotaceae, Sapindaceae and Flacourtiaceae and 16 extracts showed a substantial inhibition (>75% of alpha-amylase. The ethanolic extracts of Pouteria ramiflora obtained from stem barks and root barks decreased amylolytic activity above 95% at a final concentration of 20 µg/mL. Thus, adult male Swiss mice were treated orally with P. ramiflora in acute toxicity and glycemic control studies. Daily administration with 25, 50 and 100 mg/kg of aqueous extract of P. ramiflora for eight days can reduce significantly body weight and blood glucose level in mice. These data suggest that the crude polar extract of P. ramiflora decreases salivary amylolytic activity while lowering the blood levels of glucose.

  20. Hypoxia-induced decrease of UCP3 gene expression in rat heart parallels metabolic gene switching but fails to affect mitochondrial respiratory coupling.

    Essop, M Faadiel; Razeghi, Peter; McLeod, Chris; Young, Martin E; Taegtmeyer, Heinrich; Sack, Michael N

    2004-02-06

    Mitochondrial uncoupling proteins 2 and 3 (UCP2 and UCP3) are postulated to contribute to antioxidant defense, nutrient partitioning, and energy efficiency in the heart. To distinguish isotype function in response to metabolic stress we measured cardiac mitochondrial function and cardiac UCP gene expression following chronic hypobaric hypoxia. Isolated mitochondrial O(2) consumption and ATP synthesis rate were reduced but respiratory coupling was unchanged compared to normoxic groups. Concurrently, left ventricular UCP3 mRNA levels were significantly decreased with hypoxia (pheart as opposed to uncoupling of mitochondria. Moreover, the divergent hypoxia-induced regulation of UCP2 and UCP3 supports distinct mitochondrial regulatory functions of these inner mitochondrial membrane proteins in the heart in response to metabolic stress.

  1. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

    Tricia Hubbard-Turner, Erik A. Wikstrom, Sophie Guderian, Michael J. Turner

    2015-09-01

    Full Text Available We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL group, the transected anterior talofibular ligament (ATFL/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011. Daily duration was different between the three running groups (p = 0.048. The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046 while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028 compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019 and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005. The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately.

  2. Decreased enzymatic activity of 5,10-methylene tetrahydrofolate reductase affects the development of several diseases

    Maša Vidmar

    2016-07-01

    Full Text Available The importance of folates in human physiology is well known, as are various pathologies associated with low folate status. Folate deficiency can occur due to low dietary intake, genetic predisposition or treatment with medicines affecting the folate status. The aim of this paper is to explore the importance of determining genetic polymorphisms which influence the levels of biologically active folate. MTHFR is involved in the transformation of 5,10-methylene-THF to 5-methyl-THF. Polymorphisms of the MTHRF gene are associated with decreased enzymatic activity.Only 9.3 % of the population in Slovenia displays full activity of the MTHFR enzyme; these subjects are non-mutated homozygotes (wild-type alleles. In contrast, the average enzymatic activity in subjects with mutated alleles is between 50 and 60 %. MTHFR polymorphism is associated with an increased risk of hyperhomocysteinemia and cardiovascular diseases, neurological disorders and various types of cancer. There is also an increased risk for congenital malformations. Folic acid food fortification was introduced in some countries in order to assure an adequate folate status in the population. However, this approach does not address the decreased activity of MTHFR.Polymorphism in the key enzymes of the folate cycle is common. Determination of the genetic predisposition is therefore plausible in the most vulnerable groups of the population, such as pregnant women and patients receiving medicines influencing the folate cycle in various ways, e.g. 5-fluorouracil, methotrexate and 6-mercaptopurine. Genotyping would allow the identification of patients at high risk for suboptimal folate status.

  3. Why even active people get fatter--the asymmetric effects ofincreasing and decreasing exercise

    Williams, Paul T.

    2006-01-06

    Background: Public health policies for preventing obesityneed guidelines for active individuals who are at risk due to exerciserecidivism. Methods: Changes in adiposity were compared to the runningdistances at baseline and follow-up in men and women whose reportedexercise increased (N=4,632 and 1,953, respectively) or decreased (17,280and 5,970, respectively) during 7.7 years of follow-up. Results: PerDelta km/wk, decreases in running distance caused over four-fold greaterweight gain between 0-8 km/wk (slope+-SE, males: -0.068+ -0.005 kg/m2,females: -0.080+-0.01 kg/m2) than between 32-48 km/wk (-0.017+-0.002 and-0.010+-0.005 kg/m2, respectively). In contrast, increases in runningdistance produced the smallest weight losses between 0-8 km/wk andstatistically significant weight loss only above 16 km/wk in males and 32km/wk in females. Above 32 km/wk (30 kcal/kg) in men and 16 km/wk (15kcal/kg) in women, weight loss from increasing exercise was equal to orgreater than weight gained with decreasing exercise, otherwise weightgain exceeded weight loss. Substantial weight gain occurred in runnerswho quit running, which would be mostly retained with resumed activity.Conclusion: Public health recommendations should warn against the risksof irreversible weight gain with exercise cessation. Weight gained due toreductions in exercise below 30 kcal/kg in men and 15 kcal/kg in womenmay not be reversed by resuming prior activity. Current IOM guidelines(i.e., maintain total energy expenditure at 160 percent of basal) agreewith the men s exercise threshold for symmetric weight change withchanging exercise levels.

  4. Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

    Pols, Thijs W.H.; Ottenhoff, Roelof; Vos, Mariska; Levels, Johannes H.M.; Quax, Paul H.A.; Meijers, Joost C.M.; Pannekoek, Hans; Groen, Albert K.; Vries, Carlie J.M. de

    2008-01-01

    NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

  5. The 28-day exposure to fenpropathrin decreases locomotor activity and reduces activity of antioxidant enzymes in mice brains.

    Nieradko-Iwanicka, Barbara; Borzęcki, Andrzej

    2016-04-01

    Fenpropathrin (Fen) is a pyrethroid (Pyr) insecticide. Pyrs are used in veterinary medicine, in agriculture and for domestic purposes. As their use increases, new questions about their side effects and mode of action in non-target organisms arise. The objective of this work was to characterize dose-response relationship for in vivo motor function and memory in mice exposed to Fen for 28 days and to assess its influence on activity of antioxidant enzymes in mice brains. The experiment was performed using 64 female mice. Fen at the dose of 11.9mg/kg of body mass, 5.95mg/kg or 2.38mg/kg was administered ip to the mice for 28 consecutive days. Motor function and spatial working memory were tested on days 7, 14 and 28. On day 29, the animals were sacrificed and brains were used to determine activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Fen significantly decreased locomotor activity in mice receiving the highest dose at every stage of the experiment. Lower doses reduced locomotion on days 7 and 14. Fen did not produce memory impairment. A decrease in activities of SOD and GPx was recorded in mice brains. The decrease of SOD activity in mice brains results from direct inhibition of the enzyme by Fen and/or increased utilization due to excessive free radical formation in conditions of Fen-induced oxidative stress. The reduction in GPx activity is probably due to limited glutathione availability. The reduced locomotor activity is a behavioral demonstration of Fen-induced damage in the dopaminergic system. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Active Prompting to Decrease Cell Phone Use and Increase Seat Belt Use While Driving

    Clayton, Michael; Helms, Bridgett; Simpson, Cathy

    2006-01-01

    Automobile crashes are the leading cause of death for those aged 3 to 33, with 43,005 (118 per day) Americans killed in 2002 alone. Seat belt use reduces the risk of serious injury in an accident, and refraining from using a cell phone while driving reduces the risk of an accident. Cell phone use while driving increases accident rates, and leads to 2,600 U.S. fatalities each year. An active prompting procedure was employed to increase seat belt use and decrease cell phone use among drivers ex...

  7. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

    2016-01-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxyt...

  8. The traditional Korean dietary pattern is associated with decreased risk of metabolic syndrome: findings from the Korean National Health and Nutrition Examination Survey, 1998-2009.

    Lee, Kyung Won; Cho, Mi Sook

    2014-01-01

    The traditional Korean diet has several healthy components, including abundant vegetables, fermented foods, a variety of foodstuffs, and a balance of animal and vegetable food intake. Although the traditional Korean diet has many healthy components, few studies have been conducted on the health advantages of the Korean dietary pattern. This study is intended to clarify the relationship between Korean dietary patterns and chronic diseases using the Integrated Korean Dietary Pattern Score (I-KDPS). I-KDPS is an index for measuring Korean dietary patterns based on traditional Korean meals and reflects the complex and multifaceted characteristics of Korean food culture. I-KDPS is composed of seven items to measure the level of balance and adequacy of Korean food consumption, with a maximum score of 60. When I-KDPS was applied to the Korean National Health and Nutrition Examination Survey (1998-2009), a nationwide survey, I-KDPS was closely related to the risk of metabolic syndrome. Even though there were a few differences among the years surveyed, the risk of metabolic syndrome, obesity, hypertension, and hypertriglyceridemia significantly decreased as I-KDPS increased. These results indicate that risk of diseases, including metabolic syndrome, decreases in individuals adhering to traditional Korean dietary patterns in adequate levels and those who eat a balanced diet. The result of this study shows that the traditional Korean table setting, which comprises side dishes, including seasoned vegetables, grilled dishes, and fermented products with cooked rice (bap), soup (guk), and kimchi, contains traits that help prevent metabolic syndrome. I-KDPS coupled with the basic study of the healthfulness of the Korean dietary lifestyle is expected to help establish a foundation for continuous development of health promoting Korean foods and dietary culture.

  9. Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0) Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins

    Venn-Watson, Stephanie K.; Parry, Celeste; Baird, Mark; Stevenson, Sacha; Carlin, Kevin; Daniels, Risa; Smith, Cynthia R.; Jones, Richard; Wells, Randall S.; Ridgway, Sam; Jensen, Eric D.

    2015-01-01

    Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A) and lower (n = 19, Group B) mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B’s diet, had C17:0 (41 and 67 mg/100g, respectively). When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg), C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g); nonfat dairy products had no detectable C17:0. We hypothesize that humans’ movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome. PMID:26200116

  10. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite. : Fisetin disposition and metabolism in mice

    Touil, Yasmine,; Auzeil, Nicolas; Boulinguez, François; Saighi, Hanane; Regazzetti, Anne; Scherman, Daniel; Chabot, Guy,

    2011-01-01

    International audience; Although the natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has been recently identified as an anticancer agent with antiangiogenic properties in mice, its in vivo pharmacokinetics and metabolism are presently not characterized. Our purpose was to determine the pharmacokinetics and metabolism of fisetin in mice and determine the biological activity of a detected fisetin metabolite. After fisetin administration of an efficacious dose of 223 mg/kg i.p. in mice...

  11. Decrease in platelet activating factor stimulated phosphoinositide turnover during storage of human platelets in plasma

    Carter, M.G.; Shukla, S.D.

    1987-01-01

    Human platelet concentrate from the American Red Cross Blood Center was stored at 24 degree C in a shaker and aliquots were taken out at time intervals aseptically. Platelet activating factor (PAF) stimulated turnover of phosphoinositide (PPI) was monitored by assaying 32 P incorporation into phosphoinositides using platelet rich plasma (PRP). Platelets in PRP were incubated with 1 x 10 -7 M PAF at 37 degree C with gentle shaking and after 5 min their lipids were extracted and analysed by TLC for 32 P-phosphoinositides. The percent stimulation of 32 P incorporation by PAF (over control) into PPI was approximately 250, 100, 60, 25 and 20 on days 1, 2, 3, 5 and 6, respectively. This indicated a dramatic decrease in PAF responsive turnover of platelet PPI during storage. These findings have important implications in relation to PAF receptor activity and viability of platelets at different periods of storage

  12. Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

    Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan

    2010-01-01

    ,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region......According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C...

  13. Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis

    Kragstrup, Tue Wenzel; Jalilian, Babak; Hvid, Malene

    2014-01-01

    of arthritis patients to have anti-inflammatory functions. Here, we study the mechanisms for these alterations and their association with SpA disease activity. METHODS: Plasma levels of sCD18 in a study population with 84 SpA patients and matched healthy controls were analyzed with a time resolved......A patients compared with healthy volunteers (P levels in the HLA-B27-positive subgroup (P levels exhibited an inverse correlation with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P level of morning...... immunoflourometric assay (TRIFMA). Binding of sCD18 to endothelial cells and fibroblast-like synovial cells (FLS) was studied with confocal microscopy. Shedding of CD18 from peripheral blood mononuclear cells (PBMC) was studied with flow cytometry and TRIFMA. RESULTS: Plasma levels of sCD18 were decreased in Sp...

  14. Electronic interactions decreasing the activation barrier for the hydrogen electro-oxidation reaction

    Santos, Elizabeth; Schmickler, Wolfgang

    2008-01-01

    A unified model for electrochemical electron transfer reactions which explicitly accounts for the electronic structure of the electrode recently proposed by us is applied to the hydrogen oxidation reaction at different metal electrocatalysts. We focus on the changes produced in the transition state (saddle point) as a consequence of the interactions with d-bands. We discuss different empirical correlations between properties of the metal and catalytic activity proposed in the past. We show which role is played by the band structure of the different metals and its interaction with the molecule for decreasing the activation barrier. Finally, we demonstrate why some metals are better electrocatalysts for the hydrogen electro-oxidation reaction than others

  15. Dietary L-carnitine supplementation in obese cats alters carnitine metabolism and decreases ketosis during fasting and induced hepatic lipidosis.

    Blanchard, Géraldine; Paragon, Bernard M; Milliat, Fabien; Lutton, Claude

    2002-02-01

    This study was designed to determine whether dietary carnitine supplement could protect cats from ketosis and improve carnitine and lipid metabolism in experimental feline hepatic lipidosis (FHL). Lean spayed queens received a diet containing 40 (CL group, n = 7) or 1000 (CH group, n = 4) mg/kg of L-carnitine during obesity development. Plasma fatty acid, beta-hydroxybutyrate and carnitine, and liver and muscle carnitine concentrations were measured during experimental induction of FHL and after treatment. In control cats (CL group), fasting and FHL increased the plasma concentrations of fatty acids two- to threefold (P 10-fold (from a basal 0.22 +/- 0.03 to 1.70 +/- 0.73 after 3 wk fasting and 3.13 +/- 0.49 mmol/L during FHL). In carnitine-supplemented cats, these variables increased significantly (P < 0.0001) only during FHL (beta-hydroxybutyrate, 1.42 +/- 0.17 mmol/L). L-Carnitine supplementation significantly increased plasma, muscle and liver carnitine concentrations. Liver carnitine concentration increased dramatically from the obese state to FHL in nonsupplemented cats, but not in supplemented cats, which suggests de novo synthesis of carnitine from endogenous amino acids in control cats and reversible storage in supplemented cats. These results demonstrate the protective effect of a dietary L-carnitine supplement against fasting ketosis during obesity induction. Increasing the L-carnitine level of diets in cats with low energy requirements, such as after neutering, and a high risk of obesity could therefore be recommended.

  16. Predictors of decreased physical activity level over time among adults: a longitudinal study.

    Dai, Sulan; Wang, Feng; Morrison, Howard

    2014-08-01

    Leisure-time physical activity (LTPA) plays a key role in chronic disease prevention and health promotion. The impact of life-changing events on LTPA among adults is unknown. To examine the association between life-changing events and decreased LTPA levels. Eight cycles of Canadian National Population Health Survey data were used for this study. A total of 12,901 respondents aged ≥18 years in 1994-1995 completed biannual follow-ups until 2008-2009. The association between life-changing events and decreased LTPA in any 2-year period was assessed with adjustment of potential confounding factors. Data were analyzed in 2012. From 1994-1995 to 2008-2009, nine of ten people changed their LTPA levels. Within each 2-year period, individuals were more likely to decrease their LTPA levels if they married within the 2-year period (men); became or remained overweight/obese (women); remained a regular smoker (men); became or remained unhealthy (men and women); developed or continued to have body pain (women); and acquired social support or remained without support (men). Most people change their LTPA levels or patterns, which are significantly influenced by life-changing events. An improved understanding of factors that influence LTPA may help better target those at high risk. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  17. Bamboo vinegar decreases inflammatory mediator expression and NLRP3 inflammasome activation by inhibiting reactive oxygen species generation and protein kinase C-α/δ activation.

    Chen-Lung Ho

    Full Text Available Bamboo vinegar (BV, a natural liquid derived from the condensation produced during bamboo charcoal production, has been used in agriculture and as a food additive, but its application to immune modulation has not been reported. Here, we demonstrated that BV has anti-inflammatory activities both in vitro and in vivo. BV reduced inducible nitric oxide synthase expression and nitric oxide levels in, and interleukin-6 secretion by, lipopolysaccharide-activated macrophages without affecting tumor necrosis factor-α secretion and cyclooxygenase-2 expression. The mechanism for the anti-inflammatory effect of BV involved decreased reactive oxygen species production and protein kinase C-α/δ activation. Furthermore, creosol (2-methoxy-4-methylphenol was indentified as the major anti-inflammatory compound in BV. Impaired cytokine expression and NLR family, pyrin domain-containing 3 (NLRP3 inflammasome activation was seen in mice treated with creosol. These findings provide insights into how BV regulates inflammation and suggest that it may be a new source for the development of anti-inflammatory agents or a healthy supplement for preventing and ameliorating inflammation- and NLRP3 inflammasome-related diseases, including metabolic syndrome.

  18. Prefrontal activity during response inhibition decreases over time in the postpartum period.

    Bannbers, Elin; Gingnell, Malin; Engman, Jonas; Morell, Arvid; Sylvén, Sara; Skalkidou, Alkistis; Kask, Kristiina; Bäckström, Torbjörn; Wikström, Johan; Poromaa, Inger Sundström

    2013-03-15

    The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, during the postpartum period and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48 h of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in performance on the Go/NoGo task were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    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.

  20. Protein phosphatases decrease their activity during capacitation: a new requirement for this event.

    Janetti R Signorelli

    Full Text Available There are few reports on the role of protein phosphatases during capacitation. Here, we report on the role of PP2B, PP1, and PP2A during human sperm capacitation. Motile sperm were resuspended in non-capacitating medium (NCM, Tyrode's medium, albumin- and bicarbonate-free or in reconstituted medium (RCM, NCM plus 2.6% albumin/25 mM bicarbonate. The presence of the phosphatases was evaluated by western blotting and the subcellular localization by indirect immunofluorescence. The function of these phosphatases was analyzed by incubating the sperm with specific inhibitors: okadaic acid, I2, endothall, and deltamethrin. Different aliquots were incubated in the following media: 1 NCM; 2 NCM plus inhibitors; 3 RCM; and 4 RCM plus inhibitors. The percent capacitated sperm and phosphatase activities were evaluated using the chlortetracycline assay and a phosphatase assay kit, respectively. The results confirm the presence of PP2B and PP1 in human sperm. We also report the presence of PP2A, specifically, the catalytic subunit and the regulatory subunits PR65 and B. PP2B and PP2A were present in the tail, neck, and postacrosomal region, and PP1 was present in the postacrosomal region, neck, middle, and principal piece of human sperm. Treatment with phosphatase inhibitors rapidly (≤1 min increased the percent of sperm depicting the pattern B, reaching a maximum of ∼40% that was maintained throughout incubation; after 3 h, the percent of capacitated sperm was similar to that of the control. The enzymatic activity of the phosphatases decreased during capacitation without changes in their expression. The pattern of phosphorylation on threonine residues showed a sharp increase upon treatment with the inhibitors. In conclusion, human sperm express PP1, PP2B, and PP2A, and the activity of these phosphatases decreases during capacitation. This decline in phosphatase activities and the subsequent increase in threonine phosphorylation may be an important

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

    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.

  2. Altered polymorphonuclear leukocyte Fc gamma R expression contributes to decreased candicidal activity during intraabdominal sepsis

    Simms, H.H.; D'Amico, R.; Monfils, P.; Burchard, K.W.

    1991-01-01

    We investigated the effects of untreated intraabdominal sepsis on polymorphonuclear leukocyte (PMN) candicidal activity. Two groups of swine were studied. Group I (n=6) underwent sham laparotomy, group II (n=7) underwent cecal ligation and incision. Untreated intraabdominal sepsis resulted in a progressive decrease in PMN candicidal activity. Concomitant rosetting and phagocytosis assays demonstrated a decrease in both the attachment and phagocytosis of Candida albicans opsonized with both normal and septic swine serum by PMNs in group II. Iodine 125-labeled swine immunoglobulin G (IgG) and fluorescein isothioalanate (FITC)-labeled swine IgG were used to investigate Fc gamma receptor ligand interactions. Scatchard analyses demonstrated a progressive decline in both the binding affinity constant and number of IgG molecules bound per PMN. Stimulation of the oxidative burst markedly reduced 125I-labeled IgG binding in both group I and group II, with a greater decrement being seen in animals with intraabdominal sepsis. Further, in group II, PMN recycling of the Fc gamma receptor to the cell surface after generation of the oxidative burst was reduced by postoperative day 4. Binding of monoclonal antibodies to Fc gamma receptor II, but not Fc gamma receptor I/III markedly reduced intracellular candicidal activity. Immunofluorescence studies revealed a homogeneous pattern of FITC-IgG uptake by nearly all group I PMNs, whereas by postoperative day 8 a substantial number of PMNs from group II failed to internalize the FITC-IgG. These studies suggest that untreated intraabdominal sepsis reduces PMN candicidal activity and that this is due, in part, to altered PMN Fc gamma receptor ligand interactions

  3. The relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity.

    Keleş, Erol; Kapusuz, Zeliha; Gürsu, Mehmet Ferit; Karlıdag, Turgut; Kaygusuz, Irfan; Bulmuş, Funda Gülcü; Yalcın, Sinasi

    2014-01-01

    To determine the presence of a relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity. A total of 30 patients who had been admitted to the Ear, Nose, and Throat (ENT) Clinic of Fırat University Medical Faculty and diagnosed as metabolic presbycusis were included in the study. The control group was composed of 30 healthy volunteers. Pure tone audiometry and impedencemeter were performed on all subjects included in the study at the audiometry laboratory of the ENT clinic. The presence of a regular hearing curve, a symmetrical sensorineural hearing loss more than 25 dB with preserved speech discrimination were accepted as criteria for metabolic presbycusis. Blood samples were drawn from the patients prior to the hearing tests. The sera were separated for measurements of total cholesterol, triglyceride, high-density lipoprotein, very low-density lipoprotein, low-density lipoprotein, human serum paraoxonase and arylesterase levels, respectively. No statistically significant difference was found between the patient and the control groups in terms of age and gender. Paraoxonase, arylesterase and paraoxonase/arylesterase, high-density lipoprotein levels were found to decrease in the study group and the difference was found to be statistically significant compared to the control group (P presbycusis. Furthermore, the results of this study make us think that there could be a relationship between metabolic presbycusis and cardiovascular diseases. In this case, metabolic presbycusis may be a determining parameter in the early diagnosis of cardiovascular diseases. We consider that this study may be the pioneer for further studies conducted with larger patient numbers.

  4. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  5. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

    Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-04-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.

  6. Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages.

    Xiyuan Bai

    Full Text Available Nuclear factor-kappa B (NFκB is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB. However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy.

  7. Cryotherapy decreases synovial Doppler activity and pain in knee arthritis: A randomized-controlled trial.

    Guillot, Xavier; Tordi, Nicolas; Prati, Clément; Verhoeven, Frank; Pazart, Lionel; Wendling, Daniel

    2017-07-01

    To measure and compare the effects of 2 local cryotherapy techniques on synovial power Doppler activity (primary outcome) and pain in non-septic knee arthritis without any concurrent treatment. 30 patients were randomized (ice: 30min, n=15 or cold CO 2 : 2min, n=15 both applied twice at 8h interval). Contralateral non-treated arthritic knees were used as paired controls (n=11 and n=10 respectively). The PDUS semi-quantitative score (0-3) and pain visual analogic scale were evaluated before/after each cold application, 2min, 2h, 24h after the first application. PDUS scores were checked in double-blind by 2 ultrasonographists. The inter-class effect size of local cryotherapy on the power Doppler score remained significant the day after treatment in local cryotherapy-treated compared to contralateral non-treated knees (Global difference: -1 [95% confidence interval: -1.23; -0.77]; ice: -0.73 [-1.06; -0.4]; CO 2 : -0.7 [-1.18; -0.22]). Both techniques significantly and to the same extent reduced the power Doppler score and pain visual analogic scale at all evaluation times and globally throughout the 24 hour-study period. No dropout nor adverse event was reported. In multivariate analysis, the Power Doppler score decrease was associated with pain decrease, while pain decrease was associated with the female sex and ice technique. Local ice and cold CO 2 applied twice equally reduced synovial Power Doppler activity and pain over 24h in knee arthritis. These effects remained significant the day after treatment. ClinicalTrials.gov identifier: NCT02573298. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  8. Low adiponectin levels at baseline and decreasing adiponectin levels over 10 years of follow-up predict risk of the metabolic syndrome

    Lindberg, S; Jensen, J S; Bjerre, Mette

    2017-01-01

    AIM: Adiponectin is the most abundant adipokine and may play a key role in the interplay between obesity, inflammation, insulin resistance and the metabolic syndrome (MetS). Thus, this large population-based cohort investigated whether adiponectin at baseline and/or a decrease in adiponectin during......-up were inversely associated with an increase in the number of components of MetS (Pvs 7.0mg/L (95% CI: 6.3-7.9) for those with four to five components. CONCLUSIONS/INTERPRETATION: Low plasma...

  9. Tiamulin inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of CD73.

    Yang, Xu; Pei, Shimin; Wang, Huanan; Jin, Yipeng; Yu, Fang; Zhou, Bin; Zhang, Hong; Zhang, Di; Lin, Degui

    2017-04-11

    Metastasis is the leading cause of death in breast cancer patients. CD73, also known as ecto-5'-nucleotidase, plays a critical role in cancer development including metastasis. The existing researches indicate that overexpression of CD73 promotes growth and metastasis of breast cancer. Therefore, CD73 inhibitor can offer a promising treatment for breast cancer. Here, we determined whether tiamulin, which was found to inhibit CD73, was able to suppress breast cancer development and explored the related mechanisms. We firstly measured the effect of tiamulin hydrogen fumarate (THF) on CD73 using high performance liquid chromatography (HPLC). Then, we investigated cell proliferation, migration and invasion in MDA-MB-231 human breast cancer cell line and 4 T1 mouse breast cancer cell line treated with THF by migration assay, invasion assay and activity assay. Besides, we examined the effect of THF on syngeneic mammary tumors of mice by immunohistochemistry. Our data demonstrated that THF inhibited CD73 by decreasing the activity instead of the expression of CD73. In vitro, THF inhibited the proliferation, migration and invasion of MDA-MB-231 and 4 T1 cells by suppressing CD73 activity. In vivo, animal experiments showed that THF treatment resulted in significant reduction in syngeneic tumor growth, microvascular density and lung metastasis rate. Our results indicate that THF inhibits growth and metastasis of breast cancer by blocking the activity of CD73, which may offer a promising treatment for breast cancer therapy.

  10. UV irradiation to mouse skin decreases hippocampal neurogenesis and synaptic protein expression via HPA axis activation.

    Han, Mira; Ban, Jae-Jun; Bae, Jung-Soo; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

    2017-11-14

    The skin senses external environment, including ultraviolet light (UV). Hippocampus is a brain region that is responsible for memory and emotion. However, changes in hippocampus by UV irradiation to the skin have not been studied. In this study, after 2 weeks of UV irradiation to the mouse skin, we examined molecular changes related to cognitive functions in the hippocampus and activation of the hypothalamic-pituitary-adrenal (HPA) axis. UV exposure to the skin decreased doublecortin-positive immature neurons and synaptic proteins, including N-methyl-D-aspartate receptor 2 A and postsynaptic density protein-95, in the hippocampus. Moreover, we observed that UV irradiation to the skin down-regulated brain-derived neurotrophic factor expression and ERK signaling in the hippocampus, which are known to modulate neurogenesis and synaptic plasticity. The cutaneous and central HPA axes were activated by UV, which resulted in significant increases in serum levels of corticosterone. Subsequently, UV irradiation to the skin activated the glucocorticoid-signaling pathway in the hippocampal dentate gyrus. Interestingly, after 6 weeks of UV irradiation, mice showed depression-like behavior in the tail suspension test. Taken together, our data suggest that repeated UV exposure through the skin may negatively affect hippocampal neurogenesis and synaptic plasticity along with HPA axis activation.

  11. Mitochondrial thiol modification by a targeted electrophile inhibits metabolism in breast adenocarcinoma cells by inhibiting enzyme activity and protein levels

    M. Ryan Smith

    2016-08-01

    Full Text Available Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate group, which can be modified by certain oxidants. In the current study, we show that modification of mitochondrial protein thiols by a model compound, iodobutyl triphenylphosphonium (IBTP, decreased mitochondrial metabolism and ATP in MDA-MB 231 (MB231 breast adenocarcinoma cells up to 6 days after an initial 24 h treatment. Mitochondrial thiol modification also depressed oxygen consumption rates (OCR in a dose-dependent manner to a greater extent than a non-thiol modifying analog, suggesting that thiol reactivity is an important factor in the inhibition of cancer cell metabolism. In non-tumorigenic MCF-10A cells, IBTP also decreased OCR; however the extracellular acidification rate was significantly increased at all but the highest concentration (10 µM of IBTP indicating that thiol modification can have significantly different effects on bioenergetics in tumorigenic versus non-tumorigenic cells. ATP and other adenonucleotide levels were also decreased by thiol modification up to 6 days post-treatment, indicating a decreased overall energetic state in MB231 cells. Cellular proliferation of MB231 cells was also inhibited up to 6 days post-treatment with little change to cell viability. Targeted metabolomic analyses revealed that thiol modification caused depletion of both Krebs cycle and glutaminolysis intermediates. Further experiments revealed that the activity of the Krebs cycle enzyme, aconitase, was attenuated in response to thiol modification. Additionally, the inhibition of glutaminolysis corresponded to decreased glutaminase C (GAC protein levels, although other protein levels were

  12. The metabolic activator FOXO1 binds hepatitis B virus DNA and activates its transcription

    Shlomai, Amir; Shaul, Yosef

    2009-01-01

    Hepatitis B virus (HBV) is a small DNA virus that targets the liver and infects humans worldwide. Recently we have shown that the metabolic regulator PGC-1α coactivates HBV transcription thereby rendering the virus susceptible to fluctuations in the nutritional status of the liver. PGC-1α coactivation of HBV is mediated through the liver-enriched nuclear receptor HNF4α and through another yet unknown transcription factor(s). Here we show that the forkhead transcription factor FOXO1, a known target for PGC-1α coactivation and a central mediator of glucose metabolism in the liver, binds HBV core promoter and activates its transcription. This activation is further enhanced in the presence of PGC-1α, implying that FOXO1 is a target for PGC-1α coactivation of HBV transcription. Thus, our results identify another key metabolic regulator as an activator of HBV transcription, thereby supporting the principle that HBV gene expression is regulated in a similar way to key hepatic metabolic genes.

  13. Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines.

    Scheulen, M E; Hoensch, H; Kappus, H; Seeber, S; Schmidt, C G

    1987-01-01

    From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.

  14. Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats.

    Butler, Michael J; Hildebrandt, Ryan P; Eckel, Lisa A

    2018-05-25

    Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 μg/kg), a GPER-1 agonist (G-1; 0-1600 μg/kg), and a GPER-1 antagonist (G-36; 0-80 μg/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40 μg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 μg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect. Copyright © 2017. Published by Elsevier Inc.

  15. Valsartan decreases platelet activity and arterial thrombotic events in elderly patients with hypertension.

    Wu, Fang; Wang, Hong-Yan; Cai, Fan; Wang, Ling-Jie; Zhang, Feng-Ru; Chen, Xiao-Nan; Yang, Qian; Jiang, Meng-Hui; Wang, Xue-Feng; Shen, Wei-Feng

    2015-01-20

    Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension. Two-hundred and ten patients with hypertension and aged > 60 years were randomized to valsartan (n = 140) or amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Human aortic endothelial cells (HAECs) were stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California, USA). PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002). Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L). AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

  16. Objectively measured sedentary time, physical activity, and metabolic risk: the Australian Diabetes, Obesity and Lifestyle Study (AusDiab).

    Healy, Genevieve N; Wijndaele, Katrien; Dunstan, David W; Shaw, Jonathan E; Salmon, Jo; Zimmet, Paul Z; Owen, Neville

    2008-02-01

    We examined the associations of objectively measured sedentary time and physical activity with continuous indexes of metabolic risk in Australian adults without known diabetes. An accelerometer was used to derive the percentage of monitoring time spent sedentary and in light-intensity and moderate-to-vigorous-intensity activity, as well as mean activity intensity, in 169 Australian Diabetes, Obesity and Lifestyle Study (AusDiab) participants (mean age 53.4 years). Associations with waist circumference, triglycerides, HDL cholesterol, resting blood pressure, fasting plasma glucose, and a clustered metabolic risk score were examined. Independent of time spent in moderate-to-vigorous-intensity activity, there were significant associations of sedentary time, light-intensity time, and mean activity intensity with waist circumference and clustered metabolic risk. Independent of waist circumference, moderate-to-vigorous-intensity activity time was significantly beneficially associated with triglycerides. These findings highlight the importance of decreasing sedentary time, as well as increasing time spent in physical activity, for metabolic health.

  17. Metabolic signals and innate immune activation in obesity and exercise.

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

  18. Pyrrolizidine Alkaloids: Metabolic Activation Pathways Leading to Liver Tumor Initiation.

    Fu, Peter P

    2017-01-17

    Pyrrolizidine alkaloids (PAs) and PA N-oxides are a class of phytochemical carcinogens contained in over 6000 plant species spread around the world. It has been estimated that approximately half of the 660 PAs and PA N-oxides that have been characterized are cytotoxic, genotoxic, and tumorigenic. It was recently determined that a genotoxic mechanism of liver tumor initiation mediated by PA-derived DNA adducts is a common metabolic activation pathway of a number of PAs. We proposed this set of PA-derived DNA adducts could be a common biological biomarker of PA exposure and a potential biomarker of PA-induced liver tumor formation. We have also found that several reactive secondary pyrrolic metabolites can dissociate and interconvert to other secondary pyrrolic metabolites, resulting in the formation of the same exogenous DNA adducts. This present perspective reports the current progress on these new findings and proposes future research needed for obtaining a greater understanding of the role of this activation pathway and validating the use of this set of PA-derived DNA adducts as a biological biomarker of PA-induced liver tumor initiation.

  19. College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control

    Julia E. Cohen-Gilbert

    2017-09-01

    Full Text Available The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD multiband functional magnetic resonance imaging (fMRI to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo. Subjects were 23 college freshmen (seven male, 18–20 years who engaged in a range of drinking behavior (past 3 months’ binge episodes range = 0–19, mean = 4.6, total drinks consumed range = 0–104, mean = 32.0. Brain activation on inhibitory trials (NoGo was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations and cluster-based thresholding (z = 2.3, p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC, dorsomedial prefrontal cortex (DMPFC, and anterior cingulate cortex (ACC, brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional

  20. Impaired ALDH2 activity decreases the mitochondrial respiration in H9C2 cardiomyocytes.

    Mali, Vishal R; Deshpande, Mandar; Pan, Guodong; Thandavarayan, Rajarajan A; Palaniyandi, Suresh S

    2016-02-01

    Reactive oxygen species (ROS)-mediated reactive aldehydes induce cellular stress. In cardiovascular diseases such as ischemia-reperfusion injury, lipid-peroxidation derived reactive aldehydes such as 4-hydroxy-2-nonenal (4HNE) are known to contribute to the pathogenesis. 4HNE is involved in ROS formation, abnormal calcium handling and more importantly defective mitochondrial respiration. Aldehyde dehydrogenase (ALDH) superfamily contains NAD(P)(+)-dependent isozymes which can detoxify endogenous and exogenous aldehydes into non-toxic carboxylic acids. Therefore we hypothesize that 4HNE afflicts mitochondrial respiration and leads to cell death by impairing ALDH2 activity in cultured H9C2 cardiomyocyte cell lines. H9C2 cardiomyocytes were treated with 25, 50 and 75 μM 4HNE and its vehicle, ethanol as well as 25, 50 and 75 μM disulfiram (DSF), an inhibitor of ALDH2 and its vehicle (DMSO) for 4 h. 4HNE significantly decreased ALDH2 activity, ALDH2 protein levels, mitochondrial respiration and mitochondrial respiratory reserve capacity, and increased 4HNE adduct formation and cell death in cultured H9C2 cardiomyocytes. ALDH2 inhibition by DSF and ALDH2 siRNA attenuated ALDH2 activity besides reducing ALDH2 levels, mitochondrial respiration and mitochondrial respiratory reserve capacity and increased cell death. Our results indicate that ALDH2 impairment can lead to poor mitochondrial respiration and increased cell death in cultured H9C2 cardiomyocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

    Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

    2009-08-01

    The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

  2. Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

    Liu, Chun; Ge, Beihai [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); He, Chao [Department of Cardiology, China Three Gorges University, Yichang 433000 (China); Zhang, Yi; Liu, Xiaowen [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); Liu, Kejian [Department of Cardiology, The First Affiliated Hospital of Medical College, Shihezi University (China); Qian, Cuiping; Zhang, Yu; Peng, Wenzhong [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); Guo, Xiaomei, E-mail: xmguo@tjh.tjmu.edu.cn [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China)

    2014-07-18

    Highlights: • Mfn2 decreases cellular lipid accumulation by activating cholesterol transporters. • PPARγ is involved in the Mfn2-mediated increase of cholesterol transporter expressions. • Inactivation of ERK1/2 and p38 is involved in Mfn2-induced PPARγ expression. - Abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease.

  3. Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

    Liu, Chun; Ge, Beihai; He, Chao; Zhang, Yi; Liu, Xiaowen; Liu, Kejian; Qian, Cuiping; Zhang, Yu; Peng, Wenzhong; Guo, Xiaomei

    2014-01-01

    Highlights: • Mfn2 decreases cellular lipid accumulation by activating cholesterol transporters. • PPARγ is involved in the Mfn2-mediated increase of cholesterol transporter expressions. • Inactivation of ERK1/2 and p38 is involved in Mfn2-induced PPARγ expression. - Abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease

  4. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

  5. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

    Laura eFerreri

    2013-11-01

    Full Text Available Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC. 22 healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

  6. Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis.

    Lee, Hyo Young; Jun, Dae Won; Kim, Hyun Jung; Oh, Hyunwoo; Saeed, Waqar Khalid; Ahn, Hyeongsik; Cheung, Ramsey C; Nguyen, Mindie H

    2018-03-20

    A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis. The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines. Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], -0.30; 95% confidence interval [CI], -0.57 to -0.03) but not hepatic steatosis in RCT (SMD, -0.1; 95% CI, -0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, -3.0; 95% CI, -6.9 to 0.91). Ezetimibe decreased NAS without improving hepatic steatosis.

  7. Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes

    Alexis Valauri-Orton

    2015-01-01

    Full Text Available Dichloroacetate (DCA is a water purification byproduct that is known to be hepatotoxic and hepatocarcinogenic and to induce peripheral neuropathy and damage macrophages. This study characterizes the effects of the haloacetate on lung cells by exposing rat alveolar type II (L2 cells to 0–24 mM DCA for 6–24 hours. Increasing DCA concentration and the combination of increasing DCA concentration plus longer exposures decrease measures of cellular health. Length of exposure has no effect on oxidative stress biomarkers, glutathione, SOD, or CAT. Increasing DCA concentration alone does not affect total glutathione or its redox ratio but does increase activity in the SOD/CAT oxidative stress defense pathway. These data suggest that alveolar type II cells rely on SOD and CAT more than glutathione to combat DCA-induced stress.

  8. Encapsulation and Nano-Encapsulation of Papain Active Sites to Enhance Radiolityc Stability and Decrease Toxicity

    Lugão, A. B.; Varca, G. H.C.; Paiffer, F.; Mathor, M. B.; Lopes, P. S.; Rogero, S.; Rogero, J. R. [Comissão Nacional de Energia Nuclear (CNEN), Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo (Brazil)

    2009-07-01

    Papain is used as an ingredient in various enzymatic debridement preparations. Those paste-like preparations are based on water solution and usually are sterilized by radiation. As a consequence, there is a major decrease in papain activity. Papain containing preparations are used in chronic wounds treatment in order to clean and remove the necrotic tissue. However FDA (2008) is taking an action against such products due to severe adverse events reported in patients which were submitted to papain treatments. Thus, the main goal of this proposal is to develop encapsulated papain containing membranes based on hydrogels and silicone rubber in an attempt to achieve a controllable distribution of size and delivery profile, a toxicity reduction and provide stability towards radiation processing through nanoencapsulation with cyclodextrins, which may also provide protection to the enzyme against radiation induced radiolysis. (author)

  9. Encapsulation and Nano-Encapsulation of Papain Active Sites to Enhance Radiolityc Stability and Decrease Toxicity

    Lugão, A.B.; Varca, G.H.C.; Paiffer, F.; Mathor, M.B.; Lopes, P.S.; Rogero, S.; Rogero, J.R.

    2009-01-01

    Papain is used as an ingredient in various enzymatic debridement preparations. Those paste-like preparations are based on water solution and usually are sterilized by radiation. As a consequence, there is a major decrease in papain activity. Papain containing preparations are used in chronic wounds treatment in order to clean and remove the necrotic tissue. However FDA (2008) is taking an action against such products due to severe adverse events reported in patients which were submitted to papain treatments. Thus, the main goal of this proposal is to develop encapsulated papain containing membranes based on hydrogels and silicone rubber in an attempt to achieve a controllable distribution of size and delivery profile, a toxicity reduction and provide stability towards radiation processing through nanoencapsulation with cyclodextrins, which may also provide protection to the enzyme against radiation induced radiolysis. (author)

  10. Encapsulation and Nano-Encapsulation of Papain Active Sites to Enhance Radiolityc Stability and Decrease Toxicity

    Lugão, A. B.; Varca, G. H.C.; Mathor, M. B.; Santos Lopes, P.; Rogero, M. S.S.; Rogero, J.R., E-mail: ablugao@ipen.br [Comissão Nacional de Energia Nuclear (CNEN), Instituto de Pesquisas Energeticas e Nucleares (IPEN), Av. Prof. Lineu Prestes, 2242 Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2010-07-01

    Papain is used as an ingredient in various enzymatic debridement preparations. Those paste-like preparations are based on water solution and usually are sterilized by radiation. As a consequence, there is a major decrease in papain activity. Papain containing preparations are used in chronic wounds treatment in order to clean and remove the necrotic tissue. However FDA (2008) is taking an action against such products due to severe adverse events reported in patients submitted to papain treatments. Thus, the main goal of this proposal is to develop encapsulated papain containing membranes based on hydrogels and silicone rubber in an attempt to achieve a controllable distribution of size and delivery profile, a toxicity reduction and provide stability towards radiation processing through molecular encapsulation with β-cyclodextrin, which may also provide protection to the enzyme against radiation induced radiolysis. (author)

  11. Encapsulation and Nano-Encapsulation of Papain Active Sites to Enhance Radiolityc Stability and Decrease Toxicity

    Lugão, A.B.; Varca, G.H.C.; Mathor, M.B.; Santos Lopes, P.; Rogero, M.S.S.; Rogero, J.R.

    2010-01-01

    Papain is used as an ingredient in various enzymatic debridement preparations. Those paste-like preparations are based on water solution and usually are sterilized by radiation. As a consequence, there is a major decrease in papain activity. Papain containing preparations are used in chronic wounds treatment in order to clean and remove the necrotic tissue. However FDA (2008) is taking an action against such products due to severe adverse events reported in patients submitted to papain treatments. Thus, the main goal of this proposal is to develop encapsulated papain containing membranes based on hydrogels and silicone rubber in an attempt to achieve a controllable distribution of size and delivery profile, a toxicity reduction and provide stability towards radiation processing through molecular encapsulation with β-cyclodextrin, which may also provide protection to the enzyme against radiation induced radiolysis. (author)

  12. GABAergic inhibition through synergistic astrocytic neuronal interaction transiently decreases vasopressin neuronal activity during hypoosmotic challenge.

    Wang, Yu-Feng; Sun, Min-Yu; Hou, Qiuling; Hamilton, Kathryn A

    2013-04-01

    The neuropeptide vasopressin is crucial to mammalian osmotic regulation. Local hypoosmotic challenge transiently decreases and then increases vasopressin secretion. To investigate mechanisms underlying this transient response, we examined the effects of hypoosmotic challenge on the electrical activity of rat hypothalamic supraoptic nucleus (SON) vasopressin neurons using patch-clamp recordings. We found that 5 min exposure of hypothalamic slices to hypoosmotic solution transiently increased inhibitory postsynaptic current (IPSC) frequency and reduced the firing rate of vasopressin neurons. Recovery occurred by 10 min of exposure, even though the osmolality remained low. The γ-aminobutyric acid (GABA)A receptor blocker, gabazine, blocked the IPSCs and the hypoosmotic suppression of firing. The gliotoxin l-aminoadipic acid blocked the increase in IPSC frequency at 5 min and the recovery of firing at 10 min, indicating astrocytic involvement in hypoosmotic modulation of vasopressin neuronal activity. Moreover, β-alanine, an osmolyte of astrocytes and GABA transporter (GAT) inhibitor, blocked the increase in IPSC frequency at 5 min of hypoosmotic challenge. Confocal microscopy of immunostained SON sections revealed that astrocytes and magnocellular neurons both showed positive staining of vesicular GATs (VGAT). Hypoosmotic stimulation in vivo reduced the number of VGAT-expressing neurons, and increased co-localisation and molecular association of VGAT with glial fibrillary acidic protein that increased significantly by 10 min. By 30 min, neuronal VGAT labelling was partially restored, and astrocytic VGAT was relocated to the ventral portion while it decreased in the somatic zone of the SON. Thus, synergistic astrocytic and neuronal GABAergic inhibition could ensure that vasopressin neuron firing is only transiently suppressed under hypoosmotic conditions. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  13. Elevated nuclear sphingoid base-1-phosphates and decreased histone deacetylase activity after fumonisin B1 treatment in mouse embryonic fibroblasts

    Gardner, Nicole M., E-mail: nicolegardner@creighton.edu [Department of Pharmacology, Creighton University School of Medicine, Omaha, NE 68178 (United States); Riley, Ronald T.; Showker, Jency L.; Voss, Kenneth A. [USDA-ARS, Toxicology and Mycotoxin Research Unit, Athens, GA 30605 (United States); Sachs, Andrew J.; Maddox, Joyce R.; Gelineau-van Waes, Janee B. [Department of Pharmacology, Creighton University School of Medicine, Omaha, NE 68178 (United States)

    2016-05-01

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. Administration of FB1 to pregnant LM/Bc mice induces exencephaly in embryos, and ingestion of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs) in humans. FB1 inhibits ceramide synthase enzymes in sphingolipid biosynthesis, causing sphinganine (Sa) and bioactive sphinganine-1-phosphate (Sa1P) accumulation in blood, cells, and tissues. Sphingosine kinases (Sphk) phosphorylate Sa to form Sa1P. Upon activation, Sphk1 associates primarily with the plasma membrane, while Sphk2 is found predominantly in the nucleus. In cells over-expressing Sphk2, accumulation of Sa1P in the nuclear compartment inhibits histone deacetylase (HDAC) activity, causing increased acetylation of histone lysine residues. In this study, FB1 treatment in LM/Bc mouse embryonic fibroblasts (MEFs) resulted in significant accumulation of Sa1P in nuclear extracts relative to cytoplasmic extracts. Elevated nuclear Sa1P corresponded to decreased histone deacetylase (HDAC) activity and increased histone acetylation at H2BK12, H3K9, H3K18, and H3K23. Treatment of LM/Bc MEFs with a selective Sphk1 inhibitor, PF-543, or with ABC294640, a selective Sphk2 inhibitor, significantly reduced nuclear Sa1P accumulation after FB1, although Sa1P levels remained significantly increased relative to basal levels. Concurrent treatment with both PF-543 and ABC294640 prevented nuclear accumulation of Sa1P in response to FB1. Other HDAC inhibitors are known to cause NTDs, so these results suggest that FB1-induced disruption of sphingolipid metabolism leading to nuclear Sa1P accumulation, HDAC inhibition, and histone hyperacetylation is a potential mechanism for FB1-induced NTDs. - Highlights: • FB1 treatment results in accumulation of Sa1P primarily in the nucleus of MEFs. • FB1 treatment and elevated nuclear Sa1P are associated with HDAC inhibition. • Sphk2 inhibition alone

  14. Elevated nuclear sphingoid base-1-phosphates and decreased histone deacetylase activity after fumonisin B1 treatment in mouse embryonic fibroblasts

    Gardner, Nicole M.; Riley, Ronald T.; Showker, Jency L.; Voss, Kenneth A.; Sachs, Andrew J.; Maddox, Joyce R.; Gelineau-van Waes, Janee B.

    2016-01-01

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. Administration of FB1 to pregnant LM/Bc mice induces exencephaly in embryos, and ingestion of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs) in humans. FB1 inhibits ceramide synthase enzymes in sphingolipid biosynthesis, causing sphinganine (Sa) and bioactive sphinganine-1-phosphate (Sa1P) accumulation in blood, cells, and tissues. Sphingosine kinases (Sphk) phosphorylate Sa to form Sa1P. Upon activation, Sphk1 associates primarily with the plasma membrane, while Sphk2 is found predominantly in the nucleus. In cells over-expressing Sphk2, accumulation of Sa1P in the nuclear compartment inhibits histone deacetylase (HDAC) activity, causing increased acetylation of histone lysine residues. In this study, FB1 treatment in LM/Bc mouse embryonic fibroblasts (MEFs) resulted in significant accumulation of Sa1P in nuclear extracts relative to cytoplasmic extracts. Elevated nuclear Sa1P corresponded to decreased histone deacetylase (HDAC) activity and increased histone acetylation at H2BK12, H3K9, H3K18, and H3K23. Treatment of LM/Bc MEFs with a selective Sphk1 inhibitor, PF-543, or with ABC294640, a selective Sphk2 inhibitor, significantly reduced nuclear Sa1P accumulation after FB1, although Sa1P levels remained significantly increased relative to basal levels. Concurrent treatment with both PF-543 and ABC294640 prevented nuclear accumulation of Sa1P in response to FB1. Other HDAC inhibitors are known to cause NTDs, so these results suggest that FB1-induced disruption of sphingolipid metabolism leading to nuclear Sa1P accumulation, HDAC inhibition, and histone hyperacetylation is a potential mechanism for FB1-induced NTDs. - Highlights: • FB1 treatment results in accumulation of Sa1P primarily in the nucleus of MEFs. • FB1 treatment and elevated nuclear Sa1P are associated with HDAC inhibition. • Sphk2 inhibition alone

  15. Stoichiometry and kinetics of poly-{beta}-hydroxybutyrate metabolism in aerobic, slow growing, activated sludge cultures

    Beun, J.J.; Paletta, F.; Loosdrecht, M.C.M. Van; Heijnen, J.J.

    2000-02-20

    This paper discusses the poly-{beta}-hydroxybutyrate (PHB) metabolism in aerobic, slow growing, activated sludge cultures, based on experimental data and on a metabolic model. The dynamic conditions which occur in activated sludge processes were simulated in a 2-L sequencing batch reactor (SBR) by subjecting a mixed microbial population to successive periods of external substrate availability (feast period) and no external substrate availability (famine period). Under these conditions intracellular storage and consumption of PHB was observed. It appeared that in the feast period, 66% to almost 100% of the substrate consumed is used for storage of PHB, the remainder is used for growth and maintenance processes. Furthermore, it appeared that at high sludge retention time (SRT) the growth rate in the feast and famine periods was the same. With decreasing SRT the growth rate in the feast period increased relative to the growth rate in the famine period. Acetate consumption and PHB production in the feast period both proceeded with a zero-order rate in acetate and PHB concentration respectively. PHB consumption in the famine period could best be described kinetically with a nth order degradation equation in PHB concentration. The obtained results are discussed in the context of the general activated sludge models.

  16. Basal metabolic regulatory responses and rhythmic activity of ...

    ... Rattus sp. Low concentrations of kola nut extract stimulated the heart by increasing rate and force of contraction as well as metabolic rate. Higher concentrations reduced rate and amplitude of beat resulting, at still higher concentrations in heart failure. Keywords: Kolanut, extract, basal metabolic rate, mammalian heart ...

  17. Atorvastatin dose-dependently decreases hepatic lipase activity in type 2 diabetes: effect of sex and the LIPC promoter variant

    I.I.L. Berk-Planken (Ingrid); N. Hoogerbrugge (Nicoline); R.P. Stolk (Ronald); A.H. Bootsma (Aart); H. Jansen (Hans)

    2003-01-01

    textabstractOBJECTIVE: Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and may contribute to the atherogenic lipid profile in type 2 diabetes. Little is known about the effect of cholesterol synthesis inhibitors on HL activity in relation to sex and the

  18. Decreased torque and electromyographic activity in the extensor thigh muscles in chondromalacia patellae.

    Väätäinen, U; Airaksinen, O; Jaroma, H; Kiviranta, I

    1995-01-01

    The alterations in thigh muscle properties of chondromalacia patellae patients during isometric and dynamic endurance tests were studied using a variokinetic knee testing system linked to surface EMG. A total of 41 patients (chondromalacia group) with arthroscopically certified chondromalacia of the patella were studied. The control group consisted of 31 healthy adult volunteers with no history of knee pain or trauma. Peak torque values were 21% (p chondromalacia group than in the control group. The decrease in the ratio between integrated EMG (IEMG) and measured force were found in all parts of the quadriceps femoris muscle in patients with chondromalacia of the patella in isometric extension. No change in the normalized IEMG levels of the thigh muscles were found between chondromalacia patients and controls in dynamic endurance test. The severity of the chondromalacia of the patella did not affect the level of electromyographic activation in thigh muscles. The ratio of normalized EMG levels of vastus medialis and vastus lateralis did not differ between the groups. The present study showed that chondromalacia patellae patients have reduced force and electromyographic activation levels of quadriceps femoris muscle. Especially, the explosive strength of the quadriceps femoris muscle is reduced.

  19. Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

    Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

    2017-07-01

    Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition.

    Yamazaki, Hiroki; Lai, Yu-Chang; Tateno, Morihiro; Setoguchi, Asuka; Goto-Koshino, Yuko; Endo, Yasuyuki; Nakaichi, Munekazu; Tsujimoto, Hajime; Miura, Naoki

    2017-01-01

    We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.

  1. Abnormal metabolic network activity in REM sleep behavior disorder.

    Holtbernd, Florian; Gagnon, Jean-François; Postuma, Ron B; Ma, Yilong; Tang, Chris C; Feigin, Andrew; Dhawan, Vijay; Vendette, Mélanie; Soucy, Jean-Paul; Eidelberg, David; Montplaisir, Jacques

    2014-02-18

    To determine whether the Parkinson disease-related covariance pattern (PDRP) expression is abnormally increased in idiopathic REM sleep behavior disorder (RBD) and whether increased baseline activity is associated with greater individual risk of subsequent phenoconversion. For this cohort study, we recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects with RBD (63.5 ± 9.4 years old) and 10 healthy volunteers (62.7 ± 8.6 years old) who underwent resting-state metabolic brain imaging with (18)F-fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 ± 4.8 years old) and 17 healthy volunteers (66.6 ± 6.0 years old) who underwent resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter group was followed clinically for 4.6 ± 2.5 years by investigators blinded to the imaging results. PDRP expression was measured in both RBD groups and compared with corresponding control values. PDRP expression was elevated in both groups of subjects with RBD (cohort 1: p abnormalities in subjects with idiopathic RBD are associated with a greater likelihood of subsequent phenoconversion to a progressive neurodegenerative syndrome.

  2. Adenocarcinomas of the esophagus: Response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT

    Roedl, Johannes B.; Colen, Rivka R.; Holalkere, Nagaraj S.; Fischman, Alan J.; Choi, Noah C.; Blake, Michael A.

    2008-01-01

    Purpose: We determined whether evaluation of treatment response is feasible by measuring metabolic tumor volume parameters on 18F-FDG (Fluorodeoxyglucose) PET-CT (Positron emission tomography-Computed tomography). We compared the response evaluation based on metabolic tumor volume parameters to a histopathologic and clinical response evaluation (clinical response criteria: RECIST criteria = Response evaluation criteria in solid tumors, and WHO criteria = World health organization). Patients and methods: A total of 51 study subjects with adenocarcinomas (Type I due to Siewert classification) of the esophagus underwent PET-CT scans before and after neoadjuvant chemoradiotherapy. Tumor volume, maximum and mean standardized uptake values (SUV) were assessed before and after chemoradiotherapy. Furthermore, the total lesion glycolysis (TLG) was calculated by multiplying the tumor volume by the mean SUV of the volume. Clinical response evaluation was performed with endoscopic ultrasound and CT using RECIST and WHO criteria. The reference standard for treatment response was the postsurgical histopathology. Results: The decrease of tumor volume between the pre- and post-treatment PET-CT scans was a better predictor of histopathologic response and survival than the decrease of the SUV and of the clinical response evaluation based on RECIST and WHO criteria. The highest accuracy, however, was achieved when using the TLG for the identification of treatment responders. A decrease of the TLG by >78% between pre- and post-therapy scans predicted histopathologic response with a sensitivity and specificity of 91% and 93%, respectively. Conclusions: Tumor volume and TLG can be used to assess treatment response and survival in patients with esophageal adenocarcinoma

  3. Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0 Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in Dolphins.

    Stephanie K Venn-Watson

    Full Text Available Similar to humans, bottlenose dolphins (Tursiops truncatus can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A and lower (n = 19, Group B mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P < 0.0001 and their dietary fish. In addition to higher insulin, triglycerides, and ferritin, Group A had lower percent serum heptadecanoic acid (C17:0 compared to Group B (0.3 ± 0.1 and 1.3 ± 0.4%, respectively; P < 0.0001. Using multivariate stepwise regression, higher percent serum C17:0, a saturated fat found in dairy fat, rye, and some fish, was an independent predictor of lower insulin in dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B's diet, had C17:0 (41 and 67 mg/100g, respectively. When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg, C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g; nonfat dairy products had no detectable C17:0. We hypothesize that humans' movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome.

  4. Metabolic activity of Glomus intraradices in Arum- and Paris-type arbuscular mycorrhizal colonization

    van Aarle, IM; Cavagnaro, TR; Smith, SE; Dickson, S

    Colonization of two plant species by Glomus intraradices was studied to investigate the two morphological types (Arum and Paris), their symbiotic interfaces and metabolic activities. Root pieces and sections were stained to observe the colonization and metabolic activity of all mycorrhizal

  5. Brain energy metabolism is activated after acute and chronic administration of fenproporex in young rats.

    Rezin, Gislaine T; Jeremias, Isabela C; Ferreira, Gabriela K; Cardoso, Mariane R; Morais, Meline O S; Gomes, Lara M; Martinello, Otaviana B; Valvassori, Samira S; Quevedo, João; Streck, Emilio L

    2011-12-01

    Obesity is a chronic disease of multiple etiologies, including genetic, metabolic, environmental, social, and other factors. Pharmaceutical strategies in the treatment of obesity include drugs that regulate food intake, thermo genesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine. Studies suggest that amphetamine induces neurotoxicity through generation of free radicals and mitochondrial apoptotic pathway by cytochrome c release, accompanied by a decrease of mitochondrial membrane potential. Mitochondria are intracellular organelles that play a crucial role in ATP production. Thus, in the present study we evaluated the activities of some enzymes of Krebs cycle, mitochondrial respiratory chain complexes and creatine kinase in the brain of young rats submitted to acute and chronic administration of fenproporex. In the acute administration, the animals received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or tween. In the chronic administration, the animals received a single injection daily for 14 days of fenproporex (6.25, 12.5 or 25 mg/Kg i.p.). Two hours after the last injection, the rats were sacrificed by decapitation and the brain was removed for evaluation of biochemical parameters. Our results showed that the activities of citrate synthase, malate dehydrogenase and succinate dehydrogenase were increased by acute and chronic administration of fenproporex. Complexes I, II, II-III and IV and creatine kinase activities were also increased after acute and chronic administration of the drug. Our results are consistent with others reports that showed that some psychostimulant drugs increased brain energy metabolism in young rats. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  6. Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

    Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu

    2016-01-01

    Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation. PMID:27575945

  7. Ruptured human Achilles tendon has elevated metabolic activity up to 1 year after repair

    Eliasson, Pernilla; Couppé, Christian; Lonsdale, Markus

    2016-01-01

    PURPOSE: Following Achilles tendon rupture, running is often allowed after 6 months. However, tendon healing is slow and the metabolic status of the tendon at this point is unknown. The purpose of this study was to investigate tendon metabolism (glucose uptake) and vascularization at 3, 6 and 12...... demonstrate that the healing process as determined by metabolic activity and vascularization continues for 6 months after injury when large loads are typically allowed on the tendon. Indeed, metabolic activity remained elevated for more than 1 year after injury despite normalized vascularization. The robust...... negative correlation between tendon metabolism and patient-reported outcome suggests that a high metabolic activity 6 months after the injury may be related to a poor clinical healing outcome....

  8. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors.

    Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G

    2016-06-01

    Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

  9. A pilot of a video game (DDR) to promote physical activity and decrease sedentary screen time.

    Maloney, Ann E; Bethea, T Carter; Kelsey, Kristine S; Marks, Julie T; Paez, Sadye; Rosenberg, Angela M; Catellier, Diane J; Hamer, Robert M; Sikich, Linmarie

    2008-09-01

    We examined the feasibility of Dance Dance Revolution (DDR), a dance video game, in participants' homes, to increase physical activity (PA) and to decrease sedentary screen time (SST). Sixty children (7.5 +/- 0.5 years) were randomized in a 2:1 ratio to DDR or to wait-list control (10-week delay). DDR use was logged, PA was measured objectively by accelerometry. SST was self-reported at weeks 0 and 10. At week 28, after both groups had access to DDR, accelerometry and SST were repeated. Mean use of DDR was 89 +/- 82 (range 0-660 min) min per week (mpw). The DDR group showed increased vigorous PA and a reduction in light PA; the control group showed no increase in moderate and/or vigorous PA (MVPA) although they also had a reduction in light PA. Differences between the groups were not observed. The DDR group also reported a decrease in SST of -1.2 +/- 3.7 h per week (hpw) (P increase of +3.0 +/- 7.7 hpw (nonsignificant). The difference in SST between the groups was significant, with less SST in the DDR group. Between weeks 10 and 28, numeric reductions in SST were reported in both groups. In the DDR group, SST at week 28 (8.8 +/- 6.0 hpw) was lower than baseline (10.5 +/- 5.5 hpw; P increases in vigorous PA. Further study is needed to better characterize children and contexts in which DDR may promote a healthy lifestyle.

  10. Distribution of Metabolically Active Prokaryotes (Archaea and Bacteria) throughout the Profiles of Chernozem and Brown Semidesert Soil

    Semenov, M. V.; Manucharova, N. A.; Stepanov, A. L.

    2016-02-01

    The distribution of metabolically active cells of archaea and bacteria in the profiles of typical chernozems (Voronezh oblast) and brown semidesert soils (Astrakhan oblast) of natural and agricultural ecosystems was studied using the method of fluorescent in situ hybridization (FISH). The studied soils differed sharply in the microbial biomass and in the numbers of metabolically active cells of archaea and bacteria. The number of active bacterial cells was 3.5-7.0 times greater than that of archaea. In the arable chernozem, the numbers of active cells of archaea and bacteria were 2.6 and 1.5 times, respectively, lower than those in the chernozem under the shelterbelt. The agricultural use of the brown semidesert soil had little effect on the abundances of bacteria and archaea. The soil organic carbon content was the major factor controlling the numbers of metabolically active cells of both domains. However, the dependence of the abundance of bacteria on the organic matter content was more pronounced. The decrease in the organic carbon and total nitrogen contents down the soil profiles was accompanied by the decrease in the bacteria: archaea ratio attesting to a better adaptation of archaea to the permanent deficiency of carbon and nitrogen. The bacteria: archaea ratio can serve as an ecotrophic indicator of the state of soil microbial communities.

  11. C75, a fatty acid synthase inhibitor, modulates AMP-activated protein kinase to alter neuronal energy metabolism.

    Landree, Leslie E; Hanlon, Andrea L; Strong, David W; Rumbaugh, Gavin; Miller, Ian M; Thupari, Jagan N; Connolly, Erin C; Huganir, Richard L; Richardson, Christine; Witters, Lee A; Kuhajda, Francis P; Ronnett, Gabriele V

    2004-01-30

    C75, a synthetic inhibitor of fatty acid synthase (FAS), is hypothesized to alter the metabolism of neurons in the hypothalamus that regulate feeding behavior to contribute to the decreased food intake and profound weight loss seen with C75 treatment. In the present study, we characterize the suitability of primary cultures of cortical neurons for studies designed to investigate the consequences of C75 treatment and the alteration of fatty acid metabolism in neurons. We demonstrate that in primary cortical neurons, C75 inhibits FAS activity and stimulates carnitine palmitoyltransferase-1 (CPT-1), consistent with its effects in peripheral tissues. C75 alters neuronal ATP levels and AMP-activated protein kinase (AMPK) activity. Neuronal ATP levels are affected in a biphasic manner with C75 treatment, decreasing initially, followed by a prolonged increase above control levels. Cerulenin, a FAS inhibitor, causes a similar biphasic change in ATP levels, although levels do not exceed control. C75 and cerulenin modulate AMPK phosphorylation and activity. TOFA, an inhibitor of acetyl-CoA carboxylase, increases ATP levels, but does not affect AMPK activity. Several downstream pathways are affected by C75 treatment, including glucose metabolism and acetyl-CoA carboxylase (ACC) phosphorylation. These data demonstrate that C75 modulates the levels of energy intermediates, thus, affecting the energy sensor AMPK. Similar effects in hypothalamic neurons could form the basis for the effects of C75 on feeding behavior.

  12. Caloric restriction counteracts age-related changes in the activities of sorbitol metabolizing enzymes from mouse liver

    Hagopian, Kevork; Ramsey, Jon J.; Weindruch, Richard

    2009-01-01

    The influence of caloric restriction (CR) on hepatic sorbitol-metabolizing enzyme activities was investigated in young and old mice. Aldose reductase and sorbitol dehydrogenase activities were significantly lower in old CR mice than in old controls. Young CR mice showed decreased aldose reductase activity and a trend towards decreased sorbitol dehydrogenase when compared to controls. Metabolites of the pathway, namely sorbitol, glucose and fructose were decreased by CR in young and old mice. Pyruvate levels were decreased by CR in both young and old mice, while lactate decreased only in old CR. Malate levels increased in old CR but remained unchanged in young CR, when compared with controls. Accordingly, the lactae/pyruvate and malate/pyruvate ratios in young and old CR mice were increased, indicating increased NADH/NAD and NADPH/NADP redox couples, respectively. The results indicate that decreased glucose levels under CR conditions lead to decreased sorbitol pathway enzyme activities and metabolite levels, and could contribute to the beneficial effects of long-term CR through decreased sorbitol levels and NADPH sparing. PMID:18953666

  13. Perinatal exposure to BDE-99 causes decreased protein levels of cyclin D1 via GSK3β activation and increased ROS production in rat pup livers.

    Blanco, Jordi; Mulero, Miquel; Domingo, Jose L; Sanchez, Domènec J

    2014-02-01

    We here examined the potential liver toxicity in rat pups from dams exposed during the gestational and lactation periods to 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Dams were exposed to 0, 1, and 2mg/kg/day of BDE-99 from gestation day 6 to postnatal day 21. When the pups were weaning, the liver from 1 pup of each litter was excised to evaluate oxidative stress markers and the messenger RNA (mRNA) expression of multiple cytochrome P450 (CYP) isoforms. To determine whether thyroid hormone (TH) was disrupted, the protein and mRNA expressions of several TH receptor (TR) isoforms, as well as the protein levels of cyclin D1 and the phosphorylated protein kinases Akt and glycogen synthase kinase 3 beta (GSK3β), were evaluated. Perinatal exposure to BDE-99 produced decreased levels of cyclin D1 in rat pup livers. A decrease in the active form of Akt and an increase in the active form of GSK3β were observed. The decreased Akt pathway may be due to a potential disruption of the nongenomic actions of TH by BDE-99 and its metabolites. This possible TH disruption was noted as a decrease in TR isoforms expression. By contrast, we observed an upregulation of CYP2B1 gene expression, which is correlated with an increase in reactive oxygen species production. This outcome indicates activation of the nuclear constitutive androstane receptor, which could induce the expression of other enzymes capable of metabolizing TH. The present findings support the hypothesis that perinatal exposure to PBDEs, at levels found in humans, may have serious implications for metabolic processes in rat pup livers.

  14. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

    Lena Willkomm

    Full Text Available Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs. Lactate (La-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3 known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD vs. high intensity RE (HIT. Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  15. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

    Willkomm, Lena; Gehlert, Sebastian; Jacko, Daniel; Schiffer, Thorsten; Bloch, Wilhelm

    2017-01-01

    Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs). Lactate (La)-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK) which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3) known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM) and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC) leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE) associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD) vs. high intensity RE (HIT). Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  16. Construction of Escherichia coli Mutant with Decreased Endotoxic Activity by Modifying Lipid A Structure

    Qiong Liu

    2015-05-01

    Full Text Available Escherichia coli BL21 (DE3 and its derivatives are widely used for the production of recombinant proteins, but these purified proteins are always contaminated with lipopolysaccharide (LPS. LPS is recognized by the toll-like receptor 4 and myeloid differentiation factor 2 complex of mammalian immune cells and leads to release of pro-inflammatory cytokines. It is a vital step to remove LPS from the proteins before use for therapeutic purpose. In this study, we constructed BL21 (DE3 ∆msbB28 ∆pagP38 mutant, which produces a penta-acylated LPS with reduced endotoxicity. The plasmids harboring pagL and/or lpxE were then introduced into this mutant to further modify the LPS. The new strain (S004 carrying plasmid pQK004 (pagL and lpxE produced mono-phosphoryated tetra-acylated lipid A, which induces markedly less production of tumor necrosis factor-α in the RAW264.7 and IL-12 in the THP1, but still retains ability to produce recombinant proteins. This study provides a strategy to decrease endotoxic activity of recombinant proteins purified from E. coli BL21 backgrounds and a feasible approach to modify lipid A structure for alternative purposes such as mono-phosphoryl lipid A (MPL as vaccine adjuvants.

  17. Decreases in daily physical activity predict acute decline in attention and executive function in heart failure.

    Alosco, Michael L; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H; Hayes, Scott M; Josephson, Richard; Hughes, Joel; Gunstad, John

    2015-04-01

    Reduced physical activity (PA) may be one factor that contributes to cognitive decline and dementia in heart failure (HF). Yet, the longitudinal relationship between PA and cognition in HF is poorly understood owing to limitations of past work, including single-time assessments of PA. This is the first study to examine changes in objectively measured PA and cognition over time in HF. At baseline and 12 weeks, 57 HF patients completed psychosocial self-report measures and a neuropsychological battery and wore an accelerometer for 7 days. At baseline, HF patients spent an average of 597.83 (SD 75.91) minutes per day sedentary. Steps per day declined from baseline to the 12-week follow-up; there was also a trend for declines in moderate-vigorous PA. Regression analyses controlling for sex, HF severity, and depressive symptoms showed that decreases in light (P = .08) and moderate-vigorous (P = .04) daily PA emerged as strong predictors of declines in attention/executive function over the 12-week period, but not of memory or language. Reductions in daily PA predicted acute decline in attention/executive function in HF, but not of memory or language. Modifications to daily PA may attenuate cognitive decline, and prospective studies are needed to test this possibility. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue

    Wu, Lingyan; Zhang, Lina; Li, Bohan; Jiang, Haowen; Duan, Yanan; Xie, Zhifu; Shuai, Lin; Li, Jia; Li, Jingya

    2018-01-01

    Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic “brown-like” cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK α1/α2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a β3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPKα induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively

  19. Relation between presence-absence of a visible nucleoid and metabolic activity in bacterioplankton cells

    Choi, Joon, W.; Sherr, E.B.; Sherr, B.F. [Oregon State Univ., Corvallis, OR (United States)

    1996-09-01

    We investigated the report of Zweifel and Hagstroem that only a portion of marine bacteria contain nucleoids--the DNA-containing regions of procaryotic cells-- and that such bacteria correspond to the active or viable fraction of bacterioplankton. In Oregon coastal waters, 21-64% of bacteria had visible nucleoids; number of nucleoid-visible (NV) bacteria were greater than numbers of metabolically active bacteria, based on cells with active electron transport systems (ETS) and intact cell membranes. During log growth of a marine isolate, proportions of NV and ETS-active cells approached 100%. In stationary growth phase, the fraction of ETS-active cells decreased rapidly, while that of NV cells remained high for 7 d. When starved cells of the isolate were resupplied with nutrient (50 mg liter{sup -1} peptone), total cell number did not increase during the initial 6 h, but the proportion of NV cells increased from 27 to 100%, and that of ETS-active cells from 6 to 75%. In an analogous experiment with a bacterioplankton assemblage, a similar trend was observed: the number of NV cells double during the initial 6 h prior to an increase in total cell counts. These results show that some bacteria without visible nucleoids are capable of becoming NV cells, and thus have DNa in a nucleoid region not detectable with the method used here. 18 refs., 4 figs., 1 tab.

  20. Metabolic and hemodynamic activation of postischemic rat brain by cortical spreading depression.

    Kocher, M

    1990-07-01

    Following transient ischemia of the brain, the coupling between somatosensory activation and the hemodynamic-metabolic response is abolished for a certain period despite the partial recovery of somatosensory evoked responses. To determine whether this disturbance is due to alterations of the stimulus-induced neuronal excitation or to a breakdown of the coupling mechanisms, cortical spreading depression was used as a metabolic stimulus in rats before and after ischemia. Adult rats were subjected to 30 min of global forebrain ischemia and 3-6 h of recirculation. EEG, cortical direct current (DC) potential, and laser-Doppler flow were continuously recorded. Local CBF (LCBF), local CMRglc (LCMRglc), regional tissue contents of ATP, glucose, and lactate, and regional pH were determined by quantitative autoradiography, substrate-induced bioluminescence, and fluorometry. Amplitude and frequency of the DC shifts did not differ between groups. In control animals, spreading depression induced a 77% rise in cortical glucose consumption, a 66% rise in lactate content, and a drop in tissue pH of 0.3 unit. ATP and glucose contents were not depleted. During the passage of DC shifts, transient increases (less than 2 min) in laser-Doppler flow were observed, followed by a post-spreading depression hypoperfusion. A comparable although less expressed pattern of hemodynamic and metabolic changes was observed in the postischemic rats. Although baseline LCMRglc was depressed after ischemia, it was activated 47% during spreading depression. Lactate increased by 26%, pH decreased by 0.3 unit, and ATP and glucose remained unchanged. The extent of the transient increase in laser-Doppler flow did not differ from that of the control group, and a post-spreading depression hypoperfusion was also found.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Effects of ozone on adult and aged lung oxygen consumption, glucose metabolism and G6PDH activity

    Raska-Emery, P.; Balis, J.U.; Montgomery, M.R.

    1991-01-01

    Fischer-344 male adult (4-6 mo) and aged (24-26 mo) rats were exposed to 0-3.0 ppm O 3 for 8h, sacrificed immediately, and O 2 consumption, 1 C 14 -glucose metabolism and G6PDH activity were determined. For O 2 consumption, the exp to 0.5 ppm O 3 produced a stimulation in both age groups. Decrements in O 2 consumption were only evident in aged rats after 1.5 and 3.0 ppm. Glucose metabolism showed a marked difference rats were 40% adult rats. Control values in aged rats were 40% of adults. Exp to 0.5 ppm was stimulatory in adults and aged, while 1.5 and 3.0 pp, decreased glucose metabolism in both groups. No age-related difference in G6PDH activity between control and exposed was seen. However, in both age groups, 0.5 ppm O 3 resulted in a significant increase in activity (33-41%)l 1.5 and 3.0 ppm were without effect. The combined results show a biphasic response of adult and aged lung to severe, acute O 3 exp. One-half ppm O 3 for 8h is stimulatory for all three parameters examined in both age groups. Three ppm O 3 inhibits O 2 consumption and glucose metabolism in both age groups but is ineffective on G6PDH activity

  2. Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

    Adhikari, Mohit H; Hacker, Carl D; Siegel, Josh S; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo; Corbetta, Maurizio

    2017-04-01

    While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to

  3. Decrease of physical activity level in adolescents with limb fractures: an accelerometry-based activity monitor study

    Delhumeau Cécile

    2011-05-01

    Full Text Available Abstract Background Immobilization and associated periods of inactivity can cause osteopenia, the physiological response of the bone to disuse. Mechanical loading plays an essential role in maintaining bone integrity. Skeletal fractures represent one cause of reduction of the physical activity (PA level in adolescents. The purpose of this study was to quantify the reduction of PA in adolescents with limb fractures during the cast immobilization period compared with healthy controls. Methods Two hundred twenty adolescents were divided into three groups: those with upper limb fractures (50 cases; lower limb fractures (50 cases; and healthy cases (120 cases. Patients and their healthy peers were matched for gender, age, and seasonal assessment of PA. PA level was assessed during cast immobilization by accelerometer. Time spent in PA in each of the different intensity levels - sedentary, light, moderate, and vigorous - was determined for each participant and expressed in minutes and as a percentage of total valid time. Results Reduction in PA during cast immobilization was statistically significant in patients with limb fractures compared to healthy controls. The total PA count (total number of counts/min was significantly lower in those with upper and lower limb fractures (-30.1% and -62.4%, respectively compared with healthy controls (p p = 0.0003 and 76.6% (p p = 0.0008 and 84.4% (p Conclusions PA measured by accelerometer is a useful and valid tool to assess the decrease of PA level in adolescents with limb fractures. As cast immobilization and reduced PA are known to induce bone mineral loss, this study provides important information to quantify the decrease of skeletal loading in this patient population. The observed reduction of high intensity skeletal loading due to the decrease in vigorous PA may explain osteopenia due to disuse, and these data should be kept in mind by trauma practitioners to avoid any unnecessary prolongation of the cast

  4. Leisure-time exercise, physical activity during work and commuting, and risk of metabolic syndrome.

    Kuwahara, Keisuke; Honda, Toru; Nakagawa, Tohru; Yamamoto, Shuichiro; Akter, Shamima; Hayashi, Takeshi; Mizoue, Tetsuya

    2016-09-01

    Data are limited regarding effect of intensity of leisure-time physical activity on metabolic syndrome. Furthermore, no prospective data are available regarding effect of occupational and commuting physical activity on metabolic syndrome. We compared metabolic syndrome risk by intensity level of leisure-time exercise and by occupational and commuting physical activity in Japanese workers. We followed 22,383 participants, aged 30-64 years, without metabolic syndrome until 2014 March (maximum, 5 years of follow-up). Physical activity was self-reported. Metabolic syndrome was defined by the Joint Statement criteria. We used Cox regression models to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of metabolic syndrome. During a mean follow-up of 4.1 years, 5361 workers developed metabolic syndrome. After adjustment for covariates, compared with engaging in no exercise, the HRs (95 % CIs) for metabolic equivalent hours of exercise per week were 0.99 (0.90, 1.08), 0.99 (0.90, 1.10), and 0.95 (0.83, 1.08), respectively, among individuals engaging in moderate-intensity exercise alone; 0.93 (0.75, 1.14), 0.81 (0.64, 1.02), and 0.84 (0.66, 1.06), among individuals engaging in vigorous-intensity exercise alone; and 0.90 (0.70, 1.17), 0.74 (0.62, 0.89), and 0.81 (0.69, 0.96) among individuals engaging in the two intensities. Higher occupational physical activity was weakly but significantly associated with lower risk of metabolic syndrome. Walking to and from work was not associated with metabolic syndrome. Vigorous-intensity exercise alone or vigorous-intensity combined with moderate-intensity exercise and worksite intervention for physical activity may help prevent metabolic syndrome for Japanese workers.

  5. Thermal effects on metabolic activities of thermophilic microorganisms from the thermal discharge point of Tuticorin thermal power plant area

    Muthukkannan, N.; Murugesan, A.G.

    2002-01-01

    Metabolic activities of thermophilic microorganisms isolated from the thermal water discharge point at Tuticorin thermal power station were studied by growing the microorganisms in sterile medium and at various temperature regimes of 25, 35, 45, 55 and 65degC. The optimum temperature for the growth of the bacterium isolated from the thermal power plant station was 45 degC and beyond 65 degC the growth was gradually decreased. The bacteria isolated from open sea water were mesophiles with their growth optimum at 35 degC and microbes inhabiting the thermal discharge area were thermopiles as they were tolerant even at 55 degC. The amylase production, carbohydrate metabolism and lactose fermentation activities were optimum at 45 degC. At 25 degC and beyond 65 degC biochemical activities of the organisms were inhibited to a greater extent. (author)

  6. Type 2 Diabetic Patients with Ischemic Stroke: Decreased Insulin Sensitivity and Decreases in Antioxidant Enzyme Activity Are Related to Different Stroke Subtypes

    Aleksandra Jotic

    2013-01-01

    C (1.14±0.58, 1.00±0.26 versus 3.14±0.62 min−1/mU/l × 104, P<0.001 and in nondiabetics in D and E versus F (3.38±0.77, 3.03±0.72 versus 6.03±1.69 min−1/mU/l × 104, P<0.001. Also, GSH-Px and GR activities were lower in A and B versus C (GSH-Px: 21.96±3.56,  22.51±1.23 versus 25.12±1.67; GR: 44.37±3.58,  43.50±2.39 versus 48.58±3.67 U/gHb; P<0.001 and in D and E versus F (GSH-Px: 24.75±3.02,  25.57±1.92 versus 28.56±3.91; GR: 48.27±6.81,  49.17±6.24 versus 53.67±3.96 U/gHb; P<0.001. Decreases in Si and GR were significantly related to both ATI and LI in T2D. Our results showed that decreased IS and impaired antioxidant enzymes activity influence ischemic stroke subtypes in T2D. The influence of insulin resistance might be exerted on the level of glutathione-dependent antioxidant enzymes.

  7. Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS

    Glintborg, Dorte; Altinok, Magda Lambaa; Ravn, Pernille

    2018-01-01

    BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. METHODS......: Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n = 21) or placebo (n = 21). Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test...... (OGTT) and filled in questionnaires regarding mental health and health-related quality of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI), Short Form 36 (SF-36) and PCOS questionnaire. RESULTS: Included women were aged 31 (6) years (mean (s.d.)) and had body mass index (BMI...

  8. An in vitro model for screening estrogen activity of environmental samples after metabolism

    Chahbane, N.; Schramm, K.W. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Oekologische Chemie; Kettrup, A. [Technische Univ. Muenchen, Freising (Germany). Lehrstuhl fuer Oekologische Chemie

    2004-09-15

    For a few years, yeast estrogen assay (YES) was accepted as a reliable and economic model for screening of environmental estrogens. Though the chemicals directly act with estrogen receptor (ER) can be filtered out by this model, there are still chemicals act with ER only after metabolism and some chemicals eliminate their estrogen activities after metabolism. That is to say, their metabolites exert or have stronger estrogen activities than themselves, which can be called bio-activation. In this case, for the lack of the metabolism enzyme system as human and other animals, only the assay with recombinant yeast cells is insufficient. So, it is necessary to combine the YES with metabolism procedure to evaluate the estrogen activities of these chemicals. The most common method used currently for in vitro metabolic activation in mutagenicity testing and also be applied to the estrogen screening field is S-9 mixture. Also, there is an attempt to develop a chemical model for cytochrome P450 as a bio-mimetic metabolic activation system. All these methods can be used as in vitro models for metabolism. Compare with these models, using whole H4II E cells for metabolism is an alternative and with superiorities. It has the excellence of short experiment period as all other in vitro models, but is much more close to the real surroundings as in vivo. Furthermore, the activity of 7-ethoxyresorufin-O-deethylase (EROD) can be easily measured during the whole incubation period for us to discuss the metabolic activities in a quantitative foundation, not only in qualitative. Methoxychlor is one of the chemicals with bio-activation ability. When directly used in the YES, it shows weak estrogen activity. But a main metabolite of methoxychlor, 2,2-bis (p-hydroxyphenyl) - 1,1,1-trichloroethane (HPTE) is a known estrogen mimic. For the long time using methoxychlor as a pesticide and its clear background, it is an ideal chemical to establish this in vitro system.

  9. [Effects of waterlogging on the growth and energy-metabolic enzyme activities of different tree species].

    Wang, Gui-Bin; Cao, Fu-Liang; Zhang, Xiao-Yan; Zhang, Wang-Xiang

    2010-03-01

    Aimed to understand the waterlogging tolerance and adaptation mechanisms of different tree species, a simulated field experiment was conducted to study the growth and energy-metabolic enzyme activities of one-year-old seedlings of Taxodium distichum, Carya illinoensis, and Sapium sebiferum. Three treatments were installed, i. e., CK, waterlogging, and flooding, with the treatment duration being 60 days. Under waterlogging and flooding, the relative growth of test tree species was in the order of T. distichum > C. illinoensis > S. sebiferum, indicating that T. distichum had the strongest tolerance against waterlogging and flooding, while S. sebiferum had the weakest one. Also under waterlogging and flooding, the root/crown ratio of the three tree species increased significantly, suggesting that more photosynthates were allocated in roots, and the lactate dehydrogenase (LDH) and alcohol dehydrogenase (ADH) activities of the tree species also had a significant increase. Among the test tree species, T. distichum had the lowest increment of LDH and ADH activities under waterlogging and flooding, but the increment could maintain at a higher level in the treatment duration, while for C. illinoensis and S. sebiferum, the increment was larger during the initial and medium period, but declined rapidly during the later period of treatment. The malate dehydrogenase (MDH), phosphohexose (HPI), and glucose-6-phosphate dehydrogenase (G6PDH) -6-phosphogluconate dehydrogenase (6PGDH) activities of the tree species under waterlogging and flooding had a significant decrease, and the decrement was the largest for T. distichum, being 35.6% for MDH, 21.0% for HPI, and 22.7% for G6PDH - 6PGDH under flooding. It was suggested that under waterlogging and flooding, the tree species with strong waterlogging tolerance had a higher ability to maintain energy-metabolic balance, and thus, its growth could be maintained at a certain level.

  10. Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

    Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

    2017-11-01

    Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  11. Hydrogeochemical surveillance of La Soufriere de Guadeloupe volcano (F. W. I. ), 1979-1985: activity decrease or confining

    Bigot, S.; Hammouya, G.

    1987-04-07

    Since the 1975-1977 crisis, changes in physico-chemical characters of La Soufriere's hot springs are observed. These variations have dual origin: - decrease in exchanges between volatile compounds from deep origin and phreatic waters, because of fissures filling by hydrothermal deposits in the whole dome that involves progresive confining: - decrease of volcanic activity.

  12. Dietary patterns as compared with physical activity in relation to metabolic syndrome among Chinese adults

    He, Y.; Li, Y.; Lai, J.; Wang, D.; Zhang, J.; Fu, P.; Yang, X.; Qi, L.

    2013-01-01

    Aims: To examine the nationally-representative dietary patterns and their joint effects with physical activity on the likelihood of metabolic syndrome (MS) among 20,827 Chinese adults. Methods and results: CNNHS was a nationally representative cross-sectional observational study. Metabolic syndrome

  13. Effects of Cola-Flavored Beverages and Caffeine on Streptococcus mutans Biofilm Formation and Metabolic Activity.

    Dotsey, Roger P; Moser, Elizabeth A S; Eckert, George J; Gregory, Richard L

    To examine the effects of cola-flavored beverages and caffeine on growth and metabolism of Streptococcus mutans biofilm. This study was designed to determine if carbonated beverages or caffeine can increase S. mutans growth and biofilm formation and metabolic activity in vitro, potentially leading to increased S. mutans-associated cariogenicity in children that consume them. Six different cola-flavored products, plus pure caffeine, and pure high fructose corn syrup (HFCS), at different concentrations similar to those in the beverages were tested. A 16-hour culture of S. mutans was treated with different dilutions in bacteriological media. To test for the effect on biofilm formation, the biofilm was stained with crystal violet. The absorbance was determined to evaluate biofilm growth. Biofilm metabolic activity was measured based on biofilm having the ability to reduce XTT to a water-soluble orange compound. The inclusion of HFCS in the beverages, as well as pure HFCS, significantly enhanced bacterial biofilm formation and metabolic activity. Pure caffeine and the presence of caffeine in beverages did not significantly increase biofilm formation, but pure caffeine significantly increased metabolism, and Diet Coke had significantly greater metabolic activity than Caffeine-Free Diet Coke. HFCS increases both the biofilm formation and metabolism of S. mutans, and caffeine in some cases increases metabolism of S. mutans.

  14. Physical activity and sedentary behavior in metabolically healthy obese young women

    Studies of physical activity (PA) and sedentary behavior (SB) in metabolically healthy obese (MHO) have been limited to postmenopausal white women. We sought to determine whether PA and SB differ between MHO and metabolically abnormal obese (MAO), in young black and white women....

  15. Natural AMPK Activators: An Alternative Approach for the Treatment and Management of Metabolic Syndrome.

    Sharma, Hitender; Kumar, Sunil

    2017-01-01

    This review covers recent discoveries of phytoconstituents, herbal extracts and some semi-synthetic compounds for treating metabolic syndrome with AMPK activation as one of their mechanisms of action. Recent researches have demonstrated AMPK activation to ameliorate multiple components of metabolic syndrome by regulating a balance between anabolic and catabolic cellular reactions. The review attempts to delineate the AMPK activation by natural agents from the perspective of its functional consequences on enzymes, transcription factors and signaling molecules and also on other potential factors contributing in the amelioration of metabolic syndrome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Association between physical activity and metabolic syndrome among Malay adults in a developing country, Malaysia.

    Chu, Anne H Y; Moy, F M

    2014-03-01

    Metabolic syndrome is a highly prevalent health problem within the adult population in developing countries. We aimed to study the association of physical activity levels and metabolic risk factors among Malay adults in Malaysia. Cross-sectional. Body mass index, waist circumference, and systolic/diastolic blood pressure, fasting blood glucose, fasting triglyceride and high-density lipoprotein cholesterol levels were measured in 686 Malay participants (aged 35-74 years). Self-reported physical activity was obtained with the validated International Physical Activity Questionnaire (Malay version) and categorized into low, moderate or high activity levels. Individuals who were classified as overweight and obese predominated (65.6%). On the basis of the modified NCEP ATP III criteria, metabolic syndrome was diagnosed in 31.9% of all participants, of whom 46.1% were men and 53.9% were women. The prevalence of metabolic syndrome among participants with low, moderate or high activity levels was 13.3%, 11.7% and 7.0%, respectively (p<0.001). Statistically significant negative associations were found between a number of metabolic risk factors and activity categories (p<0.05). The odds ratios for metabolic syndrome in the moderate and high activity categories were 0.42 (95% CI: 0.27-0.65) and 0.52 (95% CI: 0.35-0.76), respectively, adjusted for gender. Moderate and high activity levels were each associated with reduced odds for metabolic syndrome independent of gender. Although a slightly lower prevalence of metabolic syndrome was associated with high activity than with moderate activity, potential health benefits were observed when moderate activity was performed. Copyright © 2013 Sports Medicine Australia. All rights reserved.

  17. Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS.

    Glintborg, Dorte; Altinok, Magda Lambaa; Ravn, Pernille; Stage, Kurt Bjerregaard; Højlund, Kurt; Andersen, Marianne

    2018-03-01

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n  = 21) or placebo ( n  = 21). Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test (OGTT) and filled in questionnaires regarding mental health and health-related quality of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI), Short Form 36 (SF-36) and PCOS questionnaire. Included women were aged 31 (6) years (mean (s.d.)) and had body mass index (BMI) 35.8 (6.5) kg/m 2 and waist 102 (12) cm. Escitalopram was associated with increased waist (median (quartiles) change 1 (0; 3) cm), P  = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test), all P   PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged. © 2018 The authors.

  18. Fibroblast activation protein (FAP as a novel metabolic target

    Miguel Angel Sánchez-Garrido

    2016-10-01

    Conclusions: We conclude that pharmacological inhibition of FAP enhances levels of FGF21 in obese mice to provide robust metabolic benefits not observed in lean animals, thus validating this enzyme as a novel drug target for the treatment of obesity and diabetes.

  19. Activating transcription factor 3 regulates immune and metabolic homeostasis

    Ryneš, J.; Donohoe, C. D.; Frommolt, P.; Brodesser, S.; Jindra, Marek; Uhlířová, M.

    2012-01-01

    Roč. 32, č. 19 (2012), s. 3949-3962 ISSN 0270-7306 R&D Projects: GA ČR(CZ) GD204/09/H058 Institutional support: RVO:60077344 Keywords : metabolic homeostasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.372, year: 2012

  20. Quantifying interictal metabolic activity in human temporal lobe epilepsy

    Henry, T.R.; Mazziotta, J.C.; Engel, J. Jr.; Christenson, P.D.; Zhang, J.X.; Phelps, M.E.; Kuhl, D.E.

    1990-01-01

    The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a single investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism

  1. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

    Kim, Young C.; Yim, Hye K.; Jung, Young S.; Park, Jae H.; Kim, Sung Y.

    2007-01-01

    Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards

  2. 3'-Azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta

    Collier, Abby C.; Helliwell, Rachel J.A.; Keelan, Jeffrey A.; Paxton, James W.; Mitchell, Murray D.; Tingle, Malcolm D.

    2003-01-01

    The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is the drug of choice for preventing maternal-fetal HIV transmission during pregnancy. Our aim was to assess the cytotoxic effects of AZT on human placenta in vitro. The mechanisms of AZT-induced effects were investigated using JEG-3 choriocarcinoma cells and primary explant cultures from term and first-trimester human placentas. Cytotoxicity measures included trypan blue exclusion, MTT, and reactive oxygen species (ROS) assays. Apoptosis was measured with an antibody specific to cleaved caspase-3 and by rescue of cells by the general caspase inhibitor Boc-D-FMK. The effect of AZT on the activities of glutathione-S-transferase, β-glucuronidase, UDP-glucuronosyl transferase, cytochrome P450 (CYP) 1A, and CYP reductase (CYPR) in the placenta was assessed using biochemical assays and immunoblotting. AZT increased ROS levels, decreased cellular proliferation rates, was toxic to mitochondria, and initiated cell death by a caspase-dependent mechanism in the human placenta in vitro. In the absence of serum, the effects of AZT were amplified in all the models used. AZT also increased the amounts of activity of GST, β-glucuronidase, and CYP1A, whereas UGT and CYPR were decreased. We conclude that AZT causes apoptosis in the placenta and alters metabolizing enzymes in human placental cells. These findings have implications for the safe administration of AZT in pregnancy with respect to the maintenance of integrity of the maternal-fetal barrier

  3. Chronic innate immune activation of TBK1 suppresses mTORC1 activity and dysregulates cellular metabolism.

    Hasan, Maroof; Gonugunta, Vijay K; Dobbs, Nicole; Ali, Aktar; Palchik, Guillermo; Calvaruso, Maria A; DeBerardinis, Ralph J; Yan, Nan

    2017-01-24

    Three-prime repair exonuclease 1 knockout (Trex1 -/- ) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1 -/- mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism. We also genetically separated the inflammatory and metabolic phenotypes by showing that Sting deficiency rescued both inflammatory and metabolic phenotypes, whereas Irf3 deficiency only rescued inflammation on the Trex1 -/- background, and many metabolic defects persist in Trex1 -/- Irf3 -/- cells and mice. We also showed that Leptin deficiency (ob/ob) increased lipogenesis and prolonged survival of Trex1 -/- mice without dampening inflammation. Mechanistically, we identified TBK1 as a key regulator of mTORC1 activity in Trex1 -/- cells. Together, our data demonstrate that chronic innate immune activation of TBK1 suppresses mTORC1 activity, leading to dysregulated cellular metabolism.

  4. Metabonomics-based analysis of Brachyspira pilosicoli's response to tiamulin reveals metabolic activity despite significant growth inhibition.

    Le Roy, Caroline Ivanne; Passey, Jade Louise; Woodward, Martin John; La Ragione, Roberto Marcello; Claus, Sandrine Paule

    2017-06-01

    Pathogenic anaerobes Brachyspira spp. are responsible for an increasing number of Intestinal Spirochaetosis (IS) cases in livestock against which few approved treatments are available. Tiamulin is used to treat swine dysentery caused by Brachyspira spp. and recently has been used to handle avian intestinal spirochaetosis (AIS). The therapeutic dose used in chickens requires further evaluation since cases of bacterial resistance to tiamulin have been reported. In this study, we evaluated the impact of tiamulin at varying concentrations on the metabolism of B. pilosicoli using a 1 H-NMR-based metabonomics approach allowing the capture of the overall bacterial metabolic response to antibiotic treatment. Based on growth curve studies, tiamulin impacted bacterial growth even at very low concentration (0.008 μg/mL) although its metabolic activity was barely affected 72 h post exposure to antibiotic treatment. Only the highest dose of tiamulin tested (0.250 μg/mL) caused a major metabolic shift. Results showed that below this concentration, bacteria could maintain a normal metabolic trajectory despite significant growth inhibition by the antibiotic, which may contribute to disease reemergence post antibiotic treatment. Indeed, we confirmed that B. pilosicoli remained viable even after exposition to the highest antibiotic dose. This paper stresses the need to ensure new evaluation of bacterial viability post bacteriostatic exposure such as tiamulin to guarantee treatment efficacy and decrease antibiotic resistance development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Metabolic evaluation of dairy cows submitted to three different strategies to decrease the effects of negative energy balance in early postpartum

    Alejandra M.B García

    2011-12-01

    Full Text Available In early lactation dairy cattle suffer metabolic alterations caused by negative energy balance, which predisposes to fatty liver and ketosis. The aim of this study was to evaluate the metabolic condition of high yielding dairy cows subjected to three treatments for preventing severe lipomobilization and ketosis in early lactation. Fifty four multiparous Holstein cows yielding >30 L/day were divided into four groups: control (CN= no treatment, glucose precursor (PG= propylene-glycol, hepatic protector (Mp= Mercepton®, and energy supplement with salts of linolenic and linoleic faty acids (Mg-E= Megalac-E®. Treatments were administrated randomly at moment of calving until 8 weeks postpartum. Blood samples were collected on days 1, 7, 14, 21, 28, 35, 42 and 49 postpartum. Body condition score (BCS was evaluated at the same periods and milk yield was recorded at 2nd, 4th, 5th, 6th, 7th, and 8th weeks of lactation. Concentrations of non-esterified fatty acids (NEFA, albumin, AST, ß-hydroxybutyrate (BHBA, cholesterol, glucose, total protein, urea and triglycerides were analyzed in blood samples. Cut-off points for subclinical ketosis were defined when BHBA >1.4 mmol/L and NEFA >0.7 mmol/L. General occurrence of subclinical ketosis was 24% during the period. An ascendant curve of cholesterol and glucose was observed from the 1st to the 8th week of lactation, while any tendency was observed with BHBA and NEFA, although differences among treatments were detected (p<0.05. BCS decreased from a mean of 3.85 at 1st week to 2.53 at 8th week of lactation (p=0.001. Milk yield was higher in the Mg-E group compared with the other treatment groups (p<0.05 Compared with the CN group, the treatments with Mp and PG did not show significant differences in blood biochemistry and milk yield. Cows receiving PG and Mg-E showed higher values of BHBA and NEFA (P<0.05, indicating accentuated lipomobilization. Supplementation with Mg-E also resulted in significant higher

  6. Quantification of metabolically active transient storage (MATS) in two reaches with contrasting transient storage and ecosystem respiration

    Alba Argerich; Roy Haggerty; Eugènia Martí; Francesc Sabater; Jay. Zarnetske

    2011-01-01

    Water transient storage zones are hotspots for metabolic activity in streams although the contribution of different types of transient storage zones to the whole�]reach metabolic activity is difficult to quantify. In this study we present a method to measure the fraction of the transient storage that is metabolically active (MATS) in two consecutive reaches...

  7. TLR-activated repression of Fe-S cluster biogenesis drives a metabolic shift and alters histone and tubulin acetylation.

    Tong, Wing-Hang; Maio, Nunziata; Zhang, De-Liang; Palmieri, Erika M; Ollivierre, Hayden; Ghosh, Manik C; McVicar, Daniel W; Rouault, Tracey A

    2018-05-22

    Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17. Previous studies have shown that the metabolic shift in Toll-like receptor (TLR)-activated myeloid cells involves rapid activation of glycolysis and subsequent mitochondrial respiratory failure due to nitric oxide (NO)-mediated damage to Fe-S proteins. Our studies indicated that TLR activation also actively suppresses many components of the Fe-S cluster biogenesis machinery, which exacerbates NO-mediated damage to Fe-S proteins by interfering with cluster recovery. These results reveal new regulatory pathways and novel roles of the Fe-S cluster biogenesis machinery in modifying the epigenome and acetylome and provide new insights into the etiology of Fe-S cluster biogenesis disorders.

  8. GPR55 receptor antagonist decreases glycolytic activity in PANC-1 pancreatic cancer cell line and tumor xenografts.

    Bernier, Michel; Catazaro, Jonathan; Singh, Nagendra S; Wnorowski, Artur; Boguszewska-Czubara, Anna; Jozwiak, Krzysztof; Powers, Robert; Wainer, Irving W

    2017-11-15

    The Warburg effect is a predominant metabolic pathway in cancer cells characterized by enhanced glucose uptake and its conversion to l-lactate and is associated with upregulated expression of HIF-1α and activation of the EGFR-MEK-ERK, Wnt-β-catenin, and PI3K-AKT signaling pathways. (R,R')-4'-methoxy-1-naphthylfenoterol ((R,R')-MNF) significantly reduces proliferation, survival, and motility of PANC-1 pancreatic cancer cells through inhibition of the GPR55 receptor. We examined (R,R')-MNF's effect on glycolysis in PANC-1 cells and tumors. Global NMR metabolomics was used to elucidate differences in the metabolome between untreated and (R,R')-MNF-treated cells. LC/MS analysis was used to quantify intracellular concentrations of β-hydroxybutyrate, carnitine, and l-lactate. Changes in target protein expression were determined by Western blot analysis. Data was also obtained from mouse PANC-1 tumor xenografts after administration of (R,R')-MNF. Metabolomics data indicate that (R,R')-MNF altered fatty acid metabolism, energy metabolism, and amino acid metabolism and increased intracellular concentrations of β-hydroxybutyrate and carnitine while reducing l-lactate content. The cellular content of phosphoinositide-dependent kinase-1 and hexokinase 2 was reduced consistent with diminished PI3K-AKT signaling and glucose metabolism. The presence of the GLUT8 transporter was established and found to be attenuated by (R,R')-MNF. Mice treated with (R,R')-MNF had significant accumulation of l-lactate in tumor tissue relative to vehicle-treated mice, together with reduced levels of the selective l-lactate transporter MCT4. Lower intratumoral levels of EGFR, pyruvate kinase M2, β-catenin, hexokinase 2, and p-glycoprotein were also observed. The data suggest that (R,R')-MNF reduces glycolysis in PANC-1 cells and tumors through reduced expression and function at multiple controlling sites in the glycolytic pathway. © 2017 UICC.

  9. Diet composition and activity level of at risk and metabolically healthy obese American adults.

    Hankinson, Arlene L; Daviglus, Martha L; Van Horn, Linda; Chan, Queenie; Brown, Ian; Holmes, Elaine; Elliott, Paul; Stamler, Jeremiah

    2013-03-01

    Obesity often clusters with other major cardiovascular disease risk factors, yet a subset of the obese appears to be protected from these risks. Two obesity phenotypes are described, (i) "metabolically healthy" obese, broadly defined as body mass index (BMI) ≥ 30 kg/m(2) and favorable levels of blood pressure, lipids, and glucose; and (ii) "at risk" obese, BMI ≥ 30 with unfavorable levels of these risk factors. More than 30% of obese American adults are metabolically healthy. Diet and activity determinants of obesity phenotypes are unclear. We hypothesized that metabolically healthy obese have more favorable behavioral factors, including less adverse diet composition and higher activity levels than at risk obese in the multi-ethnic group of 775 obese American adults ages 40-59 years from the International Population Study on Macro/Micronutrients and Blood Pressure (INTERMAP) cohort. In gender-stratified analyses, mean values for diet composition and activity behavior variables, adjusted for age, race, and education, were compared between metabolically healthy and at risk obese. Nearly one in five (149/775 or 19%) of obese American INTERMAP participants were classified as metabolically healthy obese. Diet composition and most activity behaviors were similar between obesity phenotypes, although metabolically healthy obese women reported higher sleep duration than at risk obese women. These results do not support hypotheses that diet composition and/or physical activity account for the absence of cardiometabolic abnormalities in metabolically healthy obese. Copyright © 2012 The Obesity Society.

  10. Decreased salivary sulphotransferase activity correlated with inflammation and autoimmunity parameters in Sjogren's syndrome patients

    Castro, Isabel; Aguilera, Sergio; Brockhausen, Inka

    2012-01-01

    To determine the expression and enzymatic activities of sulphotransferases involved in mucin hyposulphation in labial salivary glands (LSGs) from SS patients and to correlate sulphotransferase activity with clinical parameters such as secretion, inflammation and serology....

  11. [The study on metabolic difference of human body affected by active stress and passive stress under special events].

    Guo, Guang-hong; Gu, Feng; Dong, Zhen-nan; Yuan, Xin-hong; Wang, Ling; Tian, Ya-ping

    2010-05-01

    To study the metabolic difference of body influenced by active stress and passive stress under special events. To detect serum multiple biochemistry index of 57 earthquake rescue medical team and 13 victims of a natural calamity in Wenchuan earthquake by using Hitachi 7600 automatic analyzer. Stress affected biochemistry index deeply. To compared with rescue medical team, the serum ADA, ALP and TG of victims increased obviously and TP, ALB, MAO, Cr, UA, K, Na, Cl, Ca, ApoA1 and HDL decreased obviously. Many biochemistry index have been changed under stress and it relate with stress extent. The human body function status was better in active stress than in passive stress.

  12. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats.

    Nady Braidy

    2011-04-01

    Full Text Available The cofactor nicotinamide adenine dinucleotide (NAD+ has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose polymerase (PARP, an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD:NADH ratio in all organs by middle age (i.e.12 months compared to young (i.e. 3 month old rats. These changes in [NAD(H] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I-IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.

  14. Nutrient enrichment induces dormancy and decreases diversity of active bacteria in salt marsh sediments

    Kearns, Patrick J.; Angell, John H.; Howard, Evan M.; Deegan, Linda A.; Stanley, Rachel H. R.; Bowen, Jennifer L.

    2016-09-01

    Microorganisms control key biogeochemical pathways, thus changes in microbial diversity, community structure and activity can affect ecosystem response to environmental drivers. Understanding factors that control the proportion of active microbes in the environment and how they vary when perturbed is critical to anticipating ecosystem response to global change. Increasing supplies of anthropogenic nitrogen to ecosystems globally makes it imperative that we understand how nutrient supply alters active microbial communities. Here we show that nitrogen additions to salt marshes cause a shift in the active microbial community despite no change in the total community. The active community shift causes the proportion of dormant microbial taxa to double, from 45 to 90%, and induces diversity loss in the active portion of the community. Our results suggest that perturbations to salt marshes can drastically alter active microbial communities, however these communities may remain resilient by protecting total diversity through increased dormancy.

  15. Effects of total solar eclipse on the behavioural and metabolic activities of tropical intertidal animals

    Parulekar, A.H.; Ansari, Z.A.; Verlecar, X.N.; Harkantra, S.N.

    To study the effects of total solar eclipse of 16th Feb. 1980, on the behaviour and metabolic activities of intertidal invertebrates - nematodes, gastropods and bivalves - having different habitat preference a set of relevant observations, covering...

  16. A specific metabolic pattern related to the hallucinatory activity in schizophrenia

    Huret, J.D.; Martinot, J.L.; Lesur, A.; Mazoyer, B.; Pappata, S.; Syrota, A.; Baron, J.C.; Lemperiere, T.

    1988-01-01

    A clinical and PEI study using 18 F - fluorodesoxyglucose for measuring local cerebral glucose metabolism with the aim of showing a specific pattern related to the hallucinatory activity, is presented in schizophrenic patients all experiencing hallucinations or pseudo-halluccinations

  17. Mutagenicity of silver nanoparticles in CHO cells dependent on particle surface functionalization and metabolic activation

    Guigas, Claudia; Walz, Elke; Gräf, Volker; Heller, Knut J.; Greiner, Ralf

    2017-06-01

    The potential of engineered nanomaterials to induce genotoxic effects is an important aspect of hazard identification. In this study, cytotoxicity and mutagenicity as a function of metabolic activation of three silver nanoparticle (AgNP) preparations differing in surface coating were determined in Chinese hamster ovary (CHO) subclone K1 cells. Three silver nanoparticle preparations ( x 90,0 culture medium containing 10% fetal calf serum (FCS) than in medium without FCS. The HPRT test without metabolic activation system S9 revealed that compared to the other AgNP formulations, citrate-coated Ag showed a lower genotoxic effect. However, addition of S9 increased the mutation frequency of all AgNPs and especially influenced the genotoxicity of Citrate-Ag. The results showed that exogenous metabolic activation of nanosilver is crucial even if interactions of the metabolic activation system, nanosilver, and cells are not really understood up to now.

  18. Effectiveness of physical activity intervention among government employees with metabolic syndrome

    Chee Huei Phing

    2017-12-01

    Conclusion: The findings of this study suggest that physical activity intervention via aerobics classes is an effective strategy for improving step counts and reducing the prevalence of metabolic syndrome.

  19. Metabolic activity of boar semen stored in different extenders supplemented with ostrich egg yolk lipoproteins

    Dziekońska Anna; Kinder Marek; Fraser Leyland; Strzeżek Jerzy; Kordan Władysław

    2017-01-01

    Introduction: The aim of this study was to evaluate the effect of lipoprotein fraction isolated from ostrich egg yolk (LPFo) on the metabolic activity of boar spermatozoa following liquid semen storage in different extenders and temperatures.

  20. Metabolic activity of boar semen stored in different extenders supplemented with ostrich egg yolk lipoproteins

    Dziekońska Anna

    2017-03-01

    Full Text Available Introduction: The aim of this study was to evaluate the effect of lipoprotein fraction isolated from ostrich egg yolk (LPFo on the metabolic activity of boar spermatozoa following liquid semen storage in different extenders and temperatures.

  1. In vivo metabolic activity of hamster suprachiasmatic nuclei: use of anesthesia

    Schwartz, W.J.

    1987-01-01

    In vivo glucose utilization was measured in the suprachiasmatic nuclei (SCN) of Golden hamsters using the 14 C-labeled deoxyglucose technique. A circadian rhythm of SCN metabolic activity could be measured in this species, but only during pentobarbital sodium anesthesia when the surrounding background activity of adjacent hypothalamus was suppressed. Both the SCN's metabolic oscillation and its time-keeping ability are resistant to general anesthesia

  2. Effectiveness of physical activity intervention among government employees with metabolic syndrome

    Chee Huei Phing; Hazizi Abu Saad; M.Y. Barakatun Nisak; M.T. Mohd Nasir

    2017-01-01

    Background/Objective: Our study aimed to assess the effects of physical activity interventions via standing banners (point-of-decision prompt) and aerobics classes to promote physical activity among individuals with metabolic syndrome. Methods: We conducted a cluster randomized controlled intervention trial (16-week intervention and 8-week follow-up). Malaysian government employees in Putrajaya, Malaysia, with metabolic syndrome were randomly assigned by cluster to a point-of-decision prom...

  3. Activity of carbohydrate metabolism enzymes of bone marrow cells of rats affected by radiation

    Sukhomlinov, B.F.; Grinyuk, Yu.S.; Sibirnaya, N.A.; Starikovich, L.S.; Khmil', M.V.

    1990-01-01

    The influence of ionizing radiation (154.8 mC/kg on activity of some carbohydrate metabolism dehydrogenases in cells of the whole and fractionated rat bone marrow has been investigated. Different glucose metabolism units differently responded to radiation, the highest radiation response being exhibited by pentosophosphate cycle processes. The pattern of changes in the enzyme activity of different myelocaryocyte populations was shown to depend directly on the functional specilization of cells and the energy exchange types predominated in them

  4. In Vitro Effects of Sports and Energy Drinks on Streptococcus mutans Biofilm Formation and Metabolic Activity.

    Vinson, LaQuia A; Goodlett, Amy K; Huang, Ruijie; Eckert, George J; Gregory, Richard L

    2017-09-15

    Sports and energy drinks are being increasingly consumed and contain large amounts of sugars, which are known to increase Streptococcus mutans biofilm formation and metabolic activity. The purpose of this in vitro study was to investigate the effects of sports and energy drinks on S. mutans biofilm formation and metabolic activity. S. mutans UA159 was cultured with and without a dilution (1:3 ratio) of a variety of sports and energy drinks in bacterial media for 24 hours. The biofilm was washed, fixed, and stained. Biofilm growth was evaluated by reading absorbance of the crystal violet. Biofilm metabolic activity was measured by the biofilm-reducing XTT to a water-soluble orange compound. Gatorade Protein Recovery Shake and Starbucks Doubleshot Espresso Energy were found to significantly increase biofilm (30-fold and 22-fold, respectively) and metabolic activity (2-fold and 3-fold, respectively). However, most of the remaining drinks significantly inhibited biofilm growth and metabolic activity. Several sports and energy drinks, with sugars or sugar substitutes as their main ingredients inhibited S. mutans biofilm formation. Among the drinks evaluated, Gatorade Protein Recovery Chocolate Shake and Starbucks Doubleshot Energy appear to have cariogenic potential since they increased the biofilm formation and metabolic activity of S. mutans.

  5. Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum

    Verónica Gómez Pérez

    2016-08-01

    Full Text Available Visceral leishmaniasis (VL caused by the protozoan parasite Leishmania infantum, is one of the most important zoonotic diseases affecting dogs and humans in the Mediterranean area. The presence of infected dogs as the main reservoir host of L. infantum is regarded as the most significant risk for potential human infection. We have studied the susceptibility profile to antimony and other anti-leishmania drugs (amphotericin B, miltefosine, paromomycin in Leishmania infantum isolates extracted from a dog before and after two therapeutic interventions with meglumine antimoniate (subcutaneous Glucantime®, 100 mg/kg/day for 28 days. After the therapeutic intervention, these parasites were significantly less susceptible to antimony than pretreatment isolate, presenting a resistance index of 6-fold to SbIII for promastigotes and >3-fold to SbIII and 3-fold to SbV for intracellular amastigotes. The susceptibility profile of this resistant L. infantum line is related to a decreased antimony uptake due to lower aquaglyceroporin-1 expression levels. Additionally, other mechanisms including an increase in thiols and overexpression of enzymes involved in thiol metabolism, such as ornithine decarboxylase, trypanothione reductase, mitochondrial tryparedoxin and mitochondrial tryparedoxin peroxidase, could contribute to the resistance as antimony detoxification mechanisms. A major contribution of this study in a canine L. infantum isolate is to find an antimony-resistant mechanism similar to that previously described in other human clinical isolates.

  6. GC protein-derived macrophage-activating factor decreases ?-N-acetylgalactosaminidase levels in advanced cancer patients

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-01-01

    ?-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort ...

  7. Decreasing Stereotypy in Preschoolers with Autism Spectrum Disorder: The Role of Increased Physical Activity and Function

    McLaughlin, Constance Ann Hylton

    2010-01-01

    This study used increased physical activity during recess to reduce stereotypy in preschoolers with Autism Spectrum Disorder. Results indicate increasing physical activity can be used as an intervention to reduce automatically maintained stereotypy in preschoolers with ASD. The intervention had a lesser effect on a preschooler whose stereotypy was…

  8. Reconstruction of Oryza sativa indica Genome Scale Metabolic Model and Its Responses to Varying RuBisCO Activity, Light Intensity, and Enzymatic Cost Conditions

    Ankita Chatterjee

    2017-11-01

    Full Text Available To combat decrease in rice productivity under different stresses, an understanding of rice metabolism is needed. Though there are different genome scale metabolic models (GSMs of Oryza sativa japonica, no GSM with gene-protein-reaction association exist for Oryza sativa indica. Here, we report a GSM, OSI1136 of O.s. indica, which includes 3602 genes and 1136 metabolic reactions and transporters distributed across the cytosol, mitochondrion, peroxisome, and chloroplast compartments. Flux balance analysis of the model showed that for varying RuBisCO activity (Vc/Vo (i the activity of the chloroplastic malate valve increases to transport reducing equivalents out of the chloroplast under increased photorespiratory conditions and (ii glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase can act as source of cytosolic ATP under decreased photorespiration. Under increasing light conditions we observed metabolic flexibility, involving photorespiration, chloroplastic triose phosphate and the dicarboxylate transporters of the chloroplast and mitochondrion for redox and ATP exchanges across the intracellular compartments. Simulations under different enzymatic cost conditions revealed (i participation of peroxisomal glutathione-ascorbate cycle in photorespiratory H2O2 metabolism (ii different modes of the chloroplastic triose phosphate transporters and malate valve, and (iii two possible modes of chloroplastic Glu–Gln transporter which were related with the activity of chloroplastic and cytosolic isoforms of glutamine synthetase. Altogether, our results provide new insights into plant metabolism.

  9. The Effect of Culture Medium on Metabolic and Antibacterial Activities of Probiotic Bacteria

    Mirdavoudi F

    2012-01-01

    Full Text Available Background and Objectives: Probiotic bacteria is added directly to food components and it has beneficial effect on function and the health of organisms. The bifidogenic factors enter the colon where they contribute to an increase lactic acid bacteria population including Lactobacilli and Bifidobacteria and they inhibit enteric pathogenic bacterial growth. The aim of this study is to investigate the effect of culture medium on metabolic and antibacterial of probiotic bacteria.Methods: In this study, the probiotics bacterial and intestine pathogenic are to be used. Lactobacilli and Bifidobacterium were identified by plating samples on MRS medium, Gram Staining and standard biochemical methods. The effect of antagonistic probiotics was investigated in the presence of growth factor in the method well diffusion Ager on the Shigella flexneri (PTCC 1234, Escherichia coli (PTCC 1552, Salmonella typhi ( PTCC 1609 and the culture medium pH was measured.Results: The probiotics bacterial growth in MRS and lactose1%, sorbitol, raffinose, riboflavin were shown the effect antibacterial. The results of the study show the most antagonistic activity in commercial strain Lactobacillus acidophilus on Shigella flexneri and lower activity was in Lactobacillus casei (PTCC 1608, and Salmonella typhimurium (PTCC 1609, and also in Bbifidobacterium bifidum, it showed the most decrease pH value.Conclusion: According to the result of the study, adding growth factors to MRS medium base and lactose 1%, probiotic growth was increased and which also increased antagonistic activity.

  10. Effectiveness and feasibility of lowering playground density during recess to promote physical activity and decrease sedentary time at primary school.

    D'Haese, Sara; Van Dyck, Delfien; De Bourdeaudhuij, Ilse; Cardon, Greet

    2013-12-10

    This pilot study aimed at investigating the effectiveness of lowering playground density on increasing children's physical activity and decreasing sedentary time. Also the feasibility of this intervention was tested. Data were collected in September and October 2012 in three Belgian schools in 187, 9-12 year old children. During the intervention, playground density was decreased by splitting up recesses and decreasing the number of children sharing the playground. A within-subject design was used. Children wore accelerometers during the study week. Three-level (class - participant - measurement (baseline or intervention)) linear regression models were used to determine intervention effects. After the intervention week the school principals filled out a questionnaire concerning the feasibility of the intervention. The available play space was 12.18 ± 4.19 m²/child at baseline and increased to 24.24 ± 8.51 m²/child during intervention. During the intervention sedentary time decreased (-0.58 min/recess; -3.21%/recess) and moderate-to-vigorous physical activity (+1.04 min/recess; +5.9%/recess) increased during recess and during the entire school day (sedentary time: -3.29%/school day; moderate-to-vigorous physical activity +1.16%/school day). All principals agreed that children enjoyed the intervention; but some difficulties were reported. Lowering playground density can be an effective intervention for decreasing children's sedentary time and increasing their physical activity levels during recess; especially in least active children.

  11. Metabolic activity is necessary for activation of T suppressor cells by B cells

    Elkins, K.L.; Stashak, P.W.; Baker, P.J.

    1990-01-01

    Ag-primed B cells must express cell-surface IgM, but not IgD or Ia Ag, and must remain metabolically active, in order to activate suppressor T cells (Ts) specific for type III pneumococcal polysaccharide. Ag-primed B cells that were gamma-irradiated with 1000r, or less, retained the ability to activate Ts; however, Ag-primed B cells exposed to UV light were not able to do so. gamma-Irradiated and UV-treated Ag-primed B cells both expressed comparable levels of cell-surface IgM, and both localized to the spleen after in vivo transfer; neither could proliferate in vitro in response to mitogens. By contrast, gamma-irradiated primed B cells were still able to synthesize proteins, whereas UV-treated primed B cells could not. These findings suggest that in order for Ag-primed B cells to activate Ts, they must (a) express cell-associated IgM (sIgM) antibody bearing the idiotypic determinants of antibody specific for type III pneumococcal polysaccharide, and (b) be able to synthesize protein for either the continued expression of sIgM after cell transfer, or for the elaboration of another protein molecule that is also required for the activation of Ts; this molecule does not appear to be Ia Ag

  12. NDRG2 overexpression suppresses hepatoma cells survival during metabolic stress through disturbing the activation of fatty acid oxidation

    Pan, Tao; Zhang, Mei; Zhang, Fang; Yan, Guang; Ru, Yi; Wang, Qinhao; Zhang, Yao; Wei, Xuehui; Xu, Xinyuan; Shen, Lan; Zhang, Jian; Wu, Kaichun; Yao, Libo; Li, Xia

    2017-01-01

    Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear. In this study, we found that NDRG2 overexpression significantly reduced hepatoma cell proliferation and enhanced cell apoptosis under glucose limitation. Moreover, NDRG2 overexpression aggravated energy imbalance and oxidative stress by decreasing the intracellular ATP and NADPH generation and increasing ROS levels. Strikingly, NDRG2 inhibited the activation of fatty acid oxidation (FAO), which preserves ATP and NADPH purveyance in the absence of glucose. Finally, mechanistic investigation showed that NDRG2 overexpression suppressed the glucose-deprivation induced AMPK/ACC pathway activation in hepatoma cells, whereas the expression of a constitutively active form of AMPK abrogated glucose-deprivation induced AMPK activation and cell apoptosis. Thus, as a negative regulator of AMPK, NDRG2 disturbs the induction of FAO genes by glucose limitation, leading to dysregulation of ATP and NADPH, and thus reduces the tolerance of hepatoma cells to glucose limitation. - Highlights: • NDRG2 overexpression reduces the tolerance of hepatoma cells to glucose limitation. • NDRG2 overexpression aggravates energy imbalance and oxidative stress under glucose deprivation. • NDRG2 overexpression disturbs the activation of FAO in hepatoma cells under glucose limitation. • NDRG2 overexpression inhibits the activation of AMPK/ACC pathway in hepatoma cells during glucose starvation.

  13. Transplant experiments uncover Baltic Sea basin-specific responses in bacterioplankton community composition and metabolic activities.

    Lindh, Markus V; Figueroa, Daniela; Sjöstedt, Johanna; Baltar, Federico; Lundin, Daniel; Andersson, Agneta; Legrand, Catherine; Pinhassi, Jarone

    2015-01-01

    Anthropogenically induced changes in precipitation are projected to generate increased river runoff to semi-enclosed seas, increasing loads of terrestrial dissolved organic matter and decreasing salinity. To determine how bacterial community structure and functioning adjust to such changes, we designed microcosm transplant experiments with Baltic Proper (salinity 7.2) and Bothnian Sea (salinity 3.6) water. Baltic Proper bacteria generally reached higher abundances than Bothnian Sea bacteria in both Baltic Proper and Bothnian Sea water, indicating higher adaptability. Moreover, Baltic Proper bacteria growing in Bothnian Sea water consistently showed highest bacterial production and beta-glucosidase activity. These metabolic responses were accompanied by basin-specific changes in bacterial community structure. For example, Baltic Proper Pseudomonas and Limnobacter populations increased markedly in relative abundance in Bothnian Sea water, indicating a replacement effect. In contrast, Roseobacter and Rheinheimera populations were stable or increased in abundance when challenged by either of the waters, indicating an adjustment effect. Transplants to Bothnian Sea water triggered the initial emergence of particular Burkholderiaceae populations, and transplants to Baltic Proper water triggered Alteromonadaceae populations. Notably, in the subsequent re-transplant experiment, a priming effect resulted in further increases to dominance of these populations. Correlated changes in community composition and metabolic activity were observed only in the transplant experiment and only at relatively high phylogenetic resolution. This suggested an importance of successional progression for interpreting relationships between bacterial community composition and functioning. We infer that priming effects on bacterial community structure by natural episodic events or climate change induced forcing could translate into long-term changes in bacterial ecosystem process rates.

  14. Transplant experiments uncover Baltic Sea basin-specific responses in bacterioplankton community composition and metabolic activities

    Markus V Lindh

    2015-04-01

    Full Text Available Anthropogenically induced changes in precipitation are projected to generate increased river runoff to semi-enclosed seas, intensifying loads of terrestrial dissolved organic matter and decreasing salinity. To determine how bacterial community structure and functioning adjust to such changes, we designed microcosm transplant experiments with Baltic Proper (salinity 7.2 and Bothnian Sea (salinity 3.6 water. Baltic Proper bacteria generally reached higher abundance than Bothnian Sea bacteria in both Baltic Proper and Bothnian Sea water, indicating a higher adaptability. Moreover, Baltic Proper bacteria growing in Bothnian Sea water consistently showed highest bacterial production and beta-glucosidase activity. These metabolic responses were accompanied by basin-specific changes in bacterial community structure. For example, Baltic Proper Pseudomonas and Limnobacter populations increased markedly in relative abundance in Bothnian Sea water, indicating replacement. In contrast, Roseobacter and Rheinheimera populations were stable or increased in abundance when challenged by either of the waters, indicating adjustment. Transplants to Bothnian Sea water triggered the initial emergence of particular Burkholderiaceae populations, and transplants to Baltic Proper water triggered Alteromonadaceae populations. Notably, in the subsequent re-transplant experiment, the original triggering, or priming effect, resulted in further increases to dominance of these populations. Correlated changes in community composition and metabolic activity were observed only in the transplant experiment, and only at relatively high phylogenetic resolution. This suggested an importance of successional progression for interpreting relationships between bacterial community composition and functioning. We infer that priming effects on bacterial community structure by natural episodic events or climate change induced forcing could translate into long-term changes in bacterial

  15. Oligo-Carrageenan Kappa-Induced Reducing Redox Status and Increase in TRR/TRX Activities Promote Activation and Reprogramming of Terpenoid Metabolism in Eucalyptus Trees

    Alberto González

    2014-06-01

    Full Text Available In order to analyze whether the reducing redox status and activation of thioredoxin reductase (TRR/thioredoxin(TRX system induced by oligo-carrageenan (OC kappa in Eucalyptus globulus activate secondary metabolism increasing terpenoid synthesis, trees were sprayed on the leaves with water, with OC kappa, or with inhibitors of NAD(PH, ascorbate (ASC and (GSH synthesis and TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO and auranofine, respectively, and with OC kappa and cultivated for four months. The main terpenoids in control Eucalyptus trees were eucalyptol (76%, α-pinene (7.4%, aromadendrene (3.6%, silvestrene (2.8%, sabinene (2% and α-terpineol (0.9%. Treated trees showed a 22% increase in total essential oils as well as a decrease in eucalyptol (65% and sabinene (0.8% and an increase in aromadendrene (5%, silvestrene (7.8% and other ten terpenoids. In addition, treated Eucalyptus showed seven de novo synthesized terpenoids corresponding to carene, α-terpinene, α-fenchene, γ-maaliene, spathulenol and α-camphenolic aldehyde. Most increased and de novo synthesized terpenoids have potential insecticidal and antimicrobial activities. Trees treated with CHS-828, lycorine, BSO and auranofine and with OC kappa showed an inhibition of increased and de novo synthesized terpenoids. Thus, OC kappa-induced reducing redox status and activation of TRR/TRX system enhance secondary metabolism increasing the synthesis of terpenoids and reprogramming of terpenoid metabolism in Eucalyptus trees.

  16. Oligo-carrageenan kappa-induced reducing redox status and increase in TRR/TRX activities promote activation and reprogramming of terpenoid metabolism in Eucalyptus trees.

    González, Alberto; Gutiérrez-Cutiño, Marlen; Moenne, Alejandra

    2014-06-05

    In order to analyze whether the reducing redox status and activation of thioredoxin reductase (TRR)/thioredoxin(TRX) system induced by oligo-carrageenan (OC) kappa in Eucalyptus globulus activate secondary metabolism increasing terpenoid synthesis, trees were sprayed on the leaves with water, with OC kappa, or with inhibitors of NAD(P)H, ascorbate (ASC) and (GSH) synthesis and TRR activity, CHS-828, lycorine, buthionine sulfoximine (BSO) and auranofine, respectively, and with OC kappa and cultivated for four months. The main terpenoids in control Eucalyptus trees were eucalyptol (76%), α-pinene (7.4%), aromadendrene (3.6%), silvestrene (2.8%), sabinene (2%) and α-terpineol (0.9%). Treated trees showed a 22% increase in total essential oils as well as a decrease in eucalyptol (65%) and sabinene (0.8%) and an increase in aromadendrene (5%), silvestrene (7.8%) and other ten terpenoids. In addition, treated Eucalyptus showed seven de novo synthesized terpenoids corresponding to carene, α-terpinene, α-fenchene, γ-maaliene, spathulenol and α-camphenolic aldehyde. Most increased and de novo synthesized terpenoids have potential insecticidal and antimicrobial activities. Trees treated with CHS-828, lycorine, BSO and auranofine and with OC kappa showed an inhibition of increased and de novo synthesized terpenoids. Thus, OC kappa-induced reducing redox status and activation of TRR/TRX system enhance secondary metabolism increasing the synthesis of terpenoids and reprogramming of terpenoid metabolism in Eucalyptus trees.

  17. Metabolic enzyme activities of abyssal and hadal fishes: pressure effects and a re-evaluation of depth-related changes

    Gerringer, M. E.; Drazen, J. C.; Yancey, P. H.

    2017-07-01

    Metabolic enzyme activities of muscle tissue have been useful and widely-applied indicators of whole animal metabolic capacity, particularly in inaccessible systems such as the deep sea. Previous studies have been conducted at atmospheric pressure, regardless of organism habitat depth. However, maximum reaction rates of some of these enzymes are pressure dependent, complicating the use of metabolic enzyme activities as proxies of metabolic rates. Here, we show pressure-related rate changes in lactate and malate dehydrogenase (LDH, MDH) and pyruvate kinase (PK) in six fish species (2 hadal, 2 abyssal, 2 shallow). LDH maximal reaction rates decreased with pressure for the two shallow species, but, in contrast to previous findings, it increased for the four deep species, suggesting evolutionary changes in LDH reaction volumes. MDH maximal reaction rates increased with pressure in all species (up to 51±10% at 60 MPa), including the tide pool snailfish, Liparis florae (activity increase at 60 MPa 44±9%), suggesting an inherent negative volume change of the reaction. PK was inhibited by pressure in all species tested, including the hadal liparids (up to 34±3% at 60 MPa), suggesting a positive volume change during the reaction. The addition of 400 mM TMAO counteracted this inhibition at both 0.5 and 2.0 mM ADP concentrations for the hadal liparid, Notoliparis kermadecensis. We revisit depth-related trends in metabolic enzyme activities according to these pressure-related rate changes and new data from seven abyssal and hadal species from the Kermadec and Mariana trenches. Results show that, with abyssal and hadal species, pressure-related rate changes are another variable to be considered in the use of enzyme activities as proxies for metabolic rate, in addition to factors such as temperature and body mass. Intraspecific increases in tricarboxylic acid cycle enzymes with depth of capture, independent of body mass, in two hadal snailfishes suggest improved nutritional

  18. Antisense Suppression of 2-Cysteine Peroxiredoxin in Arabidopsis Specifically Enhances the Activities and Expression of Enzymes Associated with Ascorbate Metabolism But Not Glutathione Metabolism1

    Baier, Margarete; Noctor, Graham; Foyer, Christine H.; Dietz, Karl-Josef

    2000-01-01

    The aim of this study was to characterize the effect of decreased 2-cysteine peroxiredoxin (2-CP) on the leaf anti-oxidative system in Arabidopsis. At three stages of leaf development, two lines of transgenic Arabidopsis mutants with decreased contents of chloroplast 2-CP were compared with wild type and a control line transformed with an empty vector. Glutathione contents and redox state were similar in all plants, and no changes in transcript levels for enzymes involved in glutathione metabolism were observed. Transcript levels for chloroplastic glutathione peroxidase were much lower than those for 2-CP, and both cytosolic and chloroplastic glutathione peroxidase were not increased in the mutants. In contrast, the foliar ascorbate pool was more oxidized in the mutants, although the difference decreased with plant age. The activities of thylakoid and stromal ascorbate peroxidase and particularly monodehydroascorbate reductase were increased as were transcripts for these enzymes. No change in dehydroascorbate reductase activity was observed, and effects on transcript abundance for glutathione reductase, catalase, and superoxide dismutase were slight or absent. The results demonstrate that 2-CP forms an integral part of the anti-oxidant network of chloroplasts and is functionally interconnected with other defense systems. Suppression of 2-CP leads to increased expression of other anti-oxidative genes possibly mediated by increased oxidation state of the leaf ascorbate pool. PMID:11027730

  19. Association of physical activity with metabolic syndrome in a predominantly rural Nigerian population

    Oguoma, Victor M.; Nwose, Ezekiel U.; Nwose, Ezekiel U.

    2016-01-01

    Aims Physical activity is an essential determinant of health. However, there is dearth of evidence regarding prevalence of physical activity in developing countries, especially its association with metabolic syndrome risk factors. This study assessed the association of physical activity with meta...

  20. Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans

    Kienbaum, P.; Heuter, T.; Michel, M. C.; Peters, J.

    2000-01-01

    BACKGROUND: Cardiovascular stimulation and increased catecholamine plasma concentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition in various experimental models. However, direct recordings of efferent

  1. BLOOD AND BRAIN CONCENTRATIONS OF BIFENTHRIN CORRELATE WITH DECREASED MOTOR ACTIVITY INDEPENDENT OF TIME OF EXPOSURE

    Pyrethroids are neurotoxic insecticides used in a variety of agricultural and household activities. Due to the phase-out of organophosphate pesticides, the use of pyrethroids has increased. The potential for human exposure to pyrethroids has prompted pharmacodynamic and pharmac...

  2. Oxygen-induced Decrease in the Equilibrium Adsorptive Capacities of Activated Carbons

    Ovín Ania, María Concepción; Parra Soto, José Bernardo; Pis Martínez, José Juan

    2004-01-01

    Special attention was paid in this work to the role of surface chemistry in the adsorption of phenol and salicylic acid onto activated carbons. To this end, two commercial activated carbons (granular and powdered) were oxidised using ammonium peroxodisulphate [(NH4) 2S2O8] and nitric acid in different concentrations. The structural and chemical properties of the oxidised adsorbents were characterised via nitrogen adsorption isotherms measured at –196 ° C and Boehm titrations. Phenol adsorptio...

  3. Andrographolide powder treatment as antifeedant decreased digestive enzyme activity from Plutella xylostella (L.) larvae midgut

    Madihah, Malini, Desak Made; Roviani, Hana; Rani, Nessa Vidya; Hermawan, Wawan

    2018-02-01

    Andrographolide, an active compound of Andrographis paniculata, has shown antifeedant activity against Plutella xylostella larvae by disrupting the midgut histological structures. This study aims to determine the activity of andrographolide in crystallized powder form against several digestive enzymes from the midgut of 4th instar P. xylostella larvae. The concentrations used were 0 (control), 1000, 1600, 2500, 4000 and 6500 ppm with four replications each. No-choice antifeedant test with leaf disc method is used in a bioassay for 24 hours. The midgut was dissected from 2nd until 6th segment of 4th instar larvae and was homogenized in iced-buffer solution. Furthermore, larvae's midgut samples were centrifuged at 10,000 rpm, 4°C for 20 min and the supernatant is used as enzyme source. The results showed that andrographolide significantly reduces the amylase, invertase, protease and trypsin activity, as well as total protein concentration compared with control (p<0.05) in a dose-dependent manner. This study provides information about the mode of action of andrographolide in inhibiting feed activity by the reduced digestive enzyme activity of 4th instar P. xylostella larvae.

  4. PPARγ ligands decrease hydrostatic pressure-induced platelet aggregation and proinflammatory activity.

    Fang Rao

    Full Text Available Hypertension is known to be associated with platelet overactivity, but the direct effects of hydrostatic pressure on platelet function remain unclear. The present study sought to investigate whether elevated hydrostatic pressure is responsible for platelet activation and to address the potential role of peroxisome proliferator-activated receptor-γ (PPARγ. We observed that hypertensive patients had significantly higher platelet volume and rate of ADP-induced platelets aggregation compared to the controls. In vitro, Primary human platelets were cultured under standard (0 mmHg or increased (120, 180, 240 mmHg hydrostatic pressure for 18 h. Exposure to elevated pressure was associated with morphological changes in platelets. Platelet aggregation and PAC-1 (the active confirmation of GPIIb/IIIa binding were increased, CD40L was translocated from cytoplasm to the surface of platelet and soluble CD40L (sCD40L was released into the medium in response to elevated hydrostatic pressure (180 and 240 mmHg. The PPARγ activity was up-regulated as the pressure was increased from 120 mmHg to 180 mmHg. Pressure-induced platelet aggregation, PAC-1 binding, and translocation and release of CD40L were all attenuated by the PPARγ agonist Thiazolidinediones (TZDs. These results demonstrate that platelet activation and aggregation are increased by exposure to elevated pressure and that PPARγ may modulate platelet activation induced by high hydrostatic pressure.

  5. PPARγ ligands decrease hydrostatic pressure-induced platelet aggregation and proinflammatory activity.

    Rao, Fang; Yang, Ren-Qiang; Chen, Xiao-Shu; Xu, Jin-Song; Fu, Hui-Min; Su, Hai; Wang, Ling

    2014-01-01

    Hypertension is known to be associated with platelet overactivity, but the direct effects of hydrostatic pressure on platelet function remain unclear. The present study sought to investigate whether elevated hydrostatic pressure is responsible for platelet activation and to address the potential role of peroxisome proliferator-activated receptor-γ (PPARγ). We observed that hypertensive patients had significantly higher platelet volume and rate of ADP-induced platelets aggregation compared to the controls. In vitro, Primary human platelets were cultured under standard (0 mmHg) or increased (120, 180, 240 mmHg) hydrostatic pressure for 18 h. Exposure to elevated pressure was associated with morphological changes in platelets. Platelet aggregation and PAC-1 (the active confirmation of GPIIb/IIIa) binding were increased, CD40L was translocated from cytoplasm to the surface of platelet and soluble CD40L (sCD40L) was released into the medium in response to elevated hydrostatic pressure (180 and 240 mmHg). The PPARγ activity was up-regulated as the pressure was increased from 120 mmHg to 180 mmHg. Pressure-induced platelet aggregation, PAC-1 binding, and translocation and release of CD40L were all attenuated by the PPARγ agonist Thiazolidinediones (TZDs). These results demonstrate that platelet activation and aggregation are increased by exposure to elevated pressure and that PPARγ may modulate platelet activation induced by high hydrostatic pressure.

  6. Decreased TK activity alters growth, yield and tolerance to low temperature and low light intensity in transgenic cucumber plants.

    Bi, Huangai; Dong, Xubing; Wu, Guoxiu; Wang, Meiling; Ai, Xizhen

    2015-02-01

    Four CsTK antisense transgenic cucumber plants were obtained. Decreased TK activity decreased the photosynthetic rate, seed germination rate, growth yield, and the tolerance to low temperature and weak light stress. Transketolase (TK, EC 2.2.1.1) is a key enzyme in the photosynthetic carbon reduction cycle (Calvin cycle). A cDNA fragment (526 bp) encoding transketolase was cloned from cucumber plants (Cucumis sativa L. cv 'Jinyou 3') by RT-PCR. The antisense expression [(PBI-CsTK(-)] vector containing the CsTK gene fragment was constructed. The resulting plasmid was introduced into the cucumber inbred lines '08-1' using the agrobacterium-mediated method, and four antisense transgenic cucumber plants were obtained. Decreased CsTK expression either unaltered or slightly increased the mRNA abundance and activities of the other main enzymes in the Calvin cycle, however, it decreased the TK activity and net photosynthetic rate (Pn) in antisense transgenic cucumber leaves. Antisense plants showed decreases in the growth, ratio of female flowers and yield compared with the wild-type (WT) plants. The decrease in Pn, stomatal conductance (Gs), transpiration rate (Tr), photochemical efficiency (Fv/Fm) and actual photochemical efficiency of PSII (ΦPSII) and the increase in electrolyte leakage (EL) were greater in antisense transgenic plants than in WT plants under low temperature (5 °C) and low light intensity (100 μmol m(-2) s(-1)).

  7. Odors generated from the Maillard reaction affect autonomic nervous activity and decrease blood pressure through the olfactory system.

    Zhou, Lanxi; Ohata, Motoko; Owashi, Chisato; Nagai, Katsuya; Yokoyama, Issei; Arihara, Keizo

    2018-02-01

    Systolic blood pressure (SBP) of rats decreases significantly following exposure to the odor generated from the Maillard reaction of protein digests with xylose. This study identified active odorants that affect blood pressure and demonstrated the mechanism of action. Among the four potent odorants that contribute most to the odor of the Maillard reaction sample, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 5-methyl-2-pyrazinemethanol (MPM) decreased SBP significantly. The earliest decrease in blood pressure was observed 5 min after exposure to DMHF. Application of zinc sulfate to the nasal cavity eliminated the effect. Furthermore, gastric vagal (parasympathetic) nerve activity was elevated and renal sympathetic nerve activity was lowered after exposure to DMHF. It is indicated that DMHF affects blood pressure through the olfactory system, and the mechanism for the effect of DMHF on blood pressure involves the autonomic nervous system. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  8. Defects in TLR3 expression and RNase L activation lead to decreased MnSOD expression and insulin resistance in muscle cells of obese people

    Fabre, Odile Martine Julie; Breuker, C; Amouzou, C

    2014-01-01

    Obesity is associated with chronic low-grade inflammation and oxidative stress that blunt insulin response in its target tissues, leading to insulin resistance (IR). IR is a characteristic feature of type 2 diabetes. Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake...... with palmitate, a saturated free fatty acid (FFA) known to induce inflammation and oxidative stress via TLR4 activation. While RNase L and RLI levels remained unchanged, OAS level was decreased in primary myotubes from insulin-resistant obese subjects (OB-IR) compared with myotubes from insulin-sensitive obese......; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Interestingly, some obese people stay insulin-sensitive and metabolically healthy. With the aim of understanding this difference and identifying the mechanisms responsible for insulin sensitivity maintenance...

  9. Metabolic and environmental aspects of fusion reactor activation products: niobium

    Easterly, C.E.; Shank, K.E.

    1977-11-01

    A summary of the metabolic and environmental aspects of niobium is presented. The toxicological symptoms from exposure to niobium are given, along with lethal concentration values for acute and chronic exposures. Existing human data are presented; animal uptake and retention data are analyzed for various routes of administration. Recommended metabolic values are also presented along with comments concerning their use and appropriateness. The natural distribution of niobium is given for freshwater, seawater, and the biosphere. Concentration factors and retention of 95 Nb in the environment are discussed with reference to: plant retention via leaf absorption; plant retention via root uptake; uptake in terrestrial animals from plants; uptake in freshwater organisms; uptake in marine organisms; and movement in soil. Conclusions are drawn regarding needs for future work in these areas. This review was undertaken because niobium is expected to be a key metal in the development of commercial fusion reactors. It is recognized that niobium will likely not be used in the first generation reactors as a structural material but will appear as an alloy in such materials as superconducting wire

  10. Metabolic and environmental aspects of fusion reactor activation products: niobium

    Easterly, C.E.; Shank, K.E.

    1977-11-01

    A summary of the metabolic and environmental aspects of niobium is presented. The toxicological symptoms from exposure to niobium are given, along with lethal concentration values for acute and chronic exposures. Existing human data are presented; animal uptake and retention data are analyzed for various routes of administration. Recommended metabolic values are also presented along with comments concerning their use and appropriateness. The natural distribution of niobium is given for freshwater, seawater, and the biosphere. Concentration factors and retention of /sup 95/Nb in the environment are discussed with reference to: plant retention via leaf absorption; plant retention via root uptake; uptake in terrestrial animals from plants; uptake in freshwater organisms; uptake in marine organisms; and movement in soil. Conclusions are drawn regarding needs for future work in these areas. This review was undertaken because niobium is expected to be a key metal in the development of commercial fusion reactors. It is recognized that niobium will likely not be used in the first generation reactors as a structural material but will appear as an alloy in such materials as superconducting wire.

  11. Physical activity and risk of Metabolic Syndrome in an urban Mexican cohort

    Huitrón Gerardo

    2009-07-01

    Full Text Available Abstract Background In the Mexican population metabolic syndrome (MS is highly prevalent. It is well documented that regular physical activity (PA prevents coronary diseases, type 2 diabetes and MS. Most studies of PA have focused on moderate-vigorous leisure-time activity, because it involves higher energy expenditures, increase physical fitness, and decrease the risk of MS. However, for most people it is difficult to get a significant amount of PA from only moderately-vigorous leisure activity, so workplace activity may be an option for working populations, because, although may not be as vigorous in terms of cardio-respiratory efforts, it comprises a considerable proportion of the total daily activity with important energy expenditure. Since studies have also documented that different types and intensity of daily PA, including low-intensity, seem to confer important health benefits such as prevent MS, we sought to assess the impact of different amounts of leisure-time and workplace activities, including low-intensity level on MS prevention, in a sample of urban Mexican adults. Methods The study population consisted of 5118 employees and their relatives, aged 20 to 70 years, who were enrolled in the baseline evaluation of a cohort study. MS was assessed according to the criteria of the National Cholesterol Education Program, ATP III and physical activity with a validated self-administered questionnaire. Associations between physical activity and MS risk were assessed with multivariate logistic regression models. Results The prevalence of the components of MS in the study population were: high glucose levels 14.2%, high triglycerides 40.9%, high blood pressure 20.4%, greater than healthful waist circumference 43.2% and low-high density lipoprotein 76.9%. The prevalence of MS was 24.4%; 25.3% in men and 21.8% in women. MS risk was reduced among men (OR 0.72; 95%CI 0.57–0.95 and women (OR 0.78; 95%CI 0.64–0.94 who reported an amount of ≥30

  12. Decrease in scale invariance of activity fluctuations with aging and in patients with suprasellar tumors

    Joustra, S. D.; Gu, C.; Rohling, J. H.T.

    2018-01-01

    -matched healthy controls (age range 21.0–70.6 years). Spontaneous wrist locomotor activity was measured for 7 days with actigraphy, and detrended fluctuation analysis was applied to assess correlations over a range of time scales from minutes to 24 h. For all the subjects, complex scale-invariant correlations...... scale invariance. Conversely, activity patterns at time scales between 10 and 24 h were significantly more regular than all other time scales, and this was mostly associated with age. In conclusion, scale invariance is degraded in healthy subjects at the ages of >33 year as characterized by attenuation......Motor activity in healthy young humans displays intrinsic fluctuations that are scale-invariant over a wide range of time scales (from minutes to hours). Human postmortem and animal lesion studies showed that the intact function of the suprachiasmatic nucleus (SCN) is required to maintain...

  13. HIV protease inhibitors disrupt lipid metabolism by activating endoplasmic reticulum stress and inhibiting autophagy activity in adipocytes.

    Beth S Zha

    Full Text Available HIV protease inhibitors (PI are core components of Highly Active Antiretroviral Therapy (HAART, the most effective treatment for HIV infection currently available. However, HIV PIs have now been linked to lipodystrophy and dyslipidemia, which are major risk factors for cardiovascular disease and metabolic syndrome. Our previous studies have shown that HIV PIs activate endoplasmic reticulum (ER stress and disrupt lipid metabolism in hepatocytes and macrophages. Yet, little is known on how HIV PIs disrupt lipid metabolism in adipocytes, a major cell type involved in the pathogenesis of metabolic syndrome.Cultured and primary mouse adipocytes and human adipocytes were used to examine the effect of frequently used HIV PIs in the clinic, lopinavir/ritonavir, on adipocyte differentiation and further identify the underlying molecular mechanism of HIV PI-induced dysregulation of lipid metabolism in adipocytes. The results indicated that lopinavir alone or in combination with ritonavir, significantly activated the ER stress response, inhibited cell differentiation, and induced cell apoptosis in adipocytes. In addition, HIV PI-induced ER stress was closely linked to inhibition of autophagy activity. We also identified through the use of primary adipocytes of CHOP(-/- mice that CHOP, the major transcriptional factor of the ER stress signaling pathway, is involved in lopinavir/ritonavir-induced inhibition of cell differentiation in adipocytes. In addition, lopinavir/ritonavir-induced ER stress appears to be associated with inhibition of autophagy activity in adipocytes.Activation of ER stress and impairment of autophagy activity are involved in HIV PI-induced dysregulation of lipid metabolism in adipocytes. The key components of ER stress and autophagy signaling pathways are potential therapeutic targets for HIV PI-induced metabolic side effects in HIV patients.

  14. Decrease in catalase activity of Folsomia candida fed a Bt rice diet

    Yuan, Yiyang; Ke, Xin; Chen, Fajun

    2011-01-01

    Here we report the effects of three Bt-rice varieties and their non-Bt conventional isolines on biological traits including survival, reproduction, and the activities of three antioxidant enzymes superoxide dismutase, catalase and peroxidase, in the Collembolan, Folsomia candida. The reproduction...... was significantly lower when fed Kemingdao and Huahui1 than those feeding on their non-GM near-isogenic varieties Xiushui and Minghui63 respectively, this can be explained by the differences of plant compositions depended on variety of rice. The catalase activity of F. candida was significantly lower when fed...

  15. Nonlinear Dielectric Spectroscopy as an Indirect Probe of Metabolic Activity in Thylakoid Membrane

    John H. Miller

    2011-01-01

    Full Text Available Nonlinear dielectric spectroscopy (NDS is a non-invasive probe of cellular metabolic activity with potential application in the development of whole-cell biosensors. However, the mechanism of NDS interaction with metabolic membrane proteins is poorly understood, partly due to the inherent complexity of single cell organisms. Here we use the light-activated electron transport chain of spinach thylakoid membrane as a model system to study how NDS interacts with metabolic activity. We find protein modification, as opposed to membrane pump activity, to be the dominant source of NDS signal change in this system. Potential mechanisms for such protein modifications include reactive oxygen species generation and light-activated phosphorylation.

  16. Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate

    Green, C J; Bunprajun, T; Pedersen, B K

    2013-01-01

    in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance......  The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture...... and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism...

  17. Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

    Young-il Kim

    Full Text Available Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA, which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA, which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.

  18. Decreased Oxidative Stress in Male Patients with Active Phase Ankylosing Spondylitis Who Underwent Whole-Body Cryotherapy in Closed Cryochamber

    Agata Stanek

    2018-01-01

    Full Text Available Objective. The aim of the study was to estimate the impact of whole body cryotherapy (WBC on oxidative stress when performed in a closed cryochamber on patients with ankylosing spondylitis (AS. Material and methods. The effect of ten WBC procedures lasting 3 minutes a day with a subsequent 60-minute session kinesiotherapy on oxidative stress in male AS patients (WBC group n=16 was investigated. To assess the disease activity, the Bath Ankylosing Spondylitis Diseases Activity Index (BASDAI and Bath Ankylosing Spondylitis Functional Index (BASFI were calculated. The WBC group was compared to the kinesiotherapy only (KT; n=16 group. The routine parameters of oxidative stress (antioxidant enzymatic and nonenzymatic antioxidant status, lipid peroxidation products, total oxidative status (TOS, and oxidative stress index (OSI were estimated one day before the beginning and one day after the completion of the research program. Results. After the completion of the treatment in the WBC group, a significant decrease of oxidative stress markers (TOS and OSI and a significant increase of total antioxidant status were observed. The erythrocyte activity of glutathione peroxidase, glutathione reductase decreased significantly in both groups, but the differences of activity of that enzymes prior to post treatment values (Δ in the KT group were significantly higher as compared to the WBC group. The activity of erythrocyte catalase and plasma ZnCu isoenzyme of superoxide dismutase showed a decreased tendency; erythrocyte total superoxide dismutase activity showed an increased tendency in the WBC group after the completion of the treatment. The BASDAI and BASFI decreased significantly in both groups, but the differences of value indexes prior to post treatment (Δ were significantly higher in the WBC than KT group. Conclusion. WBC performed in a closed cryochamber decreases oxidative stress and improves BASDAI and BASFI indexes in male patients during the active

  19. Effect of CAR activation on selected metabolic pathways in normal and hyperlipidemic mouse livers.

    Rezen, Tadeja; Tamasi, Viola; Lövgren-Sandblom, Anita; Björkhem, Ingemar; Meyer, Urs A; Rozman, Damjana

    2009-08-19

    Detoxification in the liver involves activation of nuclear receptors, such as the constitutive androstane receptor (CAR), which regulate downstream genes of xenobiotic metabolism. Frequently, the metabolism of endobiotics is also modulated, resulting in potentially harmful effects. We therefore used 1,4-Bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) to study the effect of CAR activation on mouse hepatic transcriptome and lipid metabolome under conditions of diet-induced hyperlipidemia. Using gene expression profiling with a dedicated microarray, we show that xenobiotic metabolism, PPARalpha and adipocytokine signaling, and steroid synthesis are the pathways most affected by TCPOBOP in normal and hyperlipidemic mice. TCPOBOP-induced CAR activation prevented the increased hepatic and serum cholesterol caused by feeding mice a diet containing 1% cholesterol. We show that this is due to increased bile acid metabolism and up-regulated removal of LDL, even though TCPOBOP increased cholesterol synthesis under conditions of hyperlipidemia. Up-regulation of cholesterol synthesis was not accompanied by an increase in mature SREBP2 protein. As determined by studies in CAR -/- mice, up-regulation of cholesterol synthesis is however CAR-dependent; and no obvious CAR binding sites were detected in promoters of cholesterogenic genes. TCPOBOP also affected serum glucose and triglyceride levels and other metabolic processes in the liver, irrespective of the diet. Our data show that CAR activation modulates hepatic metabolism by lowering cholesterol and glucose levels, through effects on PPARalpha and adiponectin signaling pathways, and by compromising liver adaptations to hyperlipidemia.

  20. The influence of physical activity on components of metabolic ...

    African Journal for Physical Activity and Health Sciences ... Inactivity causes obesity which is related to insulin resistance, hypertension, diabetes mellitus, ... of physical activity (PA) on the MS components and vascular function in children and ...

  1. Inhibition of the central melanocortin system decreases brown adipose tissue activity

    Kooijman, S.; Boon, M.R.; Parlevliet, E.T.; Geerling, J.J.; Pol, V. van de; Romijn, J.A.; Havekes, L.M.; Meurs, I.; Rensen, P.C.N.

    2014-01-01

    The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose

  2. SRS-A leukotrienes decrease the activity of human respiratory cilia

    Bisgaard, H; Pedersen, M

    1987-01-01

    We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured...

  3. Acute lymphoblastic leukemia and obesity : increased energy intake or decreased physical activity?

    Jansen, H.; Postma, A.; Stolk, R. P.; Kamps, W. A.

    Background Obesity is a well-known problem in children with acute lymphoblastic leukemia ( ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with

  4. Blocking hexose entry into glycolysis activates alternative metabolic conversion of these sugars and upregulates pentose metabolism in Aspergillus nidulans

    Khosravi, Claire; Battaglia, Evy; Kun, Roland S.; Dalhuijsen, Sacha; Visser, Jaap; Aguilar-Pontes, Maria V.; Zhou, Miamiao; Heyman, Heino M.; Kim, Young-Mo; Baker, Scott E.; de Vries, Ronald P.

    2018-03-22

    Background: Plant biomass is the most abundant carbon source for many fungal species. In the biobased industry fungi are used to produce lignocellulolytic enzymes to degrade agricultural waste biomass. Here we evaluated if it would be possible to create an Aspergillus nidulans strain that releases but does not metabolize hexoses from plant biomass. For this purpose, metabolic mutants were generated that were impaired in glycolysis, by using hexokinase (hxkA) and glucokinase (glkA) negative strains. To prevent repression of enzyme production due to the hexose accumulation, strains were generated that combined these mutations with a deletion in creA, the repressor involved in regulating preferential use of different carbon catabolic pathways. Results: Phenotypic analysis revealed reduced growth for the hxkA1 glkA4 mutant on wheat bran. However, hexoses did not accumulate during growth of the mutants on wheat bran, suggesting that glucose metabolism is re-routed towards alternative carbon catabolic pathways. The creAΔ4 mutation in combination with preventing initial phosphorylation in glycolysis resulted in better growth than the hxkA/glkA mutant and an increased expression of pentose catabolic and pentose phosphate pathway genes. This indicates that the reduced ability to use hexoses as carbon sources created a shift towards the pentose fraction of wheat bran as a major carbon source to support growth. Conclusion: Blocking the direct entry of hexoses to glycolysis activates alternative metabolic conversion of these sugars in A. nidulans during growth on plant biomass, but also upregulates conversion of other sugars, such as pentoses.

  5. Total physical activity volume, physical activity intensity, and metabolic syndrome: 1999-2004 National Health and Nutrition Examination Survey.

    Churilla, James R; Fitzhugh, Eugene C

    2012-02-01

    This study examined the association of total physical activity volume (TPAV) and physical activity (PA) from three domains [leisure-time physical activity (LTPA), domestic, transportation] with metabolic syndrome. We also investigated the relationship between LTPA intensity and metabolic syndrome risk. Sample included adults who participated in the 1999-2004 National Health and Nutrition Examination Survey. Physical activity measures were created for TPAV, LTPA, domestic PA, and transportational PA. For each, a six-level measure based upon no PA (level 1) and quintiles (levels 2-6) of metabolic equivalents (MET)·min·wk(-1) was created. A three-level variable associated with the current Department of Health and Human Services (DHHS) PA recommendation was also created. SAS and SUDAAN were used for the statistical analysis. Adults reporting the greatest volume of TPAV and LTPA were found to be 36% [odds ratio (OR) 0.64; 95% confidence interval (CI) 0.49-0.83] and 42% (OR 0.58; 95% CI 0.43-0.77), respectively, less likely to have metabolic syndrome. Domestic and transportational PA provided no specific level of protection from metabolic syndrome. Those reporting a TPAV that met the DHHS PA recommendation were found to be 33% (OR 0.67; 95%; CI 0.55-0.83) less likely to have metabolic syndrome compared to their sedentary counterparts. Adults reporting engaging in only vigorous-intensity LTPA were found to be 37% (OR 0.63; 95 CI 0.42-0.96) to 56% (OR 0.44; 95% CI 0.29-0.67) less likely to have metabolic syndrome. Volume, intensity, and domain of PA may all play important roles in reducing the prevalence and risk of metabolic syndrome.

  6. A Metabolic Biofuel Cell: Conversion of Human Leukocyte Metabolic Activity to Electrical Currents

    Cui X Tracy

    2011-05-01

    Full Text Available Abstract An investigation of the electrochemical activity of human white blood cells (WBC for biofuel cell (BFC applications is described. WBCs isolated from whole human blood were suspended in PBS and introduced into the anode compartment of a proton exchange membrane (PEM fuel cell. The cathode compartment contained a 50 mM potassium ferricyanide solution. Average current densities between 0.9 and 1.6 μA cm-2 and open circuit potentials (Voc between 83 and 102 mV were obtained, which were both higher than control values. Cyclic voltammetry was used to investigate the electrochemical activity of the activated WBCs in an attempt to elucidate the mechanism of electron transfer between the cells and electrode. Voltammograms were obtained for the WBCs, including peripheral blood mononuclear cells (PBMCs - a lymphocyte-monocyte mixture isolated on a Ficoll gradient, a B lymphoblastoid cell line (BLCL, and two leukemia cell lines, namely K562 and Jurkat. An oxidation peak at about 363 mV vs. SCE for the PMA (phorbol ester activated primary cells, with a notable absence of a reduction peak was observed. Oxidation peaks were not observed for the BLCL, K562 or Jurkat cell lines. HPLC confirmed the release of serotonin (5-HT from the PMA activated primary cells. It is believed that serotonin, among other biochemical species released by the activated cells, contributes to the observed BFC currents.

  7. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities.

    Abraham, Paul E; Giannone, Richard J; Xiong, Weili; Hettich, Robert L

    2014-06-17

    Contemporary microbial ecology studies usually employ one or more "omics" approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other "meta-omic" approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool. Copyright © 2014 John Wiley & Sons, Inc.

  8. High sugar and butter (HSB) diet induces obesity and metabolic syndrome with decrease in regulatory T cells in adipose tissue of mice.

    Maioli, Tatiani Uceli; Gonçalves, Juliana Lauar; Miranda, Mariana Camila Gonçalves; Martins, Vinícius Dantas; Horta, Laila Sampaio; Moreira, Thais Garcias; Godard, Ana Lucia Brunialti; Santiago, Andrezza Fernanda; Faria, Ana Maria Caetano

    2016-02-01

    The purpose of the study was to develop a novel diet based on standard AIN93G diet that would be able to induce experimental obesity and impair immune regulation with high concentrations of both carbohydrate and lipids. To compare the effects of this high sugar and butter (HSB) diet with other modified diets, male C57BL/6 mice were fed either mouse chow, or AIN93G diet, or high sugar (HS) diet, or high-fat (HF) diet, or high sugar and butter (HSB) diet for 11 weeks ad libitum. HSB diet induced higher weight gain. Therefore, control AIN93G and HSB groups were chosen for additional analysis. Regulatory T cells were studied by flow cytometry, and cytokine levels were measured by ELISA. Although HF and HSB diets were able to induce a higher weight gain compatible with obesity in treated mice, HSB-fed mice presented the higher levels of serum glucose after fasting and the lowest frequency of regulatory T cells in adipose tissue. In addition, mice that were fed HSB diet presented higher levels of cholesterol and triglycerides, hyperleptinemia, increased resistin and leptin levels as well as reduced adiponectin serum levels. Importantly, we found increased frequency of CD4(+)CD44(+) effector T cells, reduction of CD4(+)CD25(+)Foxp3(+) and Th3 regulatory T cells as well as decreased levels of IL-10 and TGF-β in adipose tissue of HSB-fed mice. Therefore, HSB represents a novel model of obesity-inducing diet that was efficient in triggering alterations compatible with metabolic syndrome as well as impairment in immune regulatory parameters.

  9. Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy

    Andrys, C.; Borska, L.; Pohl, D.; Fiala, Z.; Hamakova, K.; Krejsek, J. [Faculty Hospital, Hradec Kralove (Czech Republic). Dept. of Clinical Immunology & Allergy

    2007-03-15

    Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. It was found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

  10. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hy...

  11. Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.

    Jancinová, Viera; Perecko, Tomás; Nosál, Radomír; Kostálová, Daniela; Bauerová, Katarína; Drábiková, Katarína

    2009-06-10

    Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane.

  12. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    Dues, Dylan J.; Andrews, Emily K.; Schaar, Claire E.; Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxi...

  13. A knockout mutation of a constitutive GPCR in Tetrahymena decreases both G-protein activity and chemoattraction.

    Thomas J Lampert

    Full Text Available Although G-protein coupled receptors (GPCRs are a common element in many chemosensory transduction pathways in eukaryotic cells, no GPCR or regulated G-protein activity has yet been shown in any ciliate. To study the possible role for a GPCR in the chemoresponses of the ciliate Tetrahymena, we have generated a number of macronuclear gene knockouts of putative GPCRs found in the Tetrahymena Genome database. One of these knockout mutants, called G6, is a complete knockout of a gene that we call GPCR6 (TTHERM_00925490. Based on sequence comparisons, the Gpcr6p protein belongs to the Rhodopsin Family of GPCRs. Notably, Gpcr6p shares highest amino acid sequence homologies to GPCRs from Paramecium and several plants. One of the phenotypes of the G6 mutant is a decreased responsiveness to the depolarizing ions Ba²⁺ and K⁺, suggesting a decrease in basal excitability (decrease in Ca²⁺ channel activity. The other major phenotype of G6 is a loss of chemoattraction to lysophosphatidic acid (LPA and proteose peptone (PP, two known chemoattractants in Tetrahymena. Using microsomal [³⁵S]GTPγS binding assays, we found that wild-type (CU427 have a prominent basal G-protein activity. This activity is decreased to the same level by pertussis toxin (a G-protein inhibitor, addition of chemoattractants, or the G6 mutant. Since the basal G-protein activity is decreased by the GPCR6 knockout, it is likely that this gene codes for a constitutively active GPCR in Tetrahymena. We propose that chemoattractants like LPA and PP cause attraction in Tetrahymena by decreasing the basal G-protein stimulating activity of Gpcr6p. This leads to decreased excitability in wild-type and longer runs of smooth forward swimming (less interrupted by direction changes towards the attractant. Therefore, these attractants may work as inverse agonists through the constitutively active Gpcr6p coupled to a pertussis-sensitive G-protein.

  14. Metabolic and production profiles of dairy cows in response to decreased nutrient density to increase physiological imbalance at different stages of lactation.

    Bjerre-Harpøth, V; Friggens, N C; Thorup, V M; Larsen, T; Damgaard, B M; Ingvartsen, K L; Moyes, K M

    2012-05-01

    Physiological imbalance (PI) is a situation in which physiological parameters deviate from the normal, and cows consequently have an increased risk of developing production diseases and reduced production or reproduction. Our objectives were to (1) determine the effect of stage of lactation and milk yield on metabolic and production responses of cows during a nutrient restriction period to experimentally increase PI; (2) identify major metabolites that relate to degree of PI; and (3) identify potential biomarkers in milk for on-farm detection of PI throughout lactation. Forty-seven Holstein cows in early [n=14; 49±22 d in milk (DIM); parity=1.6±0.5], mid (n=15; 159±39 DIM; parity=1.5±0.5), and late (n=18; 273±3 DIM; parity=1.3±0.5) lactation were used. Prior to restriction, all cows were fed the same total mixed ration ad libitum. All cows were then nutrient restricted for 4 d by supplementing the ration with 60% wheat straw to induce PI. After restriction, cows returned to full feed. Daily milk yield was recorded and composite milk samples were analyzed for fat, protein, lactose, citrate, somatic cells, uric acid, alkaline phosphatase, β-hydroxybutyrate (BHBA), and milk urea nitrogen. Blood was collected daily and analyzed for metabolites: nonesterified fatty acids (NEFA), BHBA, glucose, plasma urea nitrogen, and insulin. The revised quantitative insulin sensitivity check index (RQUICKI) was calculated for each cow. Liver biopsies collected before and during restriction were analyzed for triglycerides, glycogen, phospholipids, glucose, and total lipid content. A generalized linear mixed model was used to determine the effect of stage of lactation on responses during restriction. Regression analyses were used to examine the effect of pre-restriction levels on changes during restriction. Similar decreases in milk yield among groups indicate that the capacity of individual responses is dependent on milk yield but the coping strategies used are dependent on

  15. Avoidant Responses to Interpersonal Provocation Are Associated with Increased Amygdala and Decreased Mentalizing Network Activity

    Krämer, Ulrike M.

    2017-01-01

    When intentionally pushed or insulted, one can either flee from the provoker or retaliate. The implementation of such fight-or-flight decisions is a central aspect in the genesis and evolution of aggression episodes, yet it is usually investigated only indirectly or in nonsocial situations. In the present fMRI study, we aimed to distinguish brain regions associated with aggressive and avoidant responses to interpersonal provocation in humans. Participants (thirty-six healthy young women) could either avoid or face a highly (HP) and a lowly (LP) provoking opponent in a competitive reaction time task: the fight-or-escape (FOE) paradigm. Subjects avoided the HP more often, but retaliated when facing her. Moreover, they chose to fight the HP more quickly, and showed increased heart rate (HR) right before confronting her. Orbitofrontal cortex (OFC) and sensorimotor cortex were more active when participants decided to fight, whereas the mentalizing network was engaged when deciding to avoid. Importantly, avoiding the HP relative to the LP was associated with both higher activation in the right basolateral amygdala and lower relative activity in several mentalizing regions [e.g., medial and inferior frontal gyrus (IFG), temporal-parietal junction (TPJ)]. These results suggest that avoidant responses to provocation might result from heightened threat anticipation and are associated with reduced perspective taking. Furthermore, our study helps to reconcile conflicting findings on the role of the mentalizing network, the amygdala, and the OFC in aggression. PMID:28660251

  16. Using an alternate reality game to increase physical activity and decrease obesity risk of college students.

    Johnston, Jeanne D; Massey, Anne P; Marker-Hoffman, Rickie Lee

    2012-07-01

    This quasi-experimental study investigated a game intervention--specifically, an alternate reality game (ARG)--as a means to influence college students' physical activity (PA). An ARG is an interactive narrative that takes place in the real world and uses multiple media to reveal a story. Three sections of a college health course (n = 115 freshman students) were assigned either to a game group that played the ARG or to a comparison group that learned how to use exercise equipment in weekly laboratory sessions. Pre- and post-intervention measures included weight, waist circumference, body mass index (BMI), percentage body fat (PBF), and self-reported moderate physical activity (MPA) and vigorous physical activity (VPA), and PA (steps/week). A significant group x time interaction (p = .001) was detected for PA, with a significant increase in PA for the game (p students--collaborative and social, experiential and media-rich. Our results provide preliminary evidence that a game intervention can positively influence PA within the college student population. © 2012 Diabetes Technology Society.

  17. Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

    Martha Canto-Bustos

    2017-09-01

    Full Text Available Motoneurons, the final common path of the Central Nervous System (CNS, are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we confirmed that extrasynaptic α5 subunit-containing GABAA receptors localize with choline acetyltransferase (ChAT positive cells, suggesting that these receptors are expressed in turtle motoneurons as previously reported in rodents. In these cells, α5GABAA receptors are activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the monosynaptic reflex (MSR induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.

  18. Decreased somatosensory activity to non-threatening touch in combat veterans with posttraumatic stress disorder.

    Badura-Brack, Amy S; Becker, Katherine M; McDermott, Timothy J; Ryan, Tara J; Becker, Madelyn M; Hearley, Allison R; Heinrichs-Graham, Elizabeth; Wilson, Tony W

    2015-08-30

    Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder prevalent in combat veterans. Previous neuroimaging studies have demonstrated that patients with PTSD exhibit abnormal responses to non-threatening visual and auditory stimuli, but have not examined somatosensory processing. Thirty male combat veterans, 16 with PTSD and 14 without, completed a tactile stimulation task during a 306-sensor magnetoencephalography (MEG) recording. Significant oscillatory neural responses were imaged using a beamforming approach. Participants also completed clinical assessments of PTSD, combat exposure, and depression. We found that veterans with PTSD exhibited significantly reduced activity during early (0-125 ms) tactile processing compared with combat controls. Specifically, veterans with PTSD had weaker activity in the left postcentral gyrus, left superior parietal area, and right prefrontal cortex in response to nonthreatening tactile stimulation relative to veterans without PTSD. The magnitude of activity in these brain regions was inversely correlated with symptom severity, indicating that those with the most severe PTSD had the most abnormal neural responses. Our findings are consistent with a resource allocation view of perceptual processing in PTSD, which directs attention away from nonthreatening sensory information. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Metabolic activity in dormant conidia of Aspergillus niger and developmental changes during conidial outgrowth

    Novodvorska, Michaela; Stratford, Malcolm; Blythe, Martin J.; Wilson, Raymond; Beniston, Richard G.; Archer, David B.

    2016-01-01

    The early stages of development of Aspergillus niger conidia during outgrowth were explored by combining genome-wide gene expression analysis (RNAseq), proteomics, Warburg manometry and uptake studies. Resting conidia suspended in water were demonstrated for the first time to be metabolically active as low levels of oxygen uptake and the generation of carbon dioxide were detected, suggesting that low-level respiratory metabolism occurs in conidia for maintenance. Upon triggering of spore germ...

  20. Goutweed (Aegopodium podagraria L. biological activity and the possibilities of its use for the correction of the lipid metabolism disorders

    O. Tovchiga

    2017-12-01

    Full Text Available The article summarizes data concerning the biological activity of the promising herbal raw material: aerial part of goutweed (Aegopodium podagraria L., Apiaceae. This plant since time immemorial has been used as vegetable and fodder plant as well as in folk medicine including the treatment of the metabolic disorders. Nowadays the interest in this plant increases. The technology of obtaining the extract and the tincture from goutweed aerial part is described, the chemical composition of these preparations is elucidated. Pharmacological effects of the preparations obtained from goutweed are characterized with the special emphasis on the possibilities of the lipid metabolism disorders correction and prevention. The presented experimental results substantiate the efficacy of goutweed extract and the tincture under the conditions of alimentary lipemia together with their safety in the intact animals. Thus, the hypolipidemic activity of goutweed extract (1 g/kg intragastrically and goutweed tincture (1 cm3/kg intragastrically was shown in the test with olive oil loading in rats. The extract appeared to be able to decrease significantly the level of triglycerides in blood plasma, while the tincture reduced the content of plasma total lipids. In the intact rats, the extract at doses of 100 mg/kg and 1 g/kg as well as the tincture at doses of 1 and 5 cm3/kg did not influence on the values of the lipid metabolism after 12 days of administration. Total and HDL cholesterol as well as atherogenic index and plasma total lipids level remained unchanged. In contast to the data previously obtained on the models of hyperuricemia, in the intact rats there were no changes in plasma uric acid concentration (which was determined proceeding from the role of the purine metabolism disorders in metabolic syndrome pathogenesis. Thus, goutweed preparations are characterized with the regulatory mode of action and sufficient level of safety. The development of drugs as

  1. Low Levels of Serum Paraoxonase Activities are Characteristic of Metabolic Syndrome and May Influence the Metabolic-Syndrome-Related Risk of Coronary Artery Disease

    Nicola Martinelli

    2012-01-01

    Full Text Available Low concentrations of plasma high-density lipoprotein (HDLs are characteristic in metabolic syndrome (MS. The antioxidant ability of HDLs is, at least in part, attributable to pleiotropic serum paraoxonase (PON1. Different PON1 activities have been assessed in 293 subjects with (=88 or without MS (=205 and with (=195 or without (=98 angiographically proven coronary artery disease (CAD. MS subjects had low PON1 activities, with a progressively decreasing trend by increasing the number of MS abnormalities. The activity versus 7-O-diethyl phosphoryl,3-cyano,4-methyl,7-hydroxycoumarin (DEPCyMC, which is considered a surrogate marker of PON1 concentration, showed the most significant association with MS, independently of both HDL and apolipoprotein A-I levels. Subjects with MS and low DEPCyMCase activity had the highest CAD risk (OR 4.34 with 95% CI 1.44–13.10, while no significant increase of risk was found among those with MS but high DEPCyMCase activity (OR 1.45 with 95% CI 0.47–4.46. Our results suggest that low PON1 concentrations are typical in MS and may modulate the MS-related risk of CAD.

  2. Low levels of serum paraoxonase activities are characteristic of metabolic syndrome and may influence the metabolic-syndrome-related risk of coronary artery disease.

    Martinelli, Nicola; Micaglio, Roberta; Consoli, Letizia; Guarini, Patrizia; Grison, Elisa; Pizzolo, Francesca; Friso, Simonetta; Trabetti, Elisabetta; Pignatti, Pier Franco; Corrocher, Roberto; Olivieri, Oliviero; Girelli, Domenico

    2012-01-01

    Low concentrations of plasma high-density lipoprotein (HDLs) are characteristic in metabolic syndrome (MS). The antioxidant ability of HDLs is, at least in part, attributable to pleiotropic serum paraoxonase (PON1). Different PON1 activities have been assessed in 293 subjects with (n = 88) or without MS (n = 205) and with (n = 195) or without (n = 98) angiographically proven coronary artery disease (CAD). MS subjects had low PON1 activities, with a progressively decreasing trend by increasing the number of MS abnormalities. The activity versus 7-O-diethyl phosphoryl,3-cyano,4-methyl,7-hydroxycoumarin (DEPCyMC), which is considered a surrogate marker of PON1 concentration, showed the most significant association with MS, independently of both HDL and apolipoprotein A-I levels. Subjects with MS and low DEPCyMCase activity had the highest CAD risk (OR 4.34 with 95% CI 1.44-13.10), while no significant increase of risk was found among those with MS but high DEPCyMCase activity (OR 1.45 with 95% CI 0.47-4.46). Our results suggest that low PON1 concentrations are typical in MS and may modulate the MS-related risk of CAD.

  3. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-08-01

    α- N -acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy.

  4. [A PARADIGM SHIFT IN THE PERCEPTION OF HEALTH MAINTENANCE FROM INCREASING PHYSICAL ACTIVITY TO DECREASING PHYSICAL INACTIVITY].

    Rotman, Dani; Constantini, Naama

    2016-06-01

    Modern man spends most of his waking hours (50-70%) in one form or another of sedentary behavior, defined as activity conducted in a sitting or reclining position involving low energy expenditure. The remaining waking hours are spent performing low intensity physical activity (25-45%) and medium-high intensity physical activity (less than 5%): Despite this distribution, medical research has focused on the impact of increasing medium-high intensity physical activity and many health organizations' recommendations are in accordance. In recent years, research conducted has begun to examine the effect inactivity has on health and has shown that excess sedentary behaviour is an independent risk factor for a wide range of medical problems such as obesity, metabolic syndrome, poor cardiovascular health profile, diabetes mellitus, and possibly cancer. Although the higher risk brought on by sedentary behaviour is partially reduced by increasing medium-high intensity physical activity, it is not completely neutralized. One way to diminish the harm caused by long hours of sitting is to take short breaks during periods of prolonged sitting in order to walk. According to these findings, it is worthwhile to recommend reducing the hours spent in sedentary behaviour, or at least to take frequent short breaks ("activity snacks") during periods of prolonged sitting to get up and walk around.

  5. Fe biomineralization mirrors individual metabolic activity in a nitrate-dependent Fe(II-oxidizer

    Jennyfer eMIOT

    2015-09-01

    Full Text Available Microbial biomineralization sometimes leads to periplasmic encrustation, which is predicted to enhance microorganism preservation in the fossil record. Mineral precipitation within the periplasm is however thought to induce death, as a result of permeability loss preventing nutrient and waste transit across the cell wall. This hypothesis had however never been investigated down to the single cell level. Here, we cultured the nitrate reducing Fe(II oxidizing bacteria Acidovorax sp. strain BoFeN1 that have been previously shown to promote the precipitation of a diversity of Fe minerals (lepidocrocite, goethite, Fe phosphate encrusting the periplasm. We investigated the connection of Fe biomineralization with carbon assimilation at the single cell level, using a combination of electron microscopy and Nano-Secondary Ion Mass Spectrometry (NanoSIMS. Our analyses revealed strong individual heterogeneities of Fe biomineralization. Noteworthy, a small proportion of cells remaining free of any precipitate persisted even at advanced stages of biomineralization. Using pulse chase experiments with 13C-acetate, we provide evidences of individual phenotypic heterogeneities of carbon assimilation, correlated with the level of Fe biomineralization. Whereas non- and moderately encrusted cells were able to assimilate acetate, higher levels of periplasm encrustation prevented any carbon incorporation. Carbon assimilation only depended on the level of Fe encrustation and not on the nature of Fe minerals precipitated in the cell wall. Carbon assimilation decreased exponentially with increasing cell-associated Fe content. Persistence of a small proportion of non-mineralized and metabolically active cells might constitute a strategy of survival in highly ferruginous environments. Eventually, our results suggest that periplasmic Fe biomineralization may provide a signature of individual metabolic status, which could be looked for in the fossil record and in modern

  6. Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS

    Dorte Glintborg

    2018-03-01

    Full Text Available Background/aims: Polycystic ovary syndrome (PCOS is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. Methods: Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n = 21 or placebo (n = 21. Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH test, 3-h oral glucose tolerance test (OGTT and filled in questionnaires regarding mental health and health-related quality of life (HRQoL: WHO Well-Being Index (WHO-5, Major Depression Inventory (MDI, Short Form 36 (SF-36 and PCOS questionnaire. Results: Included women were aged 31 (6 years (mean (s.d. and had body mass index (BMI 35.8 (6.5 kg/m2 and waist 102 (12 cm. Escitalopram was associated with increased waist (median (quartiles change 1 (0; 3 cm, P = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test, all P < 0.05 vs changes during placebo. Escitalopram had no significant effect on measures of insulin sensitivity, insulin secretion, fasting lipids, mental health or HRQoL. Conclusion: Waist circumference and cortisol levels increased during treatment with escitalopram in women with PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged.

  7. Hydroxyapatite nanocrystals functionalized with alendronate as bioactive components for bone implant coatings to decrease osteoclastic activity

    Bosco, Ruggero; Iafisco, Michele; Tampieri, Anna; Jansen, John A.; Leeuwenburgh, Sander C. G.; van den Beucken, Jeroen J. J. P.

    2015-02-01

    The integration of bone implants within native bone tissue depends on periprosthetic bone quality, which is severely decreased in osteoporotic patients. In this work, we have synthesized bone-like hydroxyapatite nanocrystals (nHA) using an acid-base neutralization reaction and analysed their physicochemical properties. Subsequently, we have functionalized the nHA with alendronate (nHAALE), a well-known bisphosphonate drug used for the treatment of osteoporosis. An in vitro osteoclastogenesis test was carried out to evaluate the effect of nHAALE on the formation of osteoclast-like cells from monocytic precursor cells (i.e. RAW264.7 cell line) showing that nHAALE significantly promoted apoptosis of osteoclast-like cells. Subsequently, nHA and nHAALE were deposited on titanium disks using electrospray deposition (ESD), for which characterisation of the deposited coatings confirmed the presence of alendronate in nHAALE coatings with nanoscale thickness of about 700 nm. These results indicate that alendronate linked to hydroxyapatite nanocrystals has therapeutic potential and nHAALE can be considered as an appealing coating constituent material for orthopaedic and oral implants for application in osteoporotic patients.

  8. Heavy metal pollution decreases microbial abundance, diversity and activity within particle-size fractions of a paddy soil.

    Chen, Junhui; He, Feng; Zhang, Xuhui; Sun, Xuan; Zheng, Jufeng; Zheng, Jinwei

    2014-01-01

    Chemical and microbial characterisations of particle-size fractions (PSFs) from a rice paddy soil subjected to long-term heavy metal pollution (P) and nonpolluted (NP) soil were performed to investigate whether the distribution of heavy metals (Cd, Cu, Pb and Zn) regulates microbial community activity, abundance and diversity at the microenvironment scale. The soils were physically fractionated into coarse sand, fine sand, silt and clay fractions. Long-term heavy metal pollution notably decreased soil basal respiration (a measurement of the total activity of the soil microbial community) and microbial biomass carbon (MBC) across the fractions by 3-45% and 21-53%, respectively. The coarse sand fraction was more affected by pollution than the clay fraction and displayed a significantly lower MBC content and respiration and dehydrogenase activity compared with the nonpolluted soils. The abundances and diversities of bacteria were less affected within the PSFs under pollution. However, significant decreases in the abundances and diversities of fungi were noted, which may have strongly contributed to the decrease in MBC. Sequencing of denaturing gradient gel electrophoresis bands revealed that the groups Acidobacteria, Ascomycota and Chytridiomycota were clearly inhibited under pollution. Our findings suggest that long-term heavy metal pollution decreased the microbial biomass, activity and diversity in PSFs, particularly in the large-size fractions. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  9. Effects of decreased muscle activity on developing axial musculature in nic b107 mutant zebrafish (Danio rerio)

    Meulen, van der T.; Schipper, H.; Leeuwen, van J.L.; Kranenbarg, S.

    2005-01-01

    The present paper discusses the effects of decreased muscle activity (DMA) on embryonic development in the zebrafish. Wild-type zebrafish embryos become mobile around 18 h post-fertilisation, long before the axial musculature is fully differentiated. As a model for DMA, the nicb107 mutant was used.

  10. Development of low radio-activated cement. Characteristics of cement and clinker that decreased liquid phase content

    Ichitsubo, Koki

    2008-01-01

    Low radio-activated cement was developed by decreasing the parent elements of radionuclides in the materials. The characteristics of products, decreasing method of Na, Eu and Co in cement, design, tests, evaluation, and analysis of low radio-activated cement clinker are reported. In order to decrease the content of Na, Eu and Co, the raw materials have to include natural materials such as limestone and silica stone. The production method is the same as white cement. The low radio-activated cement produced by rotary kiln showed 4.9% C 3 A, 1.1% C 4 AF, 26.9% C 3 S and 61.0% C 2 S, which values were standardized by the Japanese Industrial Standards (JIS) of low temperature Portland cement. Another product that decreased a little more liquid phase content showed 4.0% C 3 A, 1.0% C 4 AF, 32.3% C 3 S and 56.5% C 2 S, which was standardized by JIS of sulfate resisting Portland cement. In the case of decommissioning reactor constructed by the low radio-activated cement, the whole amount of waste cement will be no more than the clearance level. (S.Y.)

  11. Biatriosporin D displays anti-virulence activity through decreasing the intracellular cAMP levels

    Zhang, Ming; Chang, Wenqiang; Shi, Hongzhuo; Zhou, Yanhui; Zheng, Sha; Li, Ying; Li, Lin; Lou, Hongxiang, E-mail: louhongxiang@sdu.edu.cn

    2017-05-01

    Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans. Of note is the high efficacy of BD in preventing filamentation with a much lower dose than its MIC value. Furthermore, BD prolonged the survival of worms infected by C. albicans in vivo. Quantitative real-time PCR analysis, exogenous cAMP rescue experiments and intracellular cAMP measurements revealed that BD regulates the Ras1-cAMP-Efg1 pathway by reducing cAMP levels to inhibit the hyphal formation. Further investigation showed that BD could upregulate Dpp3 to synthesize much more farnesol, which could inhibit the activity of Cdc35 and reduce the generation of cAMP. Taken together, these findings indicate that BD stimulates the expression of Dpp3 to synthesize more farnesol that directly inhibits the Cdc35 activity, reducing intracellular cAMP and thereby disrupting the morphologic transition and attenuating the virulence of C. albicans. Our study uncovers the underlying mechanism of BD as a prodrug in fighting against pathogenic C. albicans and provides a potential application of BD in fighting clinically relevant fungal infections by targeting fungal virulence. - Highlights: • BD inhibits the filamentation of C. albicans in multiple hypha-inducing conditions. • BD can prolong the survival of nematodes infected by C. albicans. • BD stimulates the expression of Dpp3 to synthesize more farnesol. • BD reduces intracellular cAMP and regulates Ras1-cAMP-PKA pathway.

  12. Goatpoxvirus ATPase activity is increased by dsDNA and decreased by zinc ion.

    Lee, Ming-Liang; Hsu, Wei-Li; Wang, Chi-Young; Chen, Hui-Yu; Lin, Fong-Yuan; Chang, Ming-Huang; Chang, Hong-You; Wong, Min-Liang; Chan, Kun-Wei

    2016-10-01

    Viral-encoded ATPase can act as a part of molecular motor in genome packaging of DNA viruses, such as vaccinia virus and adenovirus, by ATP hydrolysis and interaction with DNA. Poxviral ATPase (also called A32) is involved in genomic double-stranded DNA (dsDNA) encapsidation, and inhibition of the expression of A32 causes formation of immature virions lacking viral DNA. However, the role of A32 in goatpoxvirus genome packaging and its dsDNA binding property are not known. In this study, purified recombinant goatpoxvirus A32 protein (rA32) was examined for its dsDNA binding property as well as the effect of dsDNA on ATP hydrolysis. We found that rA32 could bind dsDNA, and its ATPase activity was significant increased with dsDNA binding. Effects of magnesium and calcium ions on ATP hydrolysis were investigated also. The ATPase activity was dramatically enhanced by dsDNA in the presence of Mg(2+); in contrast, ATPase function was not altered by Ca(2+). Furthermore, the enzyme activity of rA32 was completely blocked by Zn(2+). Regarding DNA-protein interaction, the rA32-ATP-Mg(2+) showed lower dsDNA binding affinity than that of rA32-ATP-Ca(2+). The DNA-protein binding was stronger in the presence of zinc ion. Our results implied that A32 may play a role in viral genome encapsidation and DNA condensation.

  13. Biatriosporin D displays anti-virulence activity through decreasing the intracellular cAMP levels

    Zhang, Ming; Chang, Wenqiang; Shi, Hongzhuo; Zhou, Yanhui; Zheng, Sha; Li, Ying; Li, Lin; Lou, Hongxiang

    2017-01-01

    Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans. Of note is the high efficacy of BD in preventing filamentation with a much lower dose than its MIC value. Furthermore, BD prolonged the survival of worms infected by C. albicans in vivo. Quantitative real-time PCR analysis, exogenous cAMP rescue experiments and intracellular cAMP measurements revealed that BD regulates the Ras1-cAMP-Efg1 pathway by reducing cAMP levels to inhibit the hyphal formation. Further investigation showed that BD could upregulate Dpp3 to synthesize much more farnesol, which could inhibit the activity of Cdc35 and reduce the generation of cAMP. Taken together, these findings indicate that BD stimulates the expression of Dpp3 to synthesize more farnesol that directly inhibits the Cdc35 activity, reducing intracellular cAMP and thereby disrupting the morphologic transition and attenuating the virulence of C. albicans. Our study uncovers the underlying mechanism of BD as a prodrug in fighting against pathogenic C. albicans and provides a potential application of BD in fighting clinically relevant fungal infections by targeting fungal virulence. - Highlights: • BD inhibits the filamentation of C. albicans in multiple hypha-inducing conditions. • BD can prolong the survival of nematodes infected by C. albicans. • BD stimulates the expression of Dpp3 to synthesize more farnesol. • BD reduces intracellular cAMP and regulates Ras1-cAMP-PKA pathway.

  14. METABOLIC SYNDROME AND PHYSICAL ACTIVITY IN CHILEAN IMMIGRANTS LIVING IN RIO GALLEGOS, SANTA CRUZ, ARGENTINA.

    Inger Sally Padilla

    2012-12-01

    Full Text Available To study the frequency of metabolic syndrome, its components and its relationship with physical activity in Chilean immigrants living in Río Gallegos, Santa Cruz, Argentina.314 Chilean immigrants (165 women and 149 men were interviewed in Rio Gallegos in 2010, with healthy status in medical records (2000. Anthropometry, blood pressure control, blood test to measure glucose, triglycerides and HDL cholesterol were determined. Metabolic syndrome was established by criteria of the NCEPATPIII.The metabolic syndrome had an overall prevalence of 28.9% (95%CI: 23.9 to 34. Metabolic syndrome prevalence was larger in women (32.1% than in men (25.5%. The prevalence of its components were: abdominal obesity 56%, low levels of HDL cholesterol 48.3%, high levels of triglycerides 68.1%, hypertension 46.1% and high levels of glucose 72.5%. Inadequate physical activity was 66.2% (95%CI: 60.1 to 71.5. Immigrants had more likelihood of metabolic syndrome living in Río Gallegos for 15 years or more(β: 5.74,95%CI:2,81-11,73, p=0.000 and with inadequate physical activity (β: 3.36, 95%CI: 1.57to7.21,p=0.002. The prevalence of metabolic syndrome in Chilean immigrants living in Río Gallegos is higher than that reported in Argentina and Chile

  15. Effect of Carbon Monoxide on Active Oxygen Metabolism of Postharvest Jujube

    Shaoying Zhang; Qin Li; Yulan Mao

    2014-01-01

    To prolong the shelf life postharvest jujube, the effect of carbon monoxide (CO) on senescence of postharvest jujube in relation to active oxygen metabolism was investigated. Jujubes were fumigated with CO gas at 5, 10, 20 or 40μmol/L for 1 h, and then stored for 30 days at room temperature. Changes in membrane permeability, malonaldehyde (MDA), H2O2, O2•− content, and activities of active oxygen metabolism associated enzymes including superoxide dismutase (SOD), catalase (CAT) and peroxidase...

  16. Differential CT Attenuation of Metabolically Active and Inactive Adipose Tissues — Preliminary Findings

    Hu, Houchun H.; Chung, Sandra A.; Nayak, Krishna S.; Jackson, Hollie A.; Gilsanz, Vicente

    2010-01-01

    This study investigates differences in CT Hounsfield units (HUs) between metabolically active (brown fat) and inactive adipose tissues (white fat) due to variations in their densities. PET/CT data from 101 pediatric and adolescent patients were analyzed. Regions of metabolically active and inactive adipose tissues were identified and standard uptake values (SUVs) and HUs were measured. HUs of active brown fat were more positive (p<0.001) than inactive fat (−62.4±5.3 versus −86.7±7.0) and the difference was observed in both males and females. PMID:21245691

  17. Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR

    Kavita Jadhav

    2018-03-01

    Full Text Available Objectives: Activation of the bile acid (BA receptors farnesoid X receptor (FXR or G protein-coupled bile acid receptor (GPBAR1; TGR5 improves metabolic homeostasis. In this study, we aim to determine the impact of pharmacological activation of bile acid receptors by INT-767 on reversal of diet-induced metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's effects on metabolic parameters. Methods: Wild-type (WT, Tgr5−/−, Fxr−/−, Apoe−/− and Shp−/− mice were used to investigate whether and how BA receptor activation by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet-induced metabolic disorders. Results: INT-767 reversed HFD-induced obesity dependent on activation of both TGR5 and FXR and also reversed the development of atherosclerosis and non-alcoholic fatty liver disease (NAFLD. Mechanistically, INT-767 improved hypercholesterolemia by activation of FXR and induced thermogenic genes via activation of TGR5 and/or FXR. Furthermore, INT-767 inhibited several lipogenic genes and de novo lipogenesis in the liver via activation of FXR. We identified peroxisome proliferation-activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (CEBPα as novel FXR-regulated genes. FXR inhibited PPARγ expression by inducing small heterodimer partner (SHP whereas the inhibition of CEBPα by FXR was SHP-independent. Conclusions: BA receptor activation can reverse obesity, NAFLD, and atherosclerosis by specific activation of FXR or TGR5. Our data suggest that, compared to activation of FXR or TGR5 only, dual activation of both FXR and TGR5 is a more attractive strategy for treatment of common metabolic disorders. Keywords: Farnesoid X receptor, TGR5, Atherosclerosis, Obesity, NAFLD

  18. Molecular dynamics characterization of five pathogenic factor X mutants associated with decreased catalytic activity

    Abdel-Azeim, Safwat

    2014-11-11

    Factor X (FX) is one of the major players in the blood coagulation cascade. Upon activation to FXa, it converts prothrombin to thrombin, which in turn converts fibrinogen into fibrin (blood clots). FXa deficiency causes hemostasis defects, such as intracranial bleeding, hemathrosis, and gastrointestinal blood loss. Herein, we have analyzed a pool of pathogenic mutations, located in the FXa catalytic domain and directly associated with defects in enzyme catalytic activity. Using chymotrypsinogen numbering, they correspond to D102N, T135M, V160A, G184S, and G197D. Molecular dynamics simulations were performed for 1.68 μs on the wild-type and mutated forms of FXa. Overall, our analysis shows that four of the five mutants considered, D102N, T135M, V160A, and G184S, have rigidities higher than those of the wild type, in terms of both overall protein motion and, specifically, subpocket S4 flexibility, while S1 is rather insensitive to the mutation. This acquired rigidity can clearly impact the substrate recognition of the mutants.

  19. Menadione (Vitamin K3) decreases melanin synthesis through ERK activation in Mel-Ab cells.

    Kim, Eun-Hyun; Kim, Myo-Kyoung; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Park, Kyoung-Chan; Kim, Dong-Seok

    2013-10-15

    Menadione is a synthetic vitamin K3 derivative. Here, we examined the effects of menadione on melanogenesis and its related signaling pathways. Our results showed that melanin content was significantly reduced after menadione treatment in a dose-dependent manner. However, menadione treatment did not reduce tyrosinase activity directly. Wnt signaling is known to play a major role in the control of melanin synthesis. Thus, we tested the effects of menadione treatment on GSK3β and β-catenin signaling, but found that menadione did not influence either of these signaling pathways. We also investigated changes in the phosphorylation of ERK, which is related to melanin regulation. These results indicated that menadione treatment led to the phosphorylation of ERK. Additionally, menadione treatment reduced both MITF and tyrosinase protein levels. Treatment with PD98059, a specific ERK pathway inhibitor, restored menadione-induced melanin reduction and also prevented MITF and tyrosinase downregulation by menadione. These results suggest that the hypopigmentary action of menadione is due to MITF and tyrosinase downregulation by ERK activation. © 2013 Elsevier B.V. All rights reserved.

  20. Molecular dynamics characterization of five pathogenic factor X mutants associated with decreased catalytic activity

    Abdel-Azeim, Safwat; Oliva, Romina M.; Chermak, Edrisse; De Cristofaro, Raimondo; Cavallo, Luigi

    2014-01-01

    Factor X (FX) is one of the major players in the blood coagulation cascade. Upon activation to FXa, it converts prothrombin to thrombin, which in turn converts fibrinogen into fibrin (blood clots). FXa deficiency causes hemostasis defects, such as intracranial bleeding, hemathrosis, and gastrointestinal blood loss. Herein, we have analyzed a pool of pathogenic mutations, located in the FXa catalytic domain and directly associated with defects in enzyme catalytic activity. Using chymotrypsinogen numbering, they correspond to D102N, T135M, V160A, G184S, and G197D. Molecular dynamics simulations were performed for 1.68 μs on the wild-type and mutated forms of FXa. Overall, our analysis shows that four of the five mutants considered, D102N, T135M, V160A, and G184S, have rigidities higher than those of the wild type, in terms of both overall protein motion and, specifically, subpocket S4 flexibility, while S1 is rather insensitive to the mutation. This acquired rigidity can clearly impact the substrate recognition of the mutants.

  1. NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

    Iversen, Marie Beck; Jensen, Simon Kok; Hansen, Anne Louise

    2015-01-01

    . The marine sponge derived lipid αGalCer has recently been demonstrated as a specific agonist for activation of human and murine NKT cells. In the present study we investigated the applicability of αGalCer pre-treatment for immune protection against intra-vaginal HSV-2 infection. We found that C57BL/6 WT mice...... that received local pre-treatment with αGalCer prior to intra-vaginal HSV-2 infection had a lower mean disease score, mortality and viral load in the vagina following infection, compared to mice that did not receive αGalCer pre-treatment. Further, we found increased numbers of CD45 and NK1.1 positive cells...... in vaginal tissue and elevated levels of IFN-γ in the vaginal tissue and in vaginal fluids 24h after αGalCer pre-treatment. Collectively our data demonstrate a protective effect of αGalCer induced activation of NKT cells in the innate immune protection against viral infection....

  2. Decreased physical activity attributable to higher body mass index influences fibromyalgia symptoms.

    Vincent, Ann; Clauw, Daniel; Oh, Terry H; Whipple, Mary O; Toussaint, Loren L

    2014-09-01

    Although previous studies report associations between increased body mass index (BMI) and fibromyalgia symptoms, there is uncertainty as to whether this relationship is driven by physical factors, psychological factors, or both. To assess these relationships in a clinical sample of patients with fibromyalgia. Cross-sectional study. Tertiary care facility. A total of 686 patients from an existing national fibromyalgia registry. Patients completed a demographic form and self-report questionnaires including the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), the Medical Outcomes Study Short Form-36 (SF-36), the Brief Pain Inventory (BPI), and the 30-item Profile of Mood States (30-item POMS). FIQ-R overall impact subscale. BMI was significantly correlated with fibromyalgia impact (P BMI and fibromyalgia impact was almost fully accounted for by physical factors and not by psychological factors. Despite patient report that pain hinders physical activity, clinicians who encounter patients with fibromyalgia, particularly patients with increased BMI, should be cognizant of the need to invest time and resources to counsel patients on physical factors (ie, physical activity) that could improve the patients' symptom experience. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  3. Metabolic organization and effects of feeding on enzyme activities of the dogfish shark (Squalus acanthias) rectal gland.

    Walsh, Patrick J; Kajimura, Makiko; Mommsen, Thomas P; Wood, Chris M

    2006-08-01

    In order to investigate the metabolic poise of the elasmobranch rectal gland, we conducted two lines of experimentation. First, we examined the effects of feeding on plasma metabolites and enzyme activities from several metabolic pathways in several tissues of the dogfish shark, Squalus acanthias, after starvation and at 6, 20, 30 and 48 h post-feeding. We found a rapid and sustained ten-fold decrease in plasma beta-hydroxybutyrate at 6 h and beyond compared with starved dogfish, suggesting an upregulation in the use of this substrate, a decrease in production, or both. Plasma acetoacetate levels remain unchanged, whereas there was a slight and transient decrease in plasma glucose levels at 6 h. Several enzymes showed a large increase in activity post-feeding, including beta-hydroxybutyrate dehydrogenase in rectal gland and liver, and in rectal gland, isocitrate dehydrogenase, citrate synthase, lactate dehydrogenase, aspartate amino transferase, alanine amino transferase, glutamine synthetase and Na(+)/K(+) ATPase. Also notable in these enzyme measurements was the overall high level of activity in the rectal gland in general. For example, activity of the Krebs' TCA cycle enzyme citrate synthase (over 30 U g(-1)) was similar to activities in muscle from other species of highly active fish. Surprisingly, lactate dehydrogenase activity in the gland was also high (over 150 U g(-1)), suggesting either an ability to produce lactate anaerobically or use lactate as an aerobic fuel. Given these interesting observations, in the second aspect of the study we examined the ability of several metabolic substrates (alone and in combination) to support chloride secretion by the rectal gland. Among the substrates tested at physiological concentrations (glucose, beta-hydroxybutyrate, lactate, alanine, acetoacetate, and glutamate), only glucose could consistently maintain a viable preparation. Whereas beta-hydroxybutyrate could enhance gland activity when presented in combination

  4. Metabolic in Vivo Labeling Highlights Differences of Metabolically Active Microbes from the Mucosal Gastrointestinal Microbiome between High-Fat and Normal Chow Diet

    Oberbach, Andreas; Haange, Sven Bastiaan; Schlichting, Nadine; Heinrich, Marco; Lehmann, Stefanie; Till, Holger; Hugenholtz, Floor; Kullnick, Yvonne; Smidt, Hauke; Frank, Karin; Seifert, Jana; Jehmlich, Nico; Bergen, Von Martin

    2017-01-01

    The gastrointestinal microbiota in the gut interacts metabolically and immunologically with the host tissue in the contact zone of the mucus layer. For understanding the details of these interactions and especially their dynamics it is crucial to identify the metabolically active subset of the

  5. Relationship between metabolism and ovarian activity in dairy cows with different dry period lengths

    Chen, J.C.; Soede, N.M.; Dorland, van H.A.; Remmelink, G.J.; Bruckmaier, R.M.; Kemp, B.; Knegsel, van A.T.M.

    2015-01-01

    The objectives of the present study were to evaluate the effects of dry period length on ovarian activity in cows fed a lipogenic or a glucogenic diet within 100 days in milk (DIM) and to determine relationships between ovarian activity and energy balance and metabolic status in early lactation.

  6. Effectiveness of physical activity intervention among government employees with metabolic syndrome.

    Huei Phing, Chee; Abu Saad, Hazizi; Barakatun Nisak, M Y; Mohd Nasir, M T

    2017-12-01

    Our study aimed to assess the effects of physical activity interventions via standing banners (point-of-decision prompt) and aerobics classes to promote physical activity among individuals with metabolic syndrome. We conducted a cluster randomized controlled intervention trial (16-week intervention and 8-week follow-up). Malaysian government employees in Putrajaya, Malaysia, with metabolic syndrome were randomly assigned by cluster to a point-of-decision prompt group (n = 44), an aerobics group (n = 42) or a control group (n = 103) based on sample size calculation formula. Step counts were evaluated by Lifecorder e-STEP accelerometers for all participants. Metabolic syndrome was defined according to the 'harmonizing' definition, in which individuals who have at least three of the five metabolic risk factors (waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose levels, systolic and diastolic blood pressure) will be classified as having metabolic syndrome. A total of 80% of the enrolled government employees with metabolic syndrome completed the programme. Data were analyzed using SPSS for Windows (version 20, SPSS, Chicago, IL). There were significantly higher step counts on average in the aerobics group compared to the control group over assessments. Assessments at baseline, post-intervention and follow-up showed a significant difference in step counts between the intervention and control groups. The greatest reductions in the proportions of individuals with metabolic syndrome were observed in the aerobics group with a reduction of 79.4% in the post-intervention assessment compared to the assessment at baseline. The findings of this study suggest that physical activity intervention via aerobics classes is an effective strategy for improving step counts and reducing the prevalence of metabolic syndrome.

  7. Association of physical activity with metabolic syndrome in a predominantly rural Nigerian population.

    Oguoma, Victor M; Nwose, Ezekiel U; Skinner, Timothy C; Richards, Ross S; Digban, Kester A; Onyia, Innocent C

    2016-01-01

    Physical activity is an essential determinant of health. However, there is dearth of evidence regarding prevalence of physical activity in developing countries, especially its association with metabolic syndrome risk factors. This study assessed the association of physical activity with metabolic syndrome in a Nigerian population. A cross-sectional study was carried out on apparently healthy persons who are ≥ 18 years old. The World Health Organisation (WHO) Global Physical Activity Questionnaire (GPAQ) was used to collect five domains of physical activity. Participants were classified as physically active or inactive based on meeting the cut-off value of 600 MET-min/week. Metabolic syndrome was diagnosed using the Joint Scientific Statement on Harmonizing the Metabolic Syndrome criteria. Overall prevalence of physically active individuals was 50.1% (CI: 45.6-54.7%). Physical inactivity is significantly more in females (p40 years old (pmetabolic syndrome appeared more likely to be physically active (OR=1.48, CI: 0.71-3.09); physical inactivity showed to exist more among participants who were living in urban area (OR=6.61, CI: 3.40-12.85, pmetabolic syndrome risk factors. The high prevalence of physical inactivity in this study population is a clear indication that concerted efforts to improve physical activity may be required. However, it seems that metabolic syndrome is not improved by being physically active. This suggests that interventions directed at physical activity alone may not produce optimal efficacy in this study population. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  8. RISK DECREASE PROBLEM WITH MAKING ERRORS IN ACTIVITY OF OPERATORS DEALING WITH AUTOMATIC CONTROL SYSTEMS OF GAS-DISTRIBUTION STATIONS

    V. V. Egorov

    2011-01-01

    Full Text Available The paper contains an analysis of specific features pertaining to the activity of operators dealing with automatic control systems of gas-distribution stations. The professional operator’s activity is presented in the form of the developed data model. Possible conceptual approaches to the research are analyzed in the paper. The paper describes an author’s approach to studying a risk decrease problem in the activity of operators on the basis of the analytical research results. Technology for obtaining  research results is cited in the paper. 

  9. Decrease of GSK3β phosphorylation in the rat nucleus accumbens core enhances cocaine-induced hyper-locomotor activity.

    Kim, Wha Y; Jang, Ju K; Lee, Jung W; Jang, Hyunduk; Kim, Jeong-Hoon

    2013-06-01

    Glycogen synthase kinase 3β (GSK3β), which is abundantly present in the brain, is known to contribute to psychomotor stimulant-induced locomotor behaviors. However, most studies have been focused in showing that GSK3β is able to attenuate psychomotor stimulants-induced hyperactivity by increasing its phosphorylation levels in the nucleus accumbens (NAcc). So, here we examined in the opposite direction about the effects of decreased phosphorylation of GSK3β in the NAcc core on both basal and cocaine-induced locomotor activity by a bilateral microinjection into this site of an artificially synthesized peptide, S9 (0.5 or 5.0 μg/μL), which contains sequences around N-terminal serine 9 residue of GSK3β. We found that decreased levels of GSK3β phosphorylation in the NAcc core enhance cocaine-induced hyper-locomotor activity, while leaving basal locomotor activity unchanged. This is the first demonstration, to our knowledge, that the selective decrease of GSK3β phosphorylation levels in the NAcc core may contribute positively to cocaine-induced locomotor activity, while this is not sufficient for the generation of locomotor behavior by itself without cocaine. Taken together, these findings importantly suggest that GSK3β may need other molecular targets which are co-activated (or deactivated) by psychomotor stimulants like cocaine to contribute to generation of locomotor behaviors. © 2013 International Society for Neurochemistry.

  10. Decreased bacteria activity on Si3N4 surfaces compared with PEEK or titanium

    Puckett S

    2012-09-01

    Full Text Available Deborah Gorth,1 Sabrina Puckett,1 Batur Ercan,1 Thomas J Webster,1 Mohamed Rahaman,2 B Sonny Bal31School of Engineering and Department of Orthopaedics, Brown University, Providence, RI, 2Department of Materials Science and Engineering, Missouri University of Science and Technology, Rolla, MO, 3Department of Orthopaedic Surgery, School of Medicine, University of Missouri, Columbia, MO, USAAbstract: A significant need exists for orthopedic implants that can intrinsically resist bacterial colonization. In this study, three biomaterials that are used in spinal implants – titanium (Ti, poly-ether-ether-ketone (PEEK, and silicon nitride (Si3N4 – were tested to understand their respective susceptibility to bacterial infection with Staphylococcus epidermidis, Staphlococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus. Specifically, the surface chemistry, wettability, and nanostructured topography of respective biomaterials, and the effects on bacterial biofilm formation, colonization, and growth were investigated. Ti and PEEK were received with as-machined surfaces; both materials are hydrophobic, with net negative surface charges. Two surface finishes of Si3N4 were examined: as-fired and polished. In contrast to Ti and PEEK, the surface of Si3N4 is hydrophilic, with a net positive charge. A decreased biofilm formation was found, as well as fewer live bacteria on both the as-fired and polished Si3N4. These differences may reflect differential surface chemistry and surface nanostructure properties between the biomaterials tested. Because protein adsorption on material surfaces affects bacterial adhesion, the adsorption of fibronectin, vitronectin, and laminin on Ti, PEEK, and Si3N4 were also examined. Significantly greater amounts of these proteins adhered to Si3N4 than to Ti or PEEK. The findings of this study suggest that surface properties of biomaterials lead to differential adsorption of physiologic proteins, and that this

  11. Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.

    Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer Mi; Doh, Kyung-Oh; Hui, Chi-Chung; Sung, Hoon-Ki

    2017-11-01

    Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

  12. Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage

    Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer MI; Doh, Kyung-Oh; Hui, Chi-chung; Sung, Hoon-Ki

    2017-01-01

    Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders. PMID:29039412

  13. Impaired hippocampal glucose metabolism during and after flurothyl-induced seizures in mice: Reduced phosphorylation coincides with reduced activity of pyruvate dehydrogenase.

    McDonald, Tanya S; Borges, Karin

    2017-07-01

    To determine changes in glucose metabolism and the enzymes involved in the hippocampus ictally and postictally in the acute mouse flurothyl seizure model. [U- 13 C]-Glucose was injected (i.p.) prior to, or following a 5 min flurothyl-induced seizure. Fifteen minutes later, mice were killed and the total metabolite levels and % 13 C enrichment were analyzed in the hippocampal formation using gas chromatography-mass spectrometry. Activities of key metabolic and antioxidant enzymes and the phosphorylation status of pyruvate dehydrogenase were measured, along with lipid peroxidation. During seizures, total lactate levels increased 1.7-fold; however, [M + 3] enrichment of both lactate and alanine were reduced by 30% and 43%, respectively, along with a 28% decrease in phosphofructokinase activity. Postictally the % 13 C enrichments of all measured tricarboxylic acid (TCA) cycle intermediates and the amino acids were reduced by 46-93%. At this time, pyruvate dehydrogenase (PDH) activity was 56% of that measured in controls, and there was a 1.9-fold increase in the phosphorylation of PDH at ser232. Phosphorylation of PDH is known to decrease its activity. Here, we show that the increase of lactate levels during flurothyl seizures is from a source other than [U- 13 C]-glucose, such as glycogen. Surprisingly, although we saw a reduction in phosphofructokinase activity during the seizure, metabolism of [U- 13 C]-glucose into the TCA cycle seemed unaffected. Similar to our recent findings in the chronic phase of the pilocarpine model, postictally the metabolism of glucose by glycolysis and the TCA cycle was impaired along with reduced PDH activity. Although this decrease in activity may be a protective mechanism to reduce oxidative stress, which is observed in the flurothyl model, ATP is critical to the recovery of ion and neurotransmitter balance and return to normal brain function. Thus we identified promising novel strategies to enhance energy metabolism and recovery from

  14. HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation

    Yadav, Anjana; Pati, Shibani; Nyugen, Anhthu; Barabitskaja, Oxana; Mondal, Prosanta; Anderson, Michael; Gallo, Robert C.; Huso, David L.; Reid, William

    2006-01-01

    Impaired CD4+ T cell responses, resulting in dysregulated T-helper 1 (Th1) effector and memory responses, are a common result of HIV-1 infection. These defects are often preceded by decreased expression and function of the α/β T cell receptor (TCR)-CD3 complex and of co-stimulatory molecules including CD28, resulting in altered T cell proliferation, cytokine secretion and cell survival. We have previously shown that HIV Tg rats have defective development of T cell effector function and generation of specific effector/memory T cell subsets. Here we identify abnormalities in activated HIV-1 Tg rat CD4+ T cells that include decreased pY505 dephosphorylation of Lck (required for Lck activation), decreased CD28 function, reduced expression of the anti-apoptotic molecule Bcl-xL, decreased secretion of the mitogenic lympokine interleukin-2 (IL-2) and increased activation induced apoptosis. These events likely lead to defects in antigen-specific signaling and may help explain the disruption of Th1 responses and the generation of specific effector/memory subsets in transgenic CD4+ T cells

  15. Permafrost thaw and intense thermokarst activity decreases abundance of stream benthic macroinvertebrates.

    Chin, Krista S; Lento, Jennifer; Culp, Joseph M; Lacelle, Denis; Kokelj, Steven V

    2016-08-01

    Intensification of permafrost thaw has increased the frequency and magnitude of large permafrost slope disturbances (mega slumps) in glaciated terrain of northwestern Canada. Individual thermokarst disturbances up to 40 ha in area have made large volumes of previously frozen sediments available for leaching and transport to adjacent streams, significantly increasing sediment and solute loads in these systems. To test the effects of this climate-sensitive disturbance regime on the ecology of Arctic streams, we explored the relationship between physical and chemical variables and benthic macroinvertebrate communities in disturbed and undisturbed stream reaches in the Peel Plateau, Northwest Territories, Canada. Highly disturbed and undisturbed stream reaches differed with respect to taxonomic composition and invertebrate abundance. Minimally disturbed reaches were not differentiated by these variables but rather were distributed along a disturbance gradient between highly disturbed and undisturbed sites. In particular, there was evidence of a strong negative relationship between macroinvertebrate abundance and total suspended solids, and a positive relationship between abundance and the distance from the disturbance. Increases in both sediments and nutrients appear to be the proximate cause of community differences in highly disturbed streams. Declines in macroinvertebrate abundance in response to slump activity have implications for the food webs of these systems, potentially leading to negative impacts on higher trophic levels, such as fish. Furthermore, the disturbance impacts on stream health can be expected to intensify as climate change increases the frequency and magnitude of thermokarst. © 2016 John Wiley & Sons Ltd.

  16. Esophageal button battery ingestions: decreasing time to operative intervention by level I trauma activation.

    Russell, Robert T; Griffin, Russell L; Weinstein, Elizabeth; Billmire, Deborah F

    2014-09-01

    The incidence of button battery ingestions is increasing and injury due to esophageal impaction begins within minutes of exposure. We changed our management algorithm for suspected button battery ingestions with intent to reduce time to evaluation and operative removal. A retrospective study was performed to identify and evaluate time to treatment and outcome for all esophageal button battery ingestions presenting to a major children's hospital emergency room from February 1, 2010 through February 1, 2012. During the first year, standard emergency room triage (ST) was used. During the second year, the triage protocol was changed and Trauma I triage (TT) was used. 24 children had suspected button battery ingestions with 11 having esophageal impaction. One esophageal impaction was due to 2 stacked coins. Time from arrival in emergency room to battery removal was 183minutes in ST group (n=4) and 33minutes in TT group (n=7) (p=0.04). One patient in ST developed a tracheoesophageal fistula. There were no complications in the TT group. The use of Trauma 1 activations for suspected button battery ingestions has led to more expedient evaluation and shortened time to removal of impacted esophageal batteries. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Characterization of Carbohydrate Active Enzymes Involved in Arabinogalactan Protein Metabolism

    Knoch, Eva

    and tissues, their functions and synthesis are still poorly understood. The aim of the research presented in the thesis was to characterize carbohydrate active enzymes involved in AGP biosynthesis and modification to gain insights into the biosynthesis of the glycoproteins in plants. Candidate...... glycosyltransferases and glycoside hydrolases were selected based on co-expression profiles from a transcriptomics analysis. Reverse genetics approach on a novel glucuronosyltransferase involved in AGP biosynthesis has revealed that the enzyme activity is required for normal cell elongation in etiolated seedlings....... The enzymatic activity of a hydrolase from GH family 17 was investigated, without successful determination of the activity. Members of hydrolase family 43 appeared to be localized in the Golgi-apparatus, which is also the compartment for glycan biosynthesis. The localization of these glycoside hydrolases...

  18. Leisure time physical activity in middle age predicts the metabolic syndrome in old age: results of a 28-year follow-up of men in the Oslo study

    Holme, Ingar; Tonstad, Serena; Sogaard, Anne Johanne; Larsen, Per G Lund; Haheim, Lise Lund

    2007-01-01

    Background Data are scarce on the long term relationship between leisure time physical activity, smoking and development of metabolic syndrome and diabetes. We wanted to investigate the relationship between leisure time physical activity and smoking measured in middle age and the occurrence of the metabolic syndrome and diabetes in men that participated in two cardiovascular screenings of the Oslo Study 28 years apart. Methods Men residing in Oslo and born in 1923–32 (n = 16 209) were screened for cardiovascular diseases and risk factors in 1972/3. Of the original cohort, those who also lived in same area in 2000 were invited to a repeat screening examination, attended by 6 410 men. The metabolic syndrome was defined according to a modification of the National Cholesterol Education Program criteria. Leisure time physical activity, smoking, educational attendance and the presence of diabetes were self-reported. Results Leisure time physical activity decreased between the first and second screening and tracked only moderately between the two time points (Spearman's ρ = 0.25). Leisure time physical activity adjusted for age and educational attendance was a significant predictor of both the metabolic syndrome and diabetes in 2000 (odds ratio for moderately vigorous versus sedentary/light activity was 0.65 [95% CI, 0.54–0.80] for the metabolic syndrome and 0.68 [0.52–0.91] for diabetes) (test for trend P < 0.05). However, when adjusted for more factors measured in 1972/3 including glucose, triglycerides, body mass index, treated hypertension and systolic blood pressure these associations were markedly attenuated. Smoking was associated with the metabolic syndrome but not with diabetes in 2000. Conclusion Physical activity during leisure recorded in middle age prior to the current waves of obesity and diabetes had an independent predictive association with the presence of the metabolic syndrome but not significantly so with diabetes 28 years later in life, when

  19. Metabolic activity and mRNA levels of human cardiac CYP450s involved in drug metabolism.

    Veronique Michaud

    2010-12-01

    Full Text Available Tissue-specific expression of CYP450s can regulate the intracellular concentration of drugs and explain inter-subject variability in drug action. The overall objective of our study was to determine in a large cohort of samples, mRNA levels and CYP450 activity expressed in the human heart.CYP450 mRNA levels were determined by RTPCR in left ventricular samples (n = 68 of explanted hearts from patients with end-stage heart failure. Samples were obtained from ischemic and non-ischemic hearts. In some instances (n = 7, samples were available from both the left and right ventricles. A technique for the preparation of microsomes from human heart tissue was developed and CYP450-dependent activity was determined using verapamil enantiomers as probe-drug substrates.Our results show that CYP2J2 mRNA was the most abundant isoform in all human heart left ventricular samples tested. Other CYP450 mRNAs of importance were CYP4A11, CYP2E1, CYP1A1 and CYP2C8 mRNAs while CYP2B6 and CYP2C9 mRNAs were present at low levels in only some of the hearts analyzed. CYP450 mRNAs did not differ between ischemic and non-ischemic hearts and appeared to be present at similar levels in the left and right ventricles. Incubation of verapamil with heart microsomes led to the formation of nine CYP450-dependent metabolites: a major finding was the observation that stereoselectivity was reversed compared to human liver microsomes, in which the R-enantiomer is metabolized to a greater extent.This study determined cardiac mRNA levels of various CYP450 isozymes involved in drug metabolism and demonstrated the prevalent expression of CYP2J2 mRNA. It revealed that cardiomyocytes can efficiently metabolize drugs and that cardiac CYP450s are highly relevant with regard to clearance of drugs in the heart. Our results support the claim that drug metabolism in the vicinity of a drug effector site can modulate drug effects.

  20. Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium perfringens Strains

    Miseon Park

    2014-01-01

    Full Text Available Fluoroquinolone resistance affects toxin production of Clostridium perfringens strains differently. To investigate the effect of fluoroquinolone resistance selection on global changes in metabolic activities and drug susceptibilities, four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and gatifloxacin-resistant mutants were compared in nearly 2000 assays, using phenotype microarray plates. Variations among mutant strains resulting from resistance selection were observed in all aspects of metabolism. Carbon utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant strains were affected differently in the resistant mutants depending on both the bacterial genotype and the fluoroquinolone to which the bacterium was resistant. The susceptibilities to gentamicin and erythromycin of all resistant mutants except one increased, but some resistant strains were less susceptible to amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than their wild types. Sensitivity to ethidium bromide decreased in some resistant mutants and increased in others. Microarray analysis of two gatifloxacin-resistant mutants showed changes in metabolic activities that were correlated with altered expression of various genes. Both the chemical structures of fluoroquinolones and the genomic makeup of the wild types influenced the changes found in resistant mutants, which may explain some inconsistent reports of the effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria.

  1. Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

    LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

    2016-02-01

    The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

  2. Acute and short-term effects of caloric restriction on metabolic profile and brain activation in obese, postmenopausal women.

    Jakobsdottir, S; van Nieuwpoort, I C; van Bunderen, C C; de Ruiter, M B; Twisk, J W R; Deijen, J B; Veltman, D J; Drent, M L

    2016-11-01

    Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated. An 8-week prospective intervention study of 18 healthy postmenopausal women, with a body mass index of 30-35 kg m -2 . The first 2 weeks subjects were on an isocaloric diet and 4 weeks on a 1000 kcal restricted diet followed by 2 weeks on an isocaloric diet. Anthropometric and laboratory analyses were performed weekly during the isocaloric diet and three times a week during the caloric-restricted diet. Functional magnetic resonance imaging scans were obtained before and after the caloric restriction in four separate sessions (fasting or sated). Generalized Estimating Equations analysis was used for data analysis. A mean weight loss of 4.2±0.5 kg (4.8%) and a 4.2±0.4 cm decline in waist circumference were achieved. In the first week of caloric restriction, triglyceride, leptin, resistin and adiponectin levels as well as systolic blood pressure decreased and insulin-like growth factor-binding protein 1 levels increased. During and after weight loss, a significant increase in ghrelin levels was observed. Before weight loss, increased activation of the right amygdala was seen in response to food stimuli, and free fatty acids and glucose correlated with activity in various areas involved in food reward processing. After weight loss, fasting ghrelin and sated leptin levels correlated with activity in these areas. Already in the first week of caloric restriction in obese postmenopausal women, various favourable metabolic changes occur before clinically relevant weight loss is achieved. Activity in the amygdala region and correlations of metabolic factors with activity in brain areas involved in food reward processing differ substantially before and after weight loss.

  3. Physical Activity and Sedentary Time Associations with Metabolic Health Across Weight Statuses in Children and Adolescents

    Kuzik, Nicholas; Carson, Valerie; Andersen, Lars Bo

    2017-01-01

    classification compared with metabolically healthy (MH) classification for the NW group. More MVPA was associated with lower odds of MU classification than MH classification for NW and overweight groups. For multinomial logistic regressions, more MVPA was associated with lower odds of MH-obesity classification......, as well as MU-NW, -overweight, and -obesity classifications, compared with the MH-NW group. Furthermore, more sedentary time was associated with higher odds of MU-NW classification compared with the MH-NW group. CONCLUSIONS: More MVPA was beneficial for metabolic health and weight status, whereas lower......OBJECTIVE: The aim of this study was to examine the prevalence of metabolic health across weight statuses and the associations of physical activity and sedentary time within and across metabolic health-weight status groups. METHODS: Six studies (n = 4,581) from the International Children...

  4. Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells

    Lamparter, Christina L. [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); Winn, Louise M., E-mail: winnl@queensu.ca [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L 3N6 (Canada)

    2016-09-01

    The teratogenicity of the antiepileptic drug valproic acid (VPA) is well established and its inhibition of histone deacetylases (HDAC) is proposed as an initiating factor. Recently, VPA-mediated HDAC inhibition was demonstrated to involve transcriptional downregulation of histone acetyltransferases (HATs), which was proposed to compensate for the increased acetylation resulting from HDAC inhibition. Cbp and p300 are HATs required for embryonic development and deficiencies in either are associated with congenital malformations and embryolethality. The objective of the present study was to characterize Cbp/p300 following VPA exposure in P19 cells. Consistent with previous studies, exposure to 5 mM VPA over 24 h induced a moderate decrease in Cbp/p300 mRNA, which preceded a strong decrease in total cellular protein mediated by ubiquitin-proteasome degradation. Nuclear Cbp/p300 protein was also decreased following VPA exposure, although to a lesser extent. Total cellular and nuclear p300 HAT activity was reduced proportionately to p300 protein levels, however while total cellular HAT activity also decreased, nuclear HAT activity was unaffected. Using the Cbp/p300 HAT inhibitor C646, we demonstrated that HAT inhibition similarly affected many of the same endpoints as VPA, including increased reactive oxygen species and caspase-3 cleavage, the latter of which could be attenuated by pre-treatment with the antioxidant catalase. C646 exposure also decreased NF-κB/p65 protein, which was not due to reduced mRNA and was not attenuated with catalase pre-treatment. This study provides support for an adaptive HAT response following VPA exposure and suggests that reduced Cbp/p300 HAT activity could contribute to VPA-mediated alterations. - Highlights: • VPA exposure in vitro downregulates Cbp/p300 mRNA and induces protein degradation. • Cbp/p300 histone acetyltransferase activity is similarly reduced with VPA exposure. • Inhibition of Cbp/p300 acetyltransferase activity

  5. Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice.

    Huang, S-L; Yu, R-T; Gong, J; Feng, Y; Dai, Y-L; Hu, F; Hu, Y-H; Tao, Y-D; Leng, Y

    2012-05-01

    Arctigenin is a natural compound that had never been previously demonstrated to have a glucose-lowering effect. Here it was found to activate AMP-activated protein kinase (AMPK), and the mechanism by which this occurred, as well as the effects on glucose and lipid metabolism were investigated. 2-Deoxyglucose uptake and AMPK phosphorylation were examined in L6 myotubes and isolated skeletal muscle. Gluconeogenesis and lipid synthesis were evaluated in rat primary hepatocytes. The acute and chronic effects of arctigenin on metabolic abnormalities were observed in C57BL/6J and ob/ob mice. Changes in mitochondrial membrane potential were measured using the J-aggregate-forming dye, JC-1. Analysis of respiration of L6 myotubes or isolated mitochondria was conducted in a channel oxygen system. Arctigenin increased AMPK phosphorylation and stimulated glucose uptake in L6 myotubes and isolated skeletal muscles. In primary hepatocytes, it decreased gluconeogenesis and lipid synthesis. The enhancement of glucose uptake and suppression of hepatic gluconeogenesis and lipid synthesis by arctigenin were prevented by blockade of AMPK activation. The respiration of L6 myotubes or isolated mitochondria was inhibited by arctigenin with a specific effect on respiratory complex I. A single oral dose of arctigenin reduced gluconeogenesis in C57BL/6J mice. Chronic oral administration of arctigenin lowered blood glucose and improved lipid metabolism in ob/ob mice. This study demonstrates a new role for arctigenin as a potent indirect activator of AMPK via inhibition of respiratory complex I, with beneficial effects on metabolic disorders in ob/ob mice. This highlights the potential value of arctigenin as a possible treatment of type 2 diabetes.

  6. Overexpression of Nitrate Reductase in Tobacco Delays Drought-Induced Decreases in Nitrate Reductase Activity and mRNA1

    Ferrario-Méry, Sylvie; Valadier, Marie-Hélène; Foyer, Christine H.

    1998-01-01

    Transformed (cauliflower mosaic virus 35S promoter [35S]) tobacco (Nicotiana plumbaginifolia L.) plants constitutively expressing nitrate reductase (NR) and untransformed controls were subjected to drought for 5 d. Drought-induced changes in biomass accumulation and photosynthesis were comparable in both lines of plants. After 4 d of water deprivation, a large increase in the ratio of shoot dry weight to fresh weight was observed, together with a decrease in the rate of photosynthetic CO2 assimilation. Foliar sucrose increased in both lines during water stress, but hexoses increased only in leaves from untransformed controls. Foliar NO3− decreased rapidly in both lines and was halved within 2 d of the onset of water deprivation. Total foliar amino acids decreased in leaves of both lines following water deprivation. After 4 d of water deprivation no NR activity could be detected in leaves of untransformed plants, whereas about 50% of the original activity remained in the leaves of the 35S-NR transformants. NR mRNA was much more stable than NR activity. NR mRNA abundance increased in the leaves of the 35S-NR plants and remained constant in controls for the first 3 d of drought. On the 4th d, however, NR mRNA suddenly decreased in both lines. Rehydration at d 3 caused rapid recovery (within 24 h) of 35S-NR transcripts, but no recovery was observed in the controls. The phosphorylation state of the protein was unchanged by long-term drought. There was a strong correlation between maximal extractable NR activity and ambient photosynthesis in both lines. We conclude that drought first causes increased NR protein turnover and then accelerates NR mRNA turnover. Constitutive NR expression temporarily delayed drought-induced losses in NR activity. 35S-NR expression may therefore allow more rapid recovery of N assimilation following short-term water deficit. PMID:9576799

  7. Cytochalasin E alters the cytoskeleton and decreases ENaC activity in Xenopus 2F3 cells.

    Reifenberger, Matthew S; Yu, Ling; Bao, Hui-Fang; Duke, Billie Jeanne; Liu, Bing-Chen; Ma, He-Ping; Alli, Ahmed A; Eaton, Douglas C; Alli, Abdel A

    2014-07-01

    Numerous reports have linked cytoskeleton-associated proteins with the regulation of epithelial Na(+) channel (ENaC) activity. The purpose of the present study was to determine the effect of actin cytoskeleton disruption by cytochalasin E on ENaC activity in Xenopus 2F3 cells. Here, we show that cytochalasin E treatment for 60 min can disrupt the integrity of the actin cytoskeleton in cultured Xenopus 2F3 cells. We show using single channel patch-clamp experiments and measurements of short-circuit current that ENaC activity, but not its density, is altered by cytochalasin E-induced disruption of the cytoskeleton. In nontreated cells, 8 of 33 patches (24%) had no measurable ENaC activity, whereas in cytochalasin E-treated cells, 17 of 32 patches (53%) had no activity. Analysis of those patches that did contain ENaC activity showed channel open probability significantly decreased from 0.081 ± 0.01 in nontreated cells to 0.043 ± 0.01 in cells treated with cytochalasin E. Transepithelial current from mpkCCD cells treated with cytochalasin E, cytochalasin D, or latrunculin B for 60 min was decreased compared with vehicle-treated cells. The subcellular expression of fodrin changed significantly, and several protein elements of the cytoskeleton decreased at least twofold after 60 min of cytochalasin E treatment. Cytochalasin E treatment disrupted the association between ENaC and myristoylated alanine-rich C-kinase substrate. The results presented here suggest disruption of the actin cytoskeleton by different compounds can attenuate ENaC activity through a mechanism involving changes in the subcellular expression of fodrin, several elements of the cytoskeleton, and destabilization of the ENaC-myristoylated alanine-rich C-kinase substrate complex. Copyright © 2014 the American Physiological Society.

  8. Metabolic activation of amygdala, lateral septum and accumbens circuits during food anticipatory behavior.

    Olivo, Diana; Caba, Mario; Gonzalez-Lima, Francisco; Rodríguez-Landa, Juan F; Corona-Morales, Aleph A

    2017-01-01

    When food is restricted to a brief fixed period every day, animals show an increase in temperature, corticosterone concentration and locomotor activity for 2-3h before feeding time, termed food anticipatory activity. Mechanisms and neuroanatomical circuits responsible for food anticipatory activity remain unclear, and may involve both oscillators and networks related to temporal conditioning. Rabbit pups are nursed once-a-day so they represent a natural model of circadian food anticipatory activity. Food anticipatory behavior in pups may be associated with neural circuits that temporally anticipate feeding, while the nursing event may produce consummatory effects. Therefore, we used New Zealand white rabbit pups entrained to circadian feeding to investigate the hypothesis that structures related to reward expectation and conditioned emotional responses would show a metabolic rhythm anticipatory of the nursing event, different from that shown by structures related to reward delivery. Quantitative cytochrome oxidase histochemistry was used to measure regional brain metabolic activity at eight different times during the day. We found that neural metabolism peaked before nursing, during food anticipatory behavior, in nuclei of the extended amygdala (basolateral, medial and central nuclei, bed nucleus of the stria terminalis), lateral septum and accumbens core. After pups were fed, however, maximal metabolic activity was expressed in the accumbens shell, caudate, putamen and cortical amygdala. Neural and behavioral activation persisted when animals were fasted by two cycles, at the time of expected nursing. These findings suggest that metabolic activation of amygdala-septal-accumbens circuits involved in temporal conditioning may contribute to food anticipatory activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Cytotoxicity and genotoxicity of clothianidin in human lymphocytes with or without metabolic activation system.

    Atlı Şekeroğlu, Zülal; Şekeroğlu, Vedat; Uçgun, Ebru; Kontaş Yedier, Seval; Aydın, Birsen

    2018-02-26

    Clothianidin (CHN) is a broad-spectrum neonicotinoid insecticide. Limited studies have been carried out on the cytotoxic and genotoxic effects of both CHN using different genotoxicity tests in human cells with or without human metabolic activation system (S9 mix). Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of CHN and its metabolites on human lymphocyte cultures with or without S9 mix using chromosomal aberration (CA) and micronucleus (MN) tests. The cultures were treated with 25, 50, and 100 µg/ml of CHN in the presence (3 h treatment) and absence (48 h treatment) of S9 mix. Dimethyl sulfoxide (DMSO) was used as a solvent control. CHN showed cytotoxic and genotoxic effects due to significant decreases in mitotic index (MI) and nuclear division index (NDI), and significant increases in the CAs, aberrant cells, and MN formation in the absence of S9 mix when compared with solvent control. However, CHN did not significantly induce cytotoxicity and genotoxicity in the presence of S9 mix. Our results indicated that CHN has cytotoxic, cytostatic, and genotoxic potential on human peripheral blood lymphocyte cultures, but not its metabolites under the experimental conditions.

  10. Effect of Condensed Tannins on Bacterial Diversity and Metabolic Activity in the Rat Gastrointestinal Tract

    Smith, Alexandra H.; Mackie, Roderick I.

    2004-01-01

    The effect of dietary condensed tannins (proanthocyanidins) on rat fecal bacterial populations was ascertained in order to determine whether the proportion on tannin-resistant bacteria increased and if there was a change in the predominant bacterial populations. After 3 weeks of tannin diets the proportion of tannin-resistant bacteria increased significantly (P tannin diet and to 47.2% ± 5.1% with a 2% tannin diet. The proportion of tannin-resistant bacteria returned to preexposure levels in the absence of dietary tannins. A shift in bacterial populations was confirmed by molecular fingerprinting of fecal bacterial populations by denaturing gradient gel electrophoresis (DGGE). Posttreatment samples were generally still distinguishable from controls after 3.5 weeks. Sequence analysis of DGGE bands and characterization of tannin-resistant isolates indicated that tannins selected for Enterobacteriaceae and Bacteroides species. Dot blot quantification confirmed that these gram-negative bacterial groups predominated in the presence of dietary tannins and that there was a corresponding decrease in the gram-positive Clostridium leptum group and other groups. Metabolic fingerprint patterns revealed that functional activities of culturable fecal bacteria were affected by the presence of tannins. Condensed tannins of Acacia angustissima altered fecal bacterial populations in the rat gastrointestinal tract, resulting in a shift in the predominant bacteria towards tannin-resistant gram-negative Enterobacteriaceae and Bacteroides species. PMID:14766594

  11. Impaired Circulating Angiogenic Cells Mobilization and Metalloproteinase-9 Activity after Dynamic Exercise in Early Metabolic Syndrome.

    Rocha, Natalia G; Sales, Allan R K; Penedo, Leticia A; Pereira, Felipe S; Silva, Mayra S; Miranda, Renan L; Silva, Jemima F R; Silva, Bruno M; Santos, Aline A; Nobrega, Antonio C L

    2015-01-01

    Increased levels of adhesion molecules or metalloproteinases (MMPs) may indicate endothelial dysfunction. Exercise mobilizes circulating angiogenic cells (CACs) from bone marrow in healthy subjects, improving vascular function. However, it is unclear whether this mechanism is preserved in the early stages of metabolic syndrome (early MetS). We aimed to evaluate the acute effects of exercise on adhesion molecules, angiogenic factors, MMPs, and CACs in early MetS. Fifteen subjects with early MetS and nine healthy controls underwent an exercise session and a nonexercise session, randomly. Adhesion molecules, angiogenic factors, CACs, and MMPs were evaluated before and after exercise or nonexercise sessions. At baseline, levels of sE-selectin, sICAM-1, and MMP-9 were higher in early MetS than in controls (P ≤ 0.03). After exercise, sE-selectin, sICAM-1, and MMP-9 levels were still higher in early MetS (P exercise. There was no difference between moments in nonexercise session (P > 0.05). In conclusion, subjects with early MetS already presented impaired endothelial function at rest along with a decrease in CACs and an increase in MMP-9 activity in response to exercise.

  12. New insight for activity intensity relativity, metabolic expenditure during object projection skill performance.

    Sacko, Ryan S; McIver, Kerry; Brian, Ali; Stodden, David F

    2018-04-02

    This study examined the metabolic cost (METs) of performing object projection skills at three practice trial intervals (6, 12, and 30 seconds). Forty adults (female n = 20) aged 18-30 (M = 23.7 ± 2.9 years) completed three, nine-minute sessions of skill trials performed at 6, 12, and 30 second intervals. Participants performed kicking, throwing and striking trials in a blocked schedule with maximal effort. Average METs during each session were measured using a COSMED K4b2. A three (interval condition) X two (sex) ANOVA was conducted to examine differences in METs across interval conditions and by sex. Results indicated a main effect for interval condition (F(5,114) = 187.02, p < .001, η 2  = 0.76) with decreased interval times yielding significantly higher METs [30 sec = 3.45, 12 sec = 5.68, 6 sec = 8.21]. A main effect for sex (F(5, 114) = 35.39, p < .001, η 2  = 0.24) also was found with men demonstrating higher METs across all intervals. At a rate of only two trials/min, participants elicited moderate physical activity, with 12 and 6-second intervals exhibiting vigorous PA. Demonstrating MVPA during the performance of object projection skill performance has potential implications for PA interventions.

  13. Effects of whole grain, fish and bilberries on serum metabolic profile and lipid transfer protein activities: a randomized trial (Sysdimet.

    Maria Lankinen

    Full Text Available We studied the combined effects of wholegrain, fish and bilberries on serum metabolic profile and lipid transfer protein activities in subjects with the metabolic syndrome.Altogether 131 subjects (40-70 y, BMI 26-39 kg/m(2 with impaired glucose metabolism and features of the metabolic syndrome were randomized into three groups with 12-week periods according to a parallel study design. They consumed either: a wholegrain and low postprandial insulin response grain products, fatty fish 3 times a week, and bilberries 3 portions per day (HealthyDiet, b wholegrain and low postprandial insulin response grain products (WGED, or c refined wheat breads as cereal products (Control. Altogether 106 subjects completed the study. Serum metabolic profile was studied using an NMR-based platform providing information on lipoprotein subclasses and lipids as well as low-molecular-weight metabolites.There were no significant differences in clinical characteristics between the groups at baseline or at the end of the intervention. Mixed model analyses revealed significant changes in lipid metabolites in the HealthyDiet group during the intervention compared to the Control group. All changes reflected increased polyunsaturation in plasma fatty acids, especially in n-3 PUFAs, while n-6 and n-7 fatty acids decreased. According to tertiles of changes in fish intake, a greater increase of fish intake was associated with increased concentration of large HDL particles, larger average diameter of HDL particles, and increased concentrations of large HDL lipid components, even though total levels of HDL cholesterol remained stable.The results suggest that consumption of diet rich in whole grain, bilberries and especially fatty fish causes changes in HDL particles shifting their subclass distribution toward larger particles. These changes may be related to known protective functions of HDL such as reverse cholesterol transport and could partly explain the known protective

  14. Physical activity, stress, and metabolic risk score in 8- to 18-year-old boys.

    Holmes, Megan E; Eisenmann, Joey C; Ekkekakis, Panteleimon; Gentile, Douglas

    2008-03-01

    We examined whether physical activity modifies the relationship between stress and the metabolic risk score in 8- to 18-year-old males (n = 37). Physical activity (PA) and television (TV)/videogame (VG) use were assessed via accelerometer and questionnaire, respectively. Stress was determined from self-report measures. A metabolic risk score (MRS) was created by summing age-standardized residuals for waist circumference, mean arterial pressure, glycosylated hemoglobin, and high-density lipoprotein cholesterol. Correlations between PA and MRS were low (r adolescents.

  15. [Coactivators in energy metabolism: peroxisome proliferator-activated receptor-gamma coactivator 1 family].

    Wang, Rui; Chang, Yong-sheng; Fang, Fu-de

    2009-12-01

    Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family is highly expressed in tissues with high energy metabolism. They coactivate transcription factors in regulating genes engaged in processes such as gluconeogenesis, adipose beta-oxydation, lipoprotein synthesis and secretion, mitochondrial biogenesis, and oxidative metabolism. Protein conformation studies demonstrated that they lack DNA binding domains and act as coactivators through physical interaction with transcription factors. PGC1 activity is regulated at transcription level or by multiple covalent chemical modifications such as phosphorylation, methylation and acetylation/deacetylation. Abnormal expression of PGC1 coactivators usually is closely correlated with diseases such as diabetes, obesity, hyperglycemia, hyperlipemia, and arterial and brain neuron necrosis diseases.

  16. Compensation in resting metabolism for experimentally increased activity

    Deerenberg, C; Overkamp, GJF; Visser, GH; Daan, S; Heldmaier, G.

    1998-01-01

    To study zebra finch allocation of energy to day and night at two different workloads, we assessed the daily energy turnover from: (1) metabolizable energy of the food, and (2) doubly-labeled water. In both experiments we imposed two levels of activity on captive zebra finches (Taeniopygia guttata),

  17. Understanding Fatty Acid Metabolism through an Active Learning Approach

    Fardilha, M.; Schrader, M.; da Cruz e Silva, O. A. B.; da Cruz e Silva, E. F.

    2010-01-01

    A multi-method active learning approach (MALA) was implemented in the Medical Biochemistry teaching unit of the Biomedical Sciences degree at the University of Aveiro, using problem-based learning as the main learning approach. In this type of learning strategy, students are involved beyond the mere exercise of being taught by listening. Less…

  18. Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

    Bart eEverts

    2014-05-01

    Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

  19. Radiation-induced progressive decreasing in the expression of reverse transcriptase gene of hEST2 and telomerase activity

    Zhu Hanneng; Chen Wenying; Xiong Sidong

    2000-01-01

    Telomerase is a ribonucleoprotein complex that adds heximeric repeats called telomeres to the growing ends of chromosomal DNA. Telomerase activity is present in a vast majority of tumors but is repressed in most normal tissues. Human telomerase catalytic subunit gene (hEST2) reverse transcriptase (RT) segment was cloned by PCR according to the sequence published in GeneBank. PCR was used to investigate the expression of the hEST2 RT segment in diverse tumors as well as in various normal tissues. Results indicated that hEST2 RT segment was detectable in tumor cells lines but not in normal cells and tissues. In order to identify the relationship between telomerase and the biological effect of radiation injury, HeLa cells, KB cells and A431 cells were employed to measure the change in telomerase activity after 60 Co-ray irradiation at RNA level and protein level. Quantitative PCR determined that expression of hEST2 RT segment that encodes seven motifs of the human telomeras decreased with increasing dosage of radiation. In addition, a PCR-based telomeric repeat amplification protocol was used to assay telomerase activity after exposure to radiation. The results strongly support the experiments we had made: Telomerase activity decreases with increasing dosage of radiation. We conclude that detection of the hEST2 RT segment by Northern blotting is a new method for detecting telomerase activity. Furthermore, radiation can cause a dose-dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer cells after irradiation. (author)

  20. Metabolic Features of Protochlamydia amoebophila Elementary Bodies – A Link between Activity and Infectivity in Chlamydiae

    Watzka, Margarete; Wultsch, Anna; Tziotis, Dimitrios; Montanaro, Jacqueline; Richter, Andreas; Schmitt-Kopplin, Philippe; Horn, Matthias

    2013-01-01

    The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB), has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS), ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from 13C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA) cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila EBs and provide

  1. Metabolic features of Protochlamydia amoebophila elementary bodies--a link between activity and infectivity in Chlamydiae.

    Barbara S Sixt

    Full Text Available The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB, has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS, ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS, and ultra-performance liquid chromatography mass spectrometry (UPLC-MS was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from (13C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila

  2. Influence of physical and emotional activity on the metabolic profile of blood serum of race horses

    T. I. Bayeva

    2016-09-01

    decreased, which conforms to changes of indicators in exchange of proteins. SGOT activity in the animals’ blood serum exceeded the upper rate of norm, it coincides also with rising of concentration of creatinine and sodium lactatum, and is an indicator of intensification of catabolic processes in the muscles after physical loading. Only after emotional loading, did hyperglycemia and hyperbilirubinemia occur because of a temporal spasm in the cholic paths without changes in the activity of the alkaline phosphatase and GGTP. After physical loading the level of lactatum increased (by 185.7%, activity of LDH (by 76.2%, concentration of cholesterol (by 76.2%, triacylglycerol (by 140.9%, which is an indicator of intensification of anaerobic glycolysis and lipolysis. Emotional loading is the stronger stress factor which causes negative changes in indicators of the metabolic profile. Trainers should take this into account during the training and testing of horses in order to facilitate their adaptation to the influence of various stress factors, to correct the animals’ physiological state and thus enable them to cope with intensive loading without threat to their health.

  3. Decreased material-activation of the complement system using low-energy plasma polymerized poly(vinyl pyrrolidone) coatings

    Andersen, T.E.; Kolmos, H.J.; Palarasah, Yaseelan

    2011-01-01

    In the current study we investigate the activation of blood complement on medical device silicone rubber and present a plasma polymerized vinyl pyrrolidone (ppVP) coating which strongly decreases surface-activation of the blood complement system. We show that uncoated silicone and polystyrene...... surface. The ppVP surface is furthermore characterized physically and chemically using scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR), which indicates preservation of chemical functionality by the applied plasma process. Overall, the pp...

  4. Using acupressure and Montessori-based activities to decrease agitation for residents with dementia: a cross-over trial.

    Lin, Li-Chan; Yang, Man-Hua; Kao, Chieh-Chun; Wu, Shiao-Chi; Tang, Sai-Hung; Lin, Jaung-Geng

    2009-06-01

    To explore the effectiveness of acupressure and Montessori-based activities in decreasing the agitated behaviors of residents with dementia. A double-blinded, randomized (two treatments and one control; three time periods) cross-over design was used. Six special care units for residents with dementia in long-term care facilities in Taiwan were the sites for the study. One hundred thirty-three institutionalized residents with dementia. Subjects were randomized into three treatment sequences: acupressure-presence-Montessori methods, Montessori methods-acupressure-presence and presence-Montessori methods-acupressure. All treatments were done once a day, 6 days per week, for a 4-week period. The Cohen-Mansfield Agitation Inventory, Ease-of-Care, and the Apparent Affect Rating Scale. After receiving the intervention, the acupressure and Montessori-based-activities groups saw a significant decrease in agitated behaviors, aggressive behaviors, and physically nonaggressive behaviors than the presence group. Additionally, the ease-of-care ratings for the acupressure and Montessori-based-activities groups were significantly better than for the presence group. In terms of apparent affect, positive affect in the Montessori-based-activities group was significantly better than in the presence group. This study confirms that a blending of traditional Chinese medicine and a Western activities program would be useful in elderly care and that in-service training for formal caregivers in the use of these interventions would be beneficial for patients

  5. Transgenic overexpression of active calcineurin in beta-cells results in decreased beta-cell mass and hyperglycemia.

    Ernesto Bernal-Mizrachi

    2010-08-01

    Full Text Available Glucose modulates beta-cell mass and function through an initial depolarization and Ca(2+ influx, which then triggers a number of growth regulating signaling pathways. One of the most important downstream effectors in Ca(2+ signaling is the calcium/Calmodulin activated serine threonine phosphatase, calcineurin. Recent evidence suggests that calcineurin/NFAT is essential for beta-cell proliferation, and that in its absence loss of beta-cells results in diabetes. We hypothesized that in contrast, activation of calcineurin might result in expansion of beta-cell mass and resistance to diabetes.To determine the role of activation of calcineurin signaling in the regulation of pancreatic beta-cell mass and proliferation, we created mice that expressed a constitutively active form of calcineurin under the insulin gene promoter (caCn(RIP. To our surprise, these mice exhibited glucose intolerance. In vitro studies demonstrated that while the second phase of Insulin secretion is enhanced, the overall insulin secretory response was conserved. Islet morphometric studies demonstrated decreased beta-cell mass suggesting that this was a major component responsible for altered Insulin secretion and glucose intolerance in caCn(RIP mice. The reduced beta-cell mass was accompanied by decreased proliferation and enhanced apoptosis.Our studies identify calcineurin as an important factor in controlling glucose homeostasis and indicate that chronic depolarization leading to increased calcineurin activity may contribute, along with other genetic and environmental factors, to beta-cell dysfunction and diabetes.

  6. The activity of the primary motor cortex ipsilateral to the exercising hand decreases during repetitive handgrip exercise

    Shibuya, Kenichi

    2011-01-01

    The brain function controlling muscle force production is not yet fully understood. The purpose of this study was to examine bilateral primary motor cortex (M1) oxygenation during static-handgrip exercises performed with the right hand (60% maximal voluntary contraction; 10 s exercise/75 s rest; five sets). Twelve healthy, right-handed male subjects participated in this study. Near-infrared spectroscopy probes were positioned over the bilateral M1 to measure cortical oxygenation during handgrip exercises. The maximum values of the changes in concentrations of oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (Hb) across the trials (i) did not change significantly during the contralateral M1 activation (p > 0.05), whereas (ii) in the case of the ipsilateral M1 activation a significant (p < 0.05) decrease in HbO 2 and a significant (p < 0.01) decrease in Hb could be measured. The activation in ipsilateral M1 at the fifth trial was significantly decreased compared with that in the first trial (HbO 2 : p < 0.001; Hb: p < 0.001). The present results suggest that the ipsilateral M1 is recruited during the motor task in compensation for the contralateral M1 and the habituation to motor task might alter the efficiency for interaction of the ipsilateral M1 to the contralateral M1. The interhemispheric interaction might change due to habituation to motor task

  7. Metabolic activity in striate and extrastriate cortex in the hooded rat: contralateral and ipsilateral eye input

    Thurlow, G.A.; Cooper, R.M.

    1988-01-01

    The extent of changes in glucose metabolism resulting from ipsilateral and contralateral eye activity in the posterior cortex of the hooded rat was demonstrated by means of the C-14 2-deoxyglucose autoradiographic technique. By stimulating one eye with square wave gratings and eliminating efferent activation from the other by means of enucleation or intraocular TTX injection, differences between ipsilaterally and contralaterally based visual activity in the two hemispheres were maximized. Carbon-14 levels in layer IV of autoradiographs of coronal sections were measured and combined across sections to form right and left matrices of posterior cortex metabolic activity. A difference matrix, formed by subtracting the metabolic activity matrix of cortex contralateral to the stimulated eye from the ipsilateral depressed matrix, emphasized those parts of the visual cortex that received monocular visual input. The demarcation of striate cortex by means of cholinesterase stain and the examination of autoradiographs from sections cut tangential to the cortical surface aided in the interpretation of the difference matrices. In striate cortex, differences were maximal in the medial monocular portion, and the lateral or binocular portion was shown to be divided metabolically into a far lateral contralaterally dominant strip along the cortical representation of the vertical meridian, and a more medial region of patches of more or less contralaterally dominant binocular input. Lateral peristriate differences were less than those of striate cortex, and regions of greater and lesser monocular input could be distinguished. We did not detect differences between the two hemispheres in either anterior or medial peristriate areas

  8. Genome Sequencing of Streptomyces atratus SCSIOZH16 and Activation Production of Nocardamine via Metabolic Engineering

    Yan Li

    2018-06-01

    Full Text Available The Actinomycetes are metabolically flexible microorganisms capable of producing a wide range of interesting compounds, including but by no means limited to, siderophores which have high affinity for ferric iron. In this study, we report the complete genome sequence of marine-derived Streptomyces atratus ZH16 and the activation of an embedded siderophore gene cluster via the application of metabolic engineering methods. The S. atratus ZH16 genome reveals that this strain has the potential to produce 26 categories of natural products (NPs barring the ilamycins. Our activation studies revealed S. atratus SCSIO ZH16 to be a promising source of the production of nocardamine-type (desferrioxamine compounds which are important in treating acute iron intoxication and performing ecological remediation. We conclude that metabolic engineering provides a highly effective strategy by which to discover drug-like compounds and new NPs in the genomic era.

  9. Metabolic and Co-Metabolic Transformation of Diclofenac by Enterobacter hormaechei D15 Isolated from Activated Sludge.

    Aissaoui, Salima; Ouled-Haddar, Houria; Sifour, Mohamed; Harrouche, Kamel; Sghaier, Haitham

    2017-03-01

    The presence of non-steroidal anti-inflammatory drugs, such as diclofenac (DCF), in the environment, is an emerging problem due to their harmful effects on non-target organisms, even at low concentrations. We studied the biodegradation of DCF by the strain D15 of Enterobacter hormaechei. The strain was isolated from an activated sludge, and identified as E. hormaechei based on its physiological characteristics and its 16 S RNA sequence. Using HPTLC and GC-MS methods, we demonstrated that this strain metabolized DCF at an elimination rate of 52.8%. In the presence of an external carbon source (glucose), the elimination rate increased to approximately 82%. GC-MS analysis detected and identified one metabolite as 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one; it was produced as a consequence of dehydration and lactam formation reactions.

  10. Alterations in calcium metabolism during human monocyte activation

    Scully, S.P.

    1984-01-01

    Human peripheral blood monocytes have been prepared from plateletpheresis residues by counterflow centrifugal elutriation in sufficient quantities to enable quantitative studies of cell calcium. Kinetic analysis of 45 Ca exchange data in resting monocytes was compatible with a model of cellular calcium containing three exchangeable calcium pools. These pools are thought to represent a putative ectocellular pool, a putative cytoplasmic chelated pool, and a putative organelle sequestered pool. Exposure of monocytes to the plant lectin Con A at a concentration that maximally simulated superoxide production caused an increase in the size and a doubling in the exchange rate of the putative cytoplasmic pool without a change in the other cellular pools. The cytoplasmic ionized calcium, [Ca]/sub i/, measured with the fluorescent probe, Quin 2 rose from a resting level of 83 nM to 165 mN within 30 sec of exposure to Con A. This increase in cytoplasmic calcium preceded the release of superoxide radicals. Calcium transport and calcium ATPase activities were identified and characterized in plasma membrane vesicles prepared from monocytes. Both activities were strictly dependent on ATP and Mg, had a Km/sub Ca/ in the submicromolar range and were stimulated by calmodulin. Thus, it seems that monocyte calcium is in a dynamic steady state that is a balance between efflux and influx rates, and that the activation of these cells results in the transition to a new steady state. The alteration in [Ca]/sub i/ that accompany the new steady state are essential for superoxide production by human monocytes

  11. Metabolic Genetic Screens Reveal Multidimensional Regulation of Virulence Gene Expression in Listeria monocytogenes and an Aminopeptidase That Is Critical for PrfA Protein Activation.

    Friedman, Sivan; Linsky, Marika; Lobel, Lior; Rabinovich, Lev; Sigal, Nadejda; Herskovits, Anat A

    2017-06-01

    Listeria monocytogenes is an environmental saprophyte and intracellular bacterial pathogen. Upon invading mammalian cells, the bacterium senses abrupt changes in its metabolic environment, which are rapidly transduced to regulation of virulence gene expression. To explore the relationship between L. monocytogenes metabolism and virulence, we monitored virulence gene expression dynamics across a library of genetic mutants grown under two metabolic conditions known to activate the virulent state: charcoal-treated rich medium containing glucose-1-phosphate and minimal defined medium containing limiting concentrations of branched-chain amino acids (BCAAs). We identified over 100 distinct mutants that exhibit aberrant virulence gene expression profiles, the majority of which mapped to nonessential metabolic genes. Mutants displayed enhanced, decreased, and early and late virulence gene expression profiles, as well as persistent levels, demonstrating a high plasticity in virulence gene regulation. Among the mutants, one was noteworthy for its particularly low virulence gene expression level and mapped to an X-prolyl aminopeptidase (PepP). We show that this peptidase plays a role in posttranslational activation of the major virulence regulator, PrfA. Specifically, PepP mediates recruitment of PrfA to the cytoplasmic membrane, a step identified as critical for PrfA protein activation. This study establishes a novel step in the complex mechanism of PrfA activation and further highlights the cross regulation of metabolism and virulence. Copyright © 2017 American Society for Microbiology.

  12. The effectiveness of workplace interventions to increase physical activity and decrease sedentary behaviour in adults: protocol for a systematic review.

    Loitz, Christina C; Potter, Robert J; Walker, Jessica L; McLeod, Nicole C; Johnston, Nora J

    2015-12-12

    A physically active lifestyle plays a preventative role in the development of various chronic diseases and mental health conditions. Unfortunately, few adults achieve the minimum amount of physical activity and spend excessive time sitting. Developing targeted interventions to increase active living among adults is an important endeavour for public