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Sample records for mice high levels

  1. Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice.

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    Quan Yuan

    Full Text Available Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH, Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf23(-/- and Klotho(-/- (Kl(-/- mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf23(-/- mice ameliorated the phenotype in Fgf23(-/-/PTH(-/- mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23(-/- mice, however, persisted, suggesting that a different mechanism is responsible for this mineralization defect. In the current study, we demonstrate that deletion of PTH from Kl(-/- (Kl(-/-/PTH(-/- or DKO mice corrects the abnormal skeletal phenotype. Bone turnover markers are restored to wild-type levels; and, more importantly, the skeletal mineralization defect is completely rescued in Kl(-/-/PTH(-/- mice. Interestingly, the correction of the osteomalacia is accompanied by a reduction in the high levels of osteopontin (Opn in bone and serum. Such a reduction in Opn levels could not be observed in Fgf23(-/-/PTH(-/- mice, and these mice showed sustained osteomalacia. This significant in vivo finding is corroborated by in vitro studies using calvarial osteoblast cultures that show normalized Opn expression and rescued mineralization in Kl(-/-/PTH(-/- mice. Moreover, continuous PTH infusion of Kl(-/- mice significantly increased Opn levels and osteoid volume, and decreased trabecular bone volume. In summary, our results demonstrate for the first time that PTH directly impacts the mineralization disorders and skeletal deformities of Kl(-/-, but not of Fgf23(-/- mice, possibly by regulating Opn expression. These are significant new perceptions into

  2. Crossfostering in mice selectively bred for high and low levels of open-field thigmotaxis.

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    Leppänen, Pia K; Ewalds-Kvist, S Béatrice M

    2005-02-01

    The main purpose of this research was to investigate whether the difference in open-field (OF) thigmotaxis between mice selectively bred for high and low levels of wall-seeking behavior originated from genetic or acquired sources. Unfostered, infostered, and crossfostered mice were compared in two experiments in which the effects of strain, sex, and fostering on ambulation, defecation, exploration, grooming, latency to move, radial latency, rearing, thigmotaxis, and urination were studied. These experiments revealed that OF thigmotaxis was unaffected by the foster condition and thus genetically determined. The selected strains of mice also diverged repeatedly with regard to exploration and rearing. The findings are in line with the previously described existence of an inverse relationship between emotionality and exploration.

  3. Learning and extinction of a passive avoidance response in mice with high levels of predisposition to catalepsy.

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    Dubrovina, N I; Zinov'ev, D R; Zinov'eva, D V; Kulikov, A V

    2009-06-01

    This report presents results obtained from comparative analysis of learning and the dynamics of extinction of a conditioned passive avoidance response in ASC mice, which were bred for a high level of predisposition to catalepsy, and in CBA and AKR mice. The following findings were obtained: 1) impairments to the extinction of the memory of fear represent an important symptom of depression in ASC mice; 2) extinction is delayed in CBA mice; and 3) new inhibitory learning occurs quickly in AKR mice. Prolonged retention of the fear memory in ASC mice appears to be related to increased anxiety on prolonged testing without a punishment. The deficit of inhibition of the fear reaction in ASC mice allows this strain to be regarded as a genetic model of depression.

  4. High Mutation Levels are Compatible with Normal Embryonic Development in Mlh1-Deficient Mice.

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    Fan, Xiaoyan; Li, Yan; Zhang, Yulong; Sang, Meixiang; Cai, Jianhui; Li, Qiaoxia; Ozaki, Toshinori; Ono, Tetsuya; He, Dongwei

    2016-10-01

    To elucidate the role of the mismatch repair gene Mlh1 in genome instability during the fetal stage, spontaneous mutations were studied in Mlh1-deficient lacZ-transgenic mouse fetuses. Mutation levels were high at 9.5 days post coitum (dpc) and gradually increased during the embryonic stage, after which they remained unchanged. In addition, mutations that were found in brain, liver, spleen, small intestine and thymus showed similar levels and no statistically significant difference was found. The molecular nature of mutations at 12.5 dpc in fetuses of Mlh1 +/+ and Mlh1 -/- mice showed their own unique spectra, suggesting that deletion mutations were the main causes in the deficiency of the Mlh1 gene. Of note, fetuses of irradiated mice exhibited marked differences such as post-implantation loss and Mendelian distribution. Collectively, these results strongly suggest that high mutation ofMlh1 -/- -deficient fetuses has little effect on the fetuses during their early developmental stages, whereas Mlh1 -/- -deficient fetuses from X-ray irradiated mothers are clearly effected.

  5. Increased high-density lipoprotein cholesterol levels in mice with XX versus XY sex chromosomes.

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    Link, Jenny C; Chen, Xuqi; Prien, Christopher; Borja, Mark S; Hammerson, Bradley; Oda, Michael N; Arnold, Arthur P; Reue, Karen

    2015-08-01

    The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male-female gonadal sex and XX-XY chromosome complement. Gonadectomy of adult mice revealed that the male-female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male-female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels. © 2015 American Heart Association, Inc.

  6. High Insulin Levels in KK-Ay Diabetic Mice Cause Increased Cortical Bone Mass and Impaired Trabecular Micro-Structure

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    Cen Fu

    2015-04-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD, micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD, cortical volumetric BMD (vBMD and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV, trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC, bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression.

  7. Polycythemia and high levels of erythropoietin in blood and brain blunt the hypercapnic ventilatory response in adult mice.

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    Menuet, Clément; Khemiri, Hanan; de la Poëze d'Harambure, Théodora; Gestreau, Christian

    2016-05-15

    Changes in arterial Po2, Pco2, and pH are the strongest stimuli sensed by peripheral and central chemoreceptors to adjust ventilation to the metabolic demand. Erythropoietin (Epo), the main regulator of red blood cell production, increases the hypoxic ventilatory response, an effect attributed to the presence of Epo receptors in both carotid bodies and key brainstem structures involved in integration of peripheral inputs and control of breathing. However, it is not known whether Epo also has an effect on the hypercapnic chemoreflex. In a first attempt to answer this question, we tested the hypothesis that Epo alters the ventilatory response to increased CO2 levels. Basal ventilation and hypercapnic ventilatory response (HCVR) were recorded from control mice and from two transgenic mouse lines constitutively expressing high levels of human Epo in brain only (Tg21) or in brain and plasma (Tg6), the latter leading to polycythemia. To tease apart the potential effects of polycythemia and levels of plasma Epo in the HCVR, control animals were injected with an Epo analog (Aranesp), and Tg6 mice were treated with the hemolytic agent phenylhydrazine after splenectomy. Ventilatory parameters measured by plethysmography in conscious mice were consistent with data from electrophysiological recordings in anesthetized animals and revealed a blunted HCVR in Tg6 mice. Polycythemia alone and increased levels of plasma Epo blunt the HCVR. In addition, Tg21 mice with an augmented level of cerebral Epo also had a decreased HCVR. We discuss the potential implications of these findings in several physiopathological conditions. Copyright © 2016 the American Physiological Society.

  8. Krill protein hydrolysate reduces plasma triacylglycerol level with concurrent increase in plasma bile acid level and hepatic fatty acid catabolism in high-fat fed mice

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    Marie S. Ramsvik

    2013-11-01

    Full Text Available Background: Krill powder, consisting of both lipids and proteins, has been reported to modulate hepatic lipid catabolism in animals. Fish protein hydrolysate diets have also been reported to affect lipid metabolism and to elevate bile acid (BA level in plasma. BA interacts with a number of nuclear receptors and thus affects a variety of signaling pathways, including very low density lipoprotein (VLDL secretion. The aim of the present study was to investigate whether a krill protein hydrolysate (KPH could affect lipid and BA metabolism in mice. Method: C57BL/6 mice were fed a high-fat (21%, w/w diet containing 20% crude protein (w/w as casein (control group or KPH for 6 weeks. Lipids and fatty acid composition were measured from plasma, enzyme activity and gene expression were analyzed from liver samples, and BA was measured from plasma. Results: The effect of dietary treatment with KPH resulted in reduced levels of plasma triacylglycerols (TAG and non-esterified fatty acids (NEFAs. The KPH treated mice had also a marked increased plasma BA concentration. The increased plasma BA level was associated with induction of genes related to membrane canalicular exporter proteins (Abcc2, Abcb4 and to BA exporters to blood (Abcc3 and Abcc4. Of note, we observed a 2-fold increased nuclear farnesoid X receptor (Fxr mRNA levels in the liver of mice fed KPH. We also observed increased activity of the nuclear peroxiosme proliferator-activated receptor alpha (PPARα target gene carnitine plamitoyltransferase 2 (CPT-2. Conclusion: The KPH diet showed to influence lipid and BA metabolism in high-fat fed mice. Moreover, increased mitochondrial fatty acid oxidation and elevation of BA concentration may regulate the plasma level of TAGs and NEFAs.

  9. HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets

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    Zeid Khitan

    2014-01-01

    Full Text Available Background. Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS. HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes. We examined whether the fructose-mediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction of HO-1 would decrease both isoprostane levels and adipogenesis. Methods and Results. We examined the effect of fructose, on adipogenesis in human MSCs in the presence and absence of CoPP, an inducer of HO-1. Fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets (P<0.05. Levels of heme and isoprostane in fructose treated MSC-derived adipocytes were increased. CoPP reversed these effects and markedly increased HO-1 and the Wnt signaling pathway. The high fructose diet increased heme levels in adipose tissue and increased circulating isoprostane levels (P<0.05 versus control. Fructose diets decreased HO-1 and adiponectin levels in adipose tissue. Induction of HO-1 by CoPP decreased isoprostane synthesis (P<0.05 versus fructose. Conclusion. Fructose treatment resulted in increased isoprostane production and adipocyte dysfunction, which was reversed by the increased expression of HO-1.

  10. Not So Giants: Mice Lacking Both Somatostatin and Cortistatin Have High GH Levels but Show No Changes in Growth Rate or IGF-1 Levels.

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    Pedraza-Arévalo, S; Córdoba-Chacón, J; Pozo-Salas, A I; L-López, F; de Lecea, L; Gahete, M D; Castaño, J P; Luque, R M

    2015-06-01

    Somatostatin (SST) and cortistatin (CORT) are two highly related neuropeptides involved in the regulation of various endocrine secretions. In particular, SST and CORT are two primary negative regulators of GH secretion. Consequently, single SST or CORT knockout mice exhibit elevated GH levels; however, this does not lead to increased IGF-1 levels or somatic growth. This apparent lack of correspondence has been suggested to result from compensatory mechanisms between both peptides. To test this hypothesis, in this study we explored, for the first time, the consequences of simultaneously deleting endogenous SST and CORT by generating a double SST/CORT knockout mouse model and exploring its endocrine and metabolic phenotype. Our results demonstrate that simultaneous deletion of SST and CORT induced a drastic elevation of endogenous GH levels, which, surprisingly, did not lead to changes in growth rate or IGF-1 levels, suggesting the existence of additional factors/systems that, in the absence of endogenous SST and CORT, could counteract GH actions. Notably, elevation in circulating GH levels were not accompanied by changes in pituitary GH expression or by alterations in the expression of its main regulators (GHRH and ghrelin) or their receptors (GHRH receptor, GHS receptor, or SST/CORT receptors) at the hypothalamic or pituitary level. However, although double-SST/CORT knockout male mice exhibited normal glucose and insulin levels, they had improved insulin sensitivity compared with the control mice. Therefore, these results suggest the existence of an intricate interplay among the known (SST/CORT), and likely unknown, inhibitory components of the GH/IGF-1 axis to regulate somatic growth and glucose/insulin homeostasis.

  11. Plasma levels of 27-hydroxycholesterol in humans and mice with monogenic disturbances of high density lipoprotein metabolism

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    Karuna, Ratna; Holleboom, Adriaan G; Motazacker, Mohammad M

    2011-01-01

    Secretion of 27-hydroxycholesterol (27OHC) from macrophages is considered as an alternative to HDL-mediated reverse transport of excess cholesterol. We investigated 27OHC-concentrations in plasma of humans and mice with monogenic disorders of HDL metabolism. As compared to family controls mutations...... activities of LCAT and CETP, respectively, than the formation and transfer of cholesterylesters. 27OHC plasma levels were also decreased in apoA-I-, ABCA1- or LCAT-knockout mice but increased in SR-BI-knockout mice. Transplantation of ABCA1- and/or ABCG1-deficient bone marrow into LDL receptor deficient mice...... decreased plasma levels of 27OHC. In conclusion, mutations or absence of HDL genes lead to distinct alterations in the quantity, esterification or lipoprotein distribution of 27OHC. These findings argue against the earlier suggestion that 27OHC-metabolism in plasma occurs independently of HDL....

  12. Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes.

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    Thompson, Zoe; Argueta, Donovan; Garland, Theodore; DiPatrizio, Nicholas

    2017-03-01

    The endocannabinoid system serves many physiological roles, including in the regulation of energy balance, food reward, and voluntary locomotion. Signaling at the cannabinoid type 1 receptor has been specifically implicated in motivation for rodent voluntary exercise on wheels. We studied four replicate lines of high runner (HR) mice that have been selectively bred for 81 generations based on average number of wheel revolutions on days five and six of a six-day period of wheel access. Four additional replicate lines are bred without regard to wheel running, and serve as controls (C) for random genetic effects that may cause divergence among lines. On average, mice from HR lines voluntarily run on wheels three times more than C mice on a daily basis. We tested the general hypothesis that circulating levels of endocannabinoids (i.e., 2-arachidonoylglycerol [2-AG] and anandamide [AEA]) differ between HR and C mice in a sex-specific manner. Fifty male and 50 female mice were allowed access to wheels for six days, while another 50 males and 50 females were kept without access to wheels (half HR, half C for all groups). Blood was collected by cardiac puncture during the time of peak running on the sixth night of wheel access or no wheel access, and later analyzed for 2-AG and AEA content by ultra-performance liquid chromatography coupled to tandem mass spectrometry. We observed a significant three-way interaction among sex, linetype, and wheel access for 2-AG concentrations, with females generally having lower levels than males and wheel access lowering 2-AG levels in some but not all subgroups. The number of wheel revolutions in the minutes or hours immediately prior to sampling did not quantitatively predict plasma 2-AG levels within groups. We also observed a trend for a linetype-by-wheel access interaction for AEA levels, with wheel access lowering plasma concentrations of AEA in HR mice, while raising them in C mice. In addition, females tended to have higher AEA

  13. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels.

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    Vyas, Dinesh; Javadi, Pardis; Dipasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-10-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 h after cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 h after septic insult. Our first aim was to see whether earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die on the basis of high IL-6 levels. Mice (n = 184) were subjected to CLP, had IL-6 levels drawn 6 h later, and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from 25.5 to 35.9% with earlier administration of antibiotics (P 14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas none survived if antibiotics were started later (P 14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6.

  14. Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die based upon high IL-6 levels

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    Vyas, Dinesh; Javadi, Pardis; DiPasco, Peter J; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-01-01

    Elevated interleukin (IL)-6 levels correlate with increased mortality following sepsis. IL-6 levels >14,000 pg/ml drawn 6 hours following cecal ligation and puncture (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy is initiated 12 hours after the septic insult. The first aim of this study was to see if earlier institution of antibiotic therapy could improve overall survival in septic mice and rescue the subset of animals predicted to die based upon high IL-6 levels. Mice (n=184) were subjected to CLP, had IL-6 levels drawn six hours later and then were randomized to receive imipenem, a broad spectrum antimicrobial agent, beginning six or twelve hours post-operatively. Overall one-week survival improved from 25.5% to 35.9% with earlier administration of antibiotics (p14,000 pg/ml, 25% survived if imipenem was started at 6 hours, while none survived if antibiotics were started later (p14,000 pg/ml. These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6. PMID:15947070

  15. Chronic free-choice drinking in crossed high alcohol preferring mice leads to sustained blood ethanol levels and metabolic tolerance without evidence of liver damage.

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    Matson, Liana; Liangpunsakul, Suthat; Crabb, David; Buckingham, Amy; Ross, Ruth Ann; Halcomb, Meredith; Grahame, Nicholas

    2013-02-01

    Crossed high alcohol preferring (cHAP) mice were selectively bred from a cross of the HAP1 × HAP2 replicate lines, and we demonstrate blood ethanol concentrations (BECs) during free-choice drinking that are reminiscent of those observed in alcohol-dependent humans. Therefore, this line may provide an unprecedented opportunity to learn about the consequences of excessive voluntary ethanol (EtOH) consumption, including metabolic tolerance and liver pathology. Cytochrome p450 2E1 (CYP2E1) induction plays a prominent role in driving both metabolic tolerance and EtOH-induced liver injury. In this report, we sought to characterize cHAP drinking by assessing whether pharmacologically relevant BEC levels are sustained throughout the active portion of the light-dark cycle. Given that cHAP intakes and BECs are similar to those observed in mice given an EtOH liquid diet, we assessed whether free-choice exposure results in metabolic tolerance, hepatic enzyme induction, and hepatic steatosis. In experiment 1, blood samples were taken across the dark portion of a 12:12 light-dark cycle to examine the pattern of EtOH accumulation in these mice. In experiments 1 and 2, mice were injected with EtOH following 3 to 4 weeks of access to water or 10% EtOH and water, and blood samples were taken to assess metabolic tolerance. In experiment 3, 24 mice had 4 weeks of access to 10% EtOH and water or water alone, followed by necropsy and hepatological assessment. In experiment 1, cHAP mice mean BEC values exceeded 80 mg/dl at all sampling points and approached 200 mg/dl during the middle of the dark cycle. In experiments 1 and 2, EtOH-exposed mice metabolized EtOH faster than EtOH-naïve mice, demonstrating metabolic tolerance (p alcohol dehydrogenase and aldehyde dehydrogenase. These results demonstrate that excessive intake by cHAP mice results in sustained BECs throughout the active period, leading to the development of metabolic tolerance and evidence of CYP2E1 induction

  16. Selenium and Selenoprotein Deficiencies Induce Widespread Pyogranuloma Formation in Mice, while High Levels of Dietary Selenium Decrease Liver Tumor Size Driven by TGFα

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    Zhong, Nianxin; Ward, Jerrold M.; Perella, Christine M.; Hoffmann, Victoria J.; Rogers, Keith; Combs, Gerald F.; Schweizer, Ulrich; Merlino, Glenn; Gladyshev, Vadim N.; Hatfield, Dolph L.

    2013-01-01

    Changes in dietary selenium and selenoprotein status may influence both anti- and pro-cancer pathways, making the outcome of interventions different from one study to another. To characterize such outcomes in a defined setting, we undertook a controlled hepatocarcinogenesis study involving varying levels of dietary selenium and altered selenoprotein status using mice carrying a mutant (A37G) selenocysteine tRNA transgene (TrsptG37) and/or a cancer driver TGFα transgene. The use of TrsptG37 altered selenoprotein expression in a selenoprotein and tissue specific manner and, at sufficient dietary selenium levels, separate the effect of diet and selenoprotein status. Mice were maintained on diets deficient in selenium (0.02 ppm selenium) or supplemented with 0.1, 0.4 or 2.25 ppm selenium or 30 ppm triphenylselenonium chloride (TPSC), a non-metabolized selenium compound. TrsptG37 transgenic and TGFα/TrsptG37 bi-transgenic mice subjected to selenium-deficient or TPSC diets developed a neurological phenotype associated with early morbidity and mortality prior to hepatocarcinoma development. Pathology analyses revealed widespread disseminated pyogranulomatous inflammation. Pyogranulomas occurred in liver, lungs, heart, spleen, small and large intestine, and mesenteric lymph nodes in these transgenic and bi-transgenic mice. The incidence of liver tumors was significantly increased in mice carrying the TGFα transgene, while dietary selenium and selenoprotein status did not affect tumor number and multiplicity. However, adenoma and carcinoma size and area were smaller in TGFα transgenic mice that were fed 0.4 and 2.25 versus 0.1 ppm of selenium. Thus, selenium and selenoprotein deficiencies led to widespread pyogranuloma formation, while high selenium levels inhibited the size of TGFα–induced liver tumors. PMID:23460847

  17. Mtf-1 lymphoma-susceptibility locus affects retention of large thymocytes with high ROS levels in mice after γ-irradiation

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    Maruyama, Masaki; Yamamoto, Takashi; Kohara, Yuki; Katsuragi, Yoshinori; Mishima, Yukio; Aoyagi, Yutaka; Kominami, Ryo

    2007-01-01

    Mouse strains exhibit different susceptibilities to γ-ray-induced thymic lymphomas. Our previous study identified Mtf-1 (metal responsive transcription factor-1) as a candidate susceptibility gene, which is involved in the radiation-induced signaling pathway that regulates the cellular reactive oxygen species (ROS). To reveal the mechanism for the increased susceptibility conferred by Mtf-1 locus, we examined early effects of γ-ray on ROS levels in vivo and its difference between Mtf-1 susceptible and resistant congenic mice. Here, we show the detection of clonally growing thymocytes at 4 weeks after irradiation, indicating the start of clonal expansion at a very early stage. We also show that large thymocytes with higher ROS levels and a proliferation capacity were more numerous in the Mtf-1 susceptible mice than the resistant mice when examined at 7 days after irradiation, although such tendency was not found in mice lacking one allele of Bcl11b tumor suppressor gene. This high retention of the large thymocytes, at a high risk for ROS-induced mutation, is a compensatory proliferation and regeneration response to depletion of the thymocytes after irradiation and the response is likely to augment the development of prelymphoma cells leading to thymic lymphomas

  18. Red Maca (Lepidium meyenii), a Plant from the Peruvian Highlands, Promotes Skin Wound Healing at Sea Level and at High Altitude in Adult Male Mice.

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    Nuñez, Denisse; Olavegoya, Paola; Gonzales, Gustavo F; Gonzales-Castañeda, Cynthia

    2017-12-01

    Nuñez, Denisse, Paola Olavegoya, Gustavo F. Gonzales, and Cynthia Gonzales-Castañeda. Red maca (Lepidium meyenii), a plant from the Peruvian highlands, promotes skin wound healing at sea level and at high altitude in adult male mice. High Alt Med Biol 18:373-383, 2017.-Wound healing consists of three simultaneous phases: inflammation, proliferation, and remodeling. Previous studies suggest that there is a delay in the healing process in high altitude, mainly due to alterations in the inflammatory phase. Maca (Lepidium meyenii) is a Peruvian plant with diverse biological properties, such as the ability to protect the skin from inflammatory lesions caused by ultraviolet radiation, as well as its antioxidant and immunomodulatory properties. The aim of this study was to determine the effect of high altitude on tissue repair and the effect of the topical administration of the spray-dried extract of red maca (RM) in tissue repair. Studies were conducted in male Balb/c mice at sea level and high altitude. Lesions were inflicted through a 10 mm-diameter excisional wound in the skin dorsal surface. Treatments consisted of either (1) spray-dried RM extract or (2) vehicle (VH). Animals wounded at high altitude had a delayed healing rate and an increased wound width compared with those at sea level. Moreover, wounding at high altitude was associated with an increase in inflammatory cells. Treatment with RM accelerated wound closure, decreased the level of epidermal hyperplasia, and decreased the number of inflammatory cells at the wound site. In conclusion, RM at high altitude generate a positive effect on wound healing, decreasing the number of neutrophils and increasing the number of macrophages in the wound healing at day 7 postwounding. This phenomenon is not observed at sea level.

  19. Long-term high-level expression of human beta-globin occurs following transplantation of transgenic marrow into irradiated mice.

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    Himelstein, A; Ward, M; Podda, S; de la Flor Weiss, E; Costantini, F; Bank, A

    1993-03-01

    When the human beta-globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human beta-globin into irradiated recipients. We demonstrate that long-term high level expression of the human beta-globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human beta-globin transgene expression to endogenous mouse beta-globin gene expression in donor-derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human beta-globin gene in mouse bone marrow cells following marrow transplantation.

  20. Blockade of dopamine D1-family receptors attenuates the mania-like hyperactive, risk-preferring, and high motivation behavioral profile of mice with low dopamine transporter levels.

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    Milienne-Petiot, Morgane; Groenink, Lucianne; Minassian, Arpi; Young, Jared W

    2017-10-01

    Patients with bipolar disorder mania exhibit poor cognition, impulsivity, risk-taking, and goal-directed activity that negatively impact their quality of life. To date, existing treatments for bipolar disorder do not adequately remediate cognitive dysfunction. Reducing dopamine transporter expression recreates many bipolar disorder mania-relevant behaviors (i.e. hyperactivity and risk-taking). The current study investigated whether dopamine D 1 -family receptor blockade would attenuate the risk-taking, hypermotivation, and hyperactivity of dopamine transporter knockdown mice. Dopamine transporter knockdown and wild-type littermate mice were tested in mouse versions of the Iowa Gambling Task (risk-taking), Progressive Ratio Breakpoint Test (effortful motivation), and Behavioral Pattern Monitor (activity). Prior to testing, the mice were treated with the dopamine D 1 -family receptor antagonist SCH 23390 hydrochloride (0.03, 0.1, or 0.3 mg/kg), or vehicle. Dopamine transporter knockdown mice exhibited hyperactivity and hyperexploration, hypermotivation, and risk-taking preference compared with wild-type littermates. SCH 23390 hydrochloride treatment decreased premature responding in dopamine transporter knockdown mice and attenuated their hypermotivation. SCH 23390 hydrochloride flattened the safe/risk preference, while reducing activity and exploratory levels of both genotypes similarly. Dopamine transporter knockdown mice exhibited mania-relevant behavior compared to wild-type mice. Systemic dopamine D 1 -family receptor antagonism attenuated these behaviors in dopamine transporter knockdown, but not all effects were specific to only the knockdown mice. The normalization of behavior via blockade of dopamine D 1 -family receptors supports the hypothesis that D 1 and/or D 5 receptors could contribute to the mania-relevant behaviors of dopamine transporter knockdown mice.

  1. Effects of ingredients of Korean brown rice cookies on attenuation of cholesterol level and oxidative stress in high-fat diet-fed mice.

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    Hong, Sun Hee; Kim, Mijeong; Woo, Minji; Song, Yeong Ok

    2017-10-01

    Owing to health concerns related to the consumption of traditional snacks high in sugars and fats, much effort has been made to develop functional snacks with low calorie content. In this study, a new recipe for Korean rice cookie, dasik , was developed and its antioxidative, lipid-lowering, and anti-inflammatory effects and related mechanisms were elucidated. The effects were compared with those of traditional rice cake dasik (RCD), the lipid-lowering effect of which is greater than that of traditional western-style cookies. Ginseng-added brown rice dasik (GBRD) was prepared with brown rice flour, fructooligosaccharide, red ginseng extract, and propolis. Mice were grouped (n = 7 per group) into those fed a normal AIN-76 diet, a high-fat diet (HFD), and HFD supplemented with RCD or GBRD. Dasik in the HFD accounted for 7% of the total calories. The lipid, reactive oxygen species, and peroxynitrite levels, and degree of lipid peroxidation in the plasma or liver were determined. The expression levels of proteins involved in lipid metabolism and inflammation, and those of antioxidant enzymes were determined by western blot analysis. The plasma and hepatic total cholesterol concentrations in the GBRD group were significantly decreased via downregulation of sterol regulatory element-binding protein-2 and 3-hydroxy-3-methylglutaryl-CoA reductase ( P < 0.05). The hepatic peroxynitrite level was significantly lower, whereas glutathione was higher, in the GBRD group than in the RCD group. Among the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx) were significantly upregulated in the GBRD group ( P < 0.05). In addition, nuclear factor-kappaB (NF-κB) expression in the GBRD group was significantly lower than that in the RCD group. GBRD decreases the plasma and hepatic cholesterol levels by downregulating cholesterol synthesis. This new dasik recipe also improves the antioxidative and anti-inflammatory status in HFD-fed mice via CAT and GPx upregulation and

  2. In LDL receptor-deficient mice, catabolism of remnant lipoproteins requires a high level of apoE but is inhibited by excess apoE

    NARCIS (Netherlands)

    Dijk, K.W. van; Vlijmen, B.J.M. van; Hof, H.B. van 't; Zee, A. van der; Santamarina-Fojo, S.; Berkel, T.J.C. van; Havekes, L.M.; Hofker, M.H.

    1999-01-01

    To investigate the quantitative requirement for apolipoprotein (apo) E in the clearance of lipoproteins via the non-low density lipoprotein (LDL) receptor mediated pathway, human APOE was overexpressed at various levels in the livers of mice deficient for both the endogenous Apoe and Ldlr genes

  3. High tidal volume ventilation in infant mice.

    Science.gov (United States)

    Cannizzaro, Vincenzo; Zosky, Graeme R; Hantos, Zoltán; Turner, Debra J; Sly, Peter D

    2008-06-30

    Infant mice were ventilated with either high tidal volume (V(T)) with zero end-expiratory pressure (HVZ), high V(T) with positive end-expiratory pressure (PEEP) (HVP), or low V(T) with PEEP. Thoracic gas volume (TGV) was determined plethysmographically and low-frequency forced oscillations were used to measure the input impedance of the respiratory system. Inflammatory cells, total protein, and cytokines in bronchoalveolar lavage fluid (BALF) and interleukin-6 (IL-6) in serum were measured as markers of pulmonary and systemic inflammatory response, respectively. Coefficients of tissue damping and tissue elastance increased in all ventilated mice, with the largest rise seen in the HVZ group where TGV rapidly decreased. BALF protein levels increased in the HVP group, whereas serum IL-6 rose in the HVZ group. PEEP keeps the lungs open, but provides high volumes to the entire lungs and induces lung injury. Compared to studies in adult and non-neonatal rodents, infant mice demonstrate a different response to similar ventilation strategies underscoring the need for age-specific animal models.

  4. High levels of eukaryotic Initiation Factor 6 (eIF6) are required for immune system homeostasis and for steering the glycolytic flux of TCR-stimulated CD4+ T cells in both mice and humans.

    Science.gov (United States)

    Manfrini, Nicola; Ricciardi, Sara; Miluzio, Annarita; Fedeli, Maya; Scagliola, Alessandra; Gallo, Simone; Brina, Daniela; Adler, Thure; Busch, Dirk H; Gailus-Durner, Valerie; Fuchs, Helmut; Hrabě de Angelis, Martin; Biffo, Stefano

    2017-12-01

    Eukaryotic Initiation Factor 6 (eIF6) is required for 60S ribosomal subunit biogenesis and efficient initiation of translation. Intriguingly, in both mice and humans, endogenous levels of eIF6 are detrimental as they act as tumor and obesity facilitators, raising the question on the evolutionary pressure that maintains high eIF6 levels. Here we show that, in mice and humans, high levels of eIF6 are required for proper immune functions. First, eIF6 heterozygous (het) mice show an increased mortality during viral infection and a reduction of peripheral blood CD4 + Effector Memory T cells. In human CD4 + T cells, eIF6 levels rapidly increase upon T-cell receptor activation and drive the glycolytic switch and the acquisition of effector functions. Importantly, in CD4 + T cells, eIF6 levels control interferon-γ (IFN-γ) secretion without affecting proliferation. In conclusion, the immune system has a high evolutionary pressure for the maintenance of a dynamic and powerful regulation of the translational machinery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. High-level verification

    CERN Document Server

    Lerner, Sorin; Kundu, Sudipta

    2011-01-01

    Given the growing size and heterogeneity of Systems on Chip (SOC), the design process from initial specification to chip fabrication has become increasingly complex. This growing complexity provides incentive for designers to use high-level languages such as C, SystemC, and SystemVerilog for system-level design. While a major goal of these high-level languages is to enable verification at a higher level of abstraction, allowing early exploration of system-level designs, the focus so far for validation purposes has been on traditional testing techniques such as random testing and scenario-based

  6. Exercise training performed simultaneously to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in mice

    Directory of Open Access Journals (Sweden)

    Farias JM

    2012-10-01

    Full Text Available Abstract Background The aim of the present study was to evaluate the protective effect of concurrent exercise in the degree of the insulin resistance in mice fed with a high-fat diet, and assess adiponectin receptors (ADIPOR1 and ADIPOR2 and endosomal adaptor protein APPL1 in different tissues. Methods Twenty-four mice were randomized into four groups (n = 6: chow standard diet and sedentary (C; chow standard diet and simultaneous exercise training (C-T; fed on a high-fat diet and sedentary (DIO; and fed on a high-fat diet and simultaneous exercise training (DIO-T. Simultaneously to starting high-fat diet feeding, the mice were submitted to a swimming exercise training protocol (2 x 30 minutes, with 5 minutes of interval/day, five days per week, for twelve weeks (90 days. Animals were then euthanized 48 hours after the last exercise training session, and adipose, liver, and skeletal muscle tissue were extracted for an immunoblotting analysis. Results IR, IRs, and Akt phosphorylation decreased in the DIO group in the three analyzed tissues. In addition, the DIO group exhibited ADIPOR1 (skeletal muscle and adipose tissue, ADIPOR2 (liver, and APPL1 reduced when compared with the C group. However, it was reverted when exercise training was simultaneously performed. In parallel, ADIPOR1 and 2 and APPL1 protein levels significantly increase in exercised mice. Conclusions Our findings demonstrate that exercise training performed concomitantly to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in the hepatic, adipose, and skeletal muscle tissue.

  7. The Inhibitory Effects of Purple Sweet Potato Color on Hepatic Inflammation Is Associated with Restoration of NAD⁺ Levels and Attenuation of NLRP3 Inflammasome Activation in High-Fat-Diet-Treated Mice.

    Science.gov (United States)

    Wang, Xin; Zhang, Zi-Feng; Zheng, Gui-Hong; Wang, Ai-Min; Sun, Chun-Hui; Qin, Su-Ping; Zhuang, Juan; Lu, Jun; Ma, Dai-Fu; Zheng, Yuan-Lin

    2017-08-08

    Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, exhibits beneficial effects on metabolic syndrome. Sustained inflammation plays a crucial role in the pathogenesis of metabolic syndrome. Here we explored the effects of PSPC on high-fat diet (HFD)-induced hepatic inflammation and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + PSPC group, and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. Nicotinamide riboside (NR) was used to increase NAD⁺ levels. Our results showed that PSPC effectively ameliorated obesity and liver injuries in HFD-fed mice. Moreover, PSPC notably blocked hepatic oxidative stress in HFD-treated mice. Furthermore, PSPC dramatically restored NAD⁺ level to abate endoplasmic reticulum stress (ER stress) in HFD-treated mouse livers, which was confirmed by NR treatment. Consequently, PSPC remarkably suppressed the nuclear factor-κB (NF-κB) p65 nuclear translocation and nucleotide oligomerization domain protein1/2 (NOD1/2) signaling in HFD-treated mouse livers. Thereby, PSPC markedly diminished the NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation, ultimately lowering the expressions of inflammation-related genes in HFD-treated mouse livers. In summary, PSPC protected against HFD-induced hepatic inflammation by boosting NAD⁺ level to inhibit NLRP3 inflammasome activation.

  8. High potassium level

    Science.gov (United States)

    ... level is very high, or if you have danger signs, such as changes in an ECG . Emergency ... Seifter JL. Potassium disorders. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

  9. General Algorithm (High level)

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. General Algorithm (High level). Iteratively. Use Tightness Property to remove points of P1,..,Pi. Use random sampling to get a Random Sample (of enough points) from the next largest cluster, Pi+1. Use the Random Sampling Procedure to approximate ci+1 using the ...

  10. Chronic exposure to low frequency noise at moderate levels causes impaired balance in mice.

    Directory of Open Access Journals (Sweden)

    Haruka Tamura

    Full Text Available We are routinely exposed to low frequency noise (LFN; below 0.5 kHz at moderate levels of 60-70 dB sound pressure level (SPL generated from various sources in occupational and daily environments. LFN has been reported to affect balance in humans. However, there is limited information about the influence of chronic exposure to LFN at moderate levels for balance. In this study, we investigated whether chronic exposure to LFN at a moderate level of 70 dB SPL affects the vestibule, which is one of the organs responsible for balance in mice. Wild-type ICR mice were exposed for 1 month to LFN (0.1 kHz and high frequency noise (HFN; 16 kHz at 70 dB SPL at a distance of approximately 10-20 cm. Behavior analyses including rotarod, beam-crossing and footprint analyses showed impairments of balance in LFN-exposed mice but not in non-exposed mice or HFN-exposed mice. Immunohistochemical analysis showed a decreased number of vestibular hair cells and increased levels of oxidative stress in LFN-exposed mice compared to those in non-exposed mice. Our results suggest that chronic exposure to LFN at moderate levels causes impaired balance involving morphological impairments of the vestibule with enhanced levels of oxidative stress. Thus, the results of this study indicate the importance of considering the risk of chronic exposure to LFN at a moderate level for imbalance.

  11. Increased glucose tolerance despite low adiponectin levels in obesity-resistent aP2-Ucp1 transgenic mice fed a high-fat diet

    Czech Academy of Sciences Publication Activity Database

    Rossmeisl, Martin; Jeleník, Tomáš; Ogston, N. C.; Slámová, Kristýna; Mohamed-Ali, V.; Kopecký, Jan

    2006-01-01

    Roč. 49, Suppl. 1 (2006), s. 755-755 ISSN 0012-186X. [Annual Meeting of the European Association for the Study of Diabetes /42./. 14.09.2006-17.09.2006, Copenhagen-Malmoe] R&D Projects: GA MŠk(CZ) 1M0520; GA ČR(CZ) GA303/05/2580 Institutional research plan: CEZ:AV0Z50110509 Keywords : adiponectin * transgenic mice * obesity * mitochondria * glucose tolerance * hyperinsulinemic-euglycemic clamp Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  12. High level nuclear wastes

    International Nuclear Information System (INIS)

    Lopez Perez, B.

    1987-01-01

    The transformations involved in the nuclear fuels during the burn-up at the power nuclear reactors for burn-up levels of 33.000 MWd/th are considered. Graphs and data on the radioactivity variation with the cooling time and heat power of the irradiated fuel are presented. Likewise, the cycle of the fuel in light water reactors is presented and the alternatives for the nuclear waste management are discussed. A brief description of the management of the spent fuel as a high level nuclear waste is shown, explaining the reprocessing and giving data about the fission products and their radioactivities, which must be considered on the vitrification processes. On the final storage of the nuclear waste into depth geological burials, both alternatives are coincident. The countries supporting the reprocessing are indicated and the Spanish programm defined in the Plan Energetico Nacional (PEN) is shortly reviewed. (author) 8 figs., 4 tabs

  13. High-level Gpr56 expression is dispensable for the maintenance and function of hematopoietic stem and progenitor cells in mice

    Directory of Open Access Journals (Sweden)

    Tata Nageswara Rao

    2015-05-01

    Full Text Available Blood formation by hematopoietic stem cells (HSCs is regulated by a still incompletely defined network of general and HSC-specific regulators. In this study, we analyzed the role of G-protein coupled receptor 56 (Gpr56 as a candidate HSC regulator based on its differential expression in quiescent relative to proliferating HSCs and its common targeting by core HSC regulators. Detailed expression analysis revealed that Gpr56 is abundantly expressed by HSPCs during definitive hematopoiesis in the embryo and in the adult bone marrow, but its levels are reduced substantially as HSPCs differentiate. However, despite enriched expression in HSPCs, Gpr56-deficiency did not impair HSPC maintenance or function during steady-state or myeloablative stress-induced hematopoiesis. Gpr56-deficient HSCs also responded normally to physiological and pharmacological mobilization signals, despite the reported role of this GPCR as a regulator of cell adhesion and migration in neuronal cells. Moreover, Gpr56-deficient bone marrow engrafted with equivalent efficiency as wild-type HSCs in primary recipients; however, their reconstituting ability was reduced when subjected to serial transplantation. These data indicate that although GPR56 is abundantly and selectively expressed by primitive HSPCs, its high level expression is largely dispensable for steady-state and regenerative hematopoiesis.

  14. ALICE High Level Trigger

    CERN Multimedia

    Alt, T

    2013-01-01

    The ALICE High Level Trigger (HLT) is a computing farm designed and build for the real-time, online processing of the raw data produced by the ALICE detectors. Events are fully reconstructed from the raw data, analyzed and compressed. The analysis summary together with the compressed data and a trigger decision is sent to the DAQ. In addition the reconstruction of the events allows for on-line monitoring of physical observables and this information is provided to the Data Quality Monitor (DQM). The HLT can process event rates of up to 2 kHz for proton-proton and 200 Hz for Pb-Pb central collisions.

  15. Behavioural changes in mice exposed to low level microwave fields

    International Nuclear Information System (INIS)

    Goiceanu, C.; Gradinaru, F.; Danulescu, R.; Balaceanu, G.; Sandu, D. D.; Avadanei, O. G.

    2001-01-01

    The aim of our study is to point out some changes in mice behaviour due possibly to exposure to low-level microwave fields. Animals spontaneous behaviour were monitored and the exploring behaviour and motor activity were assessed. Ten selected Swiss male mice were exposed to low-level microwave fields of about 1 mW/cm 2 power density for a relatively long period of time (13 weeks), comparing to their lifetime. The exposure system consists in a transverse electromagnetic (TEM) Cell. A control lot of ten Swiss male mice was used. All twenty mice were selected to be of same age and of 202 g initial body weight. Each animal was placed in his own holder. The behaviour of the animals, from both exposed and control lots, was assessed by using a battery of three behavioural tests. The test sessions were performed every two weeks. During exposure period it was recorded a progressive but moderate loss of motor activity for both exposed and controls, probably due to weight gain and aging. Concerning exploratory activity there is a significant difference between control and exposed animals. Control mice had approximately constant performances in time. On the other hand exposed mice showed a progressive decrease in time of their exploratory ability. Motor activity of exposed animals does not seem to be affected by microwave exposure, in spite of moderate loss in time of motor activity in both lots, as long as it was recorded a quite similar evolution. The difference in performances of exposed and controls concerning exploratory activity seem to emphasise an effect of long-term low-level microwave exposure. The progressive loss in time of exploratory activity of exposed mice, in contrast with controls, could be due to the interference of microwaves with central nervous activity. (authors)

  16. 2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

    International Nuclear Information System (INIS)

    Skillman, C.A.; Fletcher, H.P.

    1986-01-01

    The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

  17. Effect of Different Starvation Levels on Cognitive Ability in Mice

    Science.gov (United States)

    Li, Xiaobing; Zhi, Guoguo; Yu, Yi; Cai, Lingyu; Li, Peng; Zhang, Danhua; Bao, Shuting; Hu, Wenlong; Shen, Haiyan; Song, Fujuan

    2018-01-01

    Objective: To study the effect of different starvation levels on cognitive ability in mice. Method: Mice were randomly divided into four groups: normal group, dieting group A, dieting group B, dieting group C. The mice of normal group were given normal feeding amount, the rest of groups were given 3/4 of normal feeding amount, 2/4 of normal feeding amount and 1/4 of normal feeding amount. After feeding mice four days, the weight was observed and T-maze experiment, Morris water maze test, open field test and Serum Catalase activity were detected. Result: Compared with the normal group, the correct rate of the intervention group in the T-maze experiment was decreased and dieting group A> dieting group B> dieting group C. In the Morris water maze test, Compared with the normal group, the correct rate of the intervention group was increased. Among these three intervention groups, dieting group A had the highest correct rate and the difference of dieting group B and dieting group C were similar. In the open field test, Compared with the normal group, the exploration rate of the surrounding environment in the intervention group was increased. In the Serum Catalase test, Compared with the normal group, the activities of serum peroxidase in the intervention groups were decreased and dieting group A> dieting group B> dieting group C. Conclusion: A certain level of starvation could affect the cognitive ability of mice. In a certain range, the level of starvation is inversely proportional to cognitive ability in mice.

  18. Brain levels of N-acylethanolamine phospholipids in mice during pentylenetetrazol-induced seizure

    DEFF Research Database (Denmark)

    Moesgaard, B.; Hansen, H.H.; Petersen, G.

    2003-01-01

    occur in response to seizure activity. Therefore, we investigated the effect of pentylenetetrazol (PTZ)-induced seizures in PTZ-kindled mice on the level of NAPE in the brain. Male NMRI mice were kindled with PTZ injections 3 times/wk, thereby developing clonic seizures in response to PTZ. Mice were...... killed within 30 min after the clonic seizure on the test day (12th injection) and the brains were collected. Eight species of NAPE were analyzed as the glycerophospho-N-acylethanolamines by high-performance liquid chromatography-coupled electrospray ionization mass spectrometry. No effect of the PTZ...... accumulate during seizure....

  19. Some factors influencing liver metallothionein levels in rats and mice

    International Nuclear Information System (INIS)

    Jang, T.; Lee, M.

    1981-01-01

    Liver metallothionein (MT) was measured by the 203-mercury binding method of Piotrowski in the livers of rats and mice subjected to bilateral adrenalectomy or to sham adrenalectomy. Sham operation was followed by an increase in the level of MT at 24 hours; this immediately began to decrease, reaching control levels by 7 days. Adrenalectomy was also followed by an increase in MT, but the levels remained elevated for several days before beginning to decline. Mice which were adrenalectomized and allowed to recover for 28 days showed an increase in MT when subjected to sham operation. Ether anaesthesia without an incision did not increase the level of MT. Hypophysectomized mice had higher levels of MT than did controls, and these levels were further increased by sham adrenalectomy. Sprague-Dawley rats showed a similar response to adrenalectomy and to sham operation. It is concluded that the sham operation-induced increase in MT is probably not a result of a stress-induced release of adrenal hormones, but that adrenal hormones may play some role in the degradation or turnover of MT. The pituitary may also have some role in MT turnover

  20. Metabolic impacts of high dietary exposure to persistent organic pollutants in mice

    DEFF Research Database (Denmark)

    Ibrahim, Mohammad Madani; Fjære, Even; Lock, Erik-Jan

    2012-01-01

    Persistent organic pollutants (POPs) have been linked to metabolic diseases. Yet, the effects of high exposure to dietary POPs remain unclear. We therefore investigated whether elevated exposure to POPs provided by whale meat supplementation could contribute to insulin resistance. C57BL/6J mice...... were fed control (C) or very high-fat diet (VHF) containing low or high levels of POPs (VHF+POPs) for eight weeks. To elevate the dietary concentrations of POPs, casein was replaced by whale meat containing high levels of pollutants. Feeding VHF+POPs induced high POP accumulation in the adipose tissue...... of mice. However, compared with VHF-fed mice, animals fed VHF+POPs had improved insulin sensitivity and glucose tolerance, and reduced body weight. Levels of ectopic fat in skeletal muscles and liver were reduced in mice fed VHF+POPs. These mice also gained less adipose tissue and had a tendency...

  1. High blood cholesterol levels

    Science.gov (United States)

    Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... There are many types of cholesterol. The ones talked about most are: ... lipoprotein (HDL) cholesterol -- often called "good" cholesterol ...

  2. A novel mice model of metabolic syndrome: the high-fat-high-fructose diet-fed ICR mice

    Science.gov (United States)

    Zhuhua, Zhang; Zhiquan, Wang; Zhen, Yang; Yixin, Niu; Weiwei, Zhang; Xiaoyong, Li; Yueming, Liu; Hongmei, Zhang; Li, Qin; Qing, Su

    2015-01-01

    Currently, the metabolic syndrome (MS) is occurring at growing rates worldwide, raising extensive concerns on the mechanisms and therapeutic interventions for this disorder. Herein, we described a novel method of establishing MS model in rodents. Male Institute of Cancer Research (ICR) mice were fed with high-fat-high-fructose (HFHF) diet or normal chow (NC) respectively for 12 weeks. Metabolic phenotypes were assessed by glucose tolerance test, insulin tolerance test and hyperinsulinemic-euglycemic clamp. Blood pressure was measured by a tail-cuff system. At the end of the experiment, mice were sacrificed, and blood and tissues were harvested for subsequent analysis. Serum insulin levels were measured by ELISA, and lipid profiles were determined biochemically. The HFHF diet-fed ICR mice exhibited obvious characteristics of the components of MS, including obvious obesity, severe insulin resistance, hyperinsulinemia, dislipidemia, significant hypertension and hyperuricemia. Our data suggest that HFHF diet-fed ICR mice may be a robust and efficient animal model that could well mimic the basic pathogenesis of human MS. PMID:26134356

  3. A novel mice model of metabolic syndrome: the high-fat-high-fructose diet-fed ICR mice.

    Science.gov (United States)

    Zhuhua, Zhang; Zhiquan, Wang; Zhen, Yang; Yixin, Niu; Weiwei, Zhang; Xiaoyong, Li; Yueming, Liu; Hongmei, Zhang; Li, Qin; Qing, Su

    2015-01-01

    Currently, the metabolic syndrome (MS) is occurring at growing rates worldwide, raising extensive concerns on the mechanisms and therapeutic interventions for this disorder. Herein, we described a novel method of establishing MS model in rodents. Male Institute of Cancer Research (ICR) mice were fed with high-fat-high-fructose (HFHF) diet or normal chow (NC) respectively for 12 weeks. Metabolic phenotypes were assessed by glucose tolerance test, insulin tolerance test and hyperinsulinemic-euglycemic clamp. Blood pressure was measured by a tail-cuff system. At the end of the experiment, mice were sacrificed, and blood and tissues were harvested for subsequent analysis. Serum insulin levels were measured by ELISA, and lipid profiles were determined biochemically. The HFHF diet-fed ICR mice exhibited obvious characteristics of the components of MS, including obvious obesity, severe insulin resistance, hyperinsulinemia, dislipidemia, significant hypertension and hyperuricemia. Our data suggest that HFHF diet-fed ICR mice may be a robust and efficient animal model that could well mimic the basic pathogenesis of human MS.

  4. High Fat High Sugar Diet Reduces Voluntary Wheel Running in Mice Independent of Sex Hormone Involvement

    Science.gov (United States)

    Vellers, Heather L.; Letsinger, Ayland C.; Walker, Nicholas R.; Granados, Jorge Z.; Lightfoot, J. Timothy

    2017-01-01

    Introduction: Indirect results in humans suggest that chronic overfeeding decreases physical activity with few suggestions regarding what mechanism(s) may link overfeeding and decreased activity. The primary sex hormones are known regulators of activity and there are reports that chronic overfeeding alters sex hormone levels. Thepurpose of this study was to determine if chronic overfeeding altered wheel running through altered sex hormone levels. Materials and Methods: C57BL/6J mice were bred and the pups were weaned at 3-weeks of age and randomly assigned to either a control (CFD) or high fat/high sugar (HFHS) diet for 9–11 weeks depending on activity analysis. Nutritional intake, body composition, sex hormone levels, and 3-day and 2-week wheel-running activity were measured. Additionally, groups of HFHS animals were supplemented with testosterone (males) and 17β-estradiol (females) to determine if sex hormone augmentation altered diet-induced changes in activity. Results: 117 mice (56♂, 61♀) were analyzed. The HFHS mice consumed significantly more calories per day than CFD mice (male: p running-wheel distance in male (p = 0.05, 70 ± 28%) and female mice (p = 0.02, 57 ± 26%). In animals that received hormone supplementation, there was no significant effect on activity levels. Two-weeks of wheel access was not sufficient to alter HFHS-induced reductions in activity or increases in body fat. Conclusion: Chronic overfeeding reduces wheel running, but is independent of the primary sex hormones. PMID:28890701

  5. High Fat High Sugar Diet Reduces Voluntary Wheel Running in Mice Independent of Sex Hormone Involvement

    Directory of Open Access Journals (Sweden)

    Heather L. Vellers

    2017-08-01

    Full Text Available Introduction: Indirect results in humans suggest that chronic overfeeding decreases physical activity with few suggestions regarding what mechanism(s may link overfeeding and decreased activity. The primary sex hormones are known regulators of activity and there are reports that chronic overfeeding alters sex hormone levels. Thepurpose of this study was to determine if chronic overfeeding altered wheel running through altered sex hormone levels.Materials and Methods: C57BL/6J mice were bred and the pups were weaned at 3-weeks of age and randomly assigned to either a control (CFD or high fat/high sugar (HFHS diet for 9–11 weeks depending on activity analysis. Nutritional intake, body composition, sex hormone levels, and 3-day and 2-week wheel-running activity were measured. Additionally, groups of HFHS animals were supplemented with testosterone (males and 17β-estradiol (females to determine if sex hormone augmentation altered diet-induced changes in activity.Results: 117 mice (56♂, 61♀ were analyzed. The HFHS mice consumed significantly more calories per day than CFD mice (male: p < 0.0001; female: p < 0.0001 and had significantly higher body fat (male: p < 0.0001; female: p < 0.0001. The HFHS diet did not reduce sex hormone levels, but did significantly reduce acute running-wheel distance in male (p = 0.05, 70 ± 28% and female mice (p = 0.02, 57 ± 26%. In animals that received hormone supplementation, there was no significant effect on activity levels. Two-weeks of wheel access was not sufficient to alter HFHS-induced reductions in activity or increases in body fat.Conclusion: Chronic overfeeding reduces wheel running, but is independent of the primary sex hormones.

  6. Ghrelin administered spinally increases the blood glucose level in mice.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

    2014-04-01

    Ghrelin is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of ghrelin located in the spinal cord in the regulation of the blood glucose level were investigated in ICR mice. We found that intrathecal (i.t.) injection with ghrelin (from 1 to 10 μg) caused an elevation of the blood glucose level. In addition, i.t. pretreatment with YIL781 (ghrelin receptor antagonist; from 0.1 to 5 μg) markedly attenuated ghrelin-induced hyperglycemic effect. The plasma insulin level was increased by ghrelin. The enhanced plasma insulin level by ghrelin was reduced by i.t. pretreatment with YIL781. However, i.t. pretreatment with glucagon-like peptide-1 (GLP-1; 5 μg) did not affect the ghrelin-induced hyperglycemia. Furthermore, i.t. administration with ghrelin also elevated the blood glucose level, but in an additive manner, in d-glucose-fed model. Our results suggest that the activation of ghrelin receptors located in the spinal cord plays important roles for the elevation of the blood glucose level. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Immunologic and metabolic effects of high-refined carbohydrate-containing diet in food allergic mice.

    Science.gov (United States)

    Yamada, Letícia Tamie Paiva; de Oliveira, Marina Chaves; Batista, Nathália Vieira; Fonseca, Roberta Cristelli; Pereira, Rafaela Vaz Sousa; Perez, Denise Alves; Teixeira, Mauro Martins; Cara, Denise Carmona; Ferreira, Adaliene Versiani Matos

    2016-02-01

    Allergic mice show a reduction in body weight and adiposity with a higher inflammatory response in the adipose tissue similar to obese fat tissue. This study aimed to evaluate whether the low-grade inflammatory milieu of mice with diet-induced mild obesity interferes with the allergic response induced by ovalbumin (OVA). BALB/c mice were divided into four groups: 1) non-allergic (OVA-) mice fed chow diet, 2) allergic (OVA+) mice fed chow diet, 3) OVA- mice fed high-refined carbohydrate-containing (HC) diet, and 4) OVA+ mice fed HC diet. After 5 wk, allergic groups were sensitized with OVA and received a booster 14 d later. All groups received an oral OVA challenge 7 d after the booster. Allergic groups showed increased serum levels of total IgE, anti-OVA IgE, and IgG1; a high disease activity index score; aversion to OVA; and increased intestinal eosinophil infiltration. Non-allergic mild-obese mice also showed aversion to OVA and an increased number of eosinophils in the proximal jejunum. After the allergic challenge, OVA+ mice fed chow diet showed weight loss and lower adiposity in several adipose tissue depots. OVA+ mice fed HC diet showed a loss of fat mass only in the mesenteric adipose tissue. Furthermore, increased levels of TNF, IL-6, and IL-10 were observed in this tissue. Our data show that mild-obese allergic mice do not present severe pathologic features of food allergy similar to those exhibited by lean allergic mice. Mild obesity promoted by HC diet ingestion causes important intestinal disorders that appear to modulate the inflammatory response during the antigen challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice.

    Science.gov (United States)

    Kandasamy, A D; Sung, M M; Boisvenue, J J; Barr, A J; Dyck, J R B

    2012-09-10

    Adiponectin is an adipokine secreted primarily from adipose tissue that can influence circulating plasma glucose and lipid levels through multiple mechanisms involving a variety of organs. In humans, reduced plasma adiponectin levels induced by obesity are associated with insulin resistance and type 2 diabetes, suggesting that low adiponectin levels may contribute the pathogenesis of obesity-related insulin resistance. The objective of the present study was to investigate whether gene therapy designed to elevate circulating adiponectin levels is a viable strategy for ameliorating insulin resistance in mice fed a high-fat, high-sucrose (HFHS) diet. Electroporation-mediated gene transfer of mouse adiponectin plasmid DNA into gastrocnemius muscle resulted in elevated serum levels of globular and high-molecular weight adiponectin compared with control mice treated with empty plasmid. In comparison to HFHS-fed mice receiving empty plasmid, mice receiving adiponectin gene therapy displayed significantly decreased weight gain following 13 weeks of HFHS diet associated with reduced fat accumulation, and exhibited increased oxygen consumption and locomotor activity as measured by indirect calorimetry, suggesting increased energy expenditure in these mice. Consistent with improved whole-body metabolism, mice receiving adiponectin gene therapy also had lower blood glucose and insulin levels, improved glucose tolerance and reduced hepatic gluconeogenesis compared with control mice. Furthermore, immunoblot analysis of livers from mice receiving adiponectin gene therapy showed an increase in insulin-stimulated phosphorylation of insulin signaling proteins. Based on these data, we conclude that adiponectin gene therapy ameliorates the metabolic abnormalities caused by feeding mice a HFHS diet and may be a potential therapeutic strategy to improve obesity-mediated impairments in insulin sensitivity.

  9. High-level-waste immobilization

    International Nuclear Information System (INIS)

    Crandall, J.L.

    1982-01-01

    Analysis of risks, environmental effects, process feasibility, and costs for disposal of immobilized high-level wastes in geologic repositories indicates that the disposal system safety has a low sensitivity to the choice of the waste disposal form

  10. The effect of salvianolate on serum levels of tumor necrosis factor-alpha in ApoE-/- mice

    International Nuclear Information System (INIS)

    Gao Yuqi; Wu Zonggui; Liang Chun; Luo Nanping; Zhang Hongming; Xu Jun; Li Xiaoyan; Xu Lin

    2008-01-01

    Objective: To study the possible antiatherosclerotic mechanism of salvianolate, through examination of the effect of salvianolate on serum levels of tumor necrosis factor-alpha (TNF-α) in C57BL/6J ApoE -/- mice. Methods: Fifty C57BL/6J ApoE -/- mice of 8 week-old were fed high cholesterol diet for 12 weeks. After sacrificing 2 mice to examine formation of atheromatous plaques at root of aorta, the remaining 48 C57BL/6J ApoE -/- mice were divided randomly into 4 groups: (1) model group (without salvianolate treatment) (2) low dosage of salvianolate (60mg/kg) group (3) medium dosage of salvianolate (120mg/kg) group and (4) high dosage of salvianolate(240mg/kg) group. Ten C57BL/6 wild-type mice served as controls. At the end of 32nd week, serum levels of TNF-α were measured with specific radioimmunoassay. Results: The serum levels of TNF-α were decreased in ApoE -/- mice with the increase of salvianolate dosage (P 0.05). Conclusion: Salvianolate treatment can decrease the serum levels of TNF-α in C57BL/6 ApoE -/- mice and inhibit inflammation process. This may be one of the possible mechanism of antiatherosclerosis of salvianolate. (authors)

  11. Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice.

    Science.gov (United States)

    Yamaguchi, Takeshi; Nagasawa, Mao; Ikeda, Hiromi; Kodaira, Momoko; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

    2017-06-15

    Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH 4 ) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH 4 administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice.

    Science.gov (United States)

    Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

    2015-01-01

    Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

  13. Co-segregation of hyperactivity, active coping styles and cognitive dysfunction in mice selectively bred for low levels of anxiety

    Directory of Open Access Journals (Sweden)

    Yi-Chun eYen

    2013-08-01

    Full Text Available We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania and attention deficit hyperactivity disorder (ADHD share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field test with deficits in habituation, compared to mice bred for normal (NAB and high anxiety-related behavior (HAB. Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition, implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD

  14. Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety.

    Science.gov (United States)

    Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T

    2013-01-01

    We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field (OF) test with deficits in habituation, compared to mice bred for normal (NAB) and high anxiety-related behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition (PPI), implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles, and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD-like symptoms.

  15. Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety

    Science.gov (United States)

    Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T.

    2013-01-01

    We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field (OF) test with deficits in habituation, compared to mice bred for normal (NAB) and high anxiety-related behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition (PPI), implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles, and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD-like symptoms

  16. High Level Radioactive Waste Management

    International Nuclear Information System (INIS)

    1991-01-01

    The proceedings of the second annual international conference on High Level Radioactive Waste Management, held on April 28--May 3, 1991, Las Vegas, Nevada, provides information on the current technical issue related to international high level radioactive waste management activities and how they relate to society as a whole. Besides discussing such technical topics as the best form of the waste, the integrity of storage containers, design and construction of a repository, the broader social aspects of these issues are explored in papers on such subjects as conformance to regulations, transportation safety, and public education. By providing this wider perspective of high level radioactive waste management, it becomes apparent that the various disciplines involved in this field are interrelated and that they should work to integrate their waste management activities. Individual records are processed separately for the data bases

  17. High-level Petri Nets

    DEFF Research Database (Denmark)

    various journals and collections. As a result, much of this knowledge is not readily available to people who may be interested in using high-level nets. Within the Petri net community this problem has been discussed many times, and as an outcome this book has been compiled. The book contains reprints...... of some of the most important papers on the application and theory of high-level Petri nets. In this way it makes the relevant literature more available. It is our hope that the book will be a useful source of information and that, e.g., it can be used in the organization of Petri net courses. To make......High-level Petri nets are now widely used in both theoretical analysis and practical modelling of concurrent systems. The main reason for the success of this class of net models is that they make it possible to obtain much more succinct and manageable descriptions than can be obtained by means...

  18. The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice

    DEFF Research Database (Denmark)

    Baquedano, Eva; Ruiz-Lopez, Ana M; Sustarsic, Elahu G

    2014-01-01

    GH is important in metabolic control, and mice with disruption of the gene encoding the GH receptor (GHR) and GH binding protein (GHR-/- mice) are dwarf with low serum IGF-1 and insulin levels, high GH levels, and increased longevity, despite their obesity and altered lipid and metabolic profiles...

  19. Brain Levels of the Neurotoxic Pyridinium Metabolite HPP+ and Extrapyramidal Symptoms in Haloperidol-Treated Mice

    Science.gov (United States)

    Crowley, James J.; Ashraf-Khorassani, Mehdi; Castagnoli, Neal; Sullivan, Patrick F.

    2013-01-01

    The typical antipsychotic haloperidol is a highly effective treatment for schizophrenia but its use is limited by a number of serious, and often irreversible, motor side effects. These adverse drug reactions, termed extrapyramidal syndromes (EPS), result from an unknown pathophysiological mechanism. One theory relates to the observation that the haloperidol metabolite HPP+ (4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-pyridinium) is structurally similar to MPP+ (1-methyl-4-phenylpyridinium), a neurotoxin responsible for an irreversible neurodegenerative condition similar to Parkinson's disease. To determine whether HPP+ contributes to haloperidol-induced EPS, we measured brain HPP+ and haloperidol levels in strains of mice at high (C57BL/6J and NZO/HILtJ) and low (BALB/cByJ and PWK/PhJ) liability to haloperidol-induced EPS following chronic treatment (7–10 adult male mice per strain). Brain levels of HPP+ and the ratio of HPP+ to haloperidol were not significantly different between the haloperidol-sensitive and haloperidol-resistant strain groups (P = 0.50). Within each group, however, strain differences were seen (P haloperidol treatment, the findings from this study are physiologically relevant to humans. The results suggest that strain differences in steady-state HPP+ levels do not explain sensitivity to haloperidol-induced EPS in the mice we studied. PMID:24107597

  20. Chronic high-sucrose diet increases fibroblast growth factor 21 production and energy expenditure in mice.

    Science.gov (United States)

    Maekawa, Ryuya; Seino, Yusuke; Ogata, Hidetada; Murase, Masatoshi; Iida, Atsushi; Hosokawa, Kaori; Joo, Erina; Harada, Norio; Tsunekawa, Shin; Hamada, Yoji; Oiso, Yutaka; Inagaki, Nobuya; Hayashi, Yoshitaka; Arima, Hiroshi

    2017-11-01

    Excess carbohydrate intake causes obesity in humans. On the other hand, acute administration of fructose, glucose or sucrose in experimental animals has been shown to increase the plasma concentration of anti-obesity hormones such as glucagon-like peptide 1 (GLP-1) and Fibroblast growth factor 21 (FGF21), which contribute to reducing body weight. However, the secretion and action of GLP-1 and FGF21 in mice chronically fed a high-sucrose diet has not been investigated. To address the role of anti-obesity hormones in response to increased sucrose intake, we analyzed mice fed a high-sucrose diet, a high-starch diet or a normal diet for 15 weeks. Mice fed a high-sucrose diet showed resistance to body weight gain, in comparison with mice fed a high-starch diet or control diet, due to increased energy expenditure. Plasma FGF21 levels were highest among the three groups in mice fed a high-sucrose diet, whereas no significant difference in GLP-1 levels was observed. Expression levels of uncoupling protein 1 (UCP-1), FGF receptor 1c (FGFR1c) and β-klotho (KLB) mRNA in brown adipose tissue were significantly increased in high sucrose-fed mice, suggesting increases in FGF21 sensitivity and energy expenditure. Expression of carbohydrate responsive element binding protein (ChREBP) mRNA in liver and brown adipose tissue was also increased in high sucrose-fed mice. These results indicate that FGF21 production in liver and brown adipose tissue is increased in high-sucrose diet and participates in resistance to weight gain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. High-Level Radioactive Waste.

    Science.gov (United States)

    Hayden, Howard C.

    1995-01-01

    Presents a method to calculate the amount of high-level radioactive waste by taking into consideration the following factors: the fission process that yields the waste, identification of the waste, the energy required to run a 1-GWe plant for one year, and the uranium mass required to produce that energy. Briefly discusses waste disposal and…

  2. High-level radioactive wastes

    International Nuclear Information System (INIS)

    Grissom, M.C.

    1982-10-01

    This bibliography contains 812 citations on high-level radioactive wastes included in the Department of Energy's Energy Data Base from January 1981 through July 1982. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number

  3. [Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behavior efficacy].

    Science.gov (United States)

    Firstova, Iu Iu; Dolotov, O V; Kondrakhin, e A; Dubynina, E V; Grivennikov, I A; Kovalev, G I

    2009-01-01

    The influence of subchronic administration of nootropic drugs (piracetam, phenotropil, meclophenoxate, pantocalcine, semax, nooglutil) on the brain-derived neurotrophic factor (BDNF) content in hippocampal and cortical tissues in mice with different exploratory behavior--high efficacy (HE) against low efficacy (LE)--in cross-maze test has been studied. The initial BDNF concentration in hippocamp (but not in cortex) of control HE mice was higher than that in LE mice (LE, 0.091 +/- 0.005 pg/microg; HE, 0.177 +/- 0.005 pg/microg; p nootrope effects, at least partially, via increase in hippocampal BDNF level, which is achieved only under conditions of cognitive deficiency.

  4. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

    Directory of Open Access Journals (Sweden)

    Aunis Dominique

    2010-12-01

    Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

  5. Rapamycin-ameliorated diabetic symptoms involved in increasing adiponectin expression in diabetic mice on a high-fat diet.

    Science.gov (United States)

    Gong, Fang-Hua; Ye, Yan-Na; Li, Jin-Meng; Zhao, Hai-Yang; Li, Xiao-Kun

    2017-07-01

    Recent studies showed that rapamycin improved diabetic complications. Here, we investigated the metabolic effects of rapamycin in type 2 diabetes model (T2DM) mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle only for 3 weeks and were maintained on a high-fat diet. The treated diabetic mice exhibited decreased body weight, blood glucose levels, and fat mass. FGF21 expression was suppressed in C57B/L6 mice, but adiponectin expression increased both in FGF21 KO and C57B/L6 mice. These results suggest that rapamycin may alleviate FGF21 resistance in mice on a high-fat diet. The reduction of adipose tissue mass of the diabetic mice may be due to the increased adiponectin. Copyright © 2017. Published by Elsevier Taiwan.

  6. Wound healing stimulation in mice by low-level light

    Science.gov (United States)

    Demidova, Tatiana N.; Herman, Ira M.; Salomatina, Elena V.; Yaroslavsky, Anna N.; Hamblin, Michael R.

    2006-02-01

    It has been known for many years that low levels of laser or non-coherent light (LLLT) accelerate some phases of wound healing. LLLT can stimulate fibroblast and keratinocyte proliferation and migration. It is thought to work via light absorption by mitochondrial chromophores leading to an increase in ATP, reactive oxygen species and consequent gene transcription. However, despite many reports about the positive effects of LLLT on wound healing, its use remains controversial. Our laboratory has developed a model of a full thickness excisional wound in mice that allows quantitative and reproducible light dose healing response curves to be generated. We have found a biphasic dose response curve with a maximum positive effect at 2 J/cm2 of 635-nm light and successively lower beneficial effects from 3-25 J/cm2, the effect is diminished at doses below 2J/cm2 and gradually reaches control healing levels. At light doses above 25 J/cm2 healing is actually worse than controls. The two most effective wavelengths of light were found to be 635 and 820-nm. We found no difference between filtered 635+/-15-nm light from a lamp and 633-nm light from a HeNe laser. The strain and age of the mouse affected the magnitude of the effect. Light treated wounds start to contract after illumination while control wounds initially expand for the first 24 hours. Our hypothesis is that a single brief light exposure soon after wounding affects fibroblast cells in the margins of the wound. Cells may be induced to proliferate, migrate and assume a myofibroblast phenotype. Our future work will be focused on understanding the mechanisms underlying effects of light on wound healing processes.

  7. RPython high-level synthesis

    Science.gov (United States)

    Cieszewski, Radoslaw; Linczuk, Maciej

    2016-09-01

    The development of FPGA technology and the increasing complexity of applications in recent decades have forced compilers to move to higher abstraction levels. Compilers interprets an algorithmic description of a desired behavior written in High-Level Languages (HLLs) and translate it to Hardware Description Languages (HDLs). This paper presents a RPython based High-Level synthesis (HLS) compiler. The compiler get the configuration parameters and map RPython program to VHDL. Then, VHDL code can be used to program FPGA chips. In comparison of other technologies usage, FPGAs have the potential to achieve far greater performance than software as a result of omitting the fetch-decode-execute operations of General Purpose Processors (GPUs), and introduce more parallel computation. This can be exploited by utilizing many resources at the same time. Creating parallel algorithms computed with FPGAs in pure HDL is difficult and time consuming. Implementation time can be greatly reduced with High-Level Synthesis compiler. This article describes design methodologies and tools, implementation and first results of created VHDL backend for RPython compiler.

  8. Varying levels of female promiscuity in four Apodemus mice species

    Czech Academy of Sciences Publication Activity Database

    Bryja, Josef; Patzenhauerová, Hana; Albrecht, Tomáš; Mošanský, L.; Stanko, M.; Stopka, P.

    2008-01-01

    Roč. 63, č. 2 (2008), s. 251-260 ISSN 0340-5443 R&D Projects: GA MŠk MEB090802; GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60930519 Keywords : mating systems * multiple paternity * wood mice * testis size Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.917, year: 2008

  9. Ameliorative effects of curcumin on the spermatozoon tail length, count, motility and testosterone serum level in metronidazole-treated mice.

    Science.gov (United States)

    Karbalay-Doust, S; Noorafshan, A

    2011-01-01

    Metronidazole (MTZ) is used as an antiparasitic drug. Curcumin is considered as anti-oxidant and anti-inflammatory agent. The ameliorative effects of curcumin on MTZ induced toxicity on mice spermatozoon tail length, count, motility and testosterone level were investigated. MTZ was administered in 500 and 165 (high and therapeutic doses) mg/kg/day, with and without curcumin (100 mg/kg/day). After 16 days the above parameters were assessed. Spermatozoon count and motility and serum testosterone level MTZ-treated (500 and 165) mice were reduced. In the mice treated with MTZ+curcumin these parameters decreased but in a lesser extent than the MTZ-treated animals. Mid-piece and total lengths of the spermatozoon tail in control animals were 31.6 ± 9.0 μm and 100.3 ± 15.0 μm and in the mice treated with high doses (500) of MTZ were reduced. The mid-piece and total spermatozoon tail length has been decreased in a lesser extent in the mice treated with high dose MTZ+curcumin than the mice treated with high dose MTZ (paverage increase in mid-piece and total lengths in comparison with the MTZ-treated (500) animals. Stereological estimation of the sperm tail length, including sampling of spermatozoa and also counting of the intersections of their tails with the stereological grids was a rapid technique and took only 5-10 minutes. It can be concluded that curcumin has an ameliorative effect on the spermatozoon, testosterone level and tail length in MTZ-treated mice.

  10. Enhanced sensitivity of postsynaptic serotonin-1A receptors in rats and mice with high trait aggression

    NARCIS (Netherlands)

    van der Vegt, BJ; de Boer, SF; Buwalda, B; de Ruiter, AJH; de Jong, JG; Koolhaas, JM

    2001-01-01

    Individual differences in aggressive behaviour have been linked to variability in central serotonergic activity, both in humans and animals. A previous experiment in mice, selectively bred for high or low levels of aggression, showed an up-regulation of postsynaptic serotonin-1A (5-HT1A) receptors,

  11. Probiotic microbes sustain youthful serum testosterone levels and testicular size in aging mice.

    Directory of Open Access Journals (Sweden)

    Theofilos Poutahidis

    Full Text Available The decline of circulating testosterone levels in aging men is associated with adverse health effects. During studies of probiotic bacteria and obesity, we discovered that male mice routinely consuming purified lactic acid bacteria originally isolated from human milk had larger testicles and increased serum testosterone levels compared to their age-matched controls. Further investigation using microscopy-assisted histomorphometry of testicular tissue showed that mice consuming Lactobacillus reuteri in their drinking water had significantly increased seminiferous tubule cross-sectional profiles and increased spermatogenesis and Leydig cell numbers per testis when compared with matched diet counterparts This showed that criteria of gonadal aging were reduced after routinely consuming a purified microbe such as L. reuteri. We tested whether these features typical of sustained reproductive fitness may be due to anti-inflammatory properties of L. reuteri, and found that testicular mass and other indicators typical of old age were similarly restored to youthful levels using systemic administration of antibodies blocking pro-inflammatory cytokine interleukin-17A. This indicated that uncontrolled host inflammatory responses contributed to the testicular atrophy phenotype in aged mice. Reduced circulating testosterone levels have been implicated in many adverse effects; dietary L. reuteri or other probiotic supplementation may provide a viable natural approach to prevention of male hypogonadism, absent the controversy and side-effects of traditional therapies, and yield practical options for management of disorders typically associated with normal aging. These novel findings suggest a potential high impact for microbe therapy in public health by imparting hormonal and gonad features of reproductive fitness typical of much younger healthy individuals.

  12. Genotoxicity detected in wild mice living in a highly polluted wetland area in south western Spain

    Energy Technology Data Exchange (ETDEWEB)

    Mateos, Santiago; Daza, Paula; Dominguez, Inmaculada; Cardenas, Jose Antonio [University of Seville, Department of Cell Biology, Faculty of Biology, Avenida de la Reina Mercedes no 6, E-41012 Seville (Spain); Cortes, Felipe [University of Seville, Department of Cell Biology, Faculty of Biology, Avenida de la Reina Mercedes no 6, E-41012 Seville (Spain)], E-mail: cortes@us.es

    2008-06-15

    A field study was carried out in the south of the Iberian Peninsula in an industrial area in the neighbourhood of Huelva city, SW Spain, and in a natural area (Donana National Park) for comparison, to estimate the genetic risk induced by environmental pollution in wild mice. Genotoxic effects in a sentinel organism, the Algerian mice (Mus spretus) free living in the industrial area were compared with animals of the same species living in the natural protected area. The single cell gel electrophoresis, or Comet assay, was performed as a genotoxicity test in peripheral blood of mice. Our results clearly show that mice free living in the contaminated area bear a high burden of genetic damage as compared with control individuals. The results suggest that the assessing of genotoxicity levels by the Comet assay in wild mice can be used as a valuable test in pollution monitoring and environmental conservation. - We have found an increased genotoxic damage in wild mice in a highly polluted area from industry, mining and agriculture in SW Spain, as assessed by the Comet assay.

  13. ST2 Deficiency Ameliorates High Fat Diet-Induced Liver Steatosis In BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Jovicic Nemanja

    2015-03-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is strongly associated with obesity, but the molecular mechanisms of liver steatosis and its progression to non-alcoholic steatohepatitis and fibrosis are incompletely understood. Immune reactivity plays an important role in the pathogenesis of NAFLD. The IL-33/ST2 axis has a protective role in adiposity and atherosclerosis, but its role in obesity-associated metabolic disorders requires further clarification. To investigate the unresolved role of IL-33/ST2 signalling in NAFLD, we used ST2-deficient (ST2-/- and wild type (WT BALB/c mice maintained on a high-fat diet (HFD for 24 weeks. HFD-fed ST2-/- mice exhibited increased weight gain, visceral adipose tissue weight and triglyceridaemia and decreased liver weight compared with diet-matched WT mice. Compared with WT mice on an HFD, ST2 deletion significantly reduced hepatic steatosis, liver inflammation and fibrosis and downregulated the expression of genes related to lipid metabolism in the liver. The frequency of innate immune cells in the liver, including CD68+ macrophages and CD11c+ dendritic cells, was lower in HFD-fed ST2-/- mice, accompanied by lower TNFα serum levels compared with diet-matched WT mice. Less collagen deposition in the livers of ST2-/- mice on an HFD was associated with lower numbers of profibrotic CD11b+Ly6clow monocytes and CD4+IL-17+ T cells in the liver, lower hepatic gene expression of procollagen, IL-33 and IL-13, and lower serum levels of IL-33 and IL-13 compared with diet-matched WT mice.

  14. High fat diet accelerates cartilage repair in DBA/1 mice.

    Science.gov (United States)

    Wei, Wu; Bastiaansen-Jenniskens, Yvonne M; Suijkerbuijk, Mathijs; Kops, Nicole; Bos, Pieter K; Verhaar, Jan A N; Zuurmond, Anne-Marie; Dell'Accio, Francesco; van Osch, Gerjo J V M

    2017-06-01

    Obesity is a well-known risk factor for osteoarthritis, but it is unknown what it does on cartilage repair. Here we investigated whether a high fat diet (HFD) influences cartilage repair in a mouse model of cartilage repair. We fed DBA/1 mice control or HFD (60% energy from fat). After 2 weeks, a full thickness cartilage defect was made in the trochlear groove. Mice were sacrificed, 1, 8, and 24 weeks after operation. Cartilage repair was evaluated on histology. Serum glucose, insulin and amyloid A were measured 24 h before operation and at endpoints. Immunohistochemical staining was performed on synovium and adipose tissue to evaluate macrophage infiltration and phenotype. One week after operation, mice on HFD had defect filling with fibroblast-like cells and more cartilage repair as indicated by a lower Pineda score. After 8 weeks, mice on a HFD still had a lower Pineda score. After 24 weeks, no mice had complete cartilage repair and we did not detect a significant difference in cartilage repair between diets. Bodyweight was increased by HFD, whereas serum glucose, amyloid A and insulin were not influenced. Macrophage infiltration and phenotype in adipose tissue and synovium were not influenced by HFD. In contrast to common wisdom, HFD accelerated intrinsic cartilage repair in DBA/1 mice on the short term. Resistance to HFD induced inflammatory and metabolic changes could be associated with accelerated cartilage repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1258-1264, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. Removing high-level contaminants

    International Nuclear Information System (INIS)

    Wallace, Paula

    2013-01-01

    Full text: Using biomimicry, an Australian cleantech innovation making inroads intoChinas's industrial sector offers multiple benefits to miners and processors in Australia. Stephen Shelley, the executive chairman of Creative Water Technology (CWT), was on hand at a recent trade show to explain how his Melbourne company has developed world-class techniques in zero liquid discharge and fractional crystallization of minerals to apply to a wide range of water treatment and recycling applications. “Most existing technologies operate with high energy distillation, filters or biological processing. CWT's appliance uses a low temperature, thermal distillation process known as adiabatic recovery to desalinate, dewater and/or recycle highly saline and highly contaminated waste water,” said Shelley. The technology has been specifically designed to handle the high levels of contaminant that alternative technologies struggle to process, with proven water quality results for feed water samples with TDS levels over 300,000ppm converted to clean water with less than 20ppm. Comparatively, reverse osmosis struggles to process contaminant levels over 70,000ppm effectively. “CWT is able to reclaim up to 97% clean usable water and up to 100% of the contaminants contained in the feed water,” said Shelley, adding that soluble and insoluble contaminants are separately extracted and dried for sale or re-use. In industrial applications CWT has successfully processed feed water with contaminant levels over 650,000 mg/1- without the use of chemicals. “The technology would be suitable for companies in oil exploration and production, mining, smelting, biofuels, textiles and the agricultural and food production sectors,” said Shelley. When compared to a conventional desalination plant, the CWT system is able to capture the value in the brine that most plants discard, not only from the salt but the additional water it contains. “If you recover those two commodities... then you

  16. Myostatin expression, lymphocyte population, and potential cytokine production correlate with predisposition to high-fat diet induced obesity in mice.

    Directory of Open Access Journals (Sweden)

    Jeri-Anne Lyons

    2010-09-01

    Full Text Available A strong relationship exists between increased inflammatory cytokines and muscle insulin resistance in obesity. This study focused on identifying a relationship between metabolic propensity and myostatin expression in muscle and spleen cells in response to high-fat diet intake. Using a comparative approach, we analyzed the effects of high-fat diet intake on myostatin and follistatin expression, spleen cell composition, and potential cytokine expression in high-fat diet induced obesity (HFDIO resistant (SWR/J and susceptible (C57BL/6 mice models. Results demonstrated overall increased myostatin expression in muscle following high-fat diet intake in HFDIO-susceptible mice, while myostatin expression levels decreased initially in muscle from high-fat diet fed resistant mice. In HFDIO-resistant mice, myostatin expression decreased in spleen, while myostatin increased in spleen tissue from HFDIO-susceptible mice. Proinflammatory cytokine (IL-17, IL-1β, and IFNγ potential increased in splenocytes from HFDIO-susceptible mice. In comparison, C57BL/6 mice fed a high-fat diet exhibited higher frequencies of CD4(+/CD44(hi and CD8(+/CD44(hi cells in the spleen compared to control fed mice. Together, these results suggest that susceptibility to high-fat diet induced obesity could be influenced by local myostatin activity in a tissue-specific manner and that splenocytes exhibit differential cytokine production in a strain-dependent manner. This study sets the stage for future investigations into the interactions between growth, inflammation, and metabolism.

  17. [Influence of 1, 2-dichloroethane on open field behavior and levels of neurotransmitters in brain of mice].

    Science.gov (United States)

    Qi, Ying; Shi, Lei; Gao, Lan-Yue; Wang, Gao-Yang; Li, Ge-Xin; Lv, Xiu-Qiang; Jin, Ya-Ping

    2011-06-01

    To explore the effects of 1,2-dichloroethane (1,2-DCE) on the behavior and the brain neurotransmitter levels in mice. Thirty mice were randomly divided into four groups, which were control group and groups of low, middle and high exposure (225, 450 and 900 mg/m3) to 1,2-DCE for 10 days (3.5 h a day) by inhalation. After the last exposure, the open field test was performed immediately. After exposure all mice were killed and the brain tissues were taken up rapidly. The levels of aspartate (Asp), glutamate (Glu) and gamma-aminobutyric acid (GABA) in the brain were detected by high performance liquid chromatography (HPLC). Levels of Asp and Glu in all exposure groups increased with doses. As compared to the control group, levels of Glu in all exposure groups increased significantly (P open field test showed that effect of low exposure to 1,2-DCE on the behavior was stimulant, but the high exposure to 1,2-DCE inhibited behavior of exploration, excitement and sport. Subacute exposure to 1,2-DCE could result in the change of amino acid neurotransmitter content and ratio in the brain, thereby change the behavior of mice appeared, which might be the mechanism of neurotoxicity caused by 1,2-DCE in part.

  18. High level white noise generator

    International Nuclear Information System (INIS)

    Borkowski, C.J.; Blalock, T.V.

    1979-01-01

    A wide band, stable, random noise source with a high and well-defined output power spectral density is provided which may be used for accurate calibration of Johnson Noise Power Thermometers (JNPT) and other applications requiring a stable, wide band, well-defined noise power spectral density. The noise source is based on the fact that the open-circuit thermal noise voltage of a feedback resistor, connecting the output to the input of a special inverting amplifier, is available at the amplifier output from an equivalent low output impedance caused by the feedback mechanism. The noise power spectral density level at the noise source output is equivalent to the density of the open-circuit thermal noise or a 100 ohm resistor at a temperature of approximately 64,000 Kelvins. The noise source has an output power spectral density that is flat to within 0.1% (0.0043 db) in the frequency range of from 1 KHz to 100 KHz which brackets typical passbands of the signal-processing channels of JNPT's. Two embodiments, one of higher accuracy that is suitable for use as a standards instrument and another that is particularly adapted for ambient temperature operation, are illustrated in this application

  19. High level white noise generator

    Science.gov (United States)

    Borkowski, Casimer J.; Blalock, Theron V.

    1979-01-01

    A wide band, stable, random noise source with a high and well-defined output power spectral density is provided which may be used for accurate calibration of Johnson Noise Power Thermometers (JNPT) and other applications requiring a stable, wide band, well-defined noise power spectral density. The noise source is based on the fact that the open-circuit thermal noise voltage of a feedback resistor, connecting the output to the input of a special inverting amplifier, is available at the amplifier output from an equivalent low output impedance caused by the feedback mechanism. The noise power spectral density level at the noise source output is equivalent to the density of the open-circuit thermal noise or a 100 ohm resistor at a temperature of approximately 64,000 Kelvins. The noise source has an output power spectral density that is flat to within 0.1% (0.0043 db) in the frequency range of from 1 KHz to 100 KHz which brackets typical passbands of the signal-processing channels of JNPT's. Two embodiments, one of higher accuracy that is suitable for use as a standards instrument and another that is particularly adapted for ambient temperature operation, are illustrated in this application.

  20. Optimizing High Level Waste Disposal

    International Nuclear Information System (INIS)

    Dirk Gombert

    2005-01-01

    If society is ever to reap the potential benefits of nuclear energy, technologists must close the fuel-cycle completely. A closed cycle equates to a continued supply of fuel and safe reactors, but also reliable and comprehensive closure of waste issues. High level waste (HLW) disposal in borosilicate glass (BSG) is based on 1970s era evaluations. This host matrix is very adaptable to sequestering a wide variety of radionuclides found in raffinates from spent fuel reprocessing. However, it is now known that the current system is far from optimal for disposal of the diverse HLW streams, and proven alternatives are available to reduce costs by billions of dollars. The basis for HLW disposal should be reassessed to consider extensive waste form and process technology research and development efforts, which have been conducted by the United States Department of Energy (USDOE), international agencies and the private sector. Matching the waste form to the waste chemistry and using currently available technology could increase the waste content in waste forms to 50% or more and double processing rates. Optimization of the HLW disposal system would accelerate HLW disposition and increase repository capacity. This does not necessarily require developing new waste forms, the emphasis should be on qualifying existing matrices to demonstrate protection equal to or better than the baseline glass performance. Also, this proposed effort does not necessarily require developing new technology concepts. The emphasis is on demonstrating existing technology that is clearly better (reliability, productivity, cost) than current technology, and justifying its use in future facilities or retrofitted facilities. Higher waste processing and disposal efficiency can be realized by performing the engineering analyses and trade-studies necessary to select the most efficient methods for processing the full spectrum of wastes across the nuclear complex. This paper will describe technologies being

  1. Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice

    International Nuclear Information System (INIS)

    Nakashima, Ryosuke; Hayashi, Yumi; Khalequzzaman, Md.; Jia, Xiaofang; Wang, Dong; Naito, Hisao; Ito, Yuki; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

    2013-01-01

    Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPARα), peroxisome proliferator-activated receptor α-null (Pparα-null) and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, α-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARa mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPARα mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, α-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPARα mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPARα mice, similarly to triglyceride levels

  2. Prunus mume leaf extract lowers blood glucose level in diabetic mice.

    Science.gov (United States)

    Lee, Min Woo; Kwon, Jung Eun; Lee, Young-Jong; Jeong, Yong Joon; Kim, Inhye; Cho, Young Mi; Kim, Yong-Min; Kang, Se Chan

    2016-10-01

    Context Diabetes is a common metabolic disease with long-term complications. Prunus mume Sieb. et Zucc. (Rosaceae) fruits have shown to ameliorate glucose intolerance. However, the antidiabetic effects of P. mume leaves have not been investigated. Objective This study evaluated the effects of P. mume leaf 70% ethanol extract (PMLE) on alleviating diabetes in vivo and in vitro. Materials and methods PMLE was fractionated into n-hexane, dichloromethane (CH2Cl2), ethyl acetate (EtOAc), n-butanol (BuOH) and water. Polyphenol and flavonoid contents in PMLE fractions were determined using Folin-Ciocalteu reagent and the aluminium chloride colorimetric method, respectively. We evaluated α-glucosidase inhibition using a microplate reader at 400 nm. Adipocyte differentiation by lipid accumulation was measured using Nile Red staining. Male imprinting control region (ICR) mice were injected with streptozotocin (STZ, 100 mg/kg, i.p.). High-fat diets were provided for three weeks prior to PMLE treatments to induce type 2 diabetes. PMLE (0, 5, 25 or 50 mg/kg) was administrated for four weeks with high-fat diets. Results The EtOAc fraction of PMLE inhibited α-glucosidase activity (IC50 = 68.2 μg/mL) and contained 883.5 ± 14.9 mg/g of polyphenols and 820.1 ± 7.7 mg/g of flavonoids. The 50 mg/kg PMLE supplement reduced 40% of blood glucose level compared to obese/diabetes mice. Obese/diabetic mice treated with 50 mg/kg PMLE showed a lower level of triacylglycerol (320.7 ± 20.73 mg/dL) compared to obese/diabetes mice (494.9 ± 14.80 mg/dL). Conclusion The data demonstrate that P. mume leaves exert antidiabetic effects that may be attributable to high concentrations of polyphenols and flavonoids.

  3. Below background levels of blood lead impact cytokine levels in male and female mice

    International Nuclear Information System (INIS)

    Iavicoli, I.; Carelli, G.; Stanek, E.J.; Castellino, N.; Calabrese, E.J.

    2006-01-01

    A number of studies have documented that Pb exerts immunotoxic effects on T lymphocytes. In studies designed to explore this general response over a broad dose range, female Swiss mice were administered six different diets containing Pb acetate 1 day after mating. During lactation, the mothers received the same feed given during pregnancy, and the same diets were administered to the offspring for 9 months after weaning. At the end of exposure, blood Pb level in the offspring was determined, and possible changes in two type 1 cytokines (IL-2, INF-γ) and one type 2 cytokine (IL-4) in the serum were measured. At higher dietary Pb levels (40 and 400 ppm), a significant increase in IL-4 production was associated with a profound decrease in INF-γ and IL-2 production. At the lowest Pb diet level (0.02 ppm), which resulted in a blood lead level of (0.8 μg/dL), which is below background (2-3 μg/dL) values in humans, increases in INF-γ and IL-2 production along with a significant decrease in IL-4 production were observed. The findings provide evidence of a reversal of lead-induced cytokine skewing depending on the blood lead concentration. As blood lead concentration increases, there is a notable skewing toward Th2, while the pattern is reversed favoring Th1 development at lower blood lead values. The present findings are also notable since they indicate the potential for dietary Pb to have significant biological effects below normal background concentrations

  4. Metabolic risk factors in mice divergently selected for BMR fed high fat and high carb diets.

    Science.gov (United States)

    Sadowska, Julita; Gębczyński, Andrzej K; Konarzewski, Marek

    2017-01-01

    Factors affecting contribution of spontaneous physical activity (SPA; activity associated with everyday tasks) to energy balance of humans are not well understood, as it is not clear whether low activity is related to dietary habits, precedes obesity or is a result of thereof. In particular, human studies on SPA and basal metabolic rates (BMR, accounting for >50% of human energy budget) and their associations with diet composition, metabolic thrift and obesity are equivocal. To clarify these ambiguities we used a unique animal model-mice selected for divergent BMR rates (the H-BMR and L-BMR line type) presenting a 50% between-line type difference in the primary selected trait. Males of each line type were divided into three groups and fed either a high fat, high carb or a control diet. They then spent 4 months in individual cages under conditions emulating human "sedentary lifestyle", with SPA followed every month and measurements of metabolic risk indicators (body fat mass %, blood lipid profile, fasting blood glucose levels and oxidative damage in the livers, kidneys and hearts) taken at the end of study. Mice with genetically determined high BMR assimilated more energy and had higher SPA irrespective of type of diet. H-BMR individuals were characterized by lower dry body fat mass %, better lipid profile and lower fasting blood glucose levels, but higher oxidative damage in the livers and hearts. Genetically determined high BMR may be a protective factor against diet-induced obesity and most of the metabolic syndrome indicators. Elevated spontaneous activity is correlated with high BMR, and constitutes an important factor affecting individual capability to sustain energy balance even under energy dense diets.

  5. High Phenolics Rutgers Scarlet Lettuce Improves Glucose Metabolism in High Fat Diet-Induced Obese Mice

    Science.gov (United States)

    Cheng, Diana M.; Roopchand, Diana E.; Poulev, Alexander; Kuhn, Peter; Armas, Isabel; Johnson, William D.; Oren, Andrew; Ribnicky, David; Zelzion, Ehud; Bhattacharya, Debashish; Raskin, Ilya

    2016-01-01

    Scope The ability of high phenolic Rutgers Scarlet Lettuce (RSL) to attenuate metabolic syndrome and gut dysbiosis was studied in very high fat diet (VHFD)-fed mice. Phenolic absorption was assessed in vivo and in a gastrointestinal tract model. Methods and results Mice were fed VHFD, VHFD supplemented with RSL (RSL-VHFD) or store-purchased green lettuce (GL-VHFD), or low-fat diet (LFD) for 13 weeks. Compared to VHFD or GL-VHFD-fed groups, RSL-VHFD group showed significantly improved oral glucose tolerance (p<0.05). Comparison of VHFD, RSL-VHFD, and GL-VHFD groups revealed no significant differences with respect to insulin tolerance, hepatic lipids, body weight gain, fat mass, plasma glucose, triglycerides, free fatty acid, and lipopolysaccharide levels, as well as relative abundances of major bacterial phyla from 16S rDNA amplicon data sequences (from fecal and cecal samples). However, RSL and GL-supplementation increased abundance of several taxa involved in plant polysaccharide degradation/fermentation. RSL phenolics chlorogenic acid, quercetin-3-glucoside, and quercetin-malonyl-glucoside were bioaccessible in the TIM-1 digestion model, but had relatively low recovery. Conclusions RSL phenolics contributed to attenuation of postprandial hyperglycemia. Changes in gut microbiota were likely due to microbiota accessible carbohydrates in RSL and GL rather than RSL phenolics, which may be metabolized, absorbed, or degraded before reaching the colon. PMID:27529448

  6. Long-lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high-fat diet on metabolic function and energy expenditure.

    Science.gov (United States)

    Hill, Cristal M; Fang, Yimin; Miquet, Johanna G; Sun, Liou Y; Masternak, Michal M; Bartke, Andrzej

    2016-06-01

    Growth hormone (GH) signaling stimulates the production of IGF-1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high-fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet-induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  7. Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

    International Nuclear Information System (INIS)

    Zou, Yani; Leu, David; Chui, Jennifer; Fike, John R.; Huang, Ting-Ting

    2013-01-01

    Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted

  8. The role of red dragon fruit peel (Hylocereus polyrhizus) to improvement blood lipid levels of hyperlipidaemia male mice

    Science.gov (United States)

    Hernawati; Setiawan, N. A.; Shintawati, R.; Priyandoko, D.

    2018-05-01

    The purpose of this research was to know the role of red dragon fruit peel powder to total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and weight in the male hyperlipidaemic Balb-C mice (Mus musculus). This study used a completely randomized design (CRD) and four replicates for each dose treatments. Samples were 24 male mice that divided into six groups i.e. positive and negative controls, doses of 50; 100; 150 and 200 mg/kgBW/days red dragon fruit peel powder. Before being given treatment, mice were given feed containing high fat for 20 days until experiencing conditions hyperlipidaemia. The red dragon fruit peel powder was given at oral with used gavage for 30 days. Blood samples were taken from the tail on vena caudalis. Blood lipid samples were analysed at enzymatic with BIOLABO kits. The results of this study indicate that after administration of red dragon fruit peel powder total cholesterol levels, triglycerides and LDL-c decreased, along with increasing doses of red dragon fruit peel powder for 30 days. Furthermore showed that dragon fruit powder can increase HDL-c levels. The conclusion of this research was The red dragon fruit peel powder can improve blood lipid level of male Balb-c mice hyperlipidaemia.

  9. Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid Abnormalities in High-Fructose-Fed Mice.

    Science.gov (United States)

    Priyadarshini, Emayavaramban; Anuradha, Carani Venkatraman

    2017-02-01

    High intake of dietary fructose causes perturbation in lipid metabolism and provokes lipid-induced insulin resistance. A rise in glucocorticoids (GCs) has recently been suggested to be involved in fructose-induced insulin resistance. The objective of the study was to investigate the effect of GC blockade on lipid abnormalities in insulin-resistant mice. Insulin resistance was induced in mice by administering a high-fructose diet (HFrD) for 60 days. Mifepristone (RU486), a GC antagonist, was administered to HFrD-fed mice for the last 18 days, and the intracellular and extracellular GC levels, the glucocorticoid receptor (GR) activation and the expression of GC-regulated genes involved in lipid metabolism were examined. HFrD elevated the intracellular GC content in both liver and adipose tissue and enhanced the GR nuclear translocation. The plasma GC level remained unchanged. The levels of free fatty acids and triglycerides in plasma were elevated, accompanied by increased plasma insulin and glucose levels and decreased hepatic glycogen content. Treatment with RU486 reduced plasma lipid levels, tissue GC levels and the expression of GC-targeted genes involved in lipid accumulation, and it improved insulin sensitivity. This study demonstrated that HFrD-induced lipid accumulation and insulin resistance are mediated by enhanced GC in liver and adipose tissue and that GC antagonism might reduce fructose-induced lipid abnormalities and insulin resistance. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  10. Western diet increases wheel running in mice selectively bred for high voluntary wheel running.

    Science.gov (United States)

    Meek, T H; Eisenmann, J C; Garland, T

    2010-06-01

    Mice from a long-term selective breeding experiment for high voluntary wheel running offer a unique model to examine the contributions of genetic and environmental factors in determining the aspects of behavior and metabolism relevant to body-weight regulation and obesity. Starting with generation 16 and continuing through to generation 52, mice from the four replicate high runner (HR) lines have run 2.5-3-fold more revolutions per day as compared with four non-selected control (C) lines, but the nature of this apparent selection limit is not understood. We hypothesized that it might involve the availability of dietary lipids. Wheel running, food consumption (Teklad Rodent Diet (W) 8604, 14% kJ from fat; or Harlan Teklad TD.88137 Western Diet (WD), 42% kJ from fat) and body mass were measured over 1-2-week intervals in 100 males for 2 months starting 3 days after weaning. WD was obesogenic for both HR and C, significantly increasing both body mass and retroperitoneal fat pad mass, the latter even when controlling statistically for wheel-running distance and caloric intake. The HR mice had significantly less fat than C mice, explainable statistically by their greater running distance. On adjusting for body mass, HR mice showed higher caloric intake than C mice, also explainable by their higher running. Accounting for body mass and running, WD initially caused increased caloric intake in both HR and C, but this effect was reversed during the last four weeks of the study. Western diet had little or no effect on wheel running in C mice, but increased revolutions per day by as much as 75% in HR mice, mainly through increased time spent running. The remarkable stimulation of wheel running by WD in HR mice may involve fuel usage during prolonged endurance exercise and/or direct behavioral effects on motivation. Their unique behavioral responses to WD may render HR mice an important model for understanding the control of voluntary activity levels.

  11. Different perception levels of histamine-induced itch sensation in young adult mice.

    Science.gov (United States)

    Ji, Yeounjung; Jang, Yongwoo; Lee, Wook Joo; Yang, Young Duk; Shim, Won-Sik

    2018-05-01

    Itch is an unpleasant sensation that evokes behavioral responses such as scratching the skin. Interestingly, it is conceived that the perception of itch sensation is influenced by age. Indeed, accumulating evidence supports the idea that even children or younger adults show distinctive itch sensation depending on age. This evidence implies the presence of a mechanism that regulates the perception of itch sensation in an age-dependent fashion. Therefore, the purpose of the present study was to investigate a putative mechanism for the age-dependent perception of itch sensation by comparing histamine-induced scratching behaviors in 45-day old (D45) and 75-day old male "young adult" mice. The results indicated that, following histamine administration, the D75 mice spent a longer time scratching than D45 mice. However, the intensity of the calcium influx induced by histamine in primary culture of dorsal root ganglia (DRG) neurons was not different between D45 and D75 mice. Moreover, no apparent difference was observed in mRNA levels of a characteristic His-related receptor and ion channel. In contrast, the mRNA levels of Toll-Like Receptor 4 (TLR4) were increased approximately by two-fold in D75 DRG compared with D45 DRG. Additionally, D75-derived DRG neurons exhibited enhanced intracellular calcium increase by lipopolysaccharide (LPS, a TLR4 agonist) than those of D45 mice. Furthermore, intensities of calcium influx induced by histamine were significantly potentiated when co-treated with LPS in D75 DRG neurons, but not in those of D45 mice. Thus, it appears that D75 mice showed enhanced histamine-induced scratching behaviors not by increased expression levels of histamine-related genes, but probably due to augmented TLR4 expression in DRG neurons. Consequently, the current study found that different perception levels of histamine-induced itch sensation are present in different age groups of young adult mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Mice selectively bred for high voluntary wheel-running behavior conserve more fat despite increased exercise.

    Science.gov (United States)

    Hiramatsu, Layla; Garland, Theodore

    2018-04-20

    Physical activity is an important component of energy expenditure, and acute changes in activity can lead to energy imbalances that affect body composition, even under ad libitum food availability. One example of acute increases in physical activity is four replicate, selectively-bred High Runner (HR) lines of mice that voluntarily run ~3-fold more wheel revolutions per day over 6-day trials and are leaner, as compared with four non-selected control (C) lines. We expected that voluntary exercise would increase food consumption, build lean mass, and reduce fat mass, but that these effects would likely differ between HR and C lines or between the sexes. We compared wheel running, cage activity, food consumption, and body composition between HR and C lines for young adults of both sexes, and examined interrelationships of those traits across 6 days of wheel access. Before wheel testing, HR mice weighed less than C, primarily due to reduced lean mass, and females were lighter than males, entirely due to lower lean mass. Over 6 days of wheel access, all groups tended to gain small amounts of lean mass, but lose fat mass. HR mice lost less fat than C mice, in spite of much higher activity levels, resulting in convergence to a fat mass of ~1.7 g for all 4 groups. HR mice consumed more food than C mice (with body mass as a covariate), even accounting for their higher activity levels. No significant sex-by-linetype interactions were observed for any of the foregoing traits. Structural equation models showed that the four sex-by-linetype groups differed considerably in the complex phenotypic architecture of these traits. Interrelationships among traits differed by genetic background and sex, lending support to the idea that recommendations regarding weight management, diet, and exercise may need to be tailored to the individual level. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. A high-fat diet activates oncogenic Kras and COX2 to induce development of pancreatic ductal adenocarcinoma in mice.

    Science.gov (United States)

    Philip, Bincy; Roland, Christina L; Daniluk, Jaroslaw; Liu, Yan; Chatterjee, Deyali; Gomez, Sobeyda B; Ji, Baoan; Huang, Haojie; Wang, Huamin; Fleming, Jason B; Logsdon, Craig D; Cruz-Monserrate, Zobeida

    2013-12-01

    Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis. The oncogenic form of KRAS is expressed during early stages of PDAC development and is detected in almost all of these tumors. However, there is evidence that mutant KRAS requires an additional stimulus to activate its full oncogenic activity and that this stimulus involves the inflammatory response. We investigated whether the inflammation induced by a high-fat diet, and the accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity during pancreatic carcinogenesis in mice. We studied mice with acinar cell-specific expression of KrasG12D (LSL-Kras/Ela-CreERT mice) alone or crossed with COX2 conditional knockout mice (COXKO/LSL-Kras/Ela-CreERT). We also studied LSL-Kras/PDX1-Cre mice. All mice were fed isocaloric diets with different amounts of fat, and a COX2 inhibitor was administered to some LSL-Kras/Ela-CreERT mice. Pancreata were collected from mice and analyzed for Kras activity, levels of phosphorylated extracellular-regulated kinase, inflammation, fibrosis, pancreatic intraepithelial neoplasia (PanIN), and PDACs. Pancreatic tissues from LSL-Kras/Ela-CreERT mice fed high-fat diets (HFDs) had increased Kras activity, fibrotic stroma, and numbers of PanINs and PDACs than LSL-Kras/Ela-CreERT mice fed control diets; the mice fed the HFDs also had shorter survival times than mice fed control diets. Administration of a COX2 inhibitor to LSL-Kras/Ela-CreERT mice prevented these effects of HFDs. We also observed a significant reduction in survival times of mice fed HFDs. COXKO/LSL-Kras/Ela-CreERT mice fed HFDs had no evidence for increased numbers of PanIN lesions, inflammation, or fibrosis, as opposed to the increases observed in LSL-Kras/Ela-CreERT mice fed HFDs. In mice, an HFD can activate oncogenic Kras via COX2, leading to pancreatic inflammation and fibrosis and development of PanINs and PDAC. This

  14. High levels of circulating triiodothyronine induce plasma cell differentiation.

    Science.gov (United States)

    Bloise, Flavia Fonseca; Oliveira, Felipe Leite de; Nobrega, Alberto Félix; Vasconcellos, Rita; Cordeiro, Aline; Paiva, Luciana Souza de; Taub, Dennis D; Borojevic, Radovan; Pazos-Moura, Carmen Cabanelas; Mello-Coelho, Valéria de

    2014-03-01

    The effects of hyperthyroidism on B-cell physiology are still poorly known. In this study, we evaluated the influence of high-circulating levels of 3,5,3'-triiodothyronine (T3) on bone marrow, blood, and spleen B-cell subsets, more specifically on B-cell differentiation into plasma cells, in C57BL/6 mice receiving daily injections of T3 for 14 days. As analyzed by flow cytometry, T3-treated mice exhibited increased frequencies of pre-B and immature B-cells and decreased percentages of mature B-cells in the bone marrow, accompanied by an increased frequency of blood B-cells, splenic newly formed B-cells, and total CD19(+)B-cells. T3 administration also promoted an increase in the size and cellularity of the spleen as well as in the white pulp areas of the organ, as evidenced by histological analyses. In addition, a decreased frequency of splenic B220(+) cells correlating with an increased percentage of CD138(+) plasma cells was observed in the spleen and bone marrow of T3-treated mice. Using enzyme-linked immunospot assay, an increased number of splenic immunoglobulin-secreting B-cells from T3-treated mice was detected ex vivo. Similar results were observed in mice immunized with hen egg lysozyme and aluminum adjuvant alone or together with treatment with T3. In conclusion, we provide evidence that high-circulating levels of T3 stimulate plasma cytogenesis favoring an increase in plasma cells in the bone marrow, a long-lived plasma cell survival niche. These findings indicate that a stimulatory effect on plasma cell differentiation could occur in untreated patients with Graves' disease.

  15. Ajoene restored behavioral patterns and liver glutathione level in morphine treated C57BL6 mice.

    Science.gov (United States)

    Yun, Jaesuk; Oliynyk, Sergiy; Lee, Yeonju; Kim, Jieun; Yun, Kyunghwa; Jeon, Raok; Ryu, Jae-Ha; Oh, Seikwan

    2017-01-01

    Oxidative stress exacerbates drug dependence induced by administration of opiate analgesics such as morphine-induced tolerance and physical dependence associated with the reduction in hepatic glutathione (GSH) level. Ajoene obtained from garlic (Allium sativum L.) has been reported for anti-tumorigenic, anti-oxidative and neuroprotective properties, however, little is known about its effect on morphine-induced dependence. Therefore, this study aimed at the effect of ajoene on physical and/or psychological dependence and liver GSH content in morphine-treated mice. Conditioned place preference (CPP) test and measurement of morphine withdrawal syndrome were performed in C57BL6 mice for behavioral experiments. Thereafter, mice were sacrificed for measurement of serum and liver GSH levels. Ajoene restored CPP and naloxone-precipitated jumping behavior in mice exposed to morphine. Moreover, the reduced level of liver GSH content in morphine treated mice was back to normal after ajoene administration. Taken together, ajoene improved behavioral patterns in mice exposed to morphine suggesting its potential therapeutic benefit against morphine-induced dependence.

  16. Green tea extracts reduce leukocyte cell-Derived chemotaxin 2 and selenoprotein P levels in the livers of C57BL/6J mice fed a high-fat diet.

    Science.gov (United States)

    Onishi, Shintaro; Kitazawa, Hidefumi; Meguro, Shinichi; Tokimitsu, Ichiro

    2018-05-31

    Epidemiological studies suggest that green tea extracts (GTEs), including catechins such as epigallocatechin gallate and epicatechin gallate, have a beneficial effect on obesity, hyperglycemia, insulin resistance, endothelial dysfunction, and inflammation. Although several studies have shown that catechins directly modulate the cellular and molecular alterations in the liver tissue, the contributions of indirect mechanisms underlying these systemic effects of catechins remain unclear. In this study, we report that, in the C57BL/6J mouse liver, GTEs reduce high-fat diet-induced increases in the levels of hepatokines, liver-derived secretary proteins such as leukocyte cell-derived chemotaxin 2 and selenoprotein P production, which have been shown to induce systemic adverse effects, including several metabolic diseases. These findings suggest that the systemic effects of GTEs involve the regulation of hepatokine production as an indirect mechanism.

  17. Dietary supplementation of chinese ginseng prevents obesity and metabolic syndrome in high-fat diet-fed mice.

    Science.gov (United States)

    Li, Xiaoxiao; Luo, Jing; Anandh Babu, Pon Velayutham; Zhang, Wei; Gilbert, Elizabeth; Cline, Mark; McMillan, Ryan; Hulver, Matthew; Alkhalidy, Hana; Zhen, Wei; Zhang, Haiyan; Liu, Dongmin

    2014-12-01

    Obesity and diabetes are growing health problems worldwide. In this study, dietary provision of Chinese ginseng (0.5 g/kg diet) prevented body weight gain in high-fat (HF) diet-fed mice. Dietary ginseng supplementation reduced body fat mass gain, improved glucose tolerance and whole body insulin sensitivity, and prevented hypertension in HF diet-induced obese mice. Ginseng consumption led to reduced concentrations of plasma insulin and leptin, but had no effect on plasma adiponectin levels in HF diet-fed mice. Body temperature was higher in mice fed the ginseng-supplemented diet but energy expenditure, respiration rate, and locomotive activity were not significantly altered. Dietary intake of ginseng increased fatty acid oxidation in the liver but not in skeletal muscle. Expression of several transcription factors associated with adipogenesis (C/EBPα and PPARγ) were decreased in the adipose tissue of HF diet-fed mice, effects that were mitigated in mice that consumed the HF diet supplemented with ginseng. Abundance of fatty acid synthase (FASN) mRNA was greater in the adipose tissue of mice that consumed the ginseng-supplemented HF diet as compared with control or un-supplemented HF diet-fed mice. Ginseng treatment had no effect on the expression of genes involved in the regulation of food intake in the hypothalamus. These data suggest that Chinese ginseng can potently prevent the development of obesity and insulin resistance in HF diet-fed mice.

  18. Effect of individual and group housing of mice on the level of radioresistance

    Directory of Open Access Journals (Sweden)

    Dorozhkina O.V.

    2015-12-01

    Full Text Available Aim: to examine the effect of individual and group housing of mice on radioresistance. Material and methods. Effects of individual and group housing of mice on immunity and blood systems were studied on ICR (CD-1 and C57BI6 male mice before and after proton irradiation. Results. Group housing of intact animals resulted in a decline in the number of nucleated cells in the femur bone marrow and thymus mass. The irradiation with proton with energy of 171 MeV at a dose of 1 Gy causes a statistically significant greater reduction of the number of nucleated cells in the femur bone marrow in group-housed mice. A trend toward greater safety of the number of leukocytes in the peripheral blood and higher proliferative activity of bone marrow cells, as well as lower level of aberrant mitoses have been noted in individually-housed mice. Reduction processes in the recovery period of radiation sickness take place at a greater rate in group-housed mice. Conclusion. Group housing of male mice causes increased sensitivity of the blood and immunity systems to the effects of radiation and at the same time accelerates processes of radiation recovery.

  19. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior

    Directory of Open Access Journals (Sweden)

    Fuka Aizawa

    2016-12-01

    Full Text Available The free fatty acid receptor 1 (GPR40/FFAR1 is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO mice. The emotional behavior in wild and KO male mice was evaluated at 9–10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC–MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.

  20. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

    Science.gov (United States)

    Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

    2016-12-01

    The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  1. High fat diet and GLP-1 drugs induce pancreatic injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Rouse, Rodney, E-mail: rodney.rouse@fda.hhs.gov; Xu, Lin; Stewart, Sharron; Zhang, Jun

    2014-04-15

    Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment.

  2. High fat diet and GLP-1 drugs induce pancreatic injury in mice

    International Nuclear Information System (INIS)

    Rouse, Rodney; Xu, Lin; Stewart, Sharron; Zhang, Jun

    2014-01-01

    Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment

  3. Effect of aerobic exercise and fish oil supplements on plasma levels of inflammatory indexes in mice.

    Science.gov (United States)

    Alizadeh, Hamid; Bazgir, Behzad; Daryanoosh, Farhad; Koushki, Maryam; Sobhani, Vahid

    2014-01-01

    Exercise has positive and negative effects on immune system. Herein, we would like to investigate the effects of incremental aerobic training and fish oil supplementation on the plasma levels of CRP, CPK and IL-17 in trained mice. One of the major roles of immune system is to produce soluble or cellular components that provide the immunity against inflammatory agent. The purpose of this study is to investigate distinct and combine effects of incremental aerobic training and fish oil supplement on plasma levels of IL-17, CPK and CRP in trained male mice. Totally, 54 healthy male mice (2 months old, weight= 34±1 grams) were selected. At first 10 mice were killed to determine base line values, the rest of them were randomly divided into four groups, control group (C, n=11), supplement group (S, n=11), training group (T, n=11) and supplement-training group (ST, n=11).The supplement and supplement-training groups were fed with 0.2cc/day fish oil for 8 weeks. Training and supplement-training groups underwent exercise for 5 sessions per week for a period of 8 weeks on animal treadmill. SPSS 16.0 software and multivariate analysis of variance were used for statistical analysis of data Exercise and fish oil supplement lead to a decrease in CRP levels and subsequently causing a reduction in plasma levels of IL-17 and CK in mice (poil can reduce regulate inflammatory response caused by incremental exercise.

  4. Induced Ablation of Ghrelin Cells in Adult Mice Does Not Decrease Food Intake, Body Weight, or Response to High Fat Diet

    Science.gov (United States)

    McFarlane, Matthew R.; Brown, Michael S.; Goldstein, Joseph L.; Zhao, Tong-Jin

    2014-01-01

    SUMMARY Injection of the peptide hormone ghrelin stimulates food intake in mice and humans. However, mice born without ghrelin demonstrate no significant loss of appetite. This paradox suggests either that compensation develops in mice born without ghrelin or that ghrelin is not essential for appetite control. To distinguish these possibilities, we generated transgenic mice (Ghrl-DTR) that express the diphtheria toxin receptor in ghrelin-secreting cells. Injection of diphtheria toxin in adulthood ablated ghrelin cells and reduced plasma ghrelin by 80-95%. Ghrelin cell-ablated mice exhibited no loss of appetite or body weight and no resistance to a high fat diet. To stimulate food intake in mice by ghrelin injection, we had to raise plasma levels many-fold above normal. Like germline ghrelin-deficient mice, the ghrelin cell-ablated mice developed profound hypoglycemia when subjected to prolonged calorie restriction, confirming that ghrelin acts to maintain blood glucose under famine conditions. PMID:24836560

  5. Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

    Directory of Open Access Journals (Sweden)

    Liyuan Chen

    2018-03-01

    Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

  6. Alteration of putative amino acid levels and morphological findings in neural tissues of methylmercury-intoxicated mice

    Energy Technology Data Exchange (ETDEWEB)

    Hirayama, K.; Inouye, M.; Fujisaki, T.

    1985-04-01

    Methylmercury chloride was administered PO to male Kud:ddY mice at a dose of 5 mg/kg/day for 20 days. The contents of taurine, aspartate, glutamate, glycine, and ..gamma..-aminobutyric acid were determined in tissue and crude synaptosomal (P/sub 2/) fraction of cerebellum, cerebral cortex, and spinal cord of methylmercury-treated mice with or without ataxia. In the cerebellum of ataxic mice, increased levels of taurine and glycine were found in the tissue and P/sub 2/ fraction, and increased levels of glutamate were found in the P/sub 2/ fraction. In the cerebral cortex, the levels of ..gamma..-aminobutylic acid decreased in the tissue and in the P/sub 2/ fraction of ataxic mice, but increased levels were found in the tissue of non-ataxic mice. A decreased asparate level in the cerebral cortex of ataxic mice and an increased taurine level in the cerebral cortex of non-ataxic mice were also found. In the spinal cord of ataxic mice, taurine increased in the tissue and in the P/sub 2/ fraction. Glutamate level decreased in the spinal cord of ataxic mice, but increased in the P/sub 2/ fraction of non-ataxic mice. Increased glycine levels in the P/sub 2/ fraction of the spinal cord were also found in non-axtaxic mice. Histologically, some degenerative changes were demonstrated in the cerebral and cerebellar cortices of ataxic mice. Such changes were also present to a mild degree in non-ataxic mice. In conclusion, methylmercury treatment altered the levels of putative neurotransmitter amino acids in neutral tissue of mice. These alterations might be caused by specific neural cell dysfunction and could be related to the appearance of ataxia.

  7. Effect of inulin supplementation in male mice fed with high fat diet on ...

    African Journals Online (AJOL)

    Purpose: To evaluate the preventive and therapeutic effects of inulin supplementation in Naval Medical Research Institute (NMRI) male mice fed with high fat diet. Methods: NMRI male mice (n = 36) were divided into three groups. Control (C1), obese (O1) and experimental mice (E1) were fed during 8 weeks as follows: C1 ...

  8. Effects of Exercise on Progranulin Levels and Gliosis in Progranulin-Insufficient Mice.

    Science.gov (United States)

    Arrant, Andrew E; Patel, Aashka R; Roberson, Erik D

    2015-01-01

    Loss-of-function mutations in progranulin ( GRN ) are one of the most common genetic causes of frontotemporal dementia (FTD), a progressive, fatal neurodegenerative disorder with no available disease-modifying treatments. Through haploinsufficiency, these mutations reduce levels of progranulin, a protein that has neurotrophic and anti-inflammatory effects. Increasing progranulin expression from the intact allele is therefore a potential approach for treating individuals with GRN mutations. Based on the well-known effects of physical exercise on other neurotrophic factors, we hypothesized that exercise might increase brain progranulin levels. We tested this hypothesis in progranulin heterozygous ( Grn + / - ) mice, which model progranulin haploinsufficiency. We housed wild-type and progranulin-insufficient mice in standard cages or cages with exercise wheels for 4 or 7.5 weeks, and then measured brain and plasma progranulin levels. Although exercise modestly increased progranulin in very young (2-month-old) wild-type mice, this effect was limited to the hippocampus. Exercise did not increase brain progranulin mRNA or protein in multiple regions, nor did it increase plasma progranulin, in 4- to 8-month-old wild-type or Grn + / - mice, across multiple experiments and under conditions that increased hippocampal BDNF and neurogenesis. Grn - / - mice were included in the study to test for progranulin-independent benefits of exercise on gliosis. Exercise attenuated cortical microgliosis in 8-month-old Grn - / - mice, consistent with a progranulin-independent, anti-inflammatory effect of exercise. These results suggest that exercise may have some modest, nonspecific benefits for FTD patients with progranulin mutations, but do not support exercise as a strategy to raise progranulin levels.

  9. Marginal level dystrophin expression improves clinical outcome in a strain of dystrophin/utrophin double knockout mice.

    Directory of Open Access Journals (Sweden)

    Dejia Li

    2010-12-01

    Full Text Available Inactivation of all utrophin isoforms in dystrophin-deficient mdx mice results in a strain of utrophin knockout mdx (uko/mdx mice. Uko/mdx mice display severe clinical symptoms and die prematurely as in Duchenne muscular dystrophy (DMD patients. Here we tested the hypothesis that marginal level dystrophin expression may improve the clinical outcome of uko/mdx mice. It is well established that mdx3cv (3cv mice express a near-full length dystrophin protein at ∼5% of the normal level. We crossed utrophin-null mutation to the 3cv background. The resulting uko/3cv mice expressed the same level of dystrophin as 3cv mice but utrophin expression was completely eliminated. Surprisingly, uko/3cv mice showed a much milder phenotype. Compared to uko/mdx mice, uko/3cv mice had significantly higher body weight and stronger specific muscle force. Most importantly, uko/3cv outlived uko/mdx mice by several folds. Our results suggest that a threshold level dystrophin expression may provide vital clinical support in a severely affected DMD mouse model. This finding may hold clinical implications in developing novel DMD therapies.

  10. Intracage ammonia levels in static and individually ventilated cages housing C57BL/6 mice on 4 bedding substrates.

    Science.gov (United States)

    Ferrecchia, Christie E; Jensen, Kelly; Van Andel, Roger

    2014-03-01

    The relationship among ammonia levels, cage-changing frequency, and bedding types is an important and potentially controversial topic in the laboratory animal science community. Some bedding options may not provide sufficient urine absorption and bacterial regulation to minimize ammonia production during the interval between cage changes. High intracage ammonia levels can cause subclinical degeneration and inflammation of nasal passages, rhinitis and olfactory epithelial necrosis in exposed mice. Here we sought to compare the effects of 4 commonly used bedding substrates (1/4-in. irradiated corncob, reclaimed wood pulp, aspen wood chips, and recycled newspaper) on ammonia generation when housing female C57BL/6 mice in static and individually ventilated caging. Intracage ammonia levels were measured daily for 1 wk (static cage experiment) or 2 wk (IVC experiment). The results of this study suggest that the corncob, aspen wood chip, and recycled newspaper beddings that we tested are suitable for once-weekly cage changing for static cages and for changing every 2 wk for IVC. However, ammonia levels were not controlled appropriately in cages containing reclaimed wood pulp bedding, and pathologic changes occurred within 1 wk in the nares of mice housed on this bedding in static cages.

  11. Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J mice

    DEFF Research Database (Denmark)

    Tastesen, Hanne Sørup; Keenan, Alison H.; Madsen, Lise

    2014-01-01

    High-protein diets induce alterations in metabolism that may prevent diet-induced obesity. However, little is known as to whether different protein sources consumed at normal levels may affect diet-induced obesity and associated co-morbidities. We fed obesity-prone male C57BL/6J mice high-fat, high......-fed mice, but otherwise no changes in lean body mass were observed between the groups. Feed efficiency and apparent nitrogen digestibility were reduced in scallop-fed mice suggesting alterations in energy utilization and metabolism. Overnight fasted plasma triacylglyceride, non-esterified fatty acids......, glycerol and hydroxy-butyrate levels were significantly reduced, indicating reduced lipid mobilization in scallop-fed mice. The plasma HDL-to-total-cholesterol ratio was higher, suggesting increased reverse cholesterol transport or cholesterol clearance in scallop-fed mice in both fasted and non-fasted...

  12. Effects of a treatment with Se-rich rice flour high in resistant starch on enteric dysbiosis and chronic inflammation in diabetic ICR mice.

    Science.gov (United States)

    Yuan, Huaibo; Wang, Wenjuan; Chen, Deyi; Zhu, Xiping; Meng, Lina

    2017-05-01

    Enteric dysbiosis is associated with chronic inflammation and interacts with obesity and insulin resistance. Obesity and diabetes are induced in ICR (Institute of Cancer Research) mice fed a high-fat diet and administered a streptozocin injection. These mice were treated with normal rice (NR), normal rice with a high resistant starch content (NRRS) or Se-rich rice (selenium-enriched rice) with a high resistant starch content (SRRS). Faecal cell counts of Bifidobacterium, Lactobacillus and Enterococcus were significantly higher in SRRS-treated mice than in diabetic controls, while Enterobacter cloacae were lower. Similar results were also found in NRRS-treated mice. In contrast, no significant difference was found between NR-treated and diabetic control groups. The treatments with SRRS and NRRS reduced the faecal pH values of the diabetic mice. Regarding the inflammatory factor levels, lower levels of serum C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-k-gene binding (NF-κB) and leptin (LEP) and higher adiponutrin (ADPN) levels were found in the SRRS and NRRS-treated mice compared with the diabetic and NR-treated mice. In addition, the CRP, IL-6 and NF-κB levels in the SRRS-treated mice were significantly reduced compared with those observed in the NRRS-treated mice. The reverse transcription-PCR (RT-PCR) results showed that the SRRS and NRRS-treated mice presented higher expression levels of orphan G protein-coupled receptor 41 (GPR41) and orphan G protein-coupled receptor 43 (GPR43) proteins compared with diabetic mice and NR-treated mice. These results indicate that treatments with rice high in RS exert beneficial effects by improving enteric dysbiosis and chronic inflammation. In addition, selenium and RS may exert synergistic effects on chronic inflammation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  13. A tripeptide Diapin effectively lowers blood glucose levels in male type 2 diabetes mice by increasing blood levels of insulin and GLP-1.

    Directory of Open Access Journals (Sweden)

    Jifeng Zhang

    Full Text Available The prevalence of type 2 diabetes (T2D is rapidly increasing worldwide. Effective therapies, such as insulin and Glucagon-like peptide-1 (GLP-1, require injections, which are costly and result in less patient compliance. Here, we report the identification of a tripeptide with significant potential to treat T2D. The peptide, referred to as Diapin, is comprised of three natural L-amino acids, GlyGlyLeu. Glucose tolerance tests showed that oral administration of Diapin effectively lowered blood glucose after oral glucose loading in both normal C57BL/6J mice and T2D mouse models, including KKay, db/db, ob/ob mice, and high fat diet-induced obesity/T2D mice. In addition, Diapin treatment significantly reduced casual blood glucose in KKay diabetic mice in a time-dependent manner without causing hypoglycemia. Furthermore, we found that plasma GLP-1 and insulin levels in diabetic models were significantly increased with Diapin treatment compared to that in the controls. In summary, our findings establish that a peptide with minimum of three amino acids can improve glucose homeostasis and Diapin shows promise as a novel pharmaceutical agent to treat patients with T2D through its dual effects on GLP-1 and insulin secretion.

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

    Science.gov (United States)

    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.

  15. High-level language computer architecture

    CERN Document Server

    Chu, Yaohan

    1975-01-01

    High-Level Language Computer Architecture offers a tutorial on high-level language computer architecture, including von Neumann architecture and syntax-oriented architecture as well as direct and indirect execution architecture. Design concepts of Japanese-language data processing systems are discussed, along with the architecture of stack machines and the SYMBOL computer system. The conceptual design of a direct high-level language processor is also described.Comprised of seven chapters, this book first presents a classification of high-level language computer architecture according to the pr

  16. Impact of high-fat diet and voluntary running on body weight and endothelial function in LDL receptor knockout mice.

    Science.gov (United States)

    Langbein, Heike; Hofmann, Anja; Brunssen, Coy; Goettsch, Winfried; Morawietz, Henning

    2015-05-01

    Obesity and physical inactivity are important cardiovascular risk factors. Regular physical exercise has been shown to mediate beneficial effects in the prevention of cardiovascular diseases. However, the impact of physical exercise on endothelial function in proatherosclerotic low-density lipoprotein receptor deficient (LDLR(-/-)) mice has not been studied so far. Six-week-old male LDLR(-/-) mice were fed a standard diet or a high-fat diet (39 kcal% fat diet) for 20 weeks. The impact of high-fat diet and voluntary running on body weight and amount of white adipose tissue was monitored. Basal tone and endothelial function was investigated in aortic rings using a Mulvany myograph. LDLR(-/-) mice on high-fat diet had increased cumulative food energy intake, but also higher physical activity compared to mice on control diet. Body weight and amount of visceral and retroperitoneal white adipose tissue of LDLR(-/-) mice were significantly increased by high-fat diet and partially reduced by voluntary running. Endothelial function in aortae of LDLR(-/-) mice was impaired after 20 weeks on standard and high-fat diet and could not be improved by voluntary running. Basal tone showed a trend to be increased by high-fat diet. Voluntary running reduced body weight and amount of white adipose tissue in LDLR(-/-) mice. Endothelial dysfunction in LDLR(-/-) mice could not be improved by voluntary running. In a clinical context, physical exercise alone might not have an influence on functional parameters and LDL-C levels in patients with familial hypercholesterolemia. However, physical activity in these patients may be in general beneficial and should be performed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Application of a naturalistic psychogenic stressor in periadolescent mice: effect on serum corticosterone levels differs by strain but not sex

    Directory of Open Access Journals (Sweden)

    Klein Laura C

    2010-06-01

    Full Text Available Abstract Background As a first step in determining whether psychogenic stressors might be incorporated into periadolescent mouse models of stress, we evaluated whether a commonly used psychogenic stressor, exposure to red fox urine, alters serum corticosterone levels in periadolescent C57BL/6J and DBA/2J mice. Findings In a 1-day experiment, forty-eight 38-day-old C57BL/6J (N = 12 males; N = 12 females and DBA/2J (N = 12 males; N = 12 females mice were exposed to 10-min of red fox urine via cotton ball (N = 12 C57BL/6J mice; N = 12 DBA/2J mice or to a non-saturated cotton ball (N = 12 C57BL/6J mice; N = 12 DBA/2J mice. All mice were sacrificed 15-min after cotton ball exposure and serum was collected for corticosterone assessment. Overall, there was a main effect for strain such that C57BL/6J male and female mice displayed higher corticosterone levels than did male and female DBA/2J mice. There were no main effects for sex or odor exposure. However, there was a significant strain by odor exposure interaction, whereby, within odor-exposed mice, DBA/2J mice displayed lower corticosterone levels (ng/mL compared to C57BL/6J mice, regardless of sex. Further, among DBA/2J mice, predator odor exposure reduced corticosterone levels compared to no odor exposure. Conclusions Findings indicate that mouse strain, but not sex, may play an important role in the efficacy of a predator odor among periadolescent mice.

  18. Chronic mild stress increases alcohol intake in mice with low dopamine D2 receptor levels.

    Science.gov (United States)

    Delis, Foteini; Thanos, Panayotis K; Rombola, Christina; Rosko, Lauren; Grandy, David; Wang, Gene-Jack; Volkow, Nora D

    2013-02-01

    Alcohol use disorders emerge from a complex interaction between environmental and genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to play a central role in alcoholism. To better understand the interactions between DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at the end of the experiment, the animals were tested in the forced swim and open field tests. We measured ethanol intake and preference, immobility in the force swim test, and activity in the open field. We show that under no CMS, Drd2+/- and Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+. Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had significantly lower activity in the open field than Drd2+/+, whereas no genotype differences were observed in the forced swim test. Exposure to CMS increased immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed in open field test measures. These findings suggest that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  19. Effect of myostatin depletion on weight gain, hyperglycemia, and hepatic steatosis during five months of high-fat feeding in mice.

    Directory of Open Access Journals (Sweden)

    Kerri Burgess

    Full Text Available The marked hypermuscularity in mice with constitutive myostatin deficiency reduces fat accumulation and hyperglycemia induced by high-fat feeding, but it is unclear whether the smaller increase in muscle mass caused by postdevelopmental loss of myostatin activity has beneficial metabolic effects during high-fat feeding. We therefore examined how postdevelopmental myostatin knockout influenced effects of high-fat feeding. Male mice with ubiquitous expression of tamoxifen-inducible Cre recombinase were fed tamoxifen for 2 weeks at 4 months of age. This depleted myostatin in mice with floxed myostatin genes, but not in control mice with normal myostatin genes. Some mice were fed a high-fat diet (60% of energy for 22 weeks, starting 2 weeks after cessation of tamoxifen feeding. Myostatin depletion increased skeletal muscle mass ∼30%. Hypermuscular mice had ∼50% less weight gain than control mice over the first 8 weeks of high-fat feeding. During the subsequent 3 months of high-fat feeding, additional weight gain was similar in control and myostatin-deficient mice. After 5 months of high-fat feeding, the mass of epididymal and retroperitoneal fat pads was similar in control and myostatin-deficient mice even though myostatin depletion reduced the weight gain attributable to the high-fat diet (mean weight with high-fat diet minus mean weight with low-fat diet: 19.9 g in control mice, 14.1 g in myostatin-deficient mice. Myostatin depletion did not alter fasting blood glucose levels after 3 or 5 months of high-fat feeding, but reduced glucose levels measured 90 min after intraperitoneal glucose injection. Myostatin depletion also attenuated hepatic steatosis and accumulation of fat in muscle tissue. We conclude that blocking myostatin signaling after maturity can attenuate some of the adverse effects of a high-fat diet.

  20. Hypothalamic Leptin Gene Therapy Reduces Bone Marrow Adiposity in ob/ob Mice Fed Regular and High Fat Diets

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    Laurence B Lindenmaier

    2016-08-01

    Full Text Available Low bone mass is often associated with increased bone marrow adiposity. Since osteoblasts and adipocytes are derived from the same mesenchymal stem cell progenitor, adipocyte formation may increase at the expense of osteoblast formation. Leptin is an adipocyte-derived hormone known to regulate energy and bone metabolism. Genetic (e.g., leptin deficiency and high fat diet-induced (e.g., leptin resistance obesity are associated with increased marrow adipose tissue (MAT and reduced bone formation. Short-duration studies suggest that leptin treatment reduces MAT and increases bone formation in leptin-deficient ob/ob mice fed a regular diet. Here, we determined the long-duration impact of increased hypothalamic leptin on marrow adipocytes and osteoblasts in ob/ob mice using recombinant adeno-associated virus (rAAV gene therapy. In a first study, eight- to ten-week-old male ob/ob mice were randomized into 4 groups: (1 untreated, (2 rAAV-Lep, (3 rAAV-green fluorescent protein (rAAV-GFP, or (4 pair-fed to rAAV-Lep. For vector administration, mice were placed in a Kopf stereotaxic apparatus, and injected intracerebroventricularly with either rAAV-Lep or rAAV-GFP (9 × 107 particles in 1.5 µl. The mice were maintained for 30 weeks following vector administration. In a second study, the impact of increased hypothalamic leptin levels on MAT was determined in mice fed high fat diets. Eight- to ten-week-old male ob/ob mice were randomized into 2 groups and treated with either rAAV-Lep or rAAV-GFP. At 7 weeks post-vector administration, half the mice in each group were switched to a high fat diet for 8 weeks. Wild type (WT controls included age-matched mice fed regular or high fat diet. Hypothalamic leptin gene therapy increased osteoblast perimeter and osteoclast perimeter with minor change in cancellous bone architecture. The gene therapy decreased MAT levels in ob/ob mice fed regular or high fat diet to values similar to WT mice fed regular diet. These

  1. Other-than-high-level waste

    International Nuclear Information System (INIS)

    Bray, G.R.

    1976-01-01

    The main emphasis of the work in the area of partitioning transuranic elements from waste has been in the area of high-level liquid waste. But there are ''other-than-high-level wastes'' generated by the back end of the nuclear fuel cycle that are both large in volume and contaminated with significant quantities of transuranic elements. The combined volume of these other wastes is approximately 50 times that of the solidified high-level waste. These other wastes also contain up to 75% of the transuranic elements associated with waste generated by the back end of the fuel cycle. Therefore, any detailed evaluation of partitioning as a viable waste management option must address both high-level wastes and ''other-than-high-level wastes.''

  2. Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice.

    Science.gov (United States)

    Cui, Xuezhi; Navneet, Soumya; Wang, Jing; Roon, Penny; Chen, Wei; Xian, Ming; Smith, Sylvia B

    2017-04-01

    Hyperhomocysteinemia (Hhcy) is implicated in certain retinal neurovascular diseases, although whether it is causative remains uncertain. In isolated ganglion cells (GCs), mild Hhcy induces profound death, whereas retinal phenotypes in Hhcy mice caused by mutations in remethylation (methylene tetrahydrofolatereductase [Mthfr+/-]) or transsulfuration pathways (cystathionine β-synthase [Cbs+/-]) demonstrate mild GC loss and mild vasculopathy. The current work investigated compensation in vivo of one pathway for the other, and, because the transsulfuration pathway yields cysteine necessary for formation of glutathione (GSH), taurine, and hydrogen sulfide (H2S), they were analyzed also. Retinas isolated from wild-type (WT), Mthfr+/-, and Cbs+/- mice (12 and 22 weeks) were analyzed for methylene tetrahydrofolate reductase (MTHFR), cystathionine-β-synthase (CBS), and cystathionase (CTH) RNA/protein levels. Retinas were evaluated for levels of reduced:oxidized GSH (GSH:GSSG), Slc7a11 (xCT), taurine, taurine transporter (TAUT), and H2S. Aside from decreased CBS RNA/protein levels in Cbs+/- retinas, there were minimal alterations in remethylation/transsulfuration pathways in the two mutant mice strains. Glutathione and taurine levels in Mthfr+/- and Cbs+/- retinas were similar to WT, which may be due to robust levels of xCT and TAUT in mutant retinas. Interestingly, levels of H2S were markedly increased in retinas of Mthfr+/- and Cbs+/- mice compared with WT. Ganglion cell loss and vasculopathy observed in Mthfr+/- and Cbs+/- mouse retinas may be milder than expected, not because of compensatory increases of enzymes in remethylation/transsulfuration pathways, but because downstream transsulfuration pathway products GSH, taurine, and H2S are maintained at robust levels. Elevation of H2S is particularly intriguing owing to neuroprotective properties reported for this gasotransmitter.

  3. Guarana (Paullinia cupana Stimulates Mitochondrial Biogenesis in Mice Fed High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Natália da Silva Lima

    2018-01-01

    Full Text Available The aim of this study was to evaluate the effects of guarana on mitochondrial biogenesis in a high-fat diet (HFD-fed mice. C57BL6J mice were divided in two groups: high-fat diet HFD and high-fat diet + guarana (HFD-GUA. Both groups received HFD and water ad libitum and the HFD-GUA group also received a daily gavage of guarana (1 g/kg weight. Body weight and food intake was measured weekly. Glycemic, triglyceride, and cholesterol levels were determined. VO2 and energy expenditure (EE were determined by indirect calorimetry. Gene expression was evaluated by real-time PCR and protein content by western blotting. The HFD-GUA group presented lower body weight, subcutaneous, retroperitoneal, visceral, and epididyimal adipose tissue depots, and glycemic and triglyceride levels, with no change in food intake and cholesterol levels. Furthermore, the HFD-GUA group presented an increase in VO2 and basal energy expenditure (EE, as well as Pgc1α, Creb1, Ampka1, Nrf1, Nrf2, and Sirt1 expression in the muscle and brown adipose tissue. In addition, the HFD-GUA group presented an increase in mtDNA (mitochondrial deoxyribonucleic acid content in the muscle when compared to the HFD group. Thus, our data showed that guarana leads to an increase in energetic metabolism and stimulates mitochondrial biogenesis, contributing to control of weight gain, even when associated with high-fat diet.

  4. Effects of spinach nitrate on insulin resistance, endothelial dysfunction markers and inflammation in mice with high-fat and high-fructose consumption

    Directory of Open Access Journals (Sweden)

    Ting Li

    2016-09-01

    Full Text Available Background: Insulin resistance, which is associated with an increased risk of cardiovascular morbidity and mortality, has become a leading nutrition problem. Inorganic nitrate enriched in spinach has been demonstrated to reverse the pathological features of insulin resistance and endothelial dysfunction. However, the effects of a direct intake of nitrate-enriched spinach on insulin resistance and endothelial dysfunction have not been studied. Objective: To investigate the effects of spinach nitrate on insulin resistance, lipid metabolism, endothelial function, and inflammation in mice fed with a high-fat and high-fructose diet. Design: A diet intervention of spinach with or without nitrate was performed in mice. A high-fat and high-fructose diet was used to cause insulin resistance, endothelial dysfunction, and inflammation in mice. The impacts of spinach nitrate on lipid profile, insulin resistance, markers of endothelial function, and inflammation were determined in mice. Results: Spinach nitrate improved the vascular endothelial function of the mice with high-fat and high-fructose consumption, as evidenced by the elevated plasma nitrite level, increased serum nitric oxide (NO level and decreased serum ET-1 level after spinach nitrate intervention. Spinach nitrate also reduced serum triglycerides, total cholesterol, and low-density lipoprotein-cholesterol levels and elevated serum high-density lipoprotein-cholesterol levels in the mice fed with a high-fat and high-fructose diet. Mice receiving spinach with 60 mg/kg of nitrate (1.02±0.34 showed a significantly low homeostasis model assessment-insulin resistance index as compared with the model mice (2.05±0.58, which is indicating that spinach nitrate could effectively improve the insulin resistance. In addition, spinach nitrate remarkably decreased the elevated serum C-reactive protein, tumor necrosis factor α, and interleukin-6 levels induced by a high-fat and high-fructose diet

  5. Skin mites in mice (Mus musculus): high prevalence of Myobia sp. (Acari, Arachnida) in Robertsonian mice.

    Science.gov (United States)

    Sastre, Natalia; Calvete, Oriol; Martínez-Vargas, Jessica; Medarde, Nuria; Casellas, Joaquim; Altet, Laura; Sánchez, Armand; Francino, Olga; Ventura, Jacint

    2018-05-04

    Myobia sp. and Demodex sp. are two skin mites that infest mice, particularly immunodeficient or transgenic lab mice. In the present study, wild house mice from five localities from the Barcelona Roberstonian system were analysed in order to detect skin mites and compare their prevalence between standard (2n = 40) and Robertsonian mice (2n > 40). We found and identified skin mites through real-time qPCR by comparing sequences from the mitochondrial 16S rRNA and the nuclear 18S rRNA genes since no sequences are available so far using the mitochondrial gene. Fourteen positive samples were identified as Myobia musculi except for a deletion of 296 bp out to 465 bp sequenced, and one sample was identified as Demodex canis. Sampling one body site, the mite prevalence in standard and Robertsonian mice was 0 and 26%, respectively. The malfunction of the immune system elicits an overgrowth of skin mites and consequently leads to diseases such as canine demodicosis in dogs or rosacea in humans. In immunosuppressed mice, the probability of developing demodicosis is higher than in healthy mice. Since six murine toll-like receptors (TLRs) are located in four chromosomes affected by Robertsonian fusions, we cannot dismiss that differences in mite prevalence could be the consequence of the interruption of TLR function. Although ecological and/or morphological factors cannot be disregarded to explain differences in mite prevalence, the detection of translocation breakpoints in TLR genes or the analysis of TLR gene expression are needed to elucidate how Robertsonian fusions affect the immune system in mice.

  6. Plasma adiponectin is increased in mice selectively bred for high wheel-running activity, but not by wheel running per se

    NARCIS (Netherlands)

    Vaanholt, L. M.; Meerlo, P.; Garland, T.; Visser, G. H.; van Dijk, G.

    2007-01-01

    Mice selectively bred for high wheel-running activity (S) have decreased fat content compared to mice from randomly bred control (C) lines. We explored whether this difference was associated with alterations in levels of circulating hormones involved in regulation of food intake and energy balance,

  7. Serum steroid levels in intact and endocrine ablated BALB/c nude mice and their intact littermates

    DEFF Research Database (Denmark)

    Brünner, N; Svenstrup, B; Spang-Thomsen, M

    1986-01-01

    An investigation was made of the serum steroid levels found in intact and endocrine ablated nude mice of both sexes and in their intact homozygous littermates. The results showed that nude mice have a normal steroidogenesis, but with decreased levels of circulating steroids compared to those...

  8. Effects of puerarin on lipid accumulation and metabolism in high-fat diet-fed mice.

    Directory of Open Access Journals (Sweden)

    Guodong Zheng

    Full Text Available In order to investigate the mechanisms by which puerarin from kudzu root extract regulates lipid metabolism, fifty mice were randomly assigned to five groups: normal diet, high-fat diet (HFD, and HFD containing 0.2%, 0.4% or 0.8% puerarin for 12 weeks. Body weight, intraperitioneal adipose tissue (IPAT weight, serum biochemical parameters, and hepatic and feces lipids were measured. Activity and mRNA and protein expressions of hepatic lipid metabolism-related enzymes were analyzed. Compared with HFD, 0.4% and 0.8% puerarin significantly decreased body and IPAT weight. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, triglycerides and leptin in mice fed the 0.4% and 0.8% puerarin diets compared with HFD. Fatty acid synthase activity was suppressed in mice fed the 0.4% and 0.8% puerarin diets, while the activities of AMP-activated protein kinase (AMPK, carnitine acyltransferase (CAT and hormone-sensitive lipase (HSL were increased. mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ 2 was down-regulated in liver of mice fed the 0.8% diet compared with HFD, while mRNA expression of CAT and HSL was considerably up-regulated by 0.4% and 0.8% puerarin diets. The protein expression of PPARγ2 in liver was decreased and those of p-AMPK, HSL and p-HSL were increased in mice fed 0.4% and 0.8% puerarin diets. These results suggest that > 0.4% puerarin influenced the activity, mRNA and protein levels of hepatic lipid metabolism-related enzymes, decreasing serum and liver lipids, body weight gain and fat accumulation. Puerarin might be beneficial to prevent lifestyle-related diseases.

  9. Modulation of neurological related allergic reaction in mice exposed to low-level toluene

    International Nuclear Information System (INIS)

    Tin-Tin-Win-Shwe; Yamamoto, Shoji; Nakajima, Daisuke; Furuyama, Akiko; Fukushima, Atsushi; Ahmed, Sohel; Goto, Sumio; Fujimaki, Hidekazu

    2007-01-01

    The contributing role of indoor air pollution to the development of allergic disease has become increasingly evident in public health problems. It has been reported that extensive communication exists between neurons and immune cells, and neurotrophins are molecules potentially responsible for regulating and controlling this neuroimmune crosstalk. The adverse effects of volatile organic compounds which are main indoor pollutants on induction or augmentation of neuroimmune interaction have not been fully characterized yet. To investigate the effects of low-level toluene inhalation on the airway inflammatory responses, male C3H mice were exposed to filtered air (control), 9 ppm, and 90 ppm toluene for 30 min by nose-only inhalation on Days 0, 1, 2, 7, 14, 21, and 28. Some groups of mice were injected with ovalbumin intraperitoneally before starting exposure schedule and these mice were then challenged with aerosolized ovalbumin as booster dose. For analysis of airway inflammation, bronchoalveolar lavage (BAL) fluid were collected to determine inflammatory cell influx and lung tissue and blood samples were collected to determine cytokine and neurotrophin mRNA and protein expressions and plasma antibody titers using real-time RT-PCR and ELISA methods respectively. Exposure of the ovalbumin-immunized mice to low-level toluene resulted in (1) increased inflammatory cells infiltration in BAL fluid; (2) increased IL-5 mRNA, decreased nerve growth factor receptor tropomyosin-related kinase A and brain-derived neurotrophic factor mRNAs in lung; and (3) increased IgE and IgG 1 antibodies and nerve growth factor content in the plasma. These findings suggest that low-level toluene exposure aggravates the airway inflammatory responses in ovalbumin-immunized mice by modulating neuroimmune crosstalk

  10. Temporal changes in nutritional state affect hypothalamic POMC peptide levels independently of leptin in adult male mice.

    Science.gov (United States)

    Mercer, Aaron J; Stuart, Ronald C; Attard, Courtney A; Otero-Corchon, Veronica; Nillni, Eduardo A; Low, Malcolm J

    2014-04-15

    Hypothalamic proopiomelanocortin (POMC) neurons constitute a critical anorexigenic node in the central nervous system (CNS) for maintaining energy balance. These neurons directly affect energy expenditure and feeding behavior by releasing bioactive neuropeptides but are also subject to signals directly related to nutritional state such as the adipokine leptin. To further investigate the interaction of diet and leptin on hypothalamic POMC peptide levels, we exposed 8- to 10-wk-old male POMC-Discosoma red fluorescent protein (DsRed) transgenic reporter mice to either 24-48 h (acute) or 2 wk (chronic) food restriction, high-fat diet (HFD), or leptin treatment. Using semiquantitative immunofluorescence and radioimmunoassays, we discovered that acute fasting and chronic food restriction decreased the levels of adrenocorticotropic hormone (ACTH), α-melanocyte-stimulating hormone (α-MSH), and β-endorphin in the hypothalamus, together with decreased DsRed fluorescence, compared with control ad libitum-fed mice. Furthermore, acute but not chronic HFD or leptin administration selectively increased α-MSH levels in POMC fibers and increased DsRed fluorescence in POMC cell bodies. HFD and leptin treatments comparably increased circulating leptin levels at both time points, suggesting that transcription of Pomc and synthesis of POMC peptide products are not modified in direct relation to the concentration of plasma leptin. Our findings indicate that negative energy balance persistently downregulated POMC peptide levels, and this phenomenon may be partially explained by decreased leptin levels, since these changes were blocked in fasted mice treated with leptin. In contrast, sustained elevation of plasma leptin by HFD or hormone supplementation did not significantly alter POMC peptide levels, indicating that enhanced leptin signaling does not chronically increase Pomc transcription and peptide synthesis.

  11. Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

    Science.gov (United States)

    Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

    2005-09-08

    It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

  12. Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.

    Science.gov (United States)

    McDermott, Carmel M; Liu, Dan; Ade, Catherine; Schrader, Laura A

    2015-02-01

    Females experience depression, posttraumatic stress disorder (PTSD), and anxiety disorders at approximately twice the rate of males, but the mechanisms underlying this difference remain undefined. The effect of sex hormones on neural substrates presents a possible mechanism. We investigated the effect of ovariectomy at two ages, before puberty and in adulthood, and 17β-estradiol (E2) replacement administered chronically in drinking water on anxiety level, fear memory formation, and extinction. Based on previous studies, we hypothesized that estradiol replacement would impair fear memory formation and enhance extinction rate. Females, age 4 weeks and 10 weeks, were divided randomly into 4 groups; sham surgery, OVX, OVX+low E2 (200nM), and OVX+high E2 (1000nM). Chronic treatment with high levels of E2 significantly increased anxiety levels measured in the elevated plus maze. In both age groups, high levels of E2 significantly increased contextual fear memory but had no effect on cued fear memory. In addition, high E2 decreased the rate of extinction in both ages. Finally, catechol-O-methyltransferase (COMT) is important for regulation of catecholamine levels, which play a role in fear memory formation and extinction. COMT expression in the hippocampus was significantly reduced by high E2 replacement, implying increased catecholamine levels in the hippocampus of high E2 mice. These results suggest that estradiol enhanced fear memory formation, and inhibited fear memory extinction, possibly stabilizing the fear memory in female mice. This study has implications for a neurobiological mechanism for PTSD and anxiety disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

    Science.gov (United States)

    Mason, Julie K; Kharotia, Shikhil; Wiggins, Ashleigh K A; Kitson, Alex P; Chen, Jianmin; Bazinet, Richard P; Thompson, Lilian U

    2014-08-01

    Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.

  14. Neurotoxicity of low bisphenol A (BPA) exposure for young male mice: Implications for children exposed to environmental levels of BPA

    International Nuclear Information System (INIS)

    Zhou, Yuanxiu; Wang, Zhouyu; Xia, Minghan; Zhuang, Siyi; Gong, Xiaobing; Pan, Jianwen; Li, Chuhua; Fan, Ruifang; Pang, Qihua; Lu, Shaoyou

    2017-01-01

    To investigate the neuron toxicities of low-dose exposure to bisphenol A (BPA) in children, mice were used as an animal model. We examined brain cell damage and the effects of learning and memory ability after BPA exposure in male mice (4 weeks of age) that were divided into four groups and chronically received different BPA treatments for 8 weeks. The comet assay and hippocampal neuron counting were used to detect the brain cell damage. The Y-maze test was applied to test alterations in learning and memory ability. Long term potentiation induction by BPA exposure was performed to study the potential mechanism of performance. The percentages of tail DNA, tail length and tail moment in brain cells increased with increasing BPA exposure concentrations. Significant differences in DNA damage were observed among the groups, including between the low-dose and control groups. In the Y-maze test, the other three groups qualified for the learned standard one day earlier than the high-exposed group. Furthermore, the ratio of qualified mice in the high-exposed group was always the lowest among the groups, indicating that high BPA treatment significantly altered the spatial memory performance of mice. Different BPA treatments exerted different effects on the neuron numbers of different regions in the hippocampus. In the CA1 region, the high-exposed group had a significant decrease in neuron numbers. A non-monotonic relationship was observed between the exposure concentrations and neuron quantity in the CA3 region. The hippocampal slices in the control and medium-exposed groups generated long-term potentiation after induction by theta burst stimulation, but the low-exposed group did not. A significant difference was observed between the control and low-exposed groups. In conclusion, chronic exposure to a low level of BPA had adverse effects on brain cells and altered the learning and memory ability of adolescent mice. - Highlights: • Low dose BPA exposure could lead to DNA

  15. [Pulsatilla decoction inhibits vulvovaginal Candida albicans proliferation and reduces inflammatory cytokine levels in vulvovaginal candidiasis mice].

    Science.gov (United States)

    Xia, Dan; Zhang, Mengxiang; Shi, Gaoxiang; Xu, Zhiqing; Wu, Daqiang; Shao, Jing; Wang, Tianming; Wang, Changzhong

    2016-02-01

    To explore the possible regulatory effect of Pulsatilla decoction on Th17 cells and inflammatory cytokines of vulvovaginal candidiasis (VVC) mice. Seventy-two female Kunming mice were randomly assigned into six groups: a blank control group, a VVC model group, a fluconazole group and three Pulsatilla decoction groups (dose levels: 22.5, 15.0 and 7.5 g/kg, respectively). The VVC mouse models were established by vaginal inoculation with Candida albicans (C. albicans) in female mice in pseudoestrus state caused by estradiol injection. After 7-day treatment on VVC mice, the vaginal C. albicans burden was assessed using dilution spread plate method; the vaginal C. albicans morphology was observed by Gram staining method; the levels of interleukin 6 (IL-6), IL-17, IL-21 and tumor necrosis factor α (TNF-α) in sera were detected by ELISA. The content of the transcription factor retinoid related orphan receptor gamma t (RORγt) in vaginal tissues was detected by immunohistochemistry. The VVC mouse models were successfully developed. After treatment, the vaginal C. albicans burden of the fluconazole group and 22.5 g/kg Pulsatilla decoction group dropped significantly compared with that of the VVC model group. Gram staining showed that the VVC mice had lots of C. albicans hyphae in vaginal discharge, that 7.5 g/kg Pulsatilla decoction group remained the mycelia-phase C. albicans, and that 15.0 g/kg Pulsatilla decoction group had the majority of yeast-phase C. albicans and a few of mycelia-phase, while no hyphae and only very few of yeast-phase C. albicans were observed in 22.5 g/kg Pulsatilla decoction group and fluconazole group. After 7-day treatment, compared with the model group, the levels of IL-6, IL- 17, IL-21 and TNF-α in the sera of the fluconazole group, 15.0 and 22.5 g/kg Pulsatilla decoction groups were reduced significantly and the levels of RORγt in the vaginal tissues of the fluconazole group, 15.0 and 22.5 g/kg Pulsatilla decoction groups also decreased

  16. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent.

    Science.gov (United States)

    Tetri, Laura H; Basaranoglu, Metin; Brunt, Elizabeth M; Yerian, Lisa M; Neuschwander-Tetri, Brent A

    2008-11-01

    The aims of this study were to determine whether combining features of a western lifestyle in mice with trans fats in a high-fat diet, high-fructose corn syrup in the water, and interventions designed to promote sedentary behavior would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH). Male C57BL/6 mice fed ad libitum high-fat chow containing trans fats (partially hydrogenated vegetable oil) and relevant amounts of a high-fructose corn syrup (HFCS) equivalent for 1-16 wk were compared with mice fed standard chow or mice with trans fats or HFCS omitted. Cage racks were removed from western diet mice to promote sedentary behavior. By 16 wk, trans fat-fed mice became obese and developed severe hepatic steatosis with associated necroinflammatory changes. Plasma alanine aminotransferase levels increased, as did liver TNF-alpha and procollagen mRNA, indicating an inflammatory and profibrogenic response to injury. Glucose intolerance and impaired fasting glucose developed within 2 and 4 wk, respectively. Plasma insulin, resistin, and leptin levels increased in a profile similar to that seen in patients with NASH. The individual components of this diet contributed to the phenotype independently; isocaloric replacement of trans fats with lard established that trans fats played a major role in promoting hepatic steatosis and injury, whereas inclusion of HFCS promoted food consumption, obesity, and impaired insulin sensitivity. Combining risk factors for the metabolic syndrome by feeding mice trans fats and HFCS induced histological features of NASH in the context of a metabolic profile similar to patients with this disease. Because dietary trans fats promoted liver steatosis and injury, their role in the epidemic of NASH needs further evaluation.

  17. Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior.

    Directory of Open Access Journals (Sweden)

    Markus Wöhr

    Full Text Available Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1(-/- null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1(-/- mice as compared to wildtype Shank1(+/+ littermate controls. Shank1(-/- pups emitted fewer vocalizations than Shank1(+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1(-/- males deposited fewer scent marks in proximity to female urine than Shank1(+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1(+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1(-/- mice were unaffected, indicating a failure of Shank1(-/- males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1(-/- mice are consistent with a phenotype relevant to social communication deficits in autism.

  18. Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

    Science.gov (United States)

    Wöhr, Markus; Roullet, Florence I.; Hung, Albert Y.; Sheng, Morgan; Crawley, Jacqueline N.

    2011-01-01

    Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1 −/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1 −/− mice as compared to wildtype Shank1 +/+ littermate controls. Shank1 −/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1 −/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1 −/− mice were unaffected, indicating a failure of Shank1 −/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1 −/− mice are consistent with a phenotype relevant to social communication deficits in autism. PMID:21695253

  19. SIGWX Charts - High Level Significant Weather

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — High level significant weather (SIGWX) forecasts are provided for the en-route portion of international flights. NOAA's National Weather Service Aviation Center...

  20. Effect of Vaccinium bracteatum Thunb. leaves extract on blood glucose and plasma lipid levels in streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Wang, Li; Zhang, Xue Tong; Zhang, Hai Yan; Yao, Hui Yuan; Zhang, Hui

    2010-08-09

    To investigate the hypoglycemic effects of Vaccinium bracteatum Thunb. leaves (VBTL) extract in streptozotocin-induced diabetic mice. After administration of VBTL extract for 4 weeks, the body weight, organ weight, blood glucose (BG), insulin and plasma lipid levels of streptozotocin-induced diabetic mice were measured. Body weights of diabetic mice treated with VBTL extract were partly recovered. The BG levels of AEG (diabetic mice treated with VBTL aqueous extract) were reduced to 91.52 and 85.82% at week 2 and week 4, respectively (P0.05). The insulin levels of AEG and EEG were obviously higher (P<0.05) than those of MC (diabetic mice in model control group). Comparing with MC, AEG and EEG had significantly lower (P<0.05) TC or TG levels and similar HDL-cholesterol or LDL-cholesterol levels. In comparison with non-diabetic control mice, AEG had similar plasma lipid levels except higher LDL-cholesterol level, while EEG had higher TC, TG and LDL-cholesterol levels and lower HDL-cholesterol levels. Both aqueous and ethanolic extract of VBTL possess a potential hypoglycemic effect in streptozotocin-induced diabetic mice. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.

    Directory of Open Access Journals (Sweden)

    Konstantinos Gkouvatsos

    Full Text Available Hemojuvelin (Hjv is a bone morphogenetic protein (BMP co-receptor involved in the control of systemic iron homeostasis. Functional inactivation of Hjv leads to severe iron overload in humans and mice due to marked suppression of the iron-regulatory hormone hepcidin. To investigate the role of Hjv in body iron sensing, Hjv-/- mice and isogenic wild type controls were placed on a moderately low, a standard or a high iron diet for four weeks. Hjv-/- mice developed systemic iron overload under all regimens. Transferrin (Tf was highly saturated regardless of the dietary iron content, while liver iron deposition was proportional to it. Hepcidin mRNA expression responded to fluctuations in dietary iron intake, despite the absence of Hjv. Nevertheless, iron-dependent upregulation of hepcidin was more than an order of magnitude lower compared to that seen in wild type controls. Likewise, iron signaling via the BMP/Smad pathway was preserved but substantially attenuated. These findings suggest that Hjv is not required for sensing of body iron levels and merely functions as an enhancer for iron signaling to hepcidin.

  2. Effect of aerobic exercise and fish oil supplements on plasma levels of inflammatory indexes in mice

    OpenAIRE

    Alizadeh, Hamid; Bazgir, Behzad; Daryanoosh, Farhad; Koushki, Maryam; Sobhani, Vahid

    2014-01-01

    Background: Exercise has positive and negative effects on immune system. Herein, we would like to investigate the effects of incremental aerobic training and fish oil supplementation on the plasma levels of CRP, CPK and IL-17 in trained mice. One of the major roles of immune system is to produce soluble or cellular components that provide the immunity against inflammatory agent. The purpose of this study is to investigate distinct and combine effects of incremental aerobic training and fish o...

  3. Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice.

    Science.gov (United States)

    McLachlan, Stela; Page, Kathryn E; Lee, Seung-Min; Loguinov, Alex; Valore, Erika; Hui, Simon T; Jung, Grace; Zhou, Jie; Lusis, Aldons J; Fuqua, Brie; Ganz, Tomas; Nemeth, Elizabeta; Vulpe, Chris D

    2017-11-01

    Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin ( Hamp1 ) mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Two studies were done: first, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 mRNA and plasma hepcidin levels in both sexes and iron levels in the heart, kidneys, liver, pancreas, and spleen in males were measured in nine inbred/recombinant inbred strains raised on an iron-sufficient or high-iron diet. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). However, liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice fed iron-sufficient or high-iron diets, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. We also measured plasma erythroferrone, performed RNA-sequencing analysis of liver samples from six inbred strains fed the iron-sufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. NEW & NOTEWORTHY Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). Liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least

  4. Recovering method for high level radioactive material

    International Nuclear Information System (INIS)

    Fukui, Toshiki

    1998-01-01

    Offgas filters such as of nuclear fuel reprocessing facilities and waste control facilities are burnt, and the burnt ash is melted by heating, and then the molten ashes are brought into contact with a molten metal having a low boiling point to transfer the high level radioactive materials in the molten ash to the molten metal. Then, only the molten metal is evaporated and solidified by drying, and residual high level radioactive materials are recovered. According to this method, the high level radioactive materials in the molten ashes are transferred to the molten metal and separated by the difference of the distribution rate of the molten ash and the molten metal. Subsequently, the molten metal to which the high level radioactive materials are transferred is heated to a temperature higher than the boiling point so that only the molten metal is evaporated and dried to be removed, and residual high level radioactive materials are recovered easily. On the other hand, the molten ash from which the high level radioactive material is removed can be discarded as ordinary industrial wastes as they are. (T.M.)

  5. Prevention and reversal of hepatic steatosis with a high-protein diet in mice

    NARCIS (Netherlands)

    Garcia-Caraballo, Sonia C.; Comhair, Tine M.; Verheyen, Fons; Gaemers, Ingrid; Schaap, Frank G.; Houten, Sander M.; Hakvoort, Theodorus B. M.; Dejong, Cornelis H. C.; Lamers, Wouter H.; Koehler, S. Eleonore

    2013-01-01

    The hallmark of NAFLD is steatosis of unknown etiology. We tested the effect of a high-protein (HP)(2) diet on diet-induced steatosis in male C57BL/6 mice with and without pre-existing fatty liver. Mice were fed all combinations of semisynthetic low-fat (LF) or high-fat (HF) and low-protein (LP) or

  6. Effects of leptin treatment and Western diet on wheel running in selectively bred high runner mice.

    Science.gov (United States)

    Meek, Thomas H; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

    2012-05-15

    The role of leptin in regulating physical activity is varied. The behavioral effects of leptin signaling depend on the type of activity and the animal's physiological state. We used mice from lines selectively bred for high voluntary wheel running to further study how leptin regulates volitional exercise. Mice from four replicate high runner (HR) lines typically run ~3-fold more revolutions per day than those from four non-selected control (C) lines. HR mice have altered dopamine function and differences from C in brain regions known to be important in leptin-mediated behavior. Furthermore, male HR mice have been found to dramatically increase running when administered Western diet, an effect possibly mediated through leptin signaling. Male mice from generation 61 (representing three HR lines and one C line) were allowed wheel access at 24 days of age and given either Western diet (high in fat and with added sucrose) or standard chow. After four weeks, Western diet significantly increased circulating leptin, insulin, C-peptide, gastric inhibitory polypeptide, and inflammatory hormone resistin concentrations in HR mice (C mice not measured). Western diet increased running in HR mice, but did not significantly affect running in C mice. During the fifth week, all mice received two days of intra-peritoneal sham injections (physiological saline) followed by three days of murine recombinant leptin injections, and then another six days of sham injections. Leptin treatment significantly decreased caloric intake (adjusted for body mass) and body mass in all groups. Wheel running significantly increased with leptin injections in HR mice (fed Western or standard diet), but was unaffected in C mice. Whether Western diet and leptin treatment stimulate wheel running in HR mice through the same physiological pathways awaits future study. These results have implications for understanding the neural and endocrine systems that control locomotor activity, food consumption, and body

  7. High LDL levels lead to increased synovial inflammation and accelerated ectopic bone formation during experimental osteoarthritis

    NARCIS (Netherlands)

    Munter, W. de; Bosch, M.H. van den; Sloetjes, A.W.; Croce, K.J.; Vogl, T.; Roth, J.; Koenders, M.I.; Loo, F.A.J. van de; Berg, W.B. van den; Kraan, P.M. van der; Lent, P.L.E.M. van

    2016-01-01

    OBJECTIVE: A relation between osteoarthritis (OA) and increased cholesterol levels is apparent. In the present study we investigate OA pathology in apolipoprotein E (ApoE)(-)(/-) mice with and without a cholesterol-rich diet, a model for high systemic low density lipoprotein (LDL) cholesterol levels

  8. Serotonin Improves High Fat Diet Induced Obesity in Mice.

    Directory of Open Access Journals (Sweden)

    Hitoshi Watanabe

    Full Text Available There are two independent serotonin (5-HT systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

  9. Serotonin Improves High Fat Diet Induced Obesity in Mice.

    Science.gov (United States)

    Watanabe, Hitoshi; Nakano, Tatsuya; Saito, Ryo; Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

    2016-01-01

    There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

  10. Disposal of high level and intermediate level radioactive wastes

    International Nuclear Information System (INIS)

    Flowers, R.H.

    1991-01-01

    The waste products from the nuclear industry are relatively small in volume. Apart from a few minor gaseous and liquid waste streams, containing readily dispersible elements of low radiotoxicity, all these products are processed into stable solid packages for disposal in underground repositories. Because the volumes are small, and because radioactive wastes are latecomers on the industrial scene, a whole new industry with a world-wide technological infrastructure has grown up alongside the nuclear power industry to carry out the waste processing and disposal to very high standards. Some of the technical approaches used, and the Regulatory controls which have been developed, will undoubtedly find application in the future to the management of non-radioactive toxic wastes. The repository site outlined would contain even high-level radioactive wastes and spent fuels being contained without significant radiation dose rates to the public. Water pathway dose rates are likely to be lowest for vitrified high-level wastes with spent PWR fuel and intermediate level wastes being somewhat higher. (author)

  11. Current high-level waste solidification technology

    International Nuclear Information System (INIS)

    Bonner, W.F.; Ross, W.A.

    1976-01-01

    Technology has been developed in the U.S. and abroad for solidification of high-level waste from nuclear power production. Several processes have been demonstrated with actual radioactive waste and are now being prepared for use in the commercial nuclear industry. Conversion of the waste to a glass form is favored because of its high degree of nondispersibility and safety

  12. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

    Energy Technology Data Exchange (ETDEWEB)

    Kanno, Ayumi, E-mail: akanno@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Asahara, Shun-ichiro, E-mail: asahara@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Masuda, Katsuhisa, E-mail: katsuhisa.m.0707@gmail.com [Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142 (Japan); Matsuda, Tomokazu, E-mail: tomokazu@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Kimura-Koyanagi, Maki, E-mail: koyanagi@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Seino, Susumu, E-mail: seino@med.kobe-u.ac.jp [Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0047 (Japan); Ogawa, Wataru, E-mail: ogawa@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Kido, Yoshiaki, E-mail: kido@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142 (Japan)

    2015-03-13

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets.

  13. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

    International Nuclear Information System (INIS)

    Kanno, Ayumi; Asahara, Shun-ichiro; Masuda, Katsuhisa; Matsuda, Tomokazu; Kimura-Koyanagi, Maki; Seino, Susumu; Ogawa, Wataru; Kido, Yoshiaki

    2015-01-01

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets

  14. High-Level Application Framework for LCLS

    Energy Technology Data Exchange (ETDEWEB)

    Chu, P; Chevtsov, S.; Fairley, D.; Larrieu, C.; Rock, J.; Rogind, D.; White, G.; Zalazny, M.; /SLAC

    2008-04-22

    A framework for high level accelerator application software is being developed for the Linac Coherent Light Source (LCLS). The framework is based on plug-in technology developed by an open source project, Eclipse. Many existing functionalities provided by Eclipse are available to high-level applications written within this framework. The framework also contains static data storage configuration and dynamic data connectivity. Because the framework is Eclipse-based, it is highly compatible with any other Eclipse plug-ins. The entire infrastructure of the software framework will be presented. Planned applications and plug-ins based on the framework are also presented.

  15. Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate.

    Science.gov (United States)

    Bondulich, Marie K; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy; Hanger, Diane P

    2016-08-01

    Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. © The Author (2016). Published by

  16. Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate

    Science.gov (United States)

    Bondulich, Marie K.; Guo, Tong; Meehan, Christopher; Manion, John; Rodriguez Martin, Teresa; Mitchell, Jacqueline C.; Hortobagyi, Tibor; Yankova, Natalia; Stygelbout, Virginie; Brion, Jean-Pierre; Noble, Wendy

    2016-01-01

    Abstract Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter. Most existing mouse models of tauopathy overexpress mutant tau at levels that do not occur in human neurodegenerative disease, whereas Tau35 transgene expression is equivalent to less than 10% of that of endogenous mouse tau. Tau35 mice recapitulate key features of human tauopathies, including aggregated and abnormally phosphorylated tau, progressive cognitive and motor deficits, autophagic/lysosomal dysfunction, loss of synaptic protein, and reduced life-span. Importantly, we found that sodium 4-phenylbutyrate (Buphenyl®), a drug used to treat urea cycle disorders and currently in clinical trials for a range of neurodegenerative diseases, reverses the observed abnormalities in tau and autophagy, behavioural deficits, and loss of synapsin 1 in Tau35 mice. Our results show for the first time that, unlike other tau transgenic mouse models, minimal expression of a human disease-associated tau fragment in Tau35 mice causes a profound and progressive tauopathy and cognitive changes, which are rescued by pharmacological intervention using a clinically approved drug. These novel Tau35 mice therefore represent a highly disease-relevant animal model in which to investigate molecular mechanisms and to develop novel treatments for human tauopathies. PMID:27297240

  17. High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation[S

    Science.gov (United States)

    McGrath, Kristine C.; Li, Xiao Hong; Whitworth, Phillippa T.; Kasz, Robert; Tan, Joanne T.; McLennan, Susan V.; Celermajer, David S.; Barter, Philip J.; Rye, Kerry-Anne; Heather, Alison K.

    2014-01-01

    Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation. PMID:24347528

  18. Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High or Low Ethanol Preference

    Science.gov (United States)

    Lopez, Marcelo F.; Grahame, Nicholas J.; Becker, Howard C.

    2010-01-01

    did not change from baseline levels of intake. In contrast, HAP-2 females and LAP-2 mice of both sexes did not show changes in ethanol intake as a consequence of intermittent ethanol exposure. Conclusions Overall, these results indicate that the magnitude of ethanol withdrawal-related seizures is inversely related to inherited ethanol intake preference. Additionally, intermittent ethanol vapor exposure appears more likely to affect high-drinking mice (C57BL/6J and HAP-2) than low drinkers, even though these animals are less affected by ethanol withdrawal. PMID:21314693

  19. Anti-Diabetic Effects of Phenolic Extract from Rambutan Peels (Nephelium lappaceum) in High-Fat Diet and Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Ma, Qingyu; Guo, Yan; Sun, Liping; Zhuang, Yongliang

    2017-07-26

    Recent studies have shown that rambutan peel phenolic (RPP) extract demonstrate high antioxidant and antiglycation activities in vitro and in vivo. This study further evaluated the anti-diabetic activity of RPP in a mouse model of Type II diabetes induced by streptozotocin combined with high-fat diet. Results showed that RPP increased the body weight and reduced the fasting blood glucose level of the diabetic mice. RPP significantly reduced the serum levels of total cholesterol, triglyceride, creatinine, and glycated serum protein in diabetic mice in a dose-dependent manner. Glycogen content in mice liver was recovered by RPP, which further increased the activity of superoxide dismutase and glutathione peroxidase and reduced lipid peroxidation in diabetic mice. Histological analysis showed that RPP effectively protected the tissue structure of the liver, kidney, and pancreas. In addition, RPP decreased the mesangial index and inhibited the expression of TGF-β in the kidney of diabetic mice.

  20. Differential effect of walnut oil and safflower oil on the serum cholesterol level and lesion area in the aortic root of apolipoprotein E-deficient mice.

    Science.gov (United States)

    Iwamoto, Masako; Kono, Misaki; Kawamoto, Daisuke; Tomoyori, Hiroko; Sato, Masao; Imaizumi, Katsumi

    2002-01-01

    Walnut oil (WO) is a good source of alpha-linolenic acid. We compared the effects of WO and high-linoleic safflower oil (HLSO) on the serum lipid level and atherosclerosis development in male and female apolipoprotein (apo) E-deficient mice. The WO diet resulted in a higher level of serum cholesterol than with HLSO. Female mice fed on the WO diet had a greater lesion area in the aortic root than did those on the HLSO diet. There was no diet-dependent difference in the level of cholesterol and its oxidation products in the abdominal and thoracic aorta. These results suggest that the unpleasant effects of the WO diet on apo E-deficient mice may be attributable to alpha-linolenic acid.

  1. Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Rubin, Edward M.

    2002-09-15

    Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies have provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.

  2. Effects of exercise on depressive behavior and striatal levels of norepinephrine, serotonin and their metabolites in sleep-deprived mice.

    Science.gov (United States)

    Daniele, Thiago Medeiros da Costa; de Bruin, Pedro Felipe Carvalhedo; Rios, Emiliano Ricardo Vasconcelos; de Bruin, Veralice Meireles Sales

    2017-08-14

    Exercise is a promising adjunctive therapy for depressive behavior, sleep/wake abnormalities, cognition and motor dysfunction. Conversely, sleep deprivation impairs mood, cognition and functional performance. The objective of this study is to evaluate the effects of exercise on anxiety and depressive behavior and striatal levels of norepinephrine (NE), serotonin and its metabolites in mice submitted to 6h of total sleep deprivation (6h-TSD) and 72h of Rapid Eye Movement (REM) sleep deprivation (72h-REMSD). Experimental groups were: (1) mice submitted to 6h-TSD by gentle handling; (2) mice submitted to 72h-REMSD by the flower pot method; (3) exercise (treadmill for 8 weeks); (4) exercise followed by 6h-TSD; (5) exercise followed by 72h-REMSD; (6) control (home cage). Behavioral tests included the Elevated Plus Maze and tail-suspension. NE, serotonin and its metabolites were determined in the striatum using high-performance liquid chromatography (HPLC). Sleep deprivation increased depressive behavior (time of immobilization in the tail-suspension test) and previous exercise hindered it. Sleep deprivation increased striatal NE and previous exercise reduced it. Exercise only was associated with higher levels of serotonin. Furthermore, exercise reduced serotonin turnover associated with sleep deprivation. In brief, previous exercise prevented depressive behavior and reduced striatal high NE levels and serotonin turnover. The present findings confirm the effects of exercise on behavior and neurochemical alterations associated with sleep deprivation. These findings provide new avenues for understanding the mechanisms of exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Silymarin alleviates hepatic oxidative stress and protects against metabolic disorders in high-fat diet-fed mice.

    Science.gov (United States)

    Feng, Bin; Meng, Ran; Huang, Bin; Shen, Shanmei; Bi, Yan; Zhu, Dalong

    2016-01-01

    Silymarin is a potent antioxidant medicine and has been widely used for the treatment of liver diseases over 30 years. Recent studies suggest that silymarin may benefit patients with glucose intolerance. However, the mechanism underlying the action of silymarin is not clarified. The aim of this work was to assess the impact of silymarin on glucose intolerance in high-fat diet (HFD)-fed mice, and explore the potential therapeutic mechanisms. C57BL/6 mice were fed with HFD for 12 weeks, randomized, and treated orally with vehicle saline or silymarin (30 mg/kg) daily for 30 days. We found that silymarin significantly improved HFD-induced body weight gain, glucose intolerance, and insulin resistance in mice. Silymarin treatment reduced HFD-increased oxidative stress indicators (reactive oxygen species, lipid peroxidation, protein oxidation) and restored HFD-down-regulated activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) in the plasma and/or liver of the HFD-fed mice. Furthermore, silymarin decreased HFD-up-regulated hepatic NADPH oxidase expression and NF-κB activation in mice. Additionally, silymarin treatment mitigated HFD-increased plasma IL-1β, TNF-α levels, and HFD-enhanced hepatic NO, TLR4, and iNOS expression in mice. These novel data indicate that silymarin has potent anti-diabetic actions through alleviating oxidative stress and inflammatory response, partially by inhibiting hepatic NADPH oxidase expression and the NF-κB signaling.

  4. Blueberry supplementation improves memory in middle-aged mice fed a high-fat diet.

    Science.gov (United States)

    Carey, Amanda N; Gomes, Stacey M; Shukitt-Hale, Barbara

    2014-05-07

    Consuming a high-fat diet may result in behavioral deficits similar to those observed in aging animals. It has been demonstrated that blueberry supplementation can allay age-related behavioral deficits. To determine if supplementation of a high-fat diet with blueberries offers protection against putative high-fat diet-related declines, 9-month-old C57Bl/6 mice were maintained on low-fat (10% fat calories) or high-fat (60% fat calories) diets with and without 4% freeze-dried blueberry powder. Novel object recognition memory was impaired by the high-fat diet; after 4 months on the high-fat diet, mice spent 50% of their time on the novel object in the testing trial, performing no greater than chance performance. Blueberry supplementation prevented recognition memory deficits after 4 months on the diets, as mice on this diet spent 67% of their time on the novel object. After 5 months on the diets, mice consuming the high-fat diet passed through the platform location less often than mice on low-fat diets during probe trials on days 2 and 3 of Morris water maze testing, whereas mice consuming the high-fat blueberry diet passed through the platform location as often as mice on the low-fat diets. This study is a first step in determining if incorporating more nutrient-dense foods into a high-fat diet can allay cognitive dysfunction.

  5. EAP high-level product architecture

    DEFF Research Database (Denmark)

    Guðlaugsson, Tómas Vignir; Mortensen, Niels Henrik; Sarban, Rahimullah

    2013-01-01

    EAP technology has the potential to be used in a wide range of applications. This poses the challenge to the EAP component manufacturers to develop components for a wide variety of products. Danfoss Polypower A/S is developing an EAP technology platform, which can form the basis for a variety...... of EAP technology products while keeping complexity under control. High level product architecture has been developed for the mechanical part of EAP transducers, as the foundation for platform development. A generic description of an EAP transducer forms the core of the high level product architecture...... the function of the EAP transducers to be changed, by basing the EAP transducers on a different combination of organ alternatives. A model providing an overview of the high level product architecture has been developed to support daily development and cooperation across development teams. The platform approach...

  6. Beneficial effects of Allium sativum L. stem extract on lipid metabolism and antioxidant status in obese mice fed a high-fat diet.

    Science.gov (United States)

    Kim, Inhye; Kim, Haeng-Ran; Kim, Jae-Hyun; Om, Ae-Son

    2013-08-30

    This study was designed to examine the potential health benefits of Allium sativum L. (garlic) stem extract (ASSE) on obesity and related disorders in high-fat diet-induced obese mice. Obese mice were orally administered ASSE at doses of 100, 250 and 500 mg kg(-1) body weight day(-1) for 4 weeks. Consumption of ASSE significantly suppressed body weight gain and white adipose tissue (WAT) weight regardless of daily food intake. Obese mice fed ASSE also exhibited a significant decrease in WAT cell size. The decreased level of adiponectin and increased level of leptin in obese mice reverted to near normal mice levels in ASSE-treated mice. ASSE administration significantly improved lipid parameters of the serum and liver and inhibited fat accumulation in the liver by modulating the activities of hepatic lipid-regulating enzymes in obese mice. Administration of ASSE also led to significant increases in antioxidant enzymes and suppressed glutathione depletion and lipid peroxidation in hepatic tissue. These results suggest that ASSE may ameliorate obesity, insulin resistance and oxidative damage in high-fat diet-induced obese mice. © 2013 Society of Chemical Industry.

  7. Activity test of various mangosteen (Garcinia mangostana pericarp extract fractions to decrease fasting blood cholesterol levels and lipid peroxidation activity in diabetic mice

    Directory of Open Access Journals (Sweden)

    Saikhu Akhmad Husen

    2017-01-01

    Full Text Available The objectives of this study were to determine the effect of various fractions of mangosteen (Garcinia mangostana pericarp extract to the changes of the fasting blood cholesterol and serum malondialdehyde (MDA levels on diabetic mice (Mus musculus. Thirty 3-4 months old male mice strain BALB/c, weight 20-30 g were divided into six groups. The first group was KN as a non diabetic control group, KD as a diabetic control, KM as a group of diabetic mice treated with metformin, and NP, SP, and P as the treatment groups that were treated by using three different fractions from mangosteen pericarp extract, non polar, semi polar, and polar respectively. The induction of Diabetes mellitus was done by the injection of STZ, and the mice were given a high fat diet treatment to induce the hiperlipidemia condition using lard for three weeks. The blood cholesterol levels were measured in all groups before and after the injection of lard, and day 1, 7, and 14 of treatment as well. The serum MDA level as the indicator of lipid peroxidation were measured by using QuantiChrom TBARS Assay Kit (DTBA-100. The data of cholesterol levels were statistically analyzed by t-test, while the data of serum MDA levels were analyzed by variance analysis followed by Duncan test. The results showed that the polar fraction of mangosteen pericarp had effect to decrease the fasting blood cholesterol level in mice, however the non polar and semi polar fraction had no simmilar effect. All of the fractions has shown significant effect to decrease the serum MDA level in mice. Key words: cholesterol, diabetes mellitus, Garcinia mangostana, malondialdehyde (mda, obesity.

  8. Differential sensitivity of long-sleep and short-sleep mice to high doses of cocaine.

    Science.gov (United States)

    de Fiebre, C M; Ruth, J A; Collins, A C

    1989-12-01

    The cocaine sensitivity of male and female long-sleep (LS) and short-sleep (SS) mice, which have been selectively bred for differential ethanol-induced "sleep-time," was examined in a battery of behavioral and physiological tests. Differences between these two mouse lines were subtle and were seen primarily at high doses. At high doses, SS mice were more sensitive than LS mice, particularly to cocaine-induced hypothermia; however, significant hypothermia was not seen except at doses which were very near to the seizure threshold. During a 60-min test of locomotor activity, LS mice showed greater stimulation of Y-maze activity by 20 mg/kg cocaine than SS mice. Consistent with the finding of subtle differences in sensitivity to low doses of cocaine. LS and SS mice did not differ in sensitivity to cocaine inhibition of synaptosomal uptake of [3H]-dopamine, [3H]-norepinephrine or [3H]-5-hydroxytryptamine. However, consistent with the finding of differential sensitivity to high doses of cocaine, SS mice were more sensitive to the seizure-producing effects of the cocaine and lidocaine, a local anesthetic. It is hypothesized that the differential sensitivity of these mouse lines to high doses of cocaine is due to differential sensitivity to cocaine's actions on systems that regulate local anesthetic effects. Selective breeding for differential duration of alcohol-induced "sleep-time" may have resulted in differential ion channel structure or function in these mice.

  9. Decreased levels of free D-aspartic acid in the forebrain of serine racemase (Srr) knock-out mice.

    Science.gov (United States)

    Horio, Mao; Ishima, Tamaki; Fujita, Yuko; Inoue, Ran; Mori, Hisashi; Hashimoto, Kenji

    2013-05-01

    d-Serine, an endogenous co-agonist of the N-methyl-d-aspartate (NMDA) receptor is synthesized from l-serine by serine racemase (SRR). A previous study of Srr knockout (Srr-KO) mice showed that levels of d-serine in forebrain regions, such as frontal cortex, hippocampus, and striatum, but not cerebellum, of mutant mice are significantly lower than those of wild-type (WT) mice, suggesting that SRR is responsible for d-serine production in the forebrain. In this study, we attempted to determine whether SRR affects the level of other amino acids in brain tissue. We found that tissue levels of d-aspartic acid in the forebrains (frontal cortex, hippocampus and striatum) of Srr-KO mice were significantly lower than in WT mice, whereas levels of d-aspartic acid in the cerebellum were not altered. Levels of d-alanine, l-alanine, l-aspartic acid, taurine, asparagine, arginine, threonine, γ-amino butyric acid (GABA) and methionine, remained the same in frontal cortex, hippocampus, striatum and cerebellum of WT and mutant mice. Furthermore, no differences in d-aspartate oxidase (DDO) activity were detected in the forebrains of WT and Srr-KO mice. These results suggest that SRR and/or d-serine may be involved in the production of d-aspartic acid in mouse forebrains, although further detailed studies will be necessary to confirm this finding. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. The management of high-level radioactive wastes

    International Nuclear Information System (INIS)

    Lennemann, Wm.L.

    1979-01-01

    The definition of high-level radioactive wastes is given. The following aspects of high-level radioactive wastes' management are discussed: fuel reprocessing and high-level waste; storage of high-level liquid waste; solidification of high-level waste; interim storage of solidified high-level waste; disposal of high-level waste; disposal of irradiated fuel elements as a waste

  11. A herbal medicine, saikokaryukotsuboreito, improves serum testosterone levels and affects sexual behavior in old male mice.

    Science.gov (United States)

    Zang, Zhi Jun; Ji, Su Yun; Dong, Wang; Zhang, Ya Nan; Zhang, Er Hong; Bin, Zhang

    2015-06-01

    Late-onset hypogonadism (LOH) is a clinical syndrome characterized with aging and declined serum testosterone levels. Sexual symptoms are also essential for the diagnosis of LOH. Testosterone replacement therapy is used widely to treat LOH. However, the side effects of it should not be ignored, such as fluid retention, hypertension and spermatogenic suppression. Therefore, alternate treatment modalities have been pursued. Herbal medicines used widely in China have achieved satisfying results with little side effects. Nonetheless, there are few pharmacological researches on them. In this study, 24-month-old mice were used as LOH animal models to explore the pharmacological effects of a herbal medicine, saikokaryukotsuboreito (SKRBT), on serum testosterone levels and sexual functions. Furthermore, the expression of steroidogenic acute regulatory (StAR) protein, a kind of rate-limiting enzyme of testosterone synthesis, was also examined. As a result, SKRBT improved the serum testosterone levels of these mice at a dose of 300 and 450 mg/kg. Multiple measures of sexual behavior were enhanced. The expression of StAR was also increased. Therefore, this study suggested that SKRBT can improve the serum testosterone levels by activating the expression of StAR and might be a viable option to treat sexual symptoms caused by LOH.

  12. Restraint stress in lactating mice alters the levels of sulfur-containing amino acids in milk.

    Science.gov (United States)

    Nishigawa, Takuma; Nagamachi, Satsuki; Ikeda, Hiromi; Chowdhury, Vishwajit S; Furuse, Mitsuhiro

    2018-03-30

    It is well known that maternal stress during the gestation and lactation periods induces abnormal behavior in the offspring and causes a lowering of the offspring's body weight. Various causes of maternal stress during the lactation period, relating to, for example, maternal nutritional status and reduced maternal care, have been considered. However, little is known about the effects on milk of maternal stress during the lactation period. The current study aimed to determine whether free amino acids, with special reference to sulfur-containing amino acids in milk, are altered by restraint stress in lactating mice. The dams in the stress group were restrained for 30 min at postnatal days 2, 4, 6, 8, 10 and 12. Restraint stress caused a reduction in the body weight of lactating mice. The concentration of taurine and cystathionine in milk was significantly higher in the stress group, though stress did not alter their concentration in maternal plasma. The ratio of taurine concentration in milk to its concentration in maternal plasma was significantly higher in the stress group, suggesting that stress promoted taurine transportation into milk. Furthermore, taurine concentration in milk was positively correlated with corticosterone levels in plasma. In conclusion, restraint stress in lactating mice caused the changes in the metabolism and in the transportation of sulfur-containing amino acids and resulted in higher taurine concentration in milk. Taurine concentration in milk could also be a good parameter for determining stress status in dams.

  13. Social isolation after stroke leads to depressive-like behavior and decreased BDNF levels in mice.

    Science.gov (United States)

    O'Keefe, Lena M; Doran, Sarah J; Mwilambwe-Tshilobo, Laetitia; Conti, Lisa H; Venna, Venugopal R; McCullough, Louise D

    2014-03-01

    Social isolation prior to stroke leads to poorer outcomes after an ischemic injury in both animal and human studies. However, the impact of social isolation following stroke, which may be more clinically relevant as a target for therapeutic intervention, has yet to be examined. In this study, we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice. Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety. Therefore, it is important to identify patients who have perceived isolation post-stroke to hopefully prevent this exacerbation of histological damage and subsequent depression. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Polyphenol-Rich Fraction of Ecklonia cava Improves Nonalcoholic Fatty Liver Disease in High Fat Diet-Fed Mice

    Directory of Open Access Journals (Sweden)

    Eun-Young Park

    2015-11-01

    Full Text Available Ecklonia cava (E. cava; CA is an edible brown alga with beneficial effects in diabetes via regulation of various metabolic processes such as lipogenesis, lipolysis, inflammation, and the antioxidant defense system in liver and adipose tissue. We investigated the effect of the polyphenol-rich fraction of E. cava produced from Gijang (G-CA on nonalcoholic fatty liver disease (NAFLD in high-fat diet (HFD-fed mice. C57BL6 mice were fed a HFD for six weeks and then the HFD group was administered 300 mg/kg of G-CA extracts by oral intubation for 10 weeks. Body weight, fat mass, and serum biochemical parameters were reduced by G-CA extract treatment. MRI/MRS analysis showed that liver fat and liver volume in HFD-induced obese mice were reduced by G-CA extract treatment. Further, we analyzed hepatic gene expression related to inflammation and lipid metabolism. The mRNA expression levels of inflammatory cytokines and hepatic lipogenesis-related genes were decreased in G-CA-treated HFD mice. The mRNA expression levels of cholesterol 7 alpha-hydroxylase 1 (CYP7A1, the key enzyme in bile acid synthesis, were dramatically increased by G-CA treatment in HFD mice. We suggest that G-CA treatment ameliorated hepatic steatosis by inhibiting inflammation and improving lipid metabolism.

  15. High-level radioactive wastes. Supplement 1

    International Nuclear Information System (INIS)

    McLaren, L.H.

    1984-09-01

    This bibliography contains information on high-level radioactive wastes included in the Department of Energy's Energy Data Base from August 1982 through December 1983. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes, each preceded by a brief description, are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number. 1452 citations

  16. PAIRWISE BLENDING OF HIGH LEVEL WASTE

    International Nuclear Information System (INIS)

    CERTA, P.J.

    2006-01-01

    The primary objective of this study is to demonstrate a mission scenario that uses pairwise and incidental blending of high level waste (HLW) to reduce the total mass of HLW glass. Secondary objectives include understanding how recent refinements to the tank waste inventory and solubility assumptions affect the mass of HLW glass and how logistical constraints may affect the efficacy of HLW blending

  17. Materials for high-level waste containment

    International Nuclear Information System (INIS)

    Marsh, G.P.

    1982-01-01

    The function of the high-level radioactive waste container in storage and of a container/overpack combination in disposal is considered. The consequent properties required from potential fabrication materials are discussed. The strategy adopted in selecting containment materials and the experimental programme underway to evaluate them are described. (U.K.)

  18. Differences Between Tg2576 and Wild Type Mice in the NMDA Receptor-Nitric Oxide Pathway After Prolonged Application of a Diet High in Advanced Glycation End Products.

    Science.gov (United States)

    Kristofikova, Zdena; Ricny, Jan; Sirova, Jana; Ripova, Daniela; Lubitz, Irit; Schnaider-Beeri, Michal

    2015-08-01

    It has been suggested that advanced glycation end (AGE) products, via cognate receptor activation, are implicated in several diseases, including Alzheimer's disease. The NMDA receptor-nitric oxide pathway appears to be influenced by AGE products and involved in the pathogenesis of this type of dementia. In this study, C57BL/6J (WT) and transgenic (Tg2576) mice expressing human mutant amyloid precursor protein were kept on prolonged (8 months) diets containing regular or high amounts of AGE products. After the decapitation of 11-months old mice, brain tissue analyses were performed [expressions of the NR1, NR2A and NR2B subunits of NMDA receptors, activities of neuronal, endothelial and inducible nitric oxide synthase (nNOS, eNOS and iNOS)]. Moreover, levels of malondialdehyde and of human amyloid β 1-42 were estimated. We found increased activity of nNOS in WT mice maintained on a high compared to regular AGE diet; however, no similar differences were found in Tg2576 mice. In addition, we observed an increase in NR1 expression in Tg2576 compared to WT mice, both kept on a diet high in AGE products. Correlation analyses performed on mice kept on the regular AGE diet supported close links between particular subunits (NR2A-NR2B, in WT as well as in Tg2576 mice), between subunits and synthase (NR2A/NR2B-nNOS, only in WT mice) or between particular synthases (nNOS-iNOS, only in WT). Correlation analysis also revealed differences between WT mice kept on both diets (changed correlations between NR2A/NR2B-nNOS, between nNOS-eNOS and between eNOS-iNOS). Malondialdehyde levels were increased in both Tg2576 groups when compared to the corresponding WT mice, but no effects of the diets were observed. Analogously, no significant effects of diets were found in the levels of soluble or insoluble amyloid β 1-42 in Tg2576 mice. Our results demonstrate that prolonged ingestion of AGE products can influence the NMDA receptor-nitric oxide pathway in the brain and that only WT mice

  19. Daily supplementation with fresh pomegranate juice increases paraoxonase 1 expression and activity in mice fed a high-fat diet.

    Science.gov (United States)

    Estrada-Luna, D; Martínez-Hinojosa, E; Cancino-Diaz, J C; Belefant-Miller, H; López-Rodríguez, G; Betanzos-Cabrera, G

    2018-02-01

    Studies have found that pomegranate juice (PJ) consumption increases the binding of high-density lipoproteins (HDL) to paraoxonase 1 (PON1), thus increasing the catalytic activity of this enzyme. PON1 is an antioxidant arylesterase synthesized in the liver and transported in plasma in association with HDL. Decreased levels of PON1 are associated with higher levels of cholesterol. We determined the effects of PJ on body weight, cholesterol, and triacylglycerols through 5 months of supplementation. In addition, the effect of PJ on pon1 gene expression in the liver was also measured by RT-qPCR as well as the activity in serum by a semiautomated method using paraoxon as a substrate. CD-1 mice were either fed a control diet or were fed a high-fat diet 1.25% (wt/wt) cholesterol, 0.5% (wt/wt) sodium cholate, and 15% (wt/wt) saturated fat. 300 μL of PJ containing 0.35 mmol total polyphenols was administered by oral gavage to half of the high fat mice daily. The rest of the high fat mice and the control mice were administered with 300 μL of water. PJ-supplemented animals had significantly higher levels of expression of pon1 compared to the unsupplemented group. PJ-supplemented animals had twice the PON1 activity of the unsupplemented group. In addition, PJ-supplemented animals had the lowest body weight and significantly reduced cholesterol and triacylglycerol levels, although the tricylglycerol levels were not consistently decreased. These results suggest that PJ protects against the effects of a high-fat diet in body weight, and cholesterol levels.

  20. High death rate in mice treated topically with diclofenac

    DEFF Research Database (Denmark)

    Lerche, Catharina M; Philipsen, Peter A; Poulsen, Thomas

    2011-01-01

    ). Diclofenac was applied topically on the backs of hairless, female, C3.Cg/TifBomTac immunocompetent mice three times weekly followed by ultraviolet radiation (2, 3, or 4 Standard Erythema Dose) until death. There was a significant difference in survival between diclofenac-treated groups and control groups (P...

  1. Mitochondrial haplotypes are not associated with mice selectively bred for high voluntary wheel running.

    Science.gov (United States)

    Wone, Bernard W M; Yim, Won C; Schutz, Heidi; Meek, Thomas H; Garland, Theodore

    2018-04-04

    Mitochondrial haplotypes have been associated with human and rodent phenotypes, including nonshivering thermogenesis capacity, learning capability, and disease risk. Although the mammalian mitochondrial D-loop is highly polymorphic, D-loops in laboratory mice are identical, and variation occurs elsewhere mainly between nucleotides 9820 and 9830. Part of this region codes for the tRNA Arg gene and is associated with mitochondrial densities and number of mtDNA copies. We hypothesized that the capacity for high levels of voluntary wheel-running behavior would be associated with mitochondrial haplotype. Here, we analyzed the mtDNA polymorphic region in mice from each of four replicate lines selectively bred for 54 generations for high voluntary wheel running (HR) and from four control lines (Control) randomly bred for 54 generations. Sequencing the polymorphic region revealed a variable number of adenine repeats. Single nucleotide polymorphisms (SNPs) varied from 2 to 3 adenine insertions, resulting in three haplotypes. We found significant genetic differentiations between the HR and Control groups (F st  = 0.779, p ≤ 0.0001), as well as among the replicate lines of mice within groups (F sc  = 0.757, p ≤ 0.0001). Haplotypes, however, were not strongly associated with voluntary wheel running (revolutions run per day), nor with either body mass or litter size. This system provides a useful experimental model to dissect the physiological processes linking mitochondrial, genomic SNPs, epigenetics, or nuclear-mitochondrial cross-talk to exercise activity. Copyright © 2018. Published by Elsevier B.V.

  2. Effect of High-Fat Diet upon Inflammatory Markers and Aortic Stiffening in Mice

    Directory of Open Access Journals (Sweden)

    Andre Bento Chaves Santana

    2014-01-01

    Full Text Available Changes in lifestyle such as increase in high-fat food consumption are an important cause for vascular diseases. The present study aimed to investigate the involvement of ACE and TGF-β in the aorta stiffness induced by high-fat diet. C57BL/6 male mice were divided in two groups according to their diet for 8 weeks: standard diet (ST and high-fat diet (HF. At the end of the protocol, body weight gain, adipose tissue content, serum lipids and glucose levels, and aorta morphometric and biochemical measurements were performed. Analysis of collagen fibers by picrosirius staining of aorta slices showed that HF diet promoted increase of thin (55% and thick (100% collagen fibers deposition and concomitant disorganization of these fibers orientations in the aorta vascular wall (50%. To unravel the mechanism involved, myeloperoxidase (MPO and angiotensin I converting enzyme (ACE were evaluated by protein expression and enzyme activity. HF diet increased MPO (90% and ACE (28% activities, as well as protein expression of ACE. TGF-β was also increased in aorta tissue of HF diet mice after 8 weeks. Altogether, we have observed that the HF diet-induced aortic stiffening may be associated with increased oxidative stress damage and activation of the RAS in vascular tissue.

  3. High spin levels in 151Ho

    International Nuclear Information System (INIS)

    Gizon, J.; Gizon, A.; Andre, S.; Genevey, J.; Jastrzebski, J.; Kossakowski, R.; Moszinski, M.; Preibisz, Z.

    1981-02-01

    We report here on the first study of the level structure of 151 Ho. High spin levels in 151 Ho have been populated in the 141 Pr + 16 O and 144 Sm + 12 C reactions. The level structure has been established up to 6.6 MeV energy and the spins and particles determined up to 49/2 - . Most of the proposed level configurations can be explained by the coupling of hsub(11/2) protons to fsub(7/2) and/or hsub(9/2) neutrons. An isomer with 14 +- 3 ns half-life and a delayed gamma multiplicity equal to 17 +- 2 has been found. Its spin is larger than 57/2 h units

  4. Purified blueberry anthocyanins and blueberry juice alter development of obesity in mice fed an obesogenic high-fat diet.

    Science.gov (United States)

    Prior, Ronald L; E Wilkes, Samuel; R Rogers, Theodore; Khanal, Ramesh C; Wu, Xianli; Howard, Luke R

    2010-04-14

    Male C57BL/6J mice (25 days of age) were fed either a low-fat diet (10% kcal from fat) (LF) or a high-fat diet (45% kcal from fat) (HF45) for a period of 72 days. Blueberry juice or purified blueberry anthocyanins (0.2 or 1.0 mg/mL) in the drinking water were included in LF or HF45 treatments. Sucrose was added to the drinking water of one treatment to test if the sugars in blueberry juice would affect development of obesity. Total body weights (g) and body fat (%) were higher and body lean tissue (%) was lower in the HF45 fed mice compared to the LF fed mice after 72 days, but in mice fed HF45 diet plus blueberry juice or blueberry anthocyanins (0.2 mg/mL), body fat (%) was not different from those mice fed the LF diet. Anthocyanins (ACNs) decreased retroperitoneal and epididymal adipose tissue weights. Fasting serum glucose concentrations were higher in mice fed the HF45 diet. However, it was reduced to LF levels in mice fed the HF45 diet plus 0.2 mg of ACNs/mL in the drinking water, but not with blueberry juice. beta cell function (HOMA-BCF) score was lowered with HF45 feeding but returned to normal levels in mice fed the HF45 diet plus purified ACNs (0.2 mg/mL). Serum leptin was elevated in mice fed HF45 diet, and feeding either blueberry juice or purified ACNs (0.2 mg/mL) decreased serum leptin levels relative to HF45 control. Sucrose in drinking water, when consumption was restricted to the volume of juice consumed, produced lower serum leptin and insulin levels, leptin/fat, and retroperitoneal and total fat (% BW). Blueberry juice was not as effective as the low dose of anthocyanins in the drinking water in preventing obesity. Additional studies are needed to determine factors responsible for the differing responses of blueberry juice and whole blueberry in preventing the development of obesity.

  5. Disposal of high-level radioactive waste

    International Nuclear Information System (INIS)

    Glasby, G.P.

    1977-01-01

    Although controversy surrounding the possible introduction of nuclear power into New Zealand has raised many points including radiation hazards, reactor safety, capital costs, sources of uranium and earthquake risks on the one hand versus energy conservation and alternative sources of energy on the other, one problem remains paramount and is of global significance - the storage and dumping of the high-level radioactive wastes of the reactor core. The generation of abundant supplies of energy now in return for the storage of these long-lived highly radioactive wastes has been dubbed the so-called Faustian bargain. This article discusses the growth of the nuclear industry and its implications to high-level waste disposal particularly in the deep-sea bed. (auth.)

  6. Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and late-onset obesity in year-old mice.

    Science.gov (United States)

    Leasure, J Leigh; Giddabasappa, Anand; Chaney, Shawntay; Johnson, Jerry E; Pothakos, Konstantinos; Lau, Yuen Sum; Fox, Donald A

    2008-03-01

    Low-level developmental lead exposure is linked to cognitive and neurological disorders in children. However, the long-term effects of gestational lead exposure (GLE) have received little attention. Our goals were to establish a murine model of human equivalent GLE and to determine dose-response effects on body weight, motor functions, and dopamine neurochemistry in year-old offspring. We exposed female C57BL/6 mice to water containing 0, 27 (low), 55 (moderate), or 109 ppm (high) of lead from 2 weeks prior to mating, throughout gestation, and until postnatal day 10 (PN10). Maternal and litter measures, blood lead concentrations ([BPb]), and body weights were obtained throughout the experiment. Locomotor behavior in the absence and presence of amphetamine, running wheel activity, rotarod test, and dopamine utilization were examined in year-old mice. Peak [BPb] were obesity. Similarly, we observed male-specific decreased spontaneous motor activity, increased amphetamine-induced motor activity, and decreased rotarod performance in year-old GLE mice. Levels of dopamine and its major metabolite were altered in year-old male mice, although only forebrain utilization increased. GLE-induced alterations were consistently larger in low-dose GLE mice. Our novel results show that GLE produced permanent male-specific deficits. The nonmonotonic dose-dependent responses showed that low-level GLE produced the most adverse effects. These data reinforce the idea that lifetime measures of dose-response toxicant exposure should be a component of the neurotoxic risk assessment process.

  7. Effect of Ginseng (Panax ginseng Berry EtOAc Fraction on Cognitive Impairment in C57BL/6 Mice under High-Fat Diet Inducement

    Directory of Open Access Journals (Sweden)

    Chang Hyeon Park

    2015-01-01

    Full Text Available High-fat diet-induced obesity leads to type 2 diabetes. Recently, there has been growing apprehension about diabetes-associated cognitive impairment (DACM. The effect of ginseng (Panax ginseng berry ethyl acetate fraction (GBEF on mice with high-fat diet-induced cognitive impairment was investigated to confirm its physiological function. C57BL/6 mice were fed a high-fat diet for 5 weeks and then a high-fat diet with GBEF (20 and 50 mg/kg of body weight for 4 weeks. After three in vivo behavioral tests (Y-maze, passive avoidance, and Morris water maze tests, blood samples were collected from the postcaval vein for biochemical analysis, and whole brains were prepared for an ex vivo test. A method based on ultra-performance liquid chromatography (UPLC accurate-mass quadrupole time-of-flight mass spectrometry (Q-TOF/MS was used to determine major ginsenosides. GBEF decreased the fasting blood glucose levels of high-fat diet-induced diabetes mellitus (DM mice and improved hyperglycemia. Cognitive behavior tests were examined after setting up the DM mice. The in vivo experiments showed that mice treated with GBEF exhibited more improved cognitive behavior than DM mice. In addition, GBEF effectively inhibited the acetylcholinesterase (AChE activity and malondialdehyde (MDA levels of DM mice brain tissues. Q-TOF UPLC/MS analyses of GBEF showed that ginsenoside Re was the major ginsenoside.

  8. Python based high-level synthesis compiler

    Science.gov (United States)

    Cieszewski, Radosław; Pozniak, Krzysztof; Romaniuk, Ryszard

    2014-11-01

    This paper presents a python based High-Level synthesis (HLS) compiler. The compiler interprets an algorithmic description of a desired behavior written in Python and map it to VHDL. FPGA combines many benefits of both software and ASIC implementations. Like software, the mapped circuit is flexible, and can be reconfigured over the lifetime of the system. FPGAs therefore have the potential to achieve far greater performance than software as a result of bypassing the fetch-decode-execute operations of traditional processors, and possibly exploiting a greater level of parallelism. Creating parallel programs implemented in FPGAs is not trivial. This article describes design, implementation and first results of created Python based compiler.

  9. The CMS High-Level Trigger

    International Nuclear Information System (INIS)

    Covarelli, R.

    2009-01-01

    At the startup of the LHC, the CMS data acquisition is expected to be able to sustain an event readout rate of up to 100 kHz from the Level-1 trigger. These events will be read into a large processor farm which will run the 'High-Level Trigger'(HLT) selection algorithms and will output a rate of about 150 Hz for permanent data storage. In this report HLT performances are shown for selections based on muons, electrons, photons, jets, missing transverse energy, τ leptons and b quarks: expected efficiencies, background rates and CPU time consumption are reported as well as relaxation criteria foreseen for a LHC startup instantaneous luminosity.

  10. The CMS High-Level Trigger

    CERN Document Server

    Covarelli, Roberto

    2009-01-01

    At the startup of the LHC, the CMS data acquisition is expected to be able to sustain an event readout rate of up to 100 kHz from the Level-1 trigger. These events will be read into a large processor farm which will run the "High-Level Trigger" (HLT) selection algorithms and will output a rate of about 150 Hz for permanent data storage. In this report HLT performances are shown for selections based on muons, electrons, photons, jets, missing transverse energy, tau leptons and b quarks: expected efficiencies, background rates and CPU time consumption are reported as well as relaxation criteria foreseen for a LHC startup instantaneous luminosity.

  11. The CMS High-Level Trigger

    Science.gov (United States)

    Covarelli, R.

    2009-12-01

    At the startup of the LHC, the CMS data acquisition is expected to be able to sustain an event readout rate of up to 100 kHz from the Level-1 trigger. These events will be read into a large processor farm which will run the "High-Level Trigger" (HLT) selection algorithms and will output a rate of about 150 Hz for permanent data storage. In this report HLT performances are shown for selections based on muons, electrons, photons, jets, missing transverse energy, τ leptons and b quarks: expected efficiencies, background rates and CPU time consumption are reported as well as relaxation criteria foreseen for a LHC startup instantaneous luminosity.

  12. High-level waste processing and disposal

    International Nuclear Information System (INIS)

    Crandall, J.L.; Krause, H.; Sombret, C.; Uematsu, K.

    1984-01-01

    The national high-level waste disposal plans for France, the Federal Republic of Germany, Japan, and the United States are covered. Three conclusions are reached. The first conclusion is that an excellent technology already exists for high-level waste disposal. With appropriate packaging, spent fuel seems to be an acceptable waste form. Borosilicate glass reprocessing waste forms are well understood, in production in France, and scheduled for production in the next few years in a number of other countries. For final disposal, a number of candidate geological repository sites have been identified and several demonstration sites opened. The second conclusion is that adequate financing and a legal basis for waste disposal are in place in most countries. Costs of high-level waste disposal will probably add about 5 to 10% to the costs of nuclear electric power. The third conclusion is less optimistic. Political problems remain formidable in highly conservative regulations, in qualifying a final disposal site, and in securing acceptable transport routes

  13. Radix Stellariae extract prevents high-fat-diet-induced obesity in C57BL/6 mice by accelerating energy metabolism

    Directory of Open Access Journals (Sweden)

    Yin Li

    2017-05-01

    Full Text Available Stellaria dichotoma L. is widely distributed in Ningxia and surrounding areas in northwestern China. Its root, Radix Stellariae (RS, has been used in herbal formulae for treating asthenic-fever, infection, malaria, dyspepsia in children and several other symptoms. This study investigated whether the RS extract (RSE alleviates metabolic disorders. The results indicated that RSE significantly inhibited body weight gain in high-fat (HF-diet-fed C57BL/6 mice, reduced fasting glucose levels, and improved insulin tolerance. Moreover, RSE increased the body temperature of the mice and the expression of uncoupling proteins and peroxisome proliferator-activated receptors in the white adipose tissue. Thus, RSE alleviated metabolic disorders in HF-diet-fed C57BL/6 mice by potentially activating UCP and PPAR signaling.

  14. DUACS: Toward High Resolution Sea Level Products

    Science.gov (United States)

    Faugere, Y.; Gerald, D.; Ubelmann, C.; Claire, D.; Pujol, M. I.; Antoine, D.; Desjonqueres, J. D.; Picot, N.

    2016-12-01

    The DUACS system produces, as part of the CNES/SALP project, and the Copernicus Marine Environment and Monitoring Service, high quality multimission altimetry Sea Level products for oceanographic applications, climate forecasting centers, geophysic and biology communities... These products consist in directly usable and easy to manipulate Level 3 (along-track cross-calibrated SLA) and Level 4 products (multiple sensors merged as maps or time series) and are available in global and regional version (Mediterranean Sea, Arctic, European Shelves …).The quality of the products is today limited by the altimeter technology "Low Resolution Mode" (LRM), and the lack of available observations. The launch of 2 new satellites in 2016, Jason-3 and Sentinel-3A, opens new perspectives. Using the global Synthetic Aperture Radar mode (SARM) coverage of S3A and optimizing the LRM altimeter processing (retracking, editing, ...) will allow us to fully exploit the fine-scale content of the altimetric missions. Thanks to this increase of real time altimetry observations we will also be able to improve Level-4 products by combining these new Level-3 products and new mapping methodology, such as dynamic interpolation. Finally these improvements will benefit to downstream products : geostrophic currents, Lagrangian products, eddy atlas… Overcoming all these challenges will provide major upgrades of Sea Level products to better fulfill user needs.

  15. FEMALE MICE ARE RESISTANT TO Fabp1 GENE ABLATION-INDUCED ALTERATIONS IN BRAIN ENDOCANNABINOID LEVELS

    Science.gov (United States)

    Martin, Gregory G.; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K.; Dangott, Lawrence J.; Peng, Xiaoxue; Kaczocha, Martin; Murphy, Eric J.; Kier, Ann B.; Schroeder, Friedhelm

    2017-01-01

    Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing ECs, i.e arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: i) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; ii) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or iii) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO). PMID:27450559

  16. Alternative reproductive tactics in female striped mice: Solitary breeders have lower corticosterone levels than communal breeders.

    Science.gov (United States)

    Hill, Davina L; Pillay, Neville; Schradin, Carsten

    2015-05-01

    Alternative reproductive tactics (ARTs), where members of the same sex and population show distinct reproductive phenotypes governed by decision-rules, have been well-documented in males of many species, but are less well understood in females. The relative plasticity hypothesis (RPH) predicts that switches between plastic ARTs are mediated by changes in steroid hormones. This has received much support in males, but little is known about the endocrine control of female ARTs. Here, using a free-living population of African striped mice (Rhabdomys pumilio) over five breeding seasons, we tested whether females following different tactics differed in corticosterone and testosterone levels, as reported for male striped mice using ARTs, and in progesterone and oestrogen, which are important in female reproduction. Female striped mice employ three ARTs: communal breeders give birth in a shared nest and provide alloparental care, returners leave the group temporarily to give birth, and solitary breeders leave to give birth and do not return. We expected communal breeders and returners to have higher corticosterone, owing to the social stress of group-living, and lower testosterone than solitary breeders, which must defend territories alone. Solitary breeders had lower corticosterone than returners and communal breeders, as predicted, but testosterone and progesterone did not differ between ARTs. Oestrogen levels were higher in returners (measured before leaving the group) than in communal and solitary breeders, consistent with a modulatory role. Our study demonstrates hormonal differences between females following (or about to follow) different tactics, and provides the first support for the RPH in females. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The PPARalpha agonist, fenofibrate decreases levels of anorectic N-acylethanolamines in the small intestine of mice

    DEFF Research Database (Denmark)

    Diep, Thi Ai; Golbas, Golfam; Hansen, Harald S.

    2014-01-01

    contribute to the hyperphagic effect of dietary fat. Male C57BL/6 mice were fed with either chow (minced Altromin) (n=8 from Taconic and n=8 from Charles River) or chow mixed with supplemented 0.5 wt% Fenofibrate (n=8 from Taconic and n=8 from Charles River) for seven days, and intestinal levels of NAEs were...... measured by LC-MS as previously described (3,4). The levels of PEA and LEA were significantly decreased (23-64%) in both strain of mice , while the decrease in OEA only reached significance in Charles river mice. There was no difference in levels of anandamide in any strain of mice. This suggests...

  18. Cermets for high level waste containment

    International Nuclear Information System (INIS)

    Aaron, W.S.; Quinby, T.C.; Kobisk, E.H.

    1978-01-01

    Cermet materials are currently under investigation as an alternate for the primary containment of high level wastes. The cermet in this study is an iron--nickel base metal matrix containing uniformly dispersed, micron-size fission product oxides, aluminosilicates, and titanates. Cermets possess high thermal conductivity, and typical waste loading of 70 wt % with volume reduction factors of 2 to 200 and low processing volatility losses have been realized. Preliminary leach studies indicate a leach resistance comparable to other candidate waste forms; however, more quantitative data are required. Actual waste studies have begun on NFS Acid Thorex, SRP dried sludge and fresh, unneutralized SRP process wastes

  19. Timing of High-level Waste Disposal

    International Nuclear Information System (INIS)

    2008-01-01

    This study identifies key factors influencing the timing of high-level waste (HLW) disposal and examines how social acceptability, technical soundness, environmental responsibility and economic feasibility impact on national strategies for HLW management and disposal. Based on case study analyses, it also presents the strategic approaches adopted in a number of national policies to address public concerns and civil society requirements regarding long-term stewardship of high-level radioactive waste. The findings and conclusions of the study confirm the importance of informing all stakeholders and involving them in the decision-making process in order to implement HLW disposal strategies successfully. This study will be of considerable interest to nuclear energy policy makers and analysts as well as to experts in the area of radioactive waste management and disposal. (author)

  20. High-Level Waste Melter Study Report

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Joseph M.; Bickford, Dennis F.; Day, Delbert E.; Kim, Dong-Sang; Lambert, Steven L.; Marra, Sharon L.; Peeler, David K.; Strachan, Denis M.; Triplett, Mark B.; Vienna, John D.; Wittman, Richard S.

    2001-07-13

    At the Hanford Site in Richland, Washington, the path to site cleanup involves vitrification of the majority of the wastes that currently reside in large underground tanks. A Joule-heated glass melter is the equipment of choice for vitrifying the high-level fraction of these wastes. Even though this technology has general national and international acceptance, opportunities may exist to improve or change the technology to reduce the enormous cost of accomplishing the mission of site cleanup. Consequently, the U.S. Department of Energy requested the staff of the Tanks Focus Area to review immobilization technologies, waste forms, and modifications to requirements for solidification of the high-level waste fraction at Hanford to determine what aspects could affect cost reductions with reasonable long-term risk. The results of this study are summarized in this report.

  1. Antihyperglycemic and anti-inflammatory effects of fermented food paste in high-fat diet and streptozotocin-challenged mice

    Science.gov (United States)

    Zulkawi, Noraisyah; Ng, Kam Heng; Zamberi, Nur Rizi; Yeap, Swee Keong; Satharasinghe, Dilan A; Tan, Sheau Wei; Ho, Wan Yong; Abd Rashid, Nur Yuhasliza; Md Lazim, Mohd Izwan; Jamaluddin, Anisah; Alitheen, Noorjahan Banu; Long, Kamariah

    2018-01-01

    Background Fermented food has been widely consumed as health food to ameliorate or prevent several chronic diseases including diabetes. Xeniji™, a fermented food paste (FFP), has been previously reported with various bioactivities, which may be caused by the presence of several metabolites including polyphenolic acids, flavonoids, and vitamins. In this study, the anti-hyperglycemic and anti-inflammatory effects of FFP were assessed. Methods In this study, type 2 diabetes model mice were induced by streptozotocin and high-fat diet (HFD) and used to evaluate the antihyperglycemic and anti-inflammatory effects of FFP. Mice were fed with HFD and challenged with 30 mg/kg body weight (BW) of streptozotocin for 1 month followed by 6 weeks of supplementation with 0.1 and 1.0 g/kg BW of FFP. Metformin was used as positive control treatment. Results Xeniji™-supplemented hyperglycemic mice were recorded with lower glucose level after 6 weeks of duration. This effect was contributed by the improvement of insulin sensitivity in the hyperglycemic mice indicated by the oral glucose tolerance test, insulin tolerance test, and end point insulin level. In addition, gene expression study has shown that the antihyperglycemic effect of FFP is related to the improvement of lipid and glucose metabolism in the mice. Furthermore, both 0.1 and 1 g/kg BW of FFP was able to reduce hyperglycemia-related inflammation indicated by the reduction of proinflammatory cytokines, NF-kB and iNOS gene expression and nitric oxide level. Conclusion FFP potentially demonstrated in vivo antihyperglycemic and anti-inflammatory effects on HFD and streptozotocin-induced diabetic mice. PMID:29872261

  2. High-level radioactive wastes. Supplement 1

    Energy Technology Data Exchange (ETDEWEB)

    McLaren, L.H. (ed.)

    1984-09-01

    This bibliography contains information on high-level radioactive wastes included in the Department of Energy's Energy Data Base from August 1982 through December 1983. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes, each preceded by a brief description, are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number. 1452 citations.

  3. Decommissioning high-level waste surface facilities

    International Nuclear Information System (INIS)

    1978-04-01

    The protective storage, entombment and dismantlement options of decommissioning a High-Level Waste Surface Facility (HLWSF) was investigated. A reference conceptual design for the facility was developed based on the designs of similar facilities. State-of-the-art decommissioning technologies were identified. Program plans and cost estimates for decommissioning the reference conceptual designs were developed. Good engineering design concepts were on the basis of this work identified

  4. Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10

    Science.gov (United States)

    Mao, Zhigang; Wu, Jeffrey H.; Dong, Tingting; Wu, Mei X.

    2016-02-01

    Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study.

  5. Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10.

    Science.gov (United States)

    Mao, Zhigang; Wu, Jeffrey H; Dong, Tingting; Wu, Mei X

    2016-02-02

    Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study.

  6. Variations of L- and D-amino acid levels in the brain of wild-type and mutant mice lacking D-amino acid oxidase activity.

    Science.gov (United States)

    Du, Siqi; Wang, Yadi; Weatherly, Choyce A; Holden, Kylie; Armstrong, Daniel W

    2018-05-01

    D-amino acids are now recognized to be widely present in organisms and play essential roles in biological processes. Some D-amino acids are metabolized by D-amino acid oxidase (DAO), while D-Asp and D-Glu are metabolized by D-aspartate oxidase (DDO). In this study, levels of 22 amino acids and the enantiomeric compositions of the 19 chiral proteogenic entities have been determined in the whole brain of wild-type ddY mice (ddY/DAO +/+ ), mutant mice lacking DAO activity (ddY/DAO -/- ), and the heterozygous mice (ddY/DAO +/- ) using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No significant differences were observed for L-amino acid levels among the three strains except for L-Trp which was markedly elevated in the DAO +/- and DAO -/- mice. The question arises as to whether this is an unknown effect of DAO inactivity. The three highest levels of L-amino acids were L-Glu, L-Asp, and L-Gln in all the three strains. The lowest L-amino acid level was L-Cys in ddY/DAO +/- and ddY/DAO -/- mice, while L-Trp showed the lowest level in ddY/DAO +/+ mice. The highest concentration of D-amino acid was found to be D-Ser, which also had the highest % D value (~ 25%). D-Glu had the lowest % D value (~ 0.01%) in all the three strains. Significant differences of D-Leu, D-Ala, D-Ser, D-Arg, and D-Ile were observed in ddY/DAO +/- and ddY/DAO -/- mice compared to ddY/DAO +/+ mice. This work provides the most complete baseline analysis of L- and D-amino acids in the brains of ddY/DAO +/+ , ddY/DAO +/- , and ddY/DAO -/- mice yet reported. It also provides the most effective and efficient analytical approach for measuring these analytes in biological samples. This study provides fundamental information on the role of DAO in the brain and may be relevant for future development involving novel drugs for DAO regulation.

  7. The ALICE Dimuon Spectrometer High Level Trigger

    CERN Document Server

    Becker, B; Cicalo, Corrado; Das, Indranil; de Vaux, Gareth; Fearick, Roger; Lindenstruth, Volker; Marras, Davide; Sanyal, Abhijit; Siddhanta, Sabyasachi; Staley, Florent; Steinbeck, Timm; Szostak, Artur; Usai, Gianluca; Vilakazi, Zeblon

    2009-01-01

    The ALICE Dimuon Spectrometer High Level Trigger (dHLT) is an on-line processing stage whose primary function is to select interesting events that contain distinct physics signals from heavy resonance decays such as J/psi and Gamma particles, amidst unwanted background events. It forms part of the High Level Trigger of the ALICE experiment, whose goal is to reduce the large data rate of about 25 GB/s from the ALICE detectors by an order of magnitude, without loosing interesting physics events. The dHLT has been implemented as a software trigger within a high performance and fault tolerant data transportation framework, which is run on a large cluster of commodity compute nodes. To reach the required processing speeds, the system is built as a concurrent system with a hierarchy of processing steps. The main algorithms perform partial event reconstruction, starting with hit reconstruction on the level of the raw data received from the spectrometer. Then a tracking algorithm finds track candidates from the recon...

  8. Human plasma phospholipid transfer protein increases the antiatherogenic potential of high density lipoproteins in transgenic mice

    NARCIS (Netherlands)

    M.J. van Haperen (Rien); A. van Tol (Arie); P. Vermeulen; M. Jauhiainen; T. van Gent (Teus); P.M. van den Berg (Paul); S. Ehnholm (Sonja); A.W.M. van der Kamp (Arthur); M.P.G. de Crom (Rini); F.G. Grosveld (Frank)

    2000-01-01

    textabstractPlasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoprotein particles and alters high density lipoprotein (HDL) subfraction patterns in vitro, but its physiological function is poorly understood. Transgenic mice that overexpress

  9. Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice.

    Science.gov (United States)

    Acedo, Simone Coghetto; Caria, Cintia Rabelo E Paiva; Gotardo, Érica Martins Ferreira; Pereira, José Aires; Pedrazzoli, José; Ribeiro, Marcelo Lima; Gambero, Alessandra

    2015-10-28

    To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet (HFD). Male swiss mice (6-wk old) were fed a high-fat diet (HFD; 60% kcal from fat) or AIN-93 (control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally (100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis (macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue. Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor (TNF)-α in liver (156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P < 0.05). Serum aspartate aminotransferase levels were also reduced (23.2 ± 6.9 and 12.1 ± 1.6 U/L for non-treated and treated obese mice, respectively; P < 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α (106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) and interleukin-6 (340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) levels; however, leptin (8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P < 0.05) and plasminogen activator inhibitor-1 (600

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Performance of the CMS High Level Trigger

    CERN Document Server

    Perrotta, Andrea

    2015-01-01

    The CMS experiment has been designed with a 2-level trigger system. The first level is implemented using custom-designed electronics. The second level is the so-called High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. For Run II of the Large Hadron Collider, the increases in center-of-mass energy and luminosity will raise the event rate to a level challenging for the HLT algorithms. The increase in the number of interactions per bunch crossing, on average 25 in 2012, and expected to be around 40 in Run II, will be an additional complication. We present here the expected performance of the main triggers that will be used during the 2015 data taking campaign, paying particular attention to the new approaches that have been developed to cope with the challenges of the new run. This includes improvements in HLT electron and photon reconstruction as well as better performing muon triggers. We will also present the performance of the improved trac...

  12. Effects of bixin in high-fat diet-fed-induced fatty liver in C57BL/6J mice

    Institute of Scientific and Technical Information of China (English)

    Rosa Martha Perez Gutierrez; Rita Valadez Romero

    2016-01-01

    Objective: To evaluate the anti-obesity activity of bixin (BIX) on C57BL/6J mice which were fed a high-fat diet (HFD) and to determine the mechanism of this effect. Methods: C57BL/6J mice were separately fed a high-calorie diet or a normal diet for 8 weeks, then they were treated with BIX for another 13 weeks. After administration for 13 weeks, the animals were sacrificed. Body adiposity, serum lipid level, and insulin resistance were evaluated. In addition, a histological assay of pancreas and liver, an evaluation of the inhibitory properties on pancreatic lipase, and a-amylase were conducted. Results: Administration of BIX significantly decreased the body weight gain, adipocyte size, fat pad weights, hepatic lipid levels in HFD-induced obese mice. In addition, reduced liver weight exhibited decreased serum leptin levels, malic enzyme, glucose-6-phosphate dehydrogenase, hepatic fatty acid synthase, aspartate aminotransferase, alanine aminotransferase and hepatic phosphatidate phosphohydrolase activity. However, superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels were increased in hepatic tissue. BIX also decreased lipid and carbohydrates absorption due to inhibition of pancreatic lipase and a-amylase. Long term supplementation of BIX significantly decreased hyperlipidemia, insulin resistance and glucose level. Decreased levels of hepatic steatosis and the islets of Langerhans appeared less shrunken in HFD-fed mice. Conclusions: The antiobesity effect of BIX appears to be associated at least in part, to its inhibitory effect on lipids and carbohydrate digestion enzymes such as pancreatic lipase, a-glucosidase, and a-amylase. The results suggested that BIX also act as an antioxidant and may treat visceral obesity normalizing glucose levels, improving insulin resistance and increasing energy expenditure. Therefore, achiote which has a main component, the carotenoid BIX, could be a viable food for the treatment of obesity and diabetes.

  13. AMPK activation enhances the anti-atherogenic effects of high density lipoproteins in apoE-/- mice.

    Science.gov (United States)

    Ma, Ang; Wang, Jing; Yang, Liu; An, Yuanyuan; Zhu, Haibo

    2017-08-01

    HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmacological AMPK activation using A-769662, AICAR, metformin, and IMM-H007 on the atheroprotective functions of HDL in apoE-deficient (apoE -/- ) mice fed with a high-fat diet. After administration, there were no changes in serum lipid levels among the groups. However, mice treated with AMPK activators showed significantly enhanced reverse cholesterol transport in vivo and in vitro. AMPK activation also increased the expression of ABCA1 and ABCG1 in macrophages and scavenger receptor class B type I and LCAT in the liver. HDL from AMPK activation mice exhibited lower HDL inflammatory index and myeloperoxidase activity and higher paraoxonase 1 activity than HDL from untreated mice, implying superior antioxidant and anti-inflammatory capacities. Pharmacological AMPK activation also induced polarization of macrophages to the M2 state and reduced plasma lipid peroxidation, inflammatory cytokine production, and atherosclerotic plaque formation in apoE -/- mice. These observations suggest that pharmacological AMPK activation enhances the anti-atherogenic properties of HDL in vivo. This likely represents a key mechanism by which AMPK activation attenuates atherosclerosis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  14. The high level vibration test program

    International Nuclear Information System (INIS)

    Hofmayer, C.H.; Curreri, J.R.; Park, Y.J.; Kato, W.Y.; Kawakami, S.

    1989-01-01

    As part of cooperative agreements between the US and Japan, tests have been performed on the seismic vibration table at the Tadotsu Engineering Laboratory of Nuclear Power Engineering Test Center (NUPEC) in Japan. The objective of the test program was to use the NUPEC vibration table to drive large diameter nuclear power piping to substantial plastic strain with an earthquake excitation and to compare the results with state-of-the-art analysis of the problem. The test model was subjected to a maximum acceleration well beyond what nuclear power plants are designed to withstand. A modified earthquake excitation was applied and the excitation level was increased carefully to minimize the cumulative fatigue damage due to the intermediate level excitations. Since the piping was pressurized, and the high level earthquake excitation was repeated several times, it was possible to investigate the effects of ratchetting and fatigue as well. Elastic and inelastic seismic response behavior of the test model was measured in a number of test runs with an increasing excitation input level up to the limit of the vibration table. In the maximum input condition, large dynamic plastic strains were obtained in the piping. Crack initiation was detected following the second maximum excitation run. Crack growth was carefully monitored during the next two additional maximum excitation runs. The final test resulted in a maximum crack depth of approximately 94% of the wall thickness. The HLVT (high level vibration test) program has enhanced understanding of the behavior of piping systems under severe earthquake loading. As in other tests to failure of piping components, it has demonstrated significant seismic margin in nuclear power plant piping

  15. The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice.

    Science.gov (United States)

    Lopez, Marcelo F; Moorman, David E; Aston-Jones, Gary; Becker, Howard C

    2016-04-01

    The orexin/hypocretin (ORX) system plays a major role in motivation for natural and drug rewards. In particular, a number of studies have shown that ORX signaling through the orexin 1 receptor (OX1R) regulates alcohol seeking and consumption. Despite the association between ORX signaling and motivation for alcohol, no study to date has investigated what role the ORX system plays in alcohol dependence, an understanding of which would have significant clinical relevance. This study was designed to evaluate the effect of the highly selective OX1R antagonist GSK1059865 on voluntary ethanol intake in ethanol-dependent and control non-dependent mice. Mice were subjected to a protocol in which they were evaluated for baseline ethanol intake and then exposed to intermittent ethanol or air exposure in inhalation chambers. Each cycle of chronic intermittent ethanol (CIE), or air, exposure was followed by a test of ethanol intake. Once the expected effect of increased voluntary ethanol intake was obtained in ethanol dependent mice, mice were tested for the effect of GSK1059865 on ethanol and sucrose intake. Treatment with GSK1059865 significantly decreased ethanol drinking in a dose-dependent manner in CIE-exposed mice. In contrast GSK1059865 decreased drinking in air-exposed mice only at the highest dose used. There was no effect of GSK1059865 on sucrose intake. Thus, ORX signaling through the OX1R, using a highly-selective antagonist, has a profound influence on high levels of alcohol drinking induced in a dependence paradigm, but limited or no influence on moderate alcohol drinking or sucrose drinking. These results indicate that the ORX system may be an important target system for treating disorders of compulsive reward seeking such as alcoholism and other addictions in which motivation is strongly elevated. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Nature of fatty acids in high fat diets differentially delineates obesity-linked metabolic syndrome components in male and female C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    El Akoum Souhad

    2011-12-01

    Full Text Available Abstract Background Adverse effects of high-fat diets (HFD on metabolic homeostasis are linked to adipose tissue dysfunction. The goal of this study was to examine the effect of the HFD nature on adipose tissue activity, metabolic disturbances and glucose homeostasis alterations in male mice compared with female mice. Methods C57BL/6J mice were fed either a chow diet or HFD including vegetal (VD or animal (AD fat. Body weight, plasmatic parameters and adipose tissue mRNA expression levels of key genes were evaluated after 20 weeks of HFD feeding. Results HFD-fed mice were significantly heavier than control at the end of the protocol. Greater abdominal visceral fat accumulation was observed in mice fed with AD compared to those fed a chow diet or VD. Correlated with weight gain, leptin levels in systemic circulation were increased in HFD-fed mice in both sexes with a significant higher level in AD group compared to VD group. Circulating adiponectin levels as well as adipose tissue mRNA expression levels were significantly decreased in HFD-fed male mice. Although its plasma levels remained unchanged in females, adiponectin mRNA levels were significantly reduced in adipose tissue of both HFD-fed groups with a more marked decrease in AD group compared to VD group. Only HFD-fed male mice were diabetic with increased fasting glycaemia. On the other hand, insulin levels were only increased in AD-fed group in both sexes associated with increased resistin levels. VD did not induce any apparent metabolic alteration in females despite the increased weight gain. Peroxisome Proliferator-Activated Receptors gamma-2 (PPARγ2 and estrogen receptor alpha (ERα mRNA expression levels in adipose tissue were decreased up to 70% in HFD-fed mice but were more markedly reduced in male mice as compared with female mice. Conclusions The nature of dietary fat determines the extent of metabolic alterations reflected in adipocytes through modifications in the pattern of

  17. Ramifications of defining high-level waste

    International Nuclear Information System (INIS)

    Wood, D.E.; Campbell, M.H.; Shupe, M.W.

    1987-01-01

    The Nuclear Regulatory Commission (NRC) is considering rule making to provide a concentration-based definition of high-level waste (HLW) under authority derived from the Nuclear Waste Policy Act (NWPA) of 1982 and the Low Level Waste Policy Amendments Act of 1985. The Department of Energy (DOE), which has the responsibility to dispose of certain kinds of commercial waste, is supporting development of a risk-based classification system by the Oak Ridge National Laboratory to assist in developing and implementing the NRC rule. The system is two dimensional, with the axes based on the phrases highly radioactive and requires permanent isolation in the definition of HLW in the NWPA. Defining HLW will reduce the ambiguity in the present source-based definition by providing concentration limits to establish which materials are to be called HLW. The system allows the possibility of greater-confinement disposal for some wastes which do not require the degree of isolation provided by a repository. The definition of HLW will provide a firm basis for waste processing options which involve partitioning of waste into a high-activity stream for repository disposal, and a low-activity stream for disposal elsewhere. Several possible classification systems have been derived and the characteristics of each are discussed. The Defense High Level Waste Technology Lead Office at DOE - Richland Operations Office, supported by Rockwell Hanford Operations, has coordinated reviews of the ORNL work by a technical peer review group and other DOE offices. The reviews produced several recommendations and identified several issues to be addressed in the NRC rule making. 10 references, 3 figures

  18. Effects of Moxibustion Temperature on Blood Cholesterol Level in a Mice Model of Acute Hyperlipidemia: Role of TRPV1

    Directory of Open Access Journals (Sweden)

    Gui-Ying Wang

    2013-01-01

    Full Text Available Objectives. To compare the effects of moxibustion at two different temperatures (38°C and 46°C on the blood cholesterol level in a mice model of acute hyperlipidemia, to detect the different expression levels of transient receptor potential vanilloid subfamily 1 (TRPV1 in the dorsal root ganglions of the wild mice, and to explore the correlation between TRPV1 and moxibustion’s cholesterol-lowering effects. Method. Two different mice models were used: C57BL/6J wild type (WT and TRPV1 gene knockout (TRPV1−/−. Each model was randomly divided into control group and model group with three subgroups after acute hyperlipidemia was established: model control group, 38°C moxibustion group, and 46°C moxibustion group. The mice in 38°C group and 46°C group were subject to moxibustion. After the therapy, the cholesterol concentration in serum was measured, and the expression of TRPV1 was quantified. Results. In WT mice, moxibustion caused a decrease in blood cholesterol level and upregulation of TRPV1 at the mRNA level, which was significantly greater in the 46°C group. In contrast, in TRPV1−/− mice, the differences of cholesterol-lowering effects of moxibustion were lost. Conclusions. Temperature is one of the important factors affecting the effects of moxibustion, and the cholesterol -lowering effect of moxibustion is related to the activation of TRPV1.

  19. Elevated Hypothalamic Glucocorticoid Levels Are Associated With Obesity and Hyperphagia in Male Mice.

    Science.gov (United States)

    Sefton, Charlotte; Harno, Erika; Davies, Alison; Small, Helen; Allen, Tiffany-Jayne; Wray, Jonathan R; Lawrence, Catherine B; Coll, Anthony P; White, Anne

    2016-11-01

    Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However, the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone (Cort)-induced obesity and analyzed Cort levels in the hypothalamus and expression of genes relevant to Gc action. Mice were administered Cort (75 μg/mL) or ethanol (1%, vehicle) in drinking water for 4 weeks. Cort-treated mice had increased body weight, food intake, and adiposity. As expected, Cort increased plasma Cort levels at both zeitgeber time 1 and zeitgeber time 13, ablating the diurnal rhythm. Liquid chromatography dual tandem mass spectrometry revealed a 4-fold increase in hypothalamic Cort, which correlated with circulating levels and concentrations of Cort in other brain regions. This occurred despite decreased 11β-hydroxysteroid dehydrogenase (Hsd11b1) expression, the gene encoding the enzyme that regenerates active Gcs, whereas efflux transporter Abcb1 mRNA was unaltered. In addition, although Cort decreased hypothalamic GR (Nr3c1) expression 2-fold, the Gc-induced leucine zipper (Tsc22d3) mRNA increased, which indicated elevated GR activation. In keeping with the development of hyperphagia and obesity, Cort increased Agrp, but there were no changes in Pomc, Npy, or Cart mRNA in the hypothalamus. In summary, chronic Cort treatment causes chronic increases in hypothalamic Cort levels and a persistent elevation in Agrp, a mediator in the development of metabolic disturbances.

  20. Inactivated H7 Influenza Virus Vaccines Protect Mice despite Inducing Only Low Levels of Neutralizing Antibodies.

    Science.gov (United States)

    Kamal, Ram P; Blanchfield, Kristy; Belser, Jessica A; Music, Nedzad; Tzeng, Wen-Pin; Holiday, Crystal; Burroughs, Ashley; Sun, Xiangjie; Maines, Taronna R; Levine, Min Z; York, Ian A

    2017-10-15

    Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines. IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody

  1. Assessment of Dopaminergic Homeostasis in Mice by Use of High-performance Liquid Chromatography Analysis and Synaptosomal Dopamine Uptake

    DEFF Research Database (Denmark)

    Jensen, Kathrine L; Runegaard, Annika H; Weikop, Pia

    2017-01-01

    Dopamine (DA) is a modulatory neurotransmitter controlling motor activity, reward processes and cognitive function. Impairment of dopaminergic (DAergic) neurotransmission is strongly associated with several central nervous system-associated diseases such as Parkinson's disease, attention...... therapeutic targets for these diseases. Here, we present two useful experimental protocols that when combined provide a functional read-out of the DAergic system in mice. Biochemical and functional parameters on DA homeostasis are obtained through assessment of DA levels and dopamine transporter (DAT......) functionality(5). When investigating the DA system, the ability to reliably measure endogenous levels of DA from adult brain is essential. Therefore, we present how to perform high-performance liquid chromatography (HPLC) on brain tissue from mice to determine levels of DA. We perform the experiment on tissue...

  2. Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

    International Nuclear Information System (INIS)

    Straub, Adam C.; Stolz, Donna B.; Vin, Harina; Ross, Mark A.; Soucy, Nicole V.; Klei, Linda R.; Barchowsky, Aaron

    2007-01-01

    The vascular effects of arsenic in drinking water are global health concerns contributing to human disease worldwide. Arsenic targets the endothelial cells lining blood vessels, and endothelial cell activation or dysfunction may underlie the pathogenesis of both arsenic-induced vascular diseases and arsenic-enhanced tumorigenesis. The purpose of the current studies was to demonstrate that exposing mice to drinking water containing environmentally relevant levels of arsenic promoted endothelial cell dysfunction and pathologic vascular remodeling. Increased angiogenesis, neovascularization, and inflammatory cell infiltration were observed in Matrigel plugs implanted in C57BL/6 mice following 5-week exposures to 5-500 ppb arsenic [Soucy, N.V., Mayka, D., Klei, L.R., Nemec, A.A., Bauer, J.A., Barchowsky, A., 2005. Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice. Cardiovasc.Toxicol 5, 29-42]. Therefore, functional in vivo effects of arsenic on endothelial cell function and vessel remodeling in an endogenous vascular bed were investigated in the liver. Liver sinusoidal endothelial cells (LSEC) became progressively defenestrated and underwent capillarization to decrease vessel porosity following exposure to 250 ppb arsenic for 2 weeks. Sinusoidal expression of PECAM-1 and laminin-1 proteins, a hallmark of capillarization, was also increased by 2 weeks of exposure. LSEC caveolin-1 protein and caveolae expression were induced after 2 weeks of exposure indicating a compensatory change. Likewise, CD45/CD68-positive inflammatory cells did not accumulate in the livers until after LSEC porosity was decreased, indicating that inflammation is a consequence and not a cause of the arsenic-induced LSEC phenotype. The data demonstrate that the liver vasculature is an early target of pathogenic arsenic effects and that the mouse liver vasculature is a sensitive model for investigating vascular health effects of arsenic

  3. Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice.

    Directory of Open Access Journals (Sweden)

    Mateus Milani

    Full Text Available Current monitoring of acute lymphoblastic leukemia (ALL in living mice is based on FACS analysis of blood hCD45+ cells. In this work, we evaluated the use of human IGFBP2, B2M or Hsp90 as soluble markers of leukemia. ELISA for B2M and IGFBP2 resulted in high background levels in healthy animals, precluding its use. Conversely, plasma levels of Hsp90 showed low background and linear correlation to FACS results. In another experiment, we compared Hsp90 levels with percentage of hCD45+ cells in blood, bone marrow, liver and spleen of animals weekly sacrificed. Hsp90 levels proved to be a superior method for the earlier detection of ALL engraftment and correlated linearly to ALL burden and progression in all compartments, even at minimal residual disease levels. Importantly, the Hsp90/hCD45+ ratio was not altered when animals were treated with dexamethasone or a PI3K inhibitor, indicating that chemotherapy does not directly interfere with leukemia production of Hsp90. In conclusion, plasma Hsp90 was validated as a soluble biomarker of ALL, useful for earlier detection of leukemia engraftment, monitoring leukemia kinetics at residual disease levels, and pre-clinical or mouse avatar evaluations of anti-leukemic drugs.

  4. Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice

    Science.gov (United States)

    de Vasconcellos, Jaíra Ferreira; Brandalise, Silvia Regina; Nowill, Alexandre Eduardo; Yunes, José Andrés

    2015-01-01

    Current monitoring of acute lymphoblastic leukemia (ALL) in living mice is based on FACS analysis of blood hCD45+ cells. In this work, we evaluated the use of human IGFBP2, B2M or Hsp90 as soluble markers of leukemia. ELISA for B2M and IGFBP2 resulted in high background levels in healthy animals, precluding its use. Conversely, plasma levels of Hsp90 showed low background and linear correlation to FACS results. In another experiment, we compared Hsp90 levels with percentage of hCD45+ cells in blood, bone marrow, liver and spleen of animals weekly sacrificed. Hsp90 levels proved to be a superior method for the earlier detection of ALL engraftment and correlated linearly to ALL burden and progression in all compartments, even at minimal residual disease levels. Importantly, the Hsp90/hCD45+ ratio was not altered when animals were treated with dexamethasone or a PI3K inhibitor, indicating that chemotherapy does not directly interfere with leukemia production of Hsp90. In conclusion, plasma Hsp90 was validated as a soluble biomarker of ALL, useful for earlier detection of leukemia engraftment, monitoring leukemia kinetics at residual disease levels, and pre-clinical or mouse avatar evaluations of anti-leukemic drugs. PMID:26068922

  5. Intergenerational ethics of high level radioactive waste

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Kunihiko [Nagoya Univ., Graduate School of Engineering, Nagoya, Aichi (Japan); Nasu, Akiko; Maruyama, Yoshihiro [Shibaura Inst. of Tech., Tokyo (Japan)

    2003-03-01

    The validity of intergenerational ethics on the geological disposal of high level radioactive waste originating from nuclear power plants was studied. The result of the study on geological disposal technology showed that the current method of disposal can be judged to be scientifically reliable for several hundred years and the radioactivity level will be less than one tenth of the tolerable amount after 1,000 years or more. This implies that the consideration of intergenerational ethics of geological disposal is meaningless. Ethics developed in western society states that the consent of people in the future is necessary if the disposal has influence on them. Moreover, the ethics depends on generally accepted ideas in western society and preconceptions based on racism and sexism. The irrationality becomes clearer by comparing the dangers of the exhaustion of natural resources and pollution from harmful substances in a recycling society. (author)

  6. Management of high level radioactive waste

    International Nuclear Information System (INIS)

    Redon, A.; Mamelle, J.; Chambon, M.

    1977-01-01

    The world wide needs in reprocessing will reach the value of 10.000 t/y of irradiated fuels, in the mid of the 80's. Several countries will have planned, in their nuclear programme, the construction of reprocessing plants with a 1500 t/y capacity, corresponding to 50.000 MWe installed. At such a level, the solidification of the radioactive waste will become imperative. For this reason, all efforts, in France, have been directed towards the realization of industrial plants able of solidifying the fission products as a glassy material. The advantages of this decision, and the reasons for it are presented. The continuing development work, and the conditions and methods of storing the high-level wastes prior to solidification, and of the interim storage (for thermal decay) and the ultimate disposal after solidification are described [fr

  7. Intergenerational ethics of high level radioactive waste

    International Nuclear Information System (INIS)

    Takeda, Kunihiko; Nasu, Akiko; Maruyama, Yoshihiro

    2003-01-01

    The validity of intergenerational ethics on the geological disposal of high level radioactive waste originating from nuclear power plants was studied. The result of the study on geological disposal technology showed that the current method of disposal can be judged to be scientifically reliable for several hundred years and the radioactivity level will be less than one tenth of the tolerable amount after 1,000 years or more. This implies that the consideration of intergenerational ethics of geological disposal is meaningless. Ethics developed in western society states that the consent of people in the future is necessary if the disposal has influence on them. Moreover, the ethics depends on generally accepted ideas in western society and preconceptions based on racism and sexism. The irrationality becomes clearer by comparing the dangers of the exhaustion of natural resources and pollution from harmful substances in a recycling society. (author)

  8. The CMS High Level Trigger System

    CERN Document Server

    Afaq, A; Bauer, G; Biery, K; Boyer, V; Branson, J; Brett, A; Cano, E; Carboni, A; Cheung, H; Ciganek, M; Cittolin, S; Dagenhart, W; Erhan, S; Gigi, D; Glege, F; Gómez-Reino, Robert; Gulmini, M; Gutiérrez-Mlot, E; Gutleber, J; Jacobs, C; Kim, J C; Klute, M; Kowalkowski, J; Lipeles, E; Lopez-Perez, Juan Antonio; Maron, G; Meijers, F; Meschi, E; Moser, R; Murray, S; Oh, A; Orsini, L; Paus, C; Petrucci, A; Pieri, M; Pollet, L; Rácz, A; Sakulin, H; Sani, M; Schieferdecker, P; Schwick, C; Sexton-Kennedy, E; Sumorok, K; Suzuki, I; Tsirigkas, D; Varela, J

    2007-01-01

    The CMS Data Acquisition (DAQ) System relies on a purely software driven High Level Trigger (HLT) to reduce the full Level-1 accept rate of 100 kHz to approximately 100 Hz for archiving and later offline analysis. The HLT operates on the full information of events assembled by an event builder collecting detector data from the CMS front-end systems. The HLT software consists of a sequence of reconstruction and filtering modules executed on a farm of O(1000) CPUs built from commodity hardware. This paper presents the architecture of the CMS HLT, which integrates the CMS reconstruction framework in the online environment. The mechanisms to configure, control, and monitor the Filter Farm and the procedures to validate the filtering code within the DAQ environment are described.

  9. High level waste fixation in cermet form

    International Nuclear Information System (INIS)

    Kobisk, E.H.; Aaron, W.S.; Quinby, T.C.; Ramey, D.W.

    1981-01-01

    Commercial and defense high level waste fixation in cermet form is being studied by personnel of the Isotopes Research Materials Laboratory, Solid State Division (ORNL). As a corollary to earlier research and development in forming high density ceramic and cermet rods, disks, and other shapes using separated isotopes, similar chemical and physical processing methods have been applied to synthetic and real waste fixation. Generally, experimental products resulting from this approach have shown physical and chemical characteristics which are deemed suitable for long-term storage, shipping, corrosive environments, high temperature environments, high waste loading, decay heat dissipation, and radiation damage. Although leach tests are not conclusive, what little comparative data are available show cermet to withstand hydrothermal conditions in water and brine solutions. The Soxhlet leach test, using radioactive cesium as a tracer, showed that leaching of cermet was about X100 less than that of 78 to 68 glass. Using essentially uncooled, untreated waste, cermet fixation was found to accommodate up to 75% waste loading and yet, because of its high thermal conductivity, a monolith of 0.6 m diameter and 3.3 m-length would have only a maximum centerline temperature of 29 K above the ambient value

  10. Dietary coconut water vinegar for improvement of obesity-associated inflammation in high-fat-diet-treated mice

    Science.gov (United States)

    Mohamad, Nurul Elyani; Yeap, Swee Keong; Ky, Huynh; Ho, Wan Yong; Boo, Sook Yee; Chua, Joelle; Beh, Boon-Kee; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

    2017-01-01

    ABSTRACT Obesity has become a serious health problem worldwide. Various types of healthy food, including vinegar, have been proposed to manage obesity. However, different types of vinegar may have different bioactivities. This study was performed to evaluate the anti-obesity and anti-inflammatory effects of coconut water vinegar on high-fat-diet (HFD)-induced obese mice. Changes in the gut microbiota of the mice were also evaluated. To induce obesity, C57/BL mice were continuously fed an HFD for 33 weeks. Coconut water vinegar (0.08 and 2 ml/kg body weight) was fed to the obese mice from early in week 24 to the end of week 33. Changes in the body weight, fat-pad weight, serum lipid profile, expression of adipogenesis-related genes and adipokines in the fat pad, expression of inflammatory-related genes, and nitric oxide levels in the livers of the untreated and coconut water vinegar-treated mice were evaluated. Faecal samples from the untreated and coconut water vinegar-treated mice (2 ml/kg body weight) were subjected to 16S metagenomic analysis to compare their gut microbiota. The oral intake of coconut water vinegar significantly (p coconut water vinegar also reduced HFD-induced inflammation by down-regulating nuclear factor-κB and inducible nitric oxide synthase expression, which consequently reduced the nitric oxide level in the liver. Alterations in the gut microbiota due to an increase in the populations of the Bacteroides and Akkermansia genera by the coconut water vinegar may have helped to overcome the obesity and inflammation caused by the HFD. These results provide valuable insights into coconut water vinegar as a potential food ingredient with anti-obesity and anti-inflammatory effects. PMID:29056887

  11. Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet-Induced Diabetic Retinopathy.

    Science.gov (United States)

    Rajagopal, Rithwick; Bligard, Gregory W; Zhang, Sheng; Yin, Li; Lukasiewicz, Peter; Semenkovich, Clay F

    2016-04-01

    Obesity predisposes to human type 2 diabetes, the most common cause of diabetic retinopathy. To determine if high-fat diet-induced diabetes in mice can model retinal disease, we weaned mice to chow or a high-fat diet and tested the hypothesis that diet-induced metabolic disease promotes retinopathy. Compared with controls, mice fed a diet providing 42% of energy as fat developed obesity-related glucose intolerance by 6 months. There was no evidence of microvascular disease until 12 months, when trypsin digests and dye leakage assays showed high fat-fed mice had greater atrophic capillaries, pericyte ghosts, and permeability than controls. However, electroretinographic dysfunction began at 6 months in high fat-fed mice, manifested by increased latencies and reduced amplitudes of oscillatory potentials compared with controls. These electroretinographic abnormalities were correlated with glucose intolerance. Unexpectedly, retinas from high fat-fed mice manifested striking induction of stress kinase and neural inflammasome activation at 3 months, before the development of systemic glucose intolerance, electroretinographic defects, or microvascular disease. These results suggest that retinal disease in the diabetic milieu may progress through inflammatory and neuroretinal stages long before the development of vascular lesions representing the classic hallmark of diabetic retinopathy, establishing a model for assessing novel interventions to treat eye disease. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Liquid level measurement in high level nuclear waste slurries

    International Nuclear Information System (INIS)

    Weeks, G.E.; Heckendorn, F.M.; Postles, R.L.

    1990-01-01

    Accurate liquid level measurement has been a difficult problem to solve for the Defense Waste Processing Facility (DWPF). The nuclear waste sludge tends to plug or degrade most commercially available liquid-level measurement sensors. A liquid-level measurement system that meets demanding accuracy requirements for the DWPF has been developed. The system uses a pneumatic 1:1 pressure repeater as a sensor and a computerized error correction system. 2 figs

  13. Myosin heavy chain isoform expression in adult and juvenile mini-muscle mice bred for high-voluntary wheel running.

    Science.gov (United States)

    Talmadge, Robert J; Acosta, Wendy; Garland, Theodore

    2014-11-01

    The myosin heavy chain (MyHC) isoform composition of locomotor and non-locomotor muscles of mini-muscle mice were assessed at the protein and mRNA levels in both adult and juvenile (21 day old) mice. Mini-muscle mice are one outcome of a replicated artificial selection experiment in which four lines of mice were bred for high voluntary wheel running (HR lines). Two of the lines responded with an increase in frequency of a single nucleotide polymorphism in an intron in the MyHC-2b gene (myh4) that when homozygous causes a dramatic reduction in triceps surae mass. We found that both locomotor and non-locomotor muscles of adult mini-muscle mice displayed robust reductions, but not elimination, of the MyHC-2b isoform at both the protein and mRNA levels, with commensurate increases in MyHC-2x and sometimes MyHC-2a, as compared with either a line of HR mice that does not display the mini-muscle phenotype or inbred C57Bl6 mice. Immunohistochemical analyses revealed that locomotor muscles of mini-muscle mice contain fibers that express the MyHC-2b isoform, which migrates normally in SDS-PAGE gels. However, these MyHC-2b positive fibers are generally smaller than the surrounding fibers and smaller than the MyHC-2b positive fibers of non-mini-muscle mice, resulting in characteristically fast muscles that lack a substantial MyHC-2b positive (superficial) region. In contrast, the masseter, a non-locomotor muscle of mini-muscle mice contained MyHC-2b positive fibers that stained more lightly for MyHC-2b, but appeared normal in size and distribution. In adults, many of the MyHC-2b positive fibers in the mini-muscle mice also display central nuclei. Only a small proportion of small MyHC-2b fibers in mini-muscle mice stained positive for the neural cell adhesion molecule, suggesting that anatomical innervation was not compromised. In addition, weanling (21 day old), but not 5 day old mice, displayed alterations in MyHC isoform content at both the protein and mRNA levels, including

  14. Effects of high-fat diet and/or body weight on mammary tumor leptin and apoptosis signaling pathways in MMTV-TGF-α mice

    Science.gov (United States)

    Dogan, Soner; Hu, Xin; Zhang, Yan; Maihle, Nita J; Grande, Joseph P; Cleary, Margot P

    2007-01-01

    Introduction Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened mammary tumor (MT) latency in MMTV-TGF-α mice with dietary-induced obesity. One link between obesity and breast cancer is the adipokine, leptin. Here, the focus is on diet-induced obesity and MT and mammary fat pad (MFP) leptin and apoptotic signaling proteins. Methods MMTV-TGF-α mice were fed low-fat or high-fat diets from 10 to 85 weeks of age. High-Fat mice were divided into Obesity-Prone and Obesity-Resistant groups based on final body weights. Mice were followed to assess MT development and obtain serum, MFP, and MT. Results Incidence of palpable MTs was significantly different: Obesity-Prone > Obesity-Resistant > Low-Fat. Serum leptin was significantly higher in Obesity-Prone compared with Obesity-Resistant and Low-Fat mice. Low-Fat mice had higher MFP and MT ObRb (leptin receptor) protein and Jak2 (Janus kinase 2) protein and mRNA levels in comparison with High-Fat mice regardless of body weight. Leptin (mRNA) and pSTAT3 (phosphorylated signal transducer and activator of transcription 3) (mRNA and protein) also were higher in MTs from Low-Fat versus High-Fat mice. Expression of MT and MFP pro-apoptotic proteins was higher in Low-Fat versus High-Fat mice. Conclusion These results confirm a connection between body weight and MT development and between body weight and serum leptin levels. However, diet impacts MT and MFP leptin and apoptosis signaling proteins independently of body weight. PMID:18162139

  15. Antihyperlipidemic effect of Acanthopanax senticosus (Rupr. et Maxim) Harms leaves in high-fat-diet fed mice.

    Science.gov (United States)

    Nishida, Miyako; Kondo, Momoko; Shimizu, Taro; Saito, Tetsuo; Sato, Shinji; Hirayama, Masao; Konishi, Tetsuya; Nishida, Hiroshi

    2016-08-01

    Metabolic syndrome is a major risk factor for a variety of obesity-related diseases. Recently, the effects of functional foods have been investigated on lipid metabolism as a means to reduce lipid content in the blood, liver and adipose tissues associated with carnitine O-palmitoyltransferase (CPT) activity. Acanthopanax senticosus (Rupr. et Maxim) Harms (AS) is a medicinal herb possessing a wide spectra of functions including antioxidant, anti-inflammatory and anti-fatigue actions. Despite much research being focused on the cortical roots of AS, little information is available regarding its leaves, which are also expected to promote human health, for example by improving abnormal lipid metabolism. Here, we explored whether AS leaves affect lipid metabolism in mice fed a high-fat diet. The administration of AS to BALB/c mice fed a high-fat diet significantly decreased plasma triglycerides (TG). CPT activity in the liver of these mice was significantly enhanced by AS treatment. These findings indicate that AS leaves have the potential to alleviate increase in plasma TG levels due to high-fat diet intake in mice, possibly by increasing mitochondrial fatty acid β-oxidation, especially via CPT activation. Consequently, daily intake of AS leaves could promote beneficial health effects including the prevention of metabolic syndrome. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  16. Pharmacologically relevant intake during chronic, free-choice drinking rhythms in selectively bred high alcohol-preferring mice.

    Science.gov (United States)

    Matson, Liana M; Grahame, Nicholas J

    2013-11-01

    Multiple lines of high alcohol-preferring (HAP) mice were selectively bred for their intake of 10% ethanol (v/v) during 24-hour daily access over a 4-week period, with the highest drinking lines exhibiting intakes in excess of 20 g/kg/day. We observed circadian drinking patterns and resulting blood ethanol concentrations (BECs) in the HAP lines. We also compared the drinking rhythms and corresponding BECs of the highest drinking HAP lines to those of the C57BL/6J (B6) inbred strain. Adult male and female crossed HAP (cHAP), HAP replicate lines 1, 2, 3 and B6 mice had free-choice access to 10% ethanol and water for 3 weeks prior to bi-hourly assessments of intake throughout the dark portion of the light-dark cycle. All HAP lines reached and maintained a rate of alcohol intake above the rate at which HAP1 mice metabolize alcohol, and BECs were consistent with this finding. Further, cHAP and HAP1 mice maintained an excessive level of intake throughout the dark portion of the cycle, accumulating mean BEC levels of 261.5 ± 18.09 and 217.9 ± 25.02 mg/dl, respectively. B6 mice drank comparatively modestly, and did not accumulate high BEC levels (53.63 + 8.15 mg/dl). Free-choice drinking demonstrated by the HAP1 and cHAP lines may provide a unique opportunity for modeling the excessive intake that often occurs in alcohol-dependent individuals, and allow for exploration of predisposing factors for excessive consumption, as well as the development of physiological, behavioral and toxicological outcomes following alcohol exposure. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  17. Service Oriented Architecture for High Level Applications

    International Nuclear Information System (INIS)

    Chu, P.

    2012-01-01

    Standalone high level applications often suffer from poor performance and reliability due to lengthy initialization, heavy computation and rapid graphical update. Service-oriented architecture (SOA) is trying to separate the initialization and computation from applications and to distribute such work to various service providers. Heavy computation such as beam tracking will be done periodically on a dedicated server and data will be available to client applications at all time. Industrial standard service architecture can help to improve the performance, reliability and maintainability of the service. Robustness will also be improved by reducing the complexity of individual client applications.

  18. Regressive Effect of Myricetin on Hepatic Steatosis in Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Shu-Fang Xia

    2016-12-01

    Full Text Available Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD. C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS levels, and increased antioxidative enzyme activities, including catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1 and NAD(PH quinone dehydrogenase 1 (NQO1, reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway.

  19. The ARES High-level Intermediate Representation

    Energy Technology Data Exchange (ETDEWEB)

    Moss, Nicholas David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-03-03

    The LLVM intermediate representation (IR) lacks semantic constructs for depicting common high-performance operations such as parallel and concurrent execution, communication and synchronization. Currently, representing such semantics in LLVM requires either extending the intermediate form (a signi cant undertaking) or the use of ad hoc indirect means such as encoding them as intrinsics and/or the use of metadata constructs. In this paper we discuss a work in progress to explore the design and implementation of a new compilation stage and associated high-level intermediate form that is placed between the abstract syntax tree and when it is lowered to LLVM's IR. This highlevel representation is a superset of LLVM IR and supports the direct representation of these common parallel computing constructs along with the infrastructure for supporting analysis and transformation passes on this representation.

  20. The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues.

    Science.gov (United States)

    Pate, Kathryn M; Sherk, Vanessa D; Carpenter, R Dana; Weaver, Michael; Crapo, Silvia; Gally, Fabienne; Chatham, Lillian S; Goldstrohm, David A; Crapo, James D; Kohrt, Wendy M; Bowler, Russell P; Oberley-Deegan, Rebecca E; Regan, Elizabeth A

    2015-03-15

    Osteoarthritis (OA) is associated with increased mechanical damage to joint cartilage. We have previously found that extracellular superoxide dismutase (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage may play a role in OA. We explored the effect of forced running as a surrogate for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding. Transgenic mice heterozygous (Het) for the human ECSOD R213G polymorphism and 129-SvEv (wild-type, WT) mice were exposed to forced running on a treadmill for 45 min/day, 5 days/wk, over 8 wk. At the end of the running protocol, knee joint tissue was obtained for histology, immunohistochemistry, and protein analysis. Sedentary Het and WT mice were maintained for comparison. Whole tibias were studied for bone morphometry, finite element analysis, and mechanical testing. Forced running improved joint histology in WT mice. However, when ECSOD levels were reduced, this beneficial effect with running was lost. Het ECSOD runner mice had significantly worse histology scores compared with WT runner mice. Runner mice for both strains had increased bone strength in response to the running protocol, while Het mice showed evidence of a less robust bone structure in both runners and untrained mice. Reduced levels of ECSOD in cartilage produced joint damage when joints were stressed by forced running. The bone tissues responded to increased loading with hypertrophy, regardless of mouse strain. We conclude that ECSOD plays an important role in protecting cartilage from damage caused by mechanical loading. Copyright © 2015 the American Physiological Society.

  1. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels.

    Directory of Open Access Journals (Sweden)

    Yixin He

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI, a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

  2. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels.

    Science.gov (United States)

    He, Yixin; Du, Min; Gao, Yan; Liu, Hongshuai; Wang, Hongwei; Wu, Xiaojun; Wang, Zhengtao

    2013-01-01

    Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI), a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE) in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS) as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

  3. Allomyrina dichotoma (Arthropoda: Insecta Larvae Confer Resistance to Obesity in Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Young-Il Yoon

    2015-03-01

    Full Text Available To clarify the anti-obesity effect of Allomyrina dichotoma larvae (ADL, we previously reported that ADL block adipocyte differentiation on 3T3-L1 cell lines through downregulation of transcription factors, such as peroxisome proliferator-activated receptor-γ (PPARG and CCAAT/enhancer binding protein-α (CEBPA. In this study, we tested whether ADL prevent obesity in mice fed a high-fat diet (HFD and further investigated the mechanism underlying the effects of ADL. All mice were maintained on a normal-fat diet (NFD for 1 week and then assigned to one of five treatment groups: (1 NFD; (2 HFD; (3 HFD and 100 mg·kg−1·day−1 ADL; (4 HFD and 3000 mg·kg−1·day−1ADL; or (5 HFD and 3000 mg·kg−1·day−1 yerba mate (Ilex paraguariensis, positive control. ADL and yerba mate were administered orally daily. Mice were fed experimental diets and body weight was monitored weekly for 6 weeks. Our results indicated that ADL reduced body weight gain, organ weight and adipose tissue volume in a dose-dependent manner. Body weight gain was approximately 22.4% lower compared to mice fed only HFD, but the difference did not reach the level of statistical significance. Real-time polymerase chain reaction (PCR analysis revealed that gene expression levels of PPARG, CEBPA and lipoprotein lipase (LPL in the epididymal fat tissue of HFD-fed mice receiving 3000 mg·kg−1·day−1 ADL were reduced by 12.4-, 25.7-, and 12.3-fold, respectively, compared to mice fed HFD only. Moreover, mice administered ADL had lower serum levels of triglycerides and leptin than HFD-fed mice that did not receive ADL. Taken together our results suggest that ADL and its constituent bioactive compounds hold potential for the treatment and prevention of obesity.

  4. Exposure to unusually high indoor radon levels

    International Nuclear Information System (INIS)

    Rasheed, F.N.

    1993-01-01

    Unusually high indoor radon concentrations were reported in a small village in western Tyrol, Austria. The authors have measured the seasonal course of indoor radon concentrations in 390 houses of this village. 71% of houses in winter and 33% in summer, showed radon values on the ground floor above the Austrian action level of 400 Bq/cm 3 . This proportion results in an unusually high indoor radon exposure of the population. The radon source was an 8,700-year-old rock slide of granite gneiss, the largest of the alpine crystalline rocks. It has a strong emanating power because its rocks are heavily fractured and show a slightly increased uranium content. Previous reports show increased lung cancer mortality, myeloid leukemia, kidney cancer, melanoma, and prostate cancer resulting from indoor radon exposure. However, many studies fail to provide accurate information on indoor radon concentrations, classifying them merely as low, intermediate, and high, or they record only minor increases in indoor radon concentrations. Mortality data for 1970-91 were used to calculate age and sex standardized mortality rates (SMR) for 51 sites of carcinoma. The total population of Tyrol were controls. A significantly higher risk was recorded for lung cancer. The high SMR for lung cancer in female subjects is especially striking. Because the numbers were low for the other cancer sites, these were combined in one group to calculate the SMR. No significant increase in SMR was found for this group

  5. Extract of Ginkgo Biloba Ameliorates Streptozotocin-Induced Type 1 Diabetes Mellitus and High-Fat Diet-Induced Type 2 Diabetes Mellitus in Mice.

    Science.gov (United States)

    Rhee, Ki-Jong; Lee, Chang Gun; Kim, Sung Woo; Gim, Dong-Hyeon; Kim, Hyun-Cheol; Jung, Bae Dong

    2015-01-01

    Diabetes mellitus (DM) is caused by either destruction of pancreatic β-cells (type 1 DM) or unresponsiveness to insulin (type 2 DM). Conventional therapies for diabetes mellitus have been developed but still needs improvement. Many diabetic patients have complemented conventional therapy with alternative methods including oral supplementation of natural products. In this study, we assessed whether Ginkgo biloba extract (EGb) 761 could provide beneficial effects in the streptozotocin-induced type 1 DM and high-fat diet-induced type 2 DM murine model system. For the type 1 DM model, streptozotocin-induced mice were orally administered EGb 761 for 10 days prior to streptozotocin injection and then again administered EGb 761 for an additional 10 days. Streptozotocin-treated mice administered EGb 761 exhibited lower blood triglyceride levels, lower blood glucose levels and higher blood insulin levels compared to streptozotocin-treated mice. Furthermore, liver LPL and liver PPAR-α were increased whereas IL-1β and TNF-α were decreased in streptozotocin-injected mice treated with EGb 761 compared to mice injected with streptozotocin alone. For the type 2 DM model, mice were given high-fat diet for 60 days and then orally administered EGb 761 every other day for 80 days. We found that mice given a high-fat diet and EGb 761 showed decreased blood triglyceride levels, increased liver LPL, increased liver PPAR-α and decreased body weight compared to mice given high-fat diet alone. These results suggest that EGb 761 can exert protective effects in both type 1 and type 2 DM murine models.

  6. Technetium Chemistry in High-Level Waste

    International Nuclear Information System (INIS)

    Hess, Nancy J.

    2006-01-01

    Tc contamination is found within the DOE complex at those sites whose mission involved extraction of plutonium from irradiated uranium fuel or isotopic enrichment of uranium. At the Hanford Site, chemical separations and extraction processes generated large amounts of high level and transuranic wastes that are currently stored in underground tanks. The waste from these extraction processes is currently stored in underground High Level Waste (HLW) tanks. However, the chemistry of the HLW in any given tank is greatly complicated by repeated efforts to reduce volume and recover isotopes. These processes ultimately resulted in mixing of waste streams from different processes. As a result, the chemistry and the fate of Tc in HLW tanks are not well understood. This lack of understanding has been made evident in the failed efforts to leach Tc from sludge and to remove Tc from supernatants prior to immobilization. Although recent interest in Tc chemistry has shifted from pretreatment chemistry to waste residuals, both needs are served by a fundamental understanding of Tc chemistry

  7. Processing vessel for high level radioactive wastes

    International Nuclear Information System (INIS)

    Maekawa, Hiromichi

    1998-01-01

    Upon transferring an overpack having canisters containing high level radioactive wastes sealed therein and burying it into an underground processing hole, an outer shell vessel comprising a steel plate to be fit and contained in the processing hole is formed. A bury-back layer made of dug earth and sand which had been discharged upon forming the processing hole is formed on the inner circumferential wall of the outer shell vessel. A buffer layer having a predetermined thickness is formed on the inner side of the bury-back layer, and the overpack is contained in the hollow portion surrounded by the layer. The opened upper portion of the hollow portion is covered with the buffer layer and the bury-back layer. Since the processing vessel having a shielding performance previously formed on the ground, the state of packing can be observed. In addition, since an operator can directly operates upon transportation and burying of the high level radioactive wastes, remote control is no more necessary. (T.M.)

  8. Impacts of Bone Marrow Stem Cells on Caspase-3 Levels after Spinal Cord Injury in Mice

    Directory of Open Access Journals (Sweden)

    Noushin Gashmardi

    2017-11-01

    Full Text Available Spinal cord injury (SCI is a drastic disability that leads to spinal cord impairment. This study sought to determine the effects of bone marrow stem cells (BMSCs on caspase-3 levels after acute SCI in mice. Forty-two mice were randomly divided into 3 groups: control (2 subcategories, subjected to no intervention; sham (3 subcategories, subjected to acute SCI; and experimental (2 subcategories, subjected to SCI and cell transplantation. In the experimental group, 2×105 BMSCs were injected intravenously 1 day after SCI. The mesenchymal property of the cells was assessed. The animals in the 3 groups were sacrificed 1, 21, and 35 days after the induction of injury and caspase-3 levels were evaluated using a caspase-3 assay kit. The obtained values were analyzed with ANOVA and Tukey tests using GraphPad and SPSS. Based on the assessments, the transplanted cells were spindle-shaped and were negative for the hematopoietic markers of CD34 and CD45 and positive for the expression of the mesenchymal marker of CD90 and osteogenic induction. The caspase-3 levels showed a significant increase in the sham and experimental groups in comparison to the control group. One day after SCI, the caspase-3 level was significantly higher in the sham group (1.157±0.117 than in the other groups (P<0.000. Twenty-one days after SCI, the caspase-3 level was significantly lower in the experimental group than in the sham group (0.4±0.095 vs. 0.793±0.076; P˂0.000. Thirty-five days following SCI, the caspase-3 level was lower in the experimental group than in the sham group (0.223±0.027 vs. 0.643±0.058; P˂0.000. We conclude that BMSC transplantation was able to downregulate the caspase-3 level after acute SCI, underscoring the role of caspase-3 as a marker for the assessment of treatment efficacy in acute SCI.

  9. Tracking at High Level Trigger in CMS

    CERN Document Server

    Tosi, Mia

    2016-01-01

    The trigger systems of the LHC detectors play a crucial role in determining the physics capabili- ties of the experiments. A reduction of several orders of magnitude of the event rate is needed to reach values compatible with detector readout, offline storage and analysis capability. The CMS experiment has been designed with a two-level trigger system: the Level-1 Trigger (L1T), implemented on custom-designed electronics, and the High Level Trigger (HLT), a stream- lined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a trade-off between the complexity of the algorithms, the sustainable out- put rate, and the selection efficiency. With the computing power available during the 2012 data taking the maximum reconstruction time at HLT was about 200 ms per event, at the nominal L1T rate of 100 kHz. Track reconstruction algorithms are widely used in the HLT, for the reconstruction of the physics objects as well as in the identification of b-jets and ...

  10. CMS High Level Trigger Timing Measurements

    International Nuclear Information System (INIS)

    Richardson, Clint

    2015-01-01

    The two-level trigger system employed by CMS consists of the Level 1 (L1) Trigger, which is implemented using custom-built electronics, and the High Level Trigger (HLT), a farm of commercial CPUs running a streamlined version of the offline CMS reconstruction software. The operational L1 output rate of 100 kHz, together with the number of CPUs in the HLT farm, imposes a fundamental constraint on the amount of time available for the HLT to process events. Exceeding this limit impacts the experiment's ability to collect data efficiently. Hence, there is a critical need to characterize the performance of the HLT farm as well as the algorithms run prior to start up in order to ensure optimal data taking. Additional complications arise from the fact that the HLT farm consists of multiple generations of hardware and there can be subtleties in machine performance. We present our methods of measuring the timing performance of the CMS HLT, including the challenges of making such measurements. Results for the performance of various Intel Xeon architectures from 2009-2014 and different data taking scenarios are also presented. (paper)

  11. Brain mitochondrial metabolic dysfunction and glutamate level reduction in the pilocarpine model of temporal lobe epilepsy in mice

    Science.gov (United States)

    Smeland, Olav B; Hadera, Mussie G; McDonald, Tanya S; Sonnewald, Ursula; Borges, Karin

    2013-01-01

    Although certain metabolic characteristics such as interictal glucose hypometabolism are well established for temporal lobe epilepsy (TLE), its pathogenesis still remains unclear. Here, we performed a comprehensive study of brain metabolism in a mouse model of TLE, induced by pilocarpine–status epilepticus (SE). To investigate glucose metabolism, we injected mice 3.5–4 weeks after SE with [1,2-13C]glucose before microwave fixation of the head. Using 1H and 13C nuclear magnetic resonance spectroscopy, gas chromatography—mass spectrometry and high-pressure liquid chromatography, we quantified metabolites and 13C labeling in extracts of cortex and hippocampal formation (HF). Hippocampal levels of glutamate, glutathione and alanine were decreased in pilocarpine–SE mice compared with controls. Moreover, the contents of N-acetyl aspartate, succinate and reduced nicotinamide adenine dinucleotide (phosphate) NAD(P)H were decreased in HF indicating impairment of mitochondrial function. In addition, the reduction in 13C enrichment of hippocampal citrate and malate suggests decreased tricarboxylic acid (TCA) cycle turnover in this region. In cortex, we found reduced 13C labeling of glutamate, glutamine and aspartate via the pyruvate carboxylation and pyruvate dehydrogenation pathways, suggesting slower turnover of these amino acids and/or the TCA cycle. In conclusion, mitochondrial metabolic dysfunction and altered amino-acid metabolism is found in both cortex and HF in this epilepsy model. PMID:23611869

  12. Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion.

    Science.gov (United States)

    Arimura, Emi; Pulong, Wijang Pralampita; Marchianti, Ancah Caesarina Novi; Nakakuma, Miwa; Abe, Masaharu; Ushikai, Miharu; Horiuchi, Masahisa

    2017-02-01

    We previously showed the deleterious effects of increased dietary protein on renal manifestations and glucose metabolism in leptin receptor-deficient (db) mice. Here, we further examined its effects on glucose metabolism, including urinary C-peptide. We also orally administered mixtures corresponding to low- or high-protein diets to diabetic mice. In diet experiments, under pair-feeding (equivalent energy and fat) conditions using a metabolic cage, mice were fed diets with different protein content (L diet: 12 % protein, 71 % carbohydrate, 17 % fat; H diet: 24 % protein, 59 % carbohydrate, 17 % fat) for 15 days. In oral administration experiments, the respective mixtures (L mixture: 12 % proline, 71 % maltose or starch, 17 % linoleic acid; H mixture: 24 % proline, 59 % maltose or starch, 17 % linoleic acid) were supplied to mice. Biochemical parameters related to glucose metabolism were measured. The db-H diet mice showed significantly higher water intake, urinary volume, and glucose levels than db-L diet mice but similar levels of excreted urinary C-peptide. In contrast, control-H diet mice showed significantly higher C-peptide excretion than control-L diet mice. Both types of mice fed H diet excreted high levels of urinary albumin. When maltose mixtures were administered, db-L mixture mice showed significantly higher blood glucose after 30 min than db-H mixture mice. However, db mice administered starch-H mixture showed significantly higher blood glucose 120-300 min post-administration than db-L mixture mice, although both groups exhibited similar insulin levels. High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.

  13. High-fat diet exacerbates inflammation and cell survival signals in the skin of ultraviolet B-irradiated C57BL/6 mice

    International Nuclear Information System (INIS)

    Meeran, Syed M.; Singh, Tripti; Nagy, Tim R.; Katiyar, Santosh K.

    2009-01-01

    Inflammation induced by chronic exposure to ultraviolet (UV) radiation has been implicated in various skin diseases. We formulated the hypothesis that a high-fat diet may influence the UV-induced inflammatory responses in the skin. C57BL/6 mice were fed a high-fat diet or control diet and exposed to UVB radiation (120 mJ/cm 2 ) three times/week for 10 weeks. The mice were then sacrificed and skin and plasma samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. We found that the levels of inflammatory biomarkers were increased in the UVB-exposed skin of the mice fed the high-fat diet than the UVB-exposed skin of the mice fed the control diet. The levels of inflammatory biomarkers of early responses to UVB exposure (e.g., myeloperoxidase, cyclooxygenase-2, prostaglandin-E 2 ), proinflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-1β, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser 473 ) were higher in high-fat-diet-fed mouse skin than control-diet-fed mouse skin. The plasma levels of insulin growth factor-1 were greater in the UVB-irradiated mice fed the high-fat diet than the UVB-irradiated mice fed the control diet, whereas the levels of plasma adiponectin were significantly lower. This pronounced exacerbation of the UVB-induced inflammatory responses in the skin of mice fed a high-fat diet suggests that high-fat diet may increase susceptibility to inflammation-associated skin diseases, including the risk of skin cancer.

  14. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

    International Nuclear Information System (INIS)

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-01-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver.

  15. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D., E-mail: cklaasse@kumc.edu

    2012-11-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver.

  16. Quercetin Isolated from Toona sinensis Leaves Attenuates Hyperglycemia and Protects Hepatocytes in High-Carbohydrate/High-Fat Diet and Alloxan Induced Experimental Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Yali Zhang

    2016-01-01

    Full Text Available The development of diabetes mellitus is related to oxidant stress induced by a high carbohydrate/high-fat diet (HFD. Quercetin, as a major bioactive component in Toona sinensis leaves (QTL, is a natural antioxidant. However, the exact mechanism by which QTL ameliorate diabetes mellitus is still unknown. In this study, we investigated the hypoglycemic effects and hepatocytes protection of QTL on HFD and alloxan induced diabetic mice. Intragastric administration of QTL significantly reduced body weight gain, serum glucose, insulin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase serum levels compared to those of diabetic mice. Furthermore, it significantly attenuated oxidative stress, as determined by lipid peroxidation, nitric oxide content, and inducible nitric oxide synthase activity and as a result attenuated liver injury. QTL also significantly suppressed the diabetes-induced activation of the p65/NF-κB and ERK1/2/MAPK pathways, as well as caspase-9 and caspase-3 levels in liver tissues of diabetic mice. Finally, micrograph analysis of liver samples showed decreased cellular organelle injury in hepatocytes of QTL treated mice. Taken together, QTL can be viewed as a promising dietary agent that can be used to reduce the risk of diabetes mellitus and its secondary complications by ameliorating oxidative stress in the liver.

  17. Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level

    Directory of Open Access Journals (Sweden)

    Wang Jia

    2009-11-01

    Full Text Available Abstract Background Protein kinase C interacting protein (PKCI/HINT1 is a small protein belonging to the histidine triad (HIT family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models. Postmortem studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder. We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA axis function, we assessed the HPA activity through measurement of plasma corticosterone levels. Results Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST and the tail suspension (TST tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT. Conclusion PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS.

  18. Open-field behavior of house mice selectively bred for high voluntary wheel-running.

    Science.gov (United States)

    Bronikowski, A M; Carter, P A; Swallow, J G; Girard, I A; Rhodes, J S; Garland, T

    2001-05-01

    Open-field behavioral assays are commonly used to test both locomotor activity and emotionality in rodents. We performed open-field tests on house mice (Mus domesticus) from four replicate lines genetically selected for high voluntary wheel-running for 22 generations and from four replicate random-bred control lines. Individual mice were recorded by video camera for 3 min in a 1-m2 open-field arena on 2 consecutive days. Mice from selected lines showed no statistical differences from control mice with respect to distance traveled, defecation, time spent in the interior, or average distance from the center of the arena during the trial. Thus, we found little evidence that open-field behavior, as traditionally defined, is genetically correlated with wheel-running behavior. This result is a useful converse test of classical studies that report no increased wheel-running in mice selected for increased open-field activity. However, mice from selected lines turned less in their travel paths than did control-line mice, and females from selected lines had slower travel times (longer latencies) to reach the wall. We discuss these results in the context of the historical open-field test and newly defined measures of open-field activity.

  19. Treatment with anti-IL-6 receptor antibody prevented increase in serum hepcidin levels and improved anemia in mice inoculated with IL-6–producing lung carcinoma cells

    International Nuclear Information System (INIS)

    Noguchi-Sasaki, Mariko; Sasaki, Yusuke; Shimonaka, Yasushi; Mori, Kazushige; Fujimoto-Ouchi, Kaori

    2016-01-01

    Hepcidin, a key regulator of iron metabolism, is produced mainly by interleukin-6 (IL-6) during inflammation. A mechanism linking cancer-related anemia and IL-6 through hepcidin production is suggested. To clarify the hypothesis that overproduction of IL-6 elevates hepcidin levels and contributes to the development of cancer-related anemia, we evaluated anti-IL-6 receptor antibody treatment of cancer-related anemia in an IL-6–producing human lung cancer xenograft model. Nude mice were subcutaneously inoculated with cells of the IL-6–producing human lung cancer cell line LC-06-JCK and assessed as a model of cancer-related anemia. Mice bearing LC-06-JCK were administered rat anti-mouse IL-6 receptor antibody MR16-1 and their serum hepcidin levels and hematological parameters were determined. LC-06-JCK–bearing mice developed anemia according to the production of human IL-6 from xenografts, with decreased values of hemoglobin, hematocrit, and mean corpuscular volume (MCV) compared to non–tumor-bearing (NTB) mice. LC-06-JCK–bearing mice showed decreased body weight and serum albumin with increased serum amyloid A. MR16-1 treatment showed significant inhibition of decreased body weight and serum albumin levels, and suppressed serum amyloid A level. There was no difference in tumor volume between MR16-1-treated mice and immunoglobulin G (IgG)-treated control mice. Decreased hemoglobin, hematocrit, and MCV in LC-06-JCK–bearing mice was significantly relieved by MR16-1 treatment. LC-06-JCK–bearing mice showed high red blood cell counts and erythropoietin levels as compared to NTB mice, whereas MR16-1 treatment did not affect their levels. Serum hepcidin and ferritin levels were statistically elevated in mice bearing LC-06-JCK. LC-06-JCK–bearing mice showed lower values of MCV, mean corpuscular hemoglobin (MCH), and serum iron as compared to NTB mice. Administration of MR16-1 to mice bearing LC-06-JCK significantly suppressed levels of both serum hepcidin and

  20. Beam size measurement at high radiation levels

    International Nuclear Information System (INIS)

    Decker, F.J.

    1991-05-01

    At the end of the Stanford Linear Accelerator the high energy electron and positron beams are quite small. Beam sizes below 100 μm (σ) as well as the transverse distribution, especially tails, have to be determined. Fluorescent screens observed by TV cameras provide a quick two-dimensional picture, which can be analyzed by digitization. For running the SLAC Linear Collider (SLC) with low backgrounds at the interaction point, collimators are installed at the end of the linac. This causes a high radiation level so that the nearby cameras die within two weeks and so-called ''radiation hard'' cameras within two months. Therefore an optical system has been built, which guides a 5 mm wide picture with a resolution of about 30 μm over a distance of 12 m to an accessible region. The overall resolution is limited by the screen thickness, optical diffraction and the line resolution of the camera. Vibration, chromatic effects or air fluctuations play a much less important role. The pictures are colored to get fast information about the beam current, size and tails. Beside the emittance, more information about the tail size and betatron phase is obtained by using four screens. This will help to develop tail compensation schemes to decrease the emittance growth in the linac at high currents. 4 refs., 2 figs

  1. Serotonin-mediated central fatigue underlies increased endurance capacity in mice from lines selectively bred for high voluntary wheel running.

    Science.gov (United States)

    Claghorn, Gerald C; Fonseca, Ivana A T; Thompson, Zoe; Barber, Curtis; Garland, Theodore

    2016-07-01

    Serotonin (5-hydroxytryptamine; 5-HT) is implicated in central fatigue, and 5-HT1A pharmaceuticals are known to influence locomotor endurance in both rodents and humans. We studied the effects of a 5-HT1A agonist and antagonist on both forced and voluntary exercise in the same set of mice. This cohort of mice was taken from 4 replicate lines of mice that have been selectively bred for high levels of voluntary wheel running (HR) as compared with 4 non-selected control (C) lines. HR mice run voluntarily on wheels about 3× as many revolutions per day as compared with C, and have greater endurance during forced treadmill exercise. We hypothesized that drugs targeting serotonin receptors would have differential effects on locomotor behavior of HR and C mice. Subcutaneous injections of a 5-HT1A antagonist (WAY-100,635), a combination of 5-HT1A agonist and a 5-HT1A/1B partial agonist (8-OH-DPAT+pindolol), or physiological saline were given to separate groups of male mice before the start of each of three treadmill trials. The same manipulations were used later during voluntary wheel running on three separate nights. WAY-100,635 decreased treadmill endurance in HR but not C mice (dose by linetype interaction, P=0.0014). 8-OH-DPAT+pindolol affected treadmill endurance (PWheel running was reduced in HR but not C mice at the highest dose of 8-OH-DPAT+pindolol (dose by linetype, P=0.0221), but was not affected by WAY-100,635 treatment. These results provide further evidence that serotonin signaling is an important determinant of performance during both forced and voluntary exercise. Although the elevated wheel running of HR mice does not appear related to alterations in serotonin signaling, their enhanced endurance capacity does. More generally, our results indicate that both forced and voluntary exercise can be affected by an intervention that acts (primarily) centrally. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Inflammatory Signals shift from adipose to liver during high fat feeding and influence the development of steatohepatitis in mice

    Directory of Open Access Journals (Sweden)

    Greenfeder Scott

    2011-03-01

    Full Text Available Abstract Background Obesity and inflammation are highly integrated processes in the pathogenesis of insulin resistance, diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Molecular mechanisms underlying inflammatory events during high fat diet-induced obesity are poorly defined in mouse models of obesity. This work investigated gene activation signals integral to the temporal development of obesity. Methods Gene expression analysis in multiple organs from obese mice was done with Taqman Low Density Array (TLDA using a panel of 92 genes representing cell markers, cytokines, chemokines, metabolic, and activation genes. Mice were monitored for systemic changes characteristic of the disease, including hyperinsulinemia, body weight, and liver enzymes. Liver steatosis and fibrosis as well as cellular infiltrates in liver and adipose tissues were analyzed by histology and immunohistochemistry. Results Obese C57BL/6 mice were fed with high fat and cholesterol diet (HFC for 6, 16 and 26 weeks. Here we report that the mRNA levels of macrophage and inflammation associated genes were strongly upregulated at different time points in adipose tissues (6-16 weeks and liver (16-26 weeks, after the start of HFC feeding. CD11b+ and CD11c+ macrophages highly infiltrated HFC liver at 16 and 26 weeks. We found clear evidence that signals for IL-1β, IL1RN, TNF-α and TGFβ-1 are present in both adipose and liver tissues and that these are linked to the development of inflammation and insulin resistance in the HFC-fed mice. Conclusions Macrophage infiltration accompanied by severe inflammation and metabolic changes occurred in both adipose and liver tissues with a temporal shift in these signals depending upon the duration of HFC feeding. The evidences of gene expression profile, elevated serum alanine aminotransferase, and histological data support a progression towards nonalcoholic fatty liver disease and steatohepatitis in these HFC-fed mice within the

  3. An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I- symporter (NIS) knockout mice.

    Science.gov (United States)

    Ferrandino, Giuseppe; Kaspari, Rachel R; Reyna-Neyra, Andrea; Boutagy, Nabil E; Sinusas, Albert J; Carrasco, Nancy

    2017-07-13

    The sodium/iodide symporter (NIS) mediates active iodide (I - ) accumulation in the thyroid, the first step in thyroid hormone (TH) biosynthesis. Mutations in the SLC5A5 gene encoding NIS that result in a non-functional protein lead to congenital hypothyroidism due to I - transport defect (ITD). ITD is a rare autosomal disorder that, if not treated promptly in infancy, can cause mental retardation, as the TH decrease results in improper development of the nervous system. However, in some patients, hypothyroidism has been ameliorated by unusually large amounts of dietary I - . Here we report the first NIS knockout (KO) mouse model, obtained by targeting exons 6 and 7 of the Slc5a5 gene. In NIS KO mice, in the thyroid, stomach, and salivary gland, NIS is absent, and hence there is no active accumulation of the NIS substrate pertechnetate ( 99m TcO 4 - ). NIS KO mice showed undetectable serum T 4 and very low serum T 3 levels when fed a diet supplying the minimum I - requirement for rodents. These hypothyroid mice displayed oxidative stress in the thyroid, but not in the brown adipose tissue or liver. Feeding the mice a high-I - diet partially rescued TH biosynthesis, demonstrating that, at high I - concentrations, I - enters the thyroid through routes other than NIS.

  4. Endurance capacity of mice selectively bred for high voluntary wheel running.

    Science.gov (United States)

    Meek, Thomas H; Lonquich, Brian P; Hannon, Robert M; Garland, Theodore

    2009-09-15

    Mice from four lines bred for high voluntary wheel activity run approximately 3-fold more revolutions per day and have elevated maximal oxygen consumption during forced treadmill exercise, as compared with four unselected control (C) lines. We hypothesized that these high runner (HR) lines would have greater treadmill endurance-running capacity. Ninety-six mice from generation 49 were familiarized with running on a motorized treadmill for 3 days. On days 4 and 5, mice were given an incremental speed test (starting at 20 m min(-1), increased 1.5 m min(-1) every 2 min) and endurance was measured as the total time or distance run to exhaustion. Blood samples were taken to measure glucose and lactate concentrations at rest during the photophase, during peak nightly wheel running, and immediately following the second endurance test. Individual differences in endurance time were highly repeatable between days (r=0.79), and mice tended to run longer on the second day (paired t-test, Pwheel running and treadmill endurance differed between the sexes, reinforcing previous studies that indicate sex-specific responses to selective breeding. HR mice appear to have a higher endurance capacity than reported in the literature for inbred strains of mice or transgenics intended to enhance endurance.

  5. Effects of combined dietary supplementation with fenofibrate and Schisandrae Fructus pulp on lipid and glucose levels and liver function in normal and hypercholesterolemic mice

    Directory of Open Access Journals (Sweden)

    Zhu PL

    2015-02-01

    Full Text Available Pei-Li Zhu,1 Si-Yuan Pan,1 Shu-Feng Zhou,2 Yi Zhang,1 Xiao-Yan Wang,1 Nan Sun,1 Zhu-Sheng Chu,1 Zhi-Ling Yu,3 Kam-Ming Ko41Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People’s Republic of China; 4Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People’s Republic of ChinaBackground: Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF, a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb pulp (AqSF-P or an SF-related synthetic analog, bicyclol (BY, on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL mice.Methods: Male mice obtained from the Institute of Cancer Research (ICR were fed on a normal diet (ND or high cholesterol/bile salt (0.5%/0.15%, w/w diet (HCBD containing FF (0.03% or 0.1%, w/w with or without AqSF-P (0.3%-9.0%, based on crude herbal material, w/w or BY (0.025%, w/w for 10 days. Then serum lipid levels and alanine aminotransferase (ALT activity, as well as hepatic triglyceride (TG, total cholesterol (TC, and glucose levels, were measured.Results: Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79% in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67% and in HCBD-fed mice (up to 54%, when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was

  6. Effect of Genistein on reproductive parameter and serum nitric oxide levels in morphine-treated mice

    Directory of Open Access Journals (Sweden)

    Cyrus Jalili

    2016-02-01

    Full Text Available Background: The predominant phytoestrogen in soy and derived products is the isoflavone Genistein. Genistein has antioxidant properties. Morphine is a main psychoactive chemical in opium that can increase the generation of free radicals and therefore it could adversely affects the spermatogenesis. Objective: The main goal was to investigate whether the Genistein could protect morphine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone and nitric oxide in blood serum. Materials and Methods: In this study, various doses of Genistein (0, 1, 2, and 3 mg/kg and Genistein plus morphine (0, 1, 2, and 3 mg/kg were administered interaperitoneally to 48 male mice for 30 consequent days. These mice were randomly assigned to 8 groups (n=6 and sperm parameters (sperm cells viability, count, motility and morphology, testis weight and histology, testosterone hormone (ELISA method, FSH and LH hormones (immunoradiometry and serum nitric oxide (griess assay were analyzed and compared. Results: The results indicated that morphine administration significantly decreased testosterone (0.03 ng/mg LH and FSH level, histological parameters, count, viability (55.3%, morphology and motility of sperm cells (1%, testis weight (0.08 gr and increase nitric oxide compared to saline group (p=0.00. However, administration of Genistein and Genistein plus morphine significantly boosted motility, morphology, count, viability of sperm cells, seminiferous tubules diameter, germinal thickness, testosterone, LH and FSH while decrease nitric oxide level in all groups compared to morphine group (p<0.025. Conclusion: It seems that Genistein administration could increase the quality of spermatozoa and prevent morphine- induced adverse effects on sperm parameters.

  7. N-Acetyl-Cysteine Alleviates Gut Dysbiosis and Glucose Metabolic Disorder in High-Fat Diet-Induced Mice.

    Science.gov (United States)

    Zheng, Junping; Yuan, Xubing; Zhang, Chen; Jia, Peiyuan; Jiao, Siming; Zhao, Xiaoming; Yin, Heng; Du, Yuguang; Liu, Hongtao

    2018-05-30

    N-acetyl cysteine (NAC), an anti-oxidative reagent for clinical diseases, shows potential application to diabetes and other metabolic diseases. However, it is unknown how NAC modulates the gut microbiota of mice with metabolic syndrome. In present study, we aim to demonstrate the preventive effect of NAC on intestinal dysbiosis and glucose metabolic disorder. C57BL/6J mice were fed with normal chow diet (NCD), NCD plus NAC, high-fat diet (HFD) or HFD plus NAC for five months. After the treatment, the glucose level, circulating endotoxin and metabolism-related key proteins were determined. The fecal samples were analyzed by 16S rRNA sequencing. A novel analysis was carried out to predict the functional changes of gut microbiota. In addition, Spearman's correlation between metabolic biomarkers and bacterial abundance was also assayed. The results show that NAC treatment significantly reversed the glucose intolerance, fasting glucose level, body weight and plasma endotoxin in HFD-fed mice. Further, NAC upregulated the levels of Occludin protein and mucin glycoproteins in proximal colons of HFD-treated mice. Noticeably, NAC promoted the growth of beneficial bacteria such as Akkermansia, Bifidobacterium, Lactobacillus and Allobaculum, and hampered the population of diabetes-related genera including Desulfovibrio and Blautia. Also, NAC may influence the metabolic pathways of intestinal bacteria including lipopolysaccharide biosynthesis, oxidative stress and bacterial motility. Finally, the modified gut microbiota showed close association with the metabolic changes of the NAC treated HFD-fed mice. In summary, NAC may be a potential drug to prevent glucose metabolic disturbance by reshaping the structure of gut microbiota. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice.

    Science.gov (United States)

    Chartoumpekis, Dionysios V; Ziros, Panos G; Psyrogiannis, Agathoklis I; Papavassiliou, Athanasios G; Kyriazopoulou, Venetsana E; Sykiotis, Gerasimos P; Habeos, Ioannis G

    2011-10-01

    Obesity is characterized by chronic oxidative stress. Fibroblast growth factor 21 (FGF21) has recently been identified as a novel hormone that regulates metabolism. NFE2-related factor 2 (Nrf2) is a transcription factor that orchestrates the expression of a battery of antioxidant and detoxification genes under both basal and stress conditions. The current study investigated the role of Nrf2 in a mouse model of long-term high-fat diet (HFD)-induced obesity and characterized its crosstalk to FGF21 in this process. Wild-type (WT) and Nrf2 knockout (Nrf2-KO) mice were fed an HFD for 180 days. During this period, food consumption and body weights were measured. Glucose metabolism was assessed by an intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test. Total RNA was prepared from liver and adipose tissue and was used for quantitative real-time RT-PCR. Fasting plasma was collected and analyzed for blood chemistries. The ST-2 cell line was used for transfection studies. Nrf2-KO mice were partially protected from HFD-induced obesity and developed a less insulin-resistant phenotype. Importantly, Nrf2-KO mice had higher plasma FGF21 levels and higher FGF21 mRNA levels in liver and white adipose tissue than WT mice. Thus, the altered metabolic phenotype of Nrf2-KO mice under HFD was associated with higher expression and abundance of FGF21. Consistently, the overexpression of Nrf2 in ST-2 cells resulted in decreased FGF21 mRNA levels as well as in suppressed activity of a FGF21 promoter luciferase reporter. The identification of Nrf2 as a novel regulator of FGF21 expands our understanding of the crosstalk between metabolism and stress defense.

  9. A high-fat, high-protein diet attenuates the negative impact of casein-induced chronic inflammation on testicular steroidogenesis and sperm parameters in adult mice.

    Science.gov (United States)

    Zhao, Jing-Lu; Zhao, Yu-Yun; Zhu, Wei-Jie

    2017-10-01

    The interaction between obesity and chronic inflammation has been studied. Diet-induced obesity or chronic inflammation could reduce the testicular functions of males. However, the mechanism underlying the reproductive effects of fattening foods in males with or without chronic inflammation still needs further discussion. This study was aimed to investigate the effects of high-fat, high-protein diet on testicular steroidogenesis and sperm parameters in adult mice under physiological and chronic inflammatory conditions. Because casein can trigger a non-infectious systemic inflammatory response, we used casein injection to induce chronic inflammation in male adult Kunming mice. Twenty-four mice were randomly and equally divided into four groups: (i) normal diet+saline (Control); (ii) normal diet+casein (ND+CS); (iii) high-fat, high-protein diet+saline (HFPD+SI); (iv) high-fat, high-protein diet+casein (HFPD+CS). After 8weeks, there was a significant increase in body weight for groups HFPD+SI and HFPD+CS and a decrease in group ND+CS compared with the control. The serum levels of tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10) and lipid profiles were increased markedly in groups ND+CS, HFPD+SI and HFPD+CS compared with the control. A remarkable reduction of serum adiponectin level occurred in group HFPD+CS compared with group ND+CS. Sperm parameters (sperm count, viability and abnormality) were also adversely affected in groups ND+CS and HFPD+SI. Groups ND+CS and HFPD+SI showed severe pathological changes in testicular tissues. Semiquantitative RT-PCR, Western blot and immunohistochemical staining also showed significant reductions in both testicular mRNA and protein levels of steroidogenic acute regulatory (StAR) and cytochrome P450scc (CYP11A1) in groups HFPD+SI and HFPD+CS compared with the control, whereas testicular mRNA and protein levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) in groups HFPD+SI and HFPD+CS significantly increased. The m

  10. Effects of Chronic Exposure to Ultrasound of Alternating Frequencies on the Levels of Aggression and Anxiety in CBA and BALB/c mice.

    Science.gov (United States)

    Pavlov, D A; Gorlova, A V; Ushakova, V M; Zubkov, E A; Morozova, A Yu; Inozemtsev, A N; Chekhonin, V P

    2017-08-01

    Stress-induced changes in the behavior of CBA and BALB/c mice were studied after 3-week ultrasound exposure (22-45 kHz). The mice of both lines demonstrated increased aggression in the resident-intruder and social interest paradigms and reduced number of social interactions in the social interest test. Elevated plus maze test showed a decrease in anxiety level in CBA mice and an increase in this parameter in BALB/c mice. Chronic exposure to ultrasound induced an increase in aggression level in mice of both lines that was not directly related to changes in anxiety level.

  11. Lifespan studies on different strains of mice exposed chronically to low levels of whole body gamma irradiation

    International Nuclear Information System (INIS)

    Fox, L.A.; Klein, A.K.; Cain, G.R.; Rosenblatt, L.S.

    1982-01-01

    Several strains of mice, chosen for their predisposition to immunohematological disorders, were exposed to low levels of 60 irradiation continuously for four weeks. All individuals were subsequently followed throughout their lifetimes. W/W/sup v/ mice, which are tyically subject to a stem cell deficiency, had a lower cumulative survival rate for the irradiated group than for the unirradiated controls. Irradiated RF/sub j/ mice had a dramatically lower cumulative survival rate than their unirradiated controls. Conversely, BXSB mice, which have a lumphoproliferative autoimmune disorder, had a higher cumulative survival rate after chronic irradiation than did unirradiated BXSBs. Irradiation had no effect upon the survival rate curves of the NZB strain, the murine model for Lupus Erythematosus

  12. CAMAC and high-level-languages

    International Nuclear Information System (INIS)

    Degenhardt, K.H.

    1976-05-01

    A proposal for easy programming of CAMAC systems with high-level-languages (FORTRAN, RTL/2, etc.) and interpreters (BASIC, MUMTI, etc.) using a few subroutines and a LAM driver is presented. The subroutines and the LAM driver are implemented for PDP11/RSX-11M and for the CAMAC controllers DEC CA11A (branch controller), BORER type 1533A (single crate controller) and DEC CA11F (single crate controller). Mixed parallel/serial CAMAC systems employing KINETIC SYSTEMS serial driver mod. 3992 and serial crate controllers mod. 3950 are implemented for all mentioned parallel controllers, too. DMA transfers from or to CAMAC modules using non-processor-request controllers (BORER type 1542, DEC CA11FN) are available. (orig.) [de

  13. National high-level waste systems analysis

    International Nuclear Information System (INIS)

    Kristofferson, K.; O'Holleran, T.P.

    1996-01-01

    Previously, no mechanism existed that provided a systematic, interrelated view or national perspective of all high-level waste treatment and storage systems that the US Department of Energy manages. The impacts of budgetary constraints and repository availability on storage and treatment must be assessed against existing and pending negotiated milestones for their impact on the overall HLW system. This assessment can give DOE a complex-wide view of the availability of waste treatment and help project the time required to prepare HLW for disposal. Facilities, throughputs, schedules, and milestones were modeled to ascertain the treatment and storage systems resource requirements at the Hanford Site, Savannah River Site, Idaho National Engineering Laboratory, and West Valley Demonstration Project. The impacts of various treatment system availabilities on schedule and throughput were compared to repository readiness to determine the prudent application of resources. To assess the various impacts, the model was exercised against a number of plausible scenarios as discussed in this paper

  14. International high-level radioactive waste repositories

    International Nuclear Information System (INIS)

    Lin, W.

    1996-01-01

    Although nuclear technologies benefit everyone, the associated nuclear wastes are a widespread and rapidly growing problem. Nuclear power plants are in operation in 25 countries, and are under construction in others. Developing countries are hungry for electricity to promote economic growth; industrialized countries are eager to export nuclear technologies and equipment. These two ingredients, combined with the rapid shrinkage of worldwide fossil fuel reserves, will increase the utilization of nuclear power. All countries utilizing nuclear power produce at least a few tens of tons of spent fuel per year. That spent fuel (and reprocessing products, if any) constitutes high-level nuclear waste. Toxicity, long half-life, and immunity to chemical degradation make such waste an almost permanent threat to human beings. This report discusses the advantages of utilizing repositories for disposal of nuclear wastes

  15. High-level waste processing and disposal

    International Nuclear Information System (INIS)

    Crandall, J.L.; Krause, H.; Sombret, C.; Uematsu, K.

    1984-11-01

    Without reprocessing, spent LWR fuel itself is generally considered an acceptable waste form. With reprocessing, borosilicate glass canisters, have now gained general acceptance for waste immobilization. The current first choice for disposal is emplacement in an engineered structure in a mined cavern at a depth of 500-1000 meters. A variety of rock types are being investigated including basalt, clay, granite, salt, shale, and volcanic tuff. This paper gives specific coverage to the national high level waste disposal plans for France, the Federal Republic of Germany, Japan and the United States. The French nuclear program assumes prompt reprocessing of its spent fuels, and France has already constructed the AVM. Two larger borosilicate glass plants are planned for a new French reprocessing plant at La Hague. France plans to hold the glass canisters in near-surface storage for a forty to sixty year cooling period and then to place them into a mined repository. The FRG and Japan also plan reprocessing for their LWR fuels. Both are currently having some fuel reprocessed by France, but both are also planning reprocessing plants which will include waste vitrification facilities. West Germany is now constructing the PAMELA Plant at Mol, Belgium to vitrify high level reprocessing wastes at the shutdown Eurochemic Plant. Japan is now operating a vitrification mockup test facility and plans a pilot plant facility at the Tokai reprocessing plant by 1990. Both countries have active geologic repository programs. The United State program assumes little LWR fuel reprocessing and is thus primarily aimed at direct disposal of spent fuel into mined repositories. However, the US have two borosilicate glass plants under construction to vitrify existing reprocessing wastes

  16. Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate.

    Directory of Open Access Journals (Sweden)

    Maxi Meissner

    Full Text Available AIMS/HYPOTHESIS: Bile acid sequestrants (BAS reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet Colesevelam HCl (BAS for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13C]-glucose, [2-(13C]-glycerol, [1-(2H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001, a ∼300% increased glucokinase flux (p = 0.001 and a ∼200% increased total hepatic glucose production rate (p = 0.0002. BAS treatment increased glucose metabolic clearance rate by ∼37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317 but not in liver (p = 0.189. Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030 and 3-fold in db/db mice (p = 0.002. CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.

  17. Oat beta-glucan ameliorates insulin resistance in mice fed on high-fat and high-fructose diet

    Directory of Open Access Journals (Sweden)

    Jie Zheng

    2013-12-01

    Full Text Available Methods: This study sought to evaluate the impact of oat beta-glucan on insulin resistance in mice fed on high-fat and high-fructose diet with fructose (10%, w/v added in drinking water for 10 weeks. Results: The results showed that supplementation with oat beta-glucan could significantly reduce the insulin resistance both in low-dose (200 mg/kg−1 body weight and high-dose (500 mg/kg−1 body weight groups, but the high-dose group showed a more significant improvement in insulin resistance (P<0.01 compared with model control (MC group along with significant improvement in hepatic glycogen level, oral glucose, and insulin tolerance. Moreover, hepatic glucokinase activity was markedly enhanced both in low-dose and high-dose groups compared with that of MC group (P<0.05. Conclusion: These results suggested that supplementation of oat beta-glucan alleviated insulin resistance and the effect was dose dependent.

  18. In vivo variation of micronuclei in BALB/c mice after low and high doses of gamma radiation

    International Nuclear Information System (INIS)

    Strain, D.; Allen, B.J.

    1996-01-01

    Full text: An adaptive response to ionising radiation exists if a low level or priming dose reduces the effect of a subsequent high or challenge dose. This has been demonstrated in vitro using the frequency of micronuclei formation as a measure of radiation-induced DNA damage. The objective of this project was to use the same approach with an animal model to investigate the existence of an in vivo adaptive response. The experimental design involved priming doses of 0.005 or 0.01 Gy and a challenge dose of 4 Gy administered 1, 2, 4, 8 or 16 hours after the priming dose. Ten mice at a time were housed in a perspex animal cage and irradiated using Co-60 gamma radiation. For every time point (1, 2, 4, 8 or 16 hours), there were four treatment groups of 5 mice for statistical analysis. The first group acted as a non-irradiated control (0 Gy). The second group of mice received only the priming dose (0.005 Gy), while the third group of mice received only the challenge dose (4 Gy). The fourth group of mice received both the priming and challenge doses 0.005 Gy + 4 Gy). The process was repeated for the second priming dose of 0.01 Gy. A total of 200 mice were used. The animals were sacrificed by cervical dislocation 24 hours after receiving the challenge dose. Both femora were removed and cleared of adhering muscle tissue. The bone marrow cells of five mice were collected and the nucleated cells removed using filtration through a mixed cellulose column incorporating a self-locking filter. The cell suspension was placed onto microscope slides using a cytocentrifuge, air-dried and then stained for the micronuclei. Then the slides were coded, and reticulocytes were scored for the presence or absence of micronuclei. Approximately 2500 cells were scored for each treatment point, and the number of micronuclei counted ranged from 3 to 125 in this sample size. While it appears that the adaptive response may be present in 2 of 9 groups of mice pre-exposed to 0.005 or 0.01 Gy, this

  19. High Intensity Interval Training Improves Physical Performance and Frailty in Aged Mice.

    Science.gov (United States)

    Seldeen, Kenneth Ladd; Lasky, Ginger; Leiker, Merced Marie; Pang, Manhui; Personius, Kirkwood Ely; Troen, Bruce Robert

    2018-03-14

    Sarcopenia and frailty are highly prevalent in older individuals, increasing the risk of disability and loss of independence. High intensity interval training (HIIT) may provide a robust intervention for both sarcopenia and frailty by achieving both strength and endurance benefits with lower time commitments than other exercise regimens. To better understand the impacts of HIIT during aging, we compared 24-month-old C57BL/6J sedentary mice with those that were administered 10-minute uphill treadmill HIIT sessions three times per week over 16 weeks. Baseline and end point assessments included body composition, physical performance, and frailty based on criteria from the Fried physical frailty scale. HIIT-trained mice demonstrated dramatic improvement in grip strength (HIIT 10.9% vs -3.9% in sedentary mice), treadmill endurance (32.6% vs -2.0%), and gait speed (107.0% vs 39.0%). Muscles from HIIT mice also exhibited greater mass, larger fiber size, and an increase in mitochondrial biomass. Furthermore, HIIT exercise led to a dramatic reduction in frailty scores in five of six mice that were frail or prefrail at baseline, with four ultimately becoming nonfrail. The uphill treadmill HIIT exercise sessions were well tolerated by aged mice and led to performance gains, improvement in underlying muscle physiology, and reduction in frailty.

  20. Anti-diabetic effects of DA-11004, a synthetic IDPc inhibitor in high fat high sucrose diet-fed C57BL/6J mice.

    Science.gov (United States)

    Shin, Chang Yell; Jung, Mi Young; Lee, In Ki; Son, Miwon; Kim, Dong Sung; Lim, Joong In; Kim, Soon Hoe; Yoo, Moohi; Huh, Tae Lin; Sohn, Young Taek; Kim, Won Bae

    2004-01-01

    DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc) inhibitor where IC50 for IDPc is 1.49 microM. The purpose of this study was to evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced obesity in male C57BL/6J mice. After completing a 8-week period of experimentation, the mice were sacrificed 1 hr after the last DA-11004 treatment and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat) were collected. There was a significant difference in the pattern of increasing body weight between the HF control and the DA-11004 group. In the DA-11004 (100 mg/kg) treated group the increase in body weight significantly declined and a content of epididymal fat and retroperitoneal fat was also significantly decreased as opposed to the HF control. DA-11004 (100 mg/ kg) inhibited the IDPc activity, and thus, NADPH levels in plasma and the levels of free fatty acid (FFA) or glucose in plasma were less than the levels of the HF control group. In conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet-induced obesity of C57BL/6J mice.

  1. Effects of α-Galactooligosaccharides from Chickpeas on High-Fat-Diet-Induced Metabolic Syndrome in Mice.

    Science.gov (United States)

    Dai, Zhuqing; Lyu, Wanyong; Xie, Minhao; Yuan, Qingxia; Ye, Hong; Hu, Bing; Zhou, Li; Zeng, Xiaoxiong

    2017-04-19

    The gut microbiota has the ability to modulate host energy homeostasis, which may regulate metabolic disorders. Functional oligosaccharide may positively regulate the intestinal microbiota. Therefore, effects of α-galactooligosaccharides (α-GOS) from chickpea on high-fat-diet (HFD)-induced metabolic syndrome and gut bacterial dysbiosis were investigated. After 6 weeks of intervention, HFD led to significant increases in levels of blood glucose, total cholesterol, triglyceride, glycated serum protein, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol of mice compared to normal-chow-fed mice. Meanwhile, all of the α-GOS-treated groups significantly decreased above parameters compared to the HFD group. HFD could significantly decrease the content of all bacteria, especially Bacteroides (9.82 ± 0.09 versus 10.3 ± 0.10; p bacterial ecosystem in a positive way.

  2. Effects of angiotensin (1-7 on nephrosis of the mice with metabolic syndrome induced by high-salt and high-fat diet

    Directory of Open Access Journals (Sweden)

    Nan ZHU

    2013-11-01

    Full Text Available Objective  To establish a metabolic syndrome model of C57BL/6 mice by high-salt and high-fat diet, and investigate the effects of angiotensin converting enzyme 2 (ACE 2 and angiotensin (1-7 on renal damage in mice. Methods Fifty-six male C57BL/6 mice were randomly divided into 7 groups (8 each, and fed with normal diet (0.3% NaCl, 10% fat, high-salt diet (8% NaCl, 10% fat, high-fat diet (0.3% NaCl, 60% fat, high-salt and high-fat diet (8% NaCl, 60% fat, high-salt and high-fat diet with enalapril 20mg/(kg•d, with valsartan 50mg/(kg•d, and with valsartan 50mg/(kg•d plus Mas receptor antagonist (A-779 150ng/(kg•d, respectively for 16 weeks. Basal metabolic index including blood pressure, body weight, blood glucose and urinary albumin excretion rate (UAER were tested. After intraperitoneal anesthesia with chloral hydrate, the blood was collected from the carotid artery. Serum angiotensin Ⅱ and angiotensin (1-7 levels were detected by ELISA; Western blotting was performed to evaluate the expression of ACE 2 protein and collagen Ⅲ in renal tissue; renal pathological changes were observed by HE and Masson staining. Results The blood pressure, ratio of visceral fat weight/body weight, blood lipid, blood glucose and UAER increased significantly in the C57BL/6 mice fed with high-salt and high-fat diet for 16 weeks, and the renal fibrosis change was obvious, serum angiotensin Ⅱ level increased, expressions of ACE 2 and angiotensin (1-7 decreased significantly in the renal tissue. In different intervention groups, valsartan obviously alleviated the abnormal metabolism, ameliorated renal injury, promoted the expression of ACE2 and angiotensin (1-7 in the kidney and serum. However, no significant change was observed in the groups with intervention of enalapril or valsartan+A-779 compared with non-intervention group. Conclusions High-salt and high-fat diet can be used to successfully establish the model of metabolic syndrome in C57BL/6

  3. Circular swimming in mice after exposure to a high magnetic field.

    Science.gov (United States)

    Houpt, Thomas A; Houpt, Charles E

    2010-06-16

    There is increasing evidence that exposure to high magnetic fields of 4T and above perturbs the vestibular system of rodents and humans. Performance in a swim test is a sensitive test of vestibular function. In order to determine the effect of magnet field exposure on swimming in mice, mice were exposed for 30 min within a 14.1T superconducting magnet and then tested at different times after exposure in a 2-min swim test. As previously observed in open field tests, mice swam in tight counter-clockwise circles when tested immediately after magnet exposure. The counter-clockwise orientation persisted throughout the 2-min swim test. The tendency to circle was transient, because no significant circling was observed when mice were tested at 3 min or later after magnet exposure. However, mice did show a decrease in total distance swum when tested between 3 and 40 min after magnet exposure. The decrease in swimming distance was accompanied by a pronounced postural change involving a counter-clockwise twist of the pelvis and hindlimbs that was particularly severe in the first 15s of the swim test. Finally, no persistent difference from sham-exposed mice was seen in the swimming of magnet-exposed mice when tested 60 min, 24h, or 96 h after magnet exposure. This suggests that there is no long-lasting effect of magnet exposure on the ability of mice to orient or swim. The transient deficits in swimming and posture seen shortly after magnet exposure are consistent with an acute perturbation of the vestibular system by the high magnetic field. (c) 2010 Elsevier Inc. All rights reserved.

  4. Puberty is delayed in male mice with dextran sodium sulfate colitis out of proportion to changes in food intake, body weight, and serum levels of leptin.

    Science.gov (United States)

    Deboer, Mark D; Li, Yongli

    2011-01-01

    In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

  5. Effect of GABA receptor agonists or antagonists injected spinally on the blood glucose level in mice.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

    2013-05-01

    The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABAB receptor agonist; 1-10 μg/5 μl) or bicuculline (a GABAA receptor antagonist; 1-10 μg/5 μl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABAA receptor agonist; 1-5 μg/5 μl) or phaclofen (a GABAB receptor antagonist; 5-10 μg/5 μl) administered i.t. did not affect the blood glucose level. Baclofen-induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 μg/5 μl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABAB receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABAA receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.

  6. Dissociation of hepatic insulin resistance from susceptibility of nonalcoholic fatty liver disease induced by a high-fat and high-carbohydrate diet in mice.

    Science.gov (United States)

    Asai, Akihiro; Chou, Pauline M; Bu, Heng-Fu; Wang, Xiao; Rao, M Sambasiva; Jiang, Anthony; DiDonato, Christine J; Tan, Xiao-Di

    2014-03-01

    Liver steatosis in nonalcoholic fatty liver disease is affected by genetics and diet. It is associated with insulin resistance (IR) in hepatic and peripheral tissues. Here, we aimed to characterize the severity of diet-induced steatosis, obesity, and IR in two phylogenetically distant mouse strains, C57BL/6J and DBA/2J. To this end, mice (male, 8 wk old) were fed a high-fat and high-carbohydrate (HFHC) or control diet for 16 wk followed by the application of a combination of classic physiological, biochemical, and pathological studies to determine obesity and hepatic steatosis. Peripheral IR was characterized by measuring blood glucose level, serum insulin level, homeostasis model assessment of IR, glucose intolerance, insulin intolerance, and AKT phosphorylation in adipose tissues, whereas the level of hepatic IR was determined by measuring insulin-triggered hepatic AKT phosphorylation. We discovered that both C57BL/6J and DBA/2J mice developed obesity to a similar degree without the feature of liver inflammation after being fed an HFHC diet for 16 wk. C57BL/6J mice in the HFHC diet group exhibited severe pan-lobular steatosis, a marked increase in hepatic triglyceride levels, and profound peripheral IR. In contrast, DBA/2J mice in the HFHC diet group developed only a mild degree of pericentrilobular hepatic steatosis that was associated with moderate changes in peripheral IR. Interestingly, both C57BL/6J and DBA/2J developed severe hepatic IR after HFHC diet treatment. Collectively, these data suggest that the severity of diet-induced hepatic steatosis is correlated to the level of peripheral IR, not with the severity of obesity and hepatic IR. Peripheral rather than hepatic IR is a dominant factor of pathophysiology in nonalcoholic fatty liver disease.

  7. Mice selected for high versus low stress reactivity: a new animal model for affective disorders.

    Science.gov (United States)

    Touma, Chadi; Bunck, Mirjam; Glasl, Lisa; Nussbaumer, Markus; Palme, Rupert; Stein, Hendrik; Wolferstätter, Michael; Zeh, Ramona; Zimbelmann, Marina; Holsboer, Florian; Landgraf, Rainer

    2008-07-01

    Affective disorders such as major depression are among the most prevalent and costly diseases of the central nervous system, but the underlying mechanisms are still poorly understood. In recent years, it has become evident that alterations of the stress hormone system, in particular dysfunctions (hyper- or hypo-activity) of the hypothalamic-pituitary-adrenal (HPA) axis, play a prominent role in the development of major depressive disorders. Therefore, we aimed to generate a new animal model comprising these neuroendocrine core symptoms in order to unravel parameters underlying increased or decreased stress reactivity. Starting from a population of outbred mice (parental generation: 100 males and 100 females of the CD-1 strain), two breeding lines were established according to the outcome of a 'stress reactivity test' (SRT), consisting of a 15-min restraint period and tail blood samplings immediately before and after exposure to the stressor. Mice showing a very high or a very low secretion of corticosterone in the SRT, i.e. animals expressing a hyper- or a hypo-reactivity of the HPA axis, were selected for the 'high reactivity' (HR) and the 'low reactivity' (LR) breeding line, respectively. Additionally, a third breeding line was established consisting of animals with an 'intermediate reactivity' (IR) in the SRT. Already in the first generation, i.e. animals derived from breeding pairs selected from the parental generation, significant differences in the reactivity of the HPA axis between HR, IR, and LR mice were observed. Moreover, these differences were found across all subsequent generations and could be increased by selective breeding, which indicates a genetic basis of the respective phenotype. Repeated testing of individuals in the SRT furthermore proved that the observed differences in stress responsiveness are present already early in life and can be regarded as a robust genetic predisposition. Tests investigating the animal's emotionality including anxiety

  8. High-Throughput Automatic Training System for Odor-Based Learned Behaviors in Head-Fixed Mice

    Directory of Open Access Journals (Sweden)

    Zhe Han

    2018-02-01

    Full Text Available Understanding neuronal mechanisms of learned behaviors requires efficient behavioral assays. We designed a high-throughput automatic training system (HATS for olfactory behaviors in head-fixed mice. The hardware and software were constructed to enable automatic training with minimal human intervention. The integrated system was composed of customized 3D-printing supporting components, an odor-delivery unit with fast response, Arduino based hardware-controlling and data-acquisition unit. Furthermore, the customized software was designed to enable automatic training in all training phases, including lick-teaching, shaping and learning. Using HATS, we trained mice to perform delayed non-match to sample (DNMS, delayed paired association (DPA, Go/No-go (GNG, and GNG reversal tasks. These tasks probed cognitive functions including sensory discrimination, working memory, decision making and cognitive flexibility. Mice reached stable levels of performance within several days in the tasks. HATS enabled an experimenter to train eight mice simultaneously, therefore greatly enhanced the experimental efficiency. Combined with causal perturbation and activity recording techniques, HATS can greatly facilitate our understanding of the neural-circuitry mechanisms underlying learned behaviors.

  9. Galantamine Alleviates Inflammation and Other Obesity-Associated Complications in High-Fat Diet–Fed Mice

    Science.gov (United States)

    Satapathy, Sanjaya K; Ochani, Mahendar; Dancho, Meghan; Hudson, LaQueta K; Rosas-Ballina, Mauricio; Valdes-Ferrer, Sergio I; Olofsson, Peder S; Harris, Yael Tobi; Roth, Jesse; Chavan, Sangeeta; Tracey, Kevin J; Pavlov, Valentin A

    2011-01-01

    Obesity, a serious and growing health threat, is associated with low-grade inflammation that plays a role in mediating its adverse consequences. Previously, we have discovered a role for neural cholinergic signaling in controlling inflammation, and demonstrated that the cholinergic agent galantamine suppresses excessive proinflammatory cytokine release. The main objective of this study was to examine the efficacy of galantamine, a clinically-approved drug, in alleviating obesity-related inflammation and associated complications. After 8 wks on a high-fat diet, C57BL/6J mice were treated with either galantamine (4 mg/kg, intraperitoneally [i.p.]) or saline for 4 wks in parallel with mice on a low-fat diet and treated with saline. Galantamine treatment of obese mice significantly reduced body weight, food intake, abdominal adiposity, plasma cytokine and adipokine levels, and significantly improved blood glucose, insulin resistance and hepatic steatosis. In addition, galantamine alleviated impaired insulin sensitivity and glucose intolerance significantly. These results indicate a previously unrecognized potential of galantamine in alleviating obesity, inflammation and other obesity-related complications in mice. These findings are of interest for studying the efficacy of this clinically-approved drug in the context of human obesity and metabolic syndrome. PMID:21738953

  10. Puberty Is Delayed in Male Mice With Dextran Sodium Sulfate Colitis Out of Proportion to Changes in Food Intake, Body Weight, and Serum Levels of Leptin

    OpenAIRE

    DEBOER, MARK D.; LI, YONGLI

    2011-01-01

    In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the ...

  11. High-level radioactive waste management

    International Nuclear Information System (INIS)

    Schneider, K.J.; Liikala, R.C.

    1974-01-01

    High-level radioactive waste in the U.S. will be converted to an encapsulated solid and shipped to a Federal repository for retrievable storage for extended periods. Meanwhile the development of concepts for ultimate disposal of the waste which the Federal Government would manage is being actively pursued. A number of promising concepts have been proposed, for which there is high confidence that one or more will be suitable for long-term, ultimate disposal. Initial evaluations of technical (or theoretical) feasibility for the various waste disposal concepts show that in the broad category, (i.e., geologic, seabed, ice sheet, extraterrestrial, and transmutation) all meet the criteria for judging feasibility, though a few alternatives within these categories do not. Preliminary cost estimates show that, although many millions of dollars may be required, the cost for even the most exotic concepts is small relative to the total cost of electric power generation. For example, the cost estimates for terrestrial disposal concepts are less than 1 percent of the total generating costs. The cost for actinide transmutation is estimated at around 1 percent of generation costs, while actinide element disposal in space is less than 5 percent of generating costs. Thus neither technical feasibility nor cost seems to be a no-go factor in selecting a waste management system. The seabed, ice sheet, and space disposal concepts face international policy constraints. The information being developed currently in safety, environmental concern, and public response will be important factors in determining which concepts appear most promising for further development

  12. The Lack of Cytotoxic Effect and Radioadaptive Response in Splenocytes of Mice Exposed to Low Level Internal β-Particle Irradiation through Tritiated Drinking Water in Vivo

    Directory of Open Access Journals (Sweden)

    Matthew Flegal

    2013-12-01

    Full Text Available Health effects of tritium, a β-emitter and a by-product of the nuclear industry, is a subject of significant controversy. This mouse in vivo study was undertaken to monitor biological effects of low level tritium exposure. Mice were exposed to tritiated drinking water (HTO at 10 KBq/L, 1 MBq/L and 20 MBq/L concentrations for one month. The treatment did not result in a significant increase of apoptosis in splenocytes. To examine if this low level tritium exposure alters radiosensitivity, the extracted splenocytes were challenged in vitro with 2 Gy γ-radiation, and apoptotic responses at 1 and 24 h were measured. No alterations in the radiosensitivity were detected in cells from mice exposed to tritium compared to sham-treated mice. In contrast, low dose γ-irradiation at 20 or 100 mGy, resulted in a significant increase in resistance to apoptotic cell death after 2 Gy irradiation; an indication of the radioadaptive response. Overall, our data suggest that low concentrations of tritium given to mice as HTO in drinking water do not exert cytotoxic effect in splenocytes, nor do they change cellular sensitivity to additional high dose γ-radiation. The latter may be considered as the lack of a radioadaptive response, typically observed after low dose γ-irradiation.

  13. Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.

    Science.gov (United States)

    Geng, Shanshan; Zhu, Weiwei; Xie, Chunfeng; Li, Xiaoting; Wu, Jieshu; Liang, Zhaofeng; Xie, Wei; Zhu, Jianyun; Huang, Cong; Zhu, Mingming; Wu, Rui; Zhong, Caiyun

    2016-04-01

    The aim of the present study was to investigate the in vivo effects of dietary medium-chain triglyceride (MCT) on inflammation and insulin resistance as well as the underlying potential molecular mechanisms in high fat diet-induced obese mice. Male C57BL/6J mice (n = 24) were fed one of the following three diets for a period of 12 weeks: (1) a modified AIN-76 diet with 5 % corn oil (normal diet); (2) a high-fat control diet (17 % w/w lard and 3 % w/w corn oil, HFC); (3) an isocaloric high-fat diet supplemented with MCT (17 % w/w MCT and 3 % w/w corn oil, HF-MCT). Glucose metabolism was evaluated by fasting blood glucose levels and intraperitoneal glucose tolerance test. Insulin sensitivity was evaluated by fasting serum insulin levels and the index of homeostasis model assessment-insulin resistance. The levels of serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α were measured by ELISA, and hepatic activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was determined using western blot analysis. Compared to HFC diet, consumption of HF-MCT did not induce body weight gain and white adipose tissue accumulation in mice. HFC-induced increases in serum fasting glucose and insulin levels as well as glucose intolerance were prevented by HF-MCT diet. Meanwhile, HF-MCT resulted in significantly lower serum IL-6 level and higher IL-10 level, and lower expression levels of inducible nitric oxide synthase and cyclooxygenase-2 protein in liver tissues when compared to HFC. In addition, HF-MCT attenuated HFC-triggered hepatic activation of NF-κB and p38 MAPK. Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.

  14. Whey protein reduces early life weight gain in mice fed a high-fat diet

    DEFF Research Database (Denmark)

    Tranberg, Britt; Hellgren, Lars; Lykkesfeldt, Jens

    2013-01-01

    An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would...... be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel...... reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota...

  15. Vitrification of high-level liquid wastes

    International Nuclear Information System (INIS)

    Varani, J.L.; Petraitis, E.J.; Vazquez, Antonio.

    1987-01-01

    High-level radioactive liquid wastes produced in the fuel elements reprocessing require, for their disposal, a preliminary treatment by which, through a series of engineering barriers, the dispersion into the biosphere is delayed by 10 000 years. Four groups of compounds are distinguished among a great variety of final products and methods of elaboration. From these, the borosilicate glasses were chosen. Vitrification experiences were made at a laboratory scale with simulated radioactive wastes, employing different compositions of borosilicate glass. The installations are described. A series of tests were carried out on four basic formulae using always the same methodology, consisting of a dry mixture of the vitreous matrix's products and a dry simulated mixture. Several quality tests of the glasses were made 1: Behaviour in leaching following the DIN 12 111 standard; 2: Mechanical resistance; parameters related with the facility of the different glasses for increasing their surface were studied; 3: Degree of devitrification: it is shown that devitrification turns the glasses containing radioactive wastes easily leachable. From all the glasses tested, the composition SiO 2 , Al 2 O 3 , B 2 O 3 , Na 2 O, CaO shows the best retention characteristics. (M.E.L.) [es

  16. Ocean disposal of high level radioactive waste

    International Nuclear Information System (INIS)

    1983-01-01

    This study confirms, subject to limitations of current knowledge, the engineering feasibility of free fall penetrators for High Level Radioactive Waste disposal in deep ocean seabed sediments. Restricted sediment property information is presently the principal bar to an unqualified statement of feasibility. A 10m minimum embedment and a 500 year engineered barrier waste containment life are identified as appropriate basic penetrator design criteria at this stage. A range of designs are considered in which the length, weight and cross section of the penetrator are varied. Penetrators from 3m to 20m long and 2t to 100t in weight constructed of material types and thicknesses to give a 500 year containment life are evaluated. The report concludes that the greatest degree of confidence is associated with performance predictions for 75 to 200 mm thick soft iron and welded joints. A range of lengths and capacities from a 3m long single waste canister penetrator to a 20m long 12 canister design are identified as meriting further study. Estimated embedment depths for this range of penetrator designs lie between 12m and 90m. Alternative manufacture, transport and launch operations are assessed and recommendations are made. (author)

  17. Vitrification of high level wastes in France

    International Nuclear Information System (INIS)

    Sombret, C.

    1984-02-01

    A brief historical background of the research and development work conducted in France over 25 years is first presented. Then, the papers deals with the vitrification at (1) the UP1 reprocessing plant (Marcoule) and (2) the UP2 and UP3 reprocessing plants (La Hague). 1) The properties of glass required for high-level radioactive waste vitrification are recalled. The vitrification process and facility of Marcoule are presented. (2) The average characteristics (chemical composition, activity) of LWR fission product solution are given. The glass formulations developed to solidify LWR waste solution must meet the same requirements as those used in the UP1 facility at Marcoule. Three important aspects must be considered with respect to the glass fabrication process: corrosiveness of the molten glass with regard to metals, viscosity of the molten glass, and, volatization during glass fabrication. The glass properties required in view of interim storage and long-term disposal are then largely developed. Two identical vitrification facilities are planned for the site: T7, to process the UP2 throughput, and T7 for the UP3 plant. A prototype unit was built and operated at Marcoule

  18. High-level nuclear waste disposal

    International Nuclear Information System (INIS)

    Burkholder, H.C.

    1985-01-01

    The meeting was timely because many countries had begun their site selection processes and their engineering designs were becoming well-defined. The technology of nuclear waste disposal was maturing, and the institutional issues arising from the implementation of that technology were being confronted. Accordingly, the program was structured to consider both the technical and institutional aspects of the subject. The meeting started with a review of the status of the disposal programs in eight countries and three international nuclear waste management organizations. These invited presentations allowed listeners to understand the similarities and differences among the various national approaches to solving this very international problem. Then seven invited presentations describing nuclear waste disposal from different perspectives were made. These included: legal and judicial, electric utility, state governor, ethical, and technical perspectives. These invited presentations uncovered several issues that may need to be resolved before high-level nuclear wastes can be emplaced in a geologic repository in the United States. Finally, there were sixty-six contributed technical presentations organized in ten sessions around six general topics: site characterization and selection, repository design and in-situ testing, package design and testing, disposal system performance, disposal and storage system cost, and disposal in the overall waste management system context. These contributed presentations provided listeners with the results of recent applied RandD in each of the subject areas

  19. Decontamination of high-level waste canisters

    International Nuclear Information System (INIS)

    Nesbitt, J.F.; Slate, S.C.; Fetrow, L.K.

    1980-12-01

    This report presents evaluations of several methods for the in-process decontamination of metallic canisters containing any one of a number of solidified high-level waste (HLW) forms. The use of steam-water, steam, abrasive blasting, electropolishing, liquid honing, vibratory finishing and soaking have been tested or evaluated as potential techniques to decontaminate the outer surfaces of HLW canisters. Either these techniques have been tested or available literature has been examined to assess their applicability to the decontamination of HLW canisters. Electropolishing has been found to be the most thorough method to remove radionuclides and other foreign material that may be deposited on or in the outer surface of a canister during any of the HLW processes. Steam or steam-water spraying techniques may be adequate for some applications but fail to remove all contaminated forms that could be present in some of the HLW processes. Liquid honing and abrasive blasting remove contamination and foreign material very quickly and effectively from small areas and components although these blasting techniques tend to disperse the material removed from the cleaned surfaces. Vibratory finishing is very capable of removing the bulk of contamination and foreign matter from a variety of materials. However, special vibratory finishing equipment would have to be designed and adapted for a remote process. Soaking techniques take long periods of time and may not remove all of the smearable contamination. If soaking involves pickling baths that use corrosive agents, these agents may cause erosion of grain boundaries that results in rough surfaces

  20. Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high-fat diet-fed mice.

    Science.gov (United States)

    Katsumura, Masanori; Takagi, Shoko; Oya, Hana; Tamura, Shohei; Saneyasu, Takaoki; Honda, Kazuhisa; Kamisoyama, Hiroshi

    2017-08-01

    Animal by-products can be recycled and used as sources of essential nutrients. Water-soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high-fat diet. Exercise-trained mice had significantly less perirenal adipose tissue, whereas WSHI-fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone-sensitive lipase. WSHI-fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation-related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism-related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high-fat diet. © 2016 Japanese Society of Animal Science.

  1. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Wang, Dongmei; Yan, Junqiang; Chen, Jing; Wu, Wenlan; Zhu, Xiaoying; Wang, Yong

    2015-10-01

    The epidemic and experimental studies have confirmed that the obesity induced by high-fat diet not only caused neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment in mice. Naringin has been reported to posses biological functions which are beneficial to human cognitions, but its protective effects on HFD-induced cognitive deficits and underlying mechanisms have not been well characterized. In the present study Male C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then randomized into four groups treated with their respective diets including control diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin (HFDN). The behavioral performance was assessed by using novel object recognition test and Morris water maze test. Hippocampal mitochondrial parameters were analyzed. Then the protein levels of insulin signaling pathway and the AMP-activated protein kinase (AMPK) in the hippocampus were detected by Western blot method. Our results showed that oral administration of naringin significantly improved the learning and memory abilities as evidenced by increasing recognition index by 52.5% in the novel object recognition test and inducing a 1.05-fold increase in the crossing-target number in the probe test, and ameliorated mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin significantly enhanced insulin signaling pathway as indicated by a 34.5% increase in the expression levels of IRS-1, a 47.8% decrease in the p-IRS-1, a 1.43-fold increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3β in the hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity significantly increased in the naringin-treated (100 mg kg(-1) d(-1)) group. These findings suggest that an enhancement in insulin signaling and a decrease in mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms that naringin

  2. Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice.

    Science.gov (United States)

    Wang, Zhi; Li, Liaoliao; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2015-08-01

    Obesity can cause pathological changes in organs. We determined the effects of chronic high fat diet (HFD) and intermittent fasting, a paradigm providing organ protection, on mouse heart. Seven-week old CD1 male mice were randomly assigned to control, HFD and intermittent fasting groups. Control mice had free access to regular diet (RD). RD was provided every other day to mice in the intermittent fasting group. Mice in HFD group had free access to HFD. Their left ventricles were harvested 11 months after they had been on these diet regimens. HFD increased cardiomyocyte cross-section area and fibrosis. HFD decreased active caspase 3, an apoptosis marker, and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3I, an autophagy marker. HFD increased the phospho-glycogen synthase kinase-3β (GSK-3β) at Ser9, a sign of GSK-3β inhibition. Nuclear GATA binding protein 4 and yes-associated protein, two GSK-3β targeting transcription factors that can induce hypertrophy-related gene expression, were increased in HFD-fed mice. Mice on intermittent fasting did not have these changes except for the increased active caspase 3 and decreased ratio of LC3II/LC3I. These results suggest that chronic HFD induces myocardial hypertrophy and fibrosis, which may be mediated by GSK-3β inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Intestinal epithelial cell surface glycosylation in mice. I. Effect of high-protein diet.

    Science.gov (United States)

    Gupta, R; Jaswal, V M; Meenu Mahmood, A

    1992-01-01

    The effects of variation in dietary protein content have been investigated on brush border glycosylation and enzyme activities in mice small intestine. The comparison of different parameters was made between the mice fed 30% (high protein, HP) and 18% protein (pair-fed, PF, and ad libitum-fed) for 21 days. The activities of brush border sucrase, lactase, p-nitrophenyl (PNP)-beta-D-glucosidase and PNP-beta-D-galactosidase were reduced in the HP diet-fed mice compared to PF and ad libitum-fed controls. Alkaline phosphatase and leucine amino-peptidase activities were significantly enhanced while gamma-glutamyl transpeptidase activity was unaltered under these conditions. Total hexoses and sialic acid content in the brush borders were reduced significantly in the test group compared to the controls while hexosamine and fucose contents remained essentially similar in different groups. The results on the binding of wheat germ agglutinin and Ulex europaeus agglutininI to microvillus membranes corroborated the chemical analysis data on sialic acid and fucose contents of the membranes. Peanut agglutinin binding was enhanced in mice from the HP group. Incorporation of (14C)-mannose into membranes was significantly less in HP diet-fed mice. These results indicate that the feeding of HP diet to mice brings about marked alterations in small intestinal epithelial cell surface glycosylation and enzyme functions.

  4. High fat diet drives obesity regardless the composition of gut microbiota in mice.

    Science.gov (United States)

    Rabot, Sylvie; Membrez, Mathieu; Blancher, Florence; Berger, Bernard; Moine, Déborah; Krause, Lutz; Bibiloni, Rodrigo; Bruneau, Aurélia; Gérard, Philippe; Siddharth, Jay; Lauber, Christian L; Chou, Chieh Jason

    2016-08-31

    The gut microbiota is involved in many aspects of host physiology but its role in body weight and glucose metabolism remains unclear. Here we studied the compositional changes of gut microbiota in diet-induced obesity mice that were conventionally raised or received microbiota transplantation. In conventional mice, the diversity of the faecal microbiota was weakly associated with 1(st) week weight gain but transferring the microbiota of mice with contrasting weight gain to germfree mice did not change obesity development or feed efficiency of recipients regardless whether the microbiota was taken before or after 10 weeks high fat (HF) feeding. Interestingly, HF-induced glucose intolerance was influenced by microbiota inoculation and improved glucose tolerance was associated with a low Firmicutes to Bacteroidetes ratio. Transplantation of Bacteroidetes rich microbiota compared to a control microbiota ameliorated glucose intolerance caused by HF feeding. Altogether, our results demonstrate that gut microbiota is involved in the regulation of glucose metabolism and the abundance of Bacteroidetes significantly modulates HF-induced glucose intolerance but has limited impact on obesity in mice. Our results suggest that gut microbiota is a part of complex aetiology of insulin resistance syndrome, individual microbiota composition may cause phenotypic variation associated with HF feeding in mice.

  5. Hoxa5 Promotes Adipose Differentiation via Increasing DNA Methylation Level and Inhibiting PKA/HSL Signal Pathway in Mice

    Directory of Open Access Journals (Sweden)

    Weina Cao

    2018-02-01

    Full Text Available Background/Aims: Impaired adipogenesis may be the underlying cause in the development of obesity and type II diabetes. Mechanistically, the family of Homeobox transcription factors is implicated in the regulation of adipocyte fate. Hoxa5 is highly expressed in adipocytes, and its mRNA expression is decreased during differentiation. However, the function of Hoxa5 in adipose tissue has been poorly understood. The aim of this study is to unveil the role of Hoxa5 on adipocyte differentiation and its underlying mechanisms. Methods: Quantitative real-time PCR (qPCR and western blot were performed to determine Hoxa5 expression in primary adipocytes and in adipose tissues from mice. Lipid accumulation was evaluated by bodipy staining. Dual luciferase assay was applied to explore the transcription factor of Hoxa5 and the transcriptional target gene modulated by Hoxa5. All measurements were performed at least for three times at least. Results: A significant reduction of Hoxa5 expression was observed in adipose tissue of High Fat Diet (HFD induced obesity mice. We determined Hoxa5 increased adipocytes differentiation and mitochondrial biogenesis in adipocytes in vitro. CEBPβ was determined a transcription factor of Hoxa5 and inhibited methylation level of Hoxa5 by combining on the promoter of Hoxa5. Importantly, we found Fabp4, a known positive regulator of adipocytes differentiation, was transcriptional activation by Hoxa5. In addition, Hoxa5 promotes adipocytes differentiation by inhibiting PKA/HSL pathway. Conclusion: Our study demonstrated the promoting role of Hoxa5 in adipocytes differentiation and therefore bringing a new therapeutic mean to the treatment of obesity and type II diabetes.

  6. Mechanisms of an increased level of serum iron in gamma-irradiated mice

    International Nuclear Information System (INIS)

    Xie, Li-hua; Zhang, Xiao-hong; Hu, Xiao-dan; Min, Xuan-yu; Zhou, Qi-fu; Zhang, Hai-qian

    2016-01-01

    The potential mechanisms underlying the increase in serum iron concentration in gamma-irradiated mice were studied. The gamma irradiation dose used was 4 Gy, and cobalt-60 ( 60 Co) source was used for the irradiation. The dose rate was 0.25 Gy/min. In the serum of irradiated mice, the concentration of ferrous ions decreased, whereas the serum iron concentration increased. The concentration of ferrous ions in irradiated mice returned to normal at 21 day post-exposure. The concentration of reactive oxygen species in irradiated mice increased immediately following irradiation but returned to normal at 7 day post-exposure. Serum iron concentration in gamma-irradiated mice that were pretreated with reduced glutathione was significant lower (p < 0.01) than that in mice exposed to gamma radiation only. However, the serum iron concentration was still higher than that in normal mice (p < 0.01). This change was biphasic, characterized by a maximal decrease phase occurring immediately after gamma irradiation (relative to the irradiated mice) and a recovery plateau observed during the 7th and 21st day post-irradiation, but serum iron recovery was still less than that in the gamma-irradiated mice (4 Gy). In gamma-irradiated mice, ceruloplasmin activity increased and serum copper concentration decreased immediately after irradiation, and both of them were constant during the 7th and 21st day post-irradiation. It was concluded that ferrous ions in irradiated mice were oxidized to ferric ions by ionizing radiation. Free radicals induced by gamma radiation and ceruloplasmin mutually participated in this oxidation process. The ferroxidase effect of ceruloplasmin was achieved by transfer of electrons from ferrous ions to cupric ions. (orig.)

  7. The effects of Momordica charantia on obesity and lipid profiles of mice fed a high-fat diet.

    Science.gov (United States)

    Wang, Jun; Ryu, Ho Kyung

    2015-10-01

    The present study was conducted to investigate the effects of dried Momordica charantia aqueous extracts (MCA) and ethanol extracts (MCE) on obesity and lipid profiles in mice fed a high-fat diet. Forty two ICR mice were randomly divided into six groups. The normal group was fed a basal diet, and other groups were fed a 45% high-fat diet (HFD) for 7 weeks. The normal and HFD groups were also orally administered distilled water each day for 7 weeks. The remaining groups received Momordica charantia extract (0.5 or 1.0 g/kg/day MCA, and 0.5 or 1.0 g/kg/day MCE). In order to measure the anti-obesity and lipid profile improvement effects, body and visceral tissue weight, lipid profiles, plasma insulin levels, hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. Both MCA and MCE significantly decreased body and visceral tissue weight relative to those of the HFD group (P Momordica charantia extracts have anti-obesity effects and the ability to modulate lipid prolife of mice fed a HFD by suppressing body weight gain, visceral tissue weight, plasma and hepatic lipid concentrations, and lipid peroxidation along with increasing lipid metabolism.

  8. A candidate syntenic genetic locus is associated with voluntary exercise levels in mice and humans

    NARCIS (Netherlands)

    Kostrzewa, E.; Brandys, M. K.; van Lith, H. A.; Kas, M. J H

    2015-01-01

    Individual levels of physical activity, and especially of voluntary physical exercise, highly contribute to the susceptibility for developing metabolic, cardiovascular diseases, and potentially to psychiatric disorders. Here, we applied a cross-species approach to explore a candidate genetic region

  9. Effects of Exercise on Progranulin Levels and Gliosis in Progranulin-Insufficient Mice1,2,3

    Science.gov (United States)

    Arrant, Andrew E.; Patel, Aashka R.

    2015-01-01

    Abstract Loss-of-function mutations in progranulin (GRN) are one of the most common genetic causes of frontotemporal dementia (FTD), a progressive, fatal neurodegenerative disorder with no available disease-modifying treatments. Through haploinsufficiency, these mutations reduce levels of progranulin, a protein that has neurotrophic and anti-inflammatory effects. Increasing progranulin expression from the intact allele is therefore a potential approach for treating individuals with GRN mutations. Based on the well-known effects of physical exercise on other neurotrophic factors, we hypothesized that exercise might increase brain progranulin levels. We tested this hypothesis in progranulin heterozygous (Grn+/−) mice, which model progranulin haploinsufficiency. We housed wild-type and progranulin-insufficient mice in standard cages or cages with exercise wheels for 4 or 7.5 weeks, and then measured brain and plasma progranulin levels. Although exercise modestly increased progranulin in very young (2-month-old) wild-type mice, this effect was limited to the hippocampus. Exercise did not increase brain progranulin mRNA or protein in multiple regions, nor did it increase plasma progranulin, in 4- to 8-month-old wild-type or Grn+/− mice, across multiple experiments and under conditions that increased hippocampal BDNF and neurogenesis. Grn−/−mice were included in the study to test for progranulin-independent benefits of exercise on gliosis. Exercise attenuated cortical microgliosis in 8-month-old Grn−/−mice, consistent with a progranulin-independent, anti-inflammatory effect of exercise. These results suggest that exercise may have some modest, nonspecific benefits for FTD patients with progranulin mutations, but do not support exercise as a strategy to raise progranulin levels. PMID:26361634

  10. The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice.

    Directory of Open Access Journals (Sweden)

    Sharon A McGrath-Morrow

    Full Text Available Electronic cigarette (E-cigarettes emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth.Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml. After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (p<.054 trial 1; p<.006 trial 2. These studies indicate that exposure to E-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

  11. The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice.

    Science.gov (United States)

    McGrath-Morrow, Sharon A; Hayashi, Madoka; Aherrera, Angela; Lopez, Armando; Malinina, Alla; Collaco, Joseph M; Neptune, Enid; Klein, Jonathan D; Winickoff, Jonathan P; Breysse, Patrick; Lazarus, Philip; Chen, Gang

    2015-01-01

    Electronic cigarette (E-cigarettes) emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth. Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG) or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI) method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml). After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (pE-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

  12. Antihyperglycemic and anti-inflammatory effects of fermented food paste in high-fat diet and streptozotocin-challenged mice

    Directory of Open Access Journals (Sweden)

    Zulkawi N

    2018-05-01

    Full Text Available Noraisyah Zulkawi,1 Kam Heng Ng,1 Nur Rizi Zamberi,2,3 Swee Keong Yeap,4 Dilan A Satharasinghe,5 Sheau Wei Tan,2 Wan Yong Ho,6 Nur Yuhasliza Abd Rashid,3 Mohd Izwan Md Lazim,3 Anisah Jamaluddin,3 Noorjahan Banu Alitheen,2,7 Kamariah Long3 1Technical Research – Product Development Department, Elken Global Sdn. Bhd, Kuala Lumpur, Malaysia; 2Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 3Malaysian Agricultural Research and Development Institute (MARDI, Serdang, Selangor, Malaysia; 4China-ASEAN College of Marine Sciences, Xiamen University Malaysia, Sepang, Selangor, Malaysia; 5Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine & Animal Science, University of Peradeniya, Peradeniya, Sri Lanka; 6School of Biomedical Sciences, The University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia; 7Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Background: Fermented food has been widely consumed as health food to ameliorate or prevent several chronic diseases including diabetes. Xeniji™, a fermented food paste (FFP, has been previously reported with various bioactivities, which may be caused by the presence of several metabolites including polyphenolic acids, flavonoids, and vitamins. In this study, the anti-hyperglycemic and anti-inflammatory effects of FFP were assessed. Methods: In this study, type 2 diabetes model mice were induced by streptozotocin and high-fat diet (HFD and used to evaluate the antihyperglycemic and anti-inflammatory effects of FFP. Mice were fed with HFD and challenged with 30 mg/kg body weight (BW of streptozotocin for 1 month followed by 6 weeks of supplementation with 0.1 and 1.0 g/kg BW of FFP. Metformin was used as positive control treatment. Results: Xeniji™-supplemented hyperglycemic mice were recorded with lower glucose level after 6 weeks of duration

  13. TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1

    OpenAIRE

    Allam, Atef; Majji, Sai; Peachman, Kristina; Jagodzinski, Linda; Kim, Jiae; Ratto-Kim, Silvia; Wijayalath, Wathsala; Merbah, Melanie; Kim, Jerome H.; Michael, Nelson L.; Alving, Carl R.; Casares, Sofia; Rao, Mangala

    2015-01-01

    CD4+ T follicular helper cells (TFH) in germinal centers are required for maturation of B-cells. While the role of TFH-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of TFH (CXCR5+PD-1++) and precursor-TFH (CXCR5+PD-1+) cells. The majority of TFH-cells expressed CCR...

  14. DEFENSE HIGH LEVEL WASTE GLASS DEGRADATION

    International Nuclear Information System (INIS)

    Ebert, W.

    2001-01-01

    The purpose of this Analysis/Model Report (AMR) is to document the analyses that were done to develop models for radionuclide release from high-level waste (HLW) glass dissolution that can be integrated into performance assessment (PA) calculations conducted to support site recommendation and license application for the Yucca Mountain site. This report was developed in accordance with the ''Technical Work Plan for Waste Form Degradation Process Model Report for SR'' (CRWMS M andO 2000a). It specifically addresses the item, ''Defense High Level Waste Glass Degradation'', of the product technical work plan. The AP-3.15Q Attachment 1 screening criteria determines the importance for its intended use of the HLW glass model derived herein to be in the category ''Other Factors for the Postclosure Safety Case-Waste Form Performance'', and thus indicates that this factor does not contribute significantly to the postclosure safety strategy. Because the release of radionuclides from the glass will depend on the prior dissolution of the glass, the dissolution rate of the glass imposes an upper bound on the radionuclide release rate. The approach taken to provide a bound for the radionuclide release is to develop models that can be used to calculate the dissolution rate of waste glass when contacted by water in the disposal site. The release rate of a particular radionuclide can then be calculated by multiplying the glass dissolution rate by the mass fraction of that radionuclide in the glass and by the surface area of glass contacted by water. The scope includes consideration of the three modes by which water may contact waste glass in the disposal system: contact by humid air, dripping water, and immersion. The models for glass dissolution under these contact modes are all based on the rate expression for aqueous dissolution of borosilicate glasses. The mechanism and rate expression for aqueous dissolution are adequately understood; the analyses in this AMR were conducted to

  15. Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

    Science.gov (United States)

    Chao, Jung; Huo, Teh-Ia; Cheng, Hao-Yuan; Tsai, Jen-Chieh; Liao, Jiunn-Wang; Lee, Meng-Shiou; Qin, Xue-Mei; Hsieh, Ming-Tsuen; Pao, Li-Heng; Peng, Wen-Huang

    2014-01-01

    Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help

  16. Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice.

    Directory of Open Access Journals (Sweden)

    Desiree Wanders

    Full Text Available To determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity.Male C57BL/6 mice were placed on a control or high-fat diet (HFD and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2 (-/- (niacin receptor(-/- mice.Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2 (-/- mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARγ C/EBPα or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lα, or DsbA-L (key ER chaperones involved in adiponectin production and secretion. However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1β in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice.Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expression in a niacin receptor-dependent manner.

  17. Ceruloplasmin deficiency reduces levels of iron and BDNF in the cortex and striatum of young mice and increases their vulnerability to stroke.

    Directory of Open Access Journals (Sweden)

    Sarah J Texel

    Full Text Available Ceruloplasmin (Cp is an essential ferroxidase that plays important roles in cellular iron trafficking. Previous findings suggest that the proper regulation and subcellular localization of iron are very important in brain cell function and viability. Brain iron dyshomeostasis is observed during normal aging, as well as in several neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, coincident with areas more susceptible to insults. Because of their high metabolic demand and electrical excitability, neurons are particularly vulnerable to ischemic injury and death. We therefore set out to look for abnormalities in the brain of young adult mice that lack Cp. We found that iron levels in the striatum and cerebral cortex of these young animals are significantly lower than wild-type (WT controls. Also mRNA levels of the neurotrophin brain derived neurotrophic factor (BDNF, known for its role in maintenance of cell viability, were decreased in these brain areas. Chelator-mediated depletion of iron in cultured neural cells resulted in reduced BDNF expression by a posttranscriptional mechanism, suggesting a causal link between low brain iron levels and reduced BDNF expression. When the mice were subjected to middle cerebral artery occlusion, a model of focal ischemic stroke, we found increased brain damage in Cp-deficient mice compared to WT controls. Our data indicate that lack of Cp increases neuronal susceptibility to ischemic injury by a mechanism that may involve reduced levels of iron and BDNF.

  18. TFH cells accumulate in mucosal tissues of humanized-DRAG mice and are highly permissive to HIV-1

    Science.gov (United States)

    Allam, Atef; Majji, Sai; Peachman, Kristina; Jagodzinski, Linda; Kim, Jiae; Ratto-Kim, Silvia; Wijayalath, Wathsala; Merbah, Melanie; Kim, Jerome H.; Michael, Nelson L.; Alving, Carl R.; Casares, Sofia; Rao, Mangala

    2015-01-01

    CD4+ T follicular helper cells (TFH) in germinal centers are required for maturation of B-cells. While the role of TFH-cells has been studied in blood and lymph nodes of HIV-1 infected individuals, its role in the mucosal tissues has not been investigated. We show that the gut and female reproductive tract (FRT) of humanized DRAG mice have a high level of human lymphocytes and a high frequency of TFH (CXCR5+PD-1++) and precursor-TFH (CXCR5+PD-1+) cells. The majority of TFH-cells expressed CCR5 and CXCR3 and are the most permissive to HIV-1 infection. A single low-dose intravaginal HIV-1 challenge of humanized DRAG mice results in 100% infectivity with accumulation of TFH-cells mainly in the Peyer’s patches and FRT. The novel finding of TFH-cells in the FRT may contribute to the high susceptibility of DRAG mice to HIV-1 infection. This mouse model thus provides new opportunities to study TFH-cells and to evaluate HIV-1 vaccines. PMID:26034905

  19. Effect of dietary poly unsaturated fatty acids on total brain lipid concentration and anxiety levels of electron beam irradiated mice

    International Nuclear Information System (INIS)

    Suchetha Kumari; Bekal, Mahesh

    2013-01-01

    The whole brain irradiation causes injury to the nervous system at various levels. Omega-3 poly unsaturated fatty acids are very much essential for the growth and development of nervous system. Dietary supplementation of these nutrients will promote the development of injured neuronal cells. Therefore this study was undertaken to establish the role of Omega-3 poly unsaturated fatty acids on total brain lipid concentration, lipid peroxidation and anxiety levels in the irradiated mice. The effect of Electron Beam Radiation (EBR) on total brain lipid concentration, lipid peroxidation and anxiety level were investigated in male Swiss albino mice. The study groups were subjected to a sub-lethal dose of EBR and also the flax seed extract and fish oil were given orally to the irradiated mice. Irradiated groups show significant elevation in anxiety levels when compared to control group, indicating the acute radiation effects on the central nervous system. But the oral supplementation of dietary PUFA source decrees the anxiety level in the irradiated group. The analysis of lipid peroxidation showed a significant level of changes when compared between control and radiation groups. Dietary PUFA supplementation showed a significant level of decrease in the lipid peroxidation in the irradiated groups. The observation of total lipids in brain shows decrease in concentration in the irradiated groups, the differences in the variables follow the similar patterns as of that the MDA levels. This study suggests that the dietary intake of PUFAs may help in prevention and recovery of the oxidative stress caused by radiation. (author)

  20. High fat diet prevents over-crowding induced decrease of sex ratio in mice.

    Directory of Open Access Journals (Sweden)

    Madhukar Shivajirao Dama

    Full Text Available Adaptive theory predicts that mothers would be advantaged by adjusting the sex ratio of their offspring in relation to their offspring's future reproductive success. In the present study, we tested the effect of housing mice under crowded condition on the sex ratio and whether the fat content of the diet has any influence on the outcome of pregnancies. Three-week-old mice were placed on the control diet (NFD for 3 weeks. Thereafter the mice were allotted randomly to two groups of 7 cages each with 4, 6, 8, 10, 12, 14, and 16 mice in every cage to create increasing crowding gradient and fed either NFD or high fat diet (HFD. After 4 weeks, dams were bred and outcomes of pregnancy were analyzed. The average dam body weight (DBW at conception, litter size (LS and SR were significantly higher in HFD fed dams. Further, male biased litters declined with increasing crowding in NFD group but not in HFD. The LS and SR in NFD declined significantly with increasing crowding, whereas only LS was reduced in HFD group. We conclude that female mice housed under overcrowding conditions shift offspring SR in favor of daughters in consistent with the TW hypothesis and high fat diet reduces this influence of overcrowding.

  1. The Intra- or Extracellular Redox State Was Not Affected by a High vs. Low Glycemic Response Diet in Mice

    Science.gov (United States)

    Kleckner, Amber S.; Wong, Siu; Corkey, Barbara E.

    2015-01-01

    A low glycemic response (LGR) vs. high glycemic response (HGR) diet helps curtail the development of obesity and diabetes, though the mechanisms are unknown. We hypothesized that consumption of a HGR vs. a LGR diet would lead to a more oxidized circulating redox state and predicted that a HGR diet would increase fat accumulation, reduce insulin sensitivity, and impair metabolic acclimation to a high fat diet in a mouse model. Hence, male C57BL/6 mice consumed a HGR or LGR diet for 16 weeks and a subset of the mice subsequently consumed a high fat diet for 4 weeks. We found that body mass increased at a faster rate for those consuming the HGR diet. Percent body fat was greater and percent lean mass was lesser in the HGR group starting at 12 weeks. However, the groups did not differ in terms of glucose tolerance at week 14 and metabolic parameters (respiratory exchange ratio, heat production, activity) at weeks 4 or 15. Moreover, mice on either diet did not show differences in metabolic acclimation to the high fat leg of the study. At the termination of the study, the groups did not differ in terms of redox pairs (lactate/pyruvate and β-hydroxybutyrate/acetoacetate) or thioredoxin reductase activity in blood. Also, total and oxidized glutathione levels and lipid peroxidation were similar in blood and liver. Correlations between baseline measures, longitudinal parameters, environmental conditions, and terminal metrics revealed that individual mice have innate propensities to metabolic regulation that may be difficult to perturb with diet alone; for example, starting mass correlated negatively with energy expenditure 4 weeks into the study and total hepatic glutathione at the end of the study. In conclusion, these data suggest that the mechanism by which HGR carbohydrates contributes to obesity is not via prolonged oxidation of the circulating redox state. PMID:26030878

  2. The Intra- or Extracellular Redox State Was Not Affected by a High vs. Low Glycemic Response Diet in Mice.

    Directory of Open Access Journals (Sweden)

    Amber S Kleckner

    Full Text Available A low glycemic response (LGR vs. high glycemic response (HGR diet helps curtail the development of obesity and diabetes, though the mechanisms are unknown. We hypothesized that consumption of a HGR vs. a LGR diet would lead to a more oxidized circulating redox state and predicted that a HGR diet would increase fat accumulation, reduce insulin sensitivity, and impair metabolic acclimation to a high fat diet in a mouse model. Hence, male C57BL/6 mice consumed a HGR or LGR diet for 16 weeks and a subset of the mice subsequently consumed a high fat diet for 4 weeks. We found that body mass increased at a faster rate for those consuming the HGR diet. Percent body fat was greater and percent lean mass was lesser in the HGR group starting at 12 weeks. However, the groups did not differ in terms of glucose tolerance at week 14 and metabolic parameters (respiratory exchange ratio, heat production, activity at weeks 4 or 15. Moreover, mice on either diet did not show differences in metabolic acclimation to the high fat leg of the study. At the termination of the study, the groups did not differ in terms of redox pairs (lactate/pyruvate and β-hydroxybutyrate/acetoacetate or thioredoxin reductase activity in blood. Also, total and oxidized glutathione levels and lipid peroxidation were similar in blood and liver. Correlations between baseline measures, longitudinal parameters, environmental conditions, and terminal metrics revealed that individual mice have innate propensities to metabolic regulation that may be difficult to perturb with diet alone; for example, starting mass correlated negatively with energy expenditure 4 weeks into the study and total hepatic glutathione at the end of the study. In conclusion, these data suggest that the mechanism by which HGR carbohydrates contributes to obesity is not via prolonged oxidation of the circulating redox state.

  3. Nova performance at ultra high fluence levels

    International Nuclear Information System (INIS)

    Hunt, J.T.

    1986-01-01

    Nova is a ten beam high power Nd:glass laser used for interial confinement fusion research. It was operated in the high power high energy regime following the completion of construction in December 1984. During this period several interesting nonlinear optical phenomena were observed. These phenomena are discussed in the text. 11 refs., 5 figs

  4. High basal metabolic rate does not elevate oxidative stress during reproduction in laboratory mice.

    Science.gov (United States)

    Brzęk, Paweł; Książek, Aneta; Ołdakowski, Łukasz; Konarzewski, Marek

    2014-05-01

    Increased oxidative stress (OS) has been suggested as a physiological cost of reproduction. However, previous studies reported ambiguous results, with some even showing a reduction of oxidative damage during reproduction. We tested whether the link between reproduction and OS is mediated by basal metabolic rate (BMR), which has been hypothesized to affect both the rate of radical oxygen species production and antioxidative capacity. We studied the effect of reproduction on OS in females of laboratory mice divergently selected for high (H-BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental investment. Non-reproducing L-BMR females showed higher oxidative damage to lipids (quantified as the level of malondialdehyde in internal organ tissues) and DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females. Reproduction did not affect oxidative damage to lipids in either line; however, it reduced damage to DNA in L-BMR females. Reproduction increased catalase activity in liver (significantly stronger in L-BMR females) and decreased it in kidneys. We conclude that the effect of reproduction on OS depends on the initial variation in BMR and varies between studied internal organs and markers of OS.

  5. Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice

    International Nuclear Information System (INIS)

    Hufbauer, M.; Lazic, D.; Akguel, B.; Brandsma, J.L.; Pfister, H.; Weissenborn, S.J.

    2010-01-01

    Human papillomavirus 8 (HPV8) is involved in skin cancer development in epidermodysplasia verruciformis patients. Transgenic mice expressing HPV8 early genes (HPV8-CER) developed papillomas, dysplasias and squamous cell carcinomas. UVA/B-irradiation and mechanical wounding of HPV8-CER mouse skin led to prompt papilloma induction in about 3 weeks. The aim of this study was to analyze the kinetics and level of transgene expression in response to skin irritations. Transgene expression was already enhanced 1 to 2 days after UVA/B-irradiation or tape-stripping and maintained during papilloma development. The enhanced transgene expression could be assigned to UVB and not to UVA. Papilloma development was thus always paralleled by an increased transgene expression irrespective of the type of skin irritation. A knock-down of E6 mRNA by tattooing HPV8-E6-specific siRNA led to a delay and a lower incidence of papilloma development. This indicates that the early increase of viral oncogene expression is crucial for induction of papillomatosis.

  6. T-cell independent reconstitution of the immunoglobulin levels in nu/nu mice

    International Nuclear Information System (INIS)

    Mannhardt, W.; Schulte-Wissermann, H.; Gardilcic, S.; Leon, F. de

    1982-01-01

    Nude mice were transplanted under the renal capsule either with allogeneic or human thymus that were long-term precultured or pretreated in vitro with Carrageenan for three days. None of the thymus tissue transplants showed lymphatic repopulation 9 wk after transplantation. Histological investigation of the peripheral lymphatic tissue did not reveal any change in the thymus-dependent area. On the other hand, plasma cells and germinal centers could be found in significantly increased numbers. In addition, a normalization of the serum immunoglobulin concentrations could be found, as no specific antibodies against thymus-dependent antigens were present after immunization and T-cell function did not improve. Similar results were obtained 9 wk after injection of irradiated thymocyte suspensions or of peritoneal macrophages from immunocompetent donors. It is concluded that thymus epithelial cells could act via macrophages on the polyclonal maturation and differentiation of B cells without involvement of T cells. This would be in agreement with the experience in some patients with severe combined immunodeficiency (SCID) in which reconstitution of the immunoglobulin levels is observed after transplantation of cultured thymus tissue before T-cell reconstitution can be demonstrated. (Auth.)

  7. The effect of low level laser therapy on ventilator-induced lung injury in mice (Conference Presentation)

    Science.gov (United States)

    Szabari, Margit V.; Miller, Alyssa J.; Hariri, Lida P.; Hamblin, Michael R.; Musch, Guido; Stroh, Helene; Suter, Melissa J.

    2016-03-01

    Although mechanical ventilation (MV) is necessary to support gas exchange in critically ill patients, it can contribute to the development of lung injury and multiple organ dysfunction. It is known that high tidal volume (Vt) MV can cause ventilator-induced lung injury (VILI) in healthy lungs and increase the mortality of patients with Acute Respiratory Distress Syndrome. Low level laser therapy (LLLT) has demonstrated to have anti-inflammatory effects. We investigated whether LLLT could alleviate inflammation from injurious MV in mice. Adult mice were assigned to 2 groups: VILI+LLLT group (3 h of injurious MV: Vt=25-30 ml/kg, respiratory rate (RR)=50/min, positive end-expiratory pressure (PEEP)=0 cmH20, followed by 3 h of protective MV: Vt=9 ml/kg, RR=140/min, PEEP=2 cmH20) and VILI+no LLLT group. LLLT was applied during the first 30 min of the MV (810 nm LED system, 5 J/cm2, 1 cm above the chest). Respiratory impedance was measured in vivo with forced oscillation technique and lung mechanics were calculated by fitting the constant phase model. At the end of the MV, bronchoalveolar lavage (BAL) was performed and inflammatory cells counted. Lungs were removed en-bloc and fixed for histological evaluation. We hypothesize that LLLT can reduce lung injury and inflammation from VILI. This therapy could be translated into clinical practice, where it can potentially improve outcomes in patients requiring mechanical ventilation in the operating room or in the intensive care units.

  8. Anti-diabetic effect of balanced deep-sea water and its mode of action in high-fat diet induced diabetic mice.

    Science.gov (United States)

    Ha, Byung Geun; Shin, Eun Ji; Park, Jung-Eun; Shon, Yun Hee

    2013-10-29

    In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of 500-2000. Mice given an HFD with BDSW showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that BDSW improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that BDSW recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with BDSW. BDSW increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. BDSW stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that BDSW has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake.

  9. Effects of High Fat Feeding and Diabetes on Regression of Atherosclerosis Induced by Low-Density Lipoprotein Receptor Gene Therapy in LDL Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Florian Willecke

    Full Text Available We tested whether a high fat diet (HFD containing the inflammatory dietary fatty acid palmitate or insulin deficient diabetes altered the remodeling of atherosclerotic plaques in LDL receptor knockout (Ldlr-/- mice. Cholesterol reduction was achieved by using a helper-dependent adenovirus (HDAd carrying the gene for the low-density lipoprotein receptor (Ldlr; HDAd-LDLR. After injection of the HDAd-LDLR, mice consuming either HFD, which led to insulin resistance but not hyperglycemia, or low fat diet (LFD, showed regression compared to baseline. However there was no difference between the two groups in terms of atherosclerotic lesion size, or CD68+ cell and lipid content. Because of the lack of effects of these two diets, we then tested whether viral-mediated cholesterol reduction would lead to defective regression in mice with greater hyperglycemia. In both normoglycemic and streptozotocin (STZ-treated hyperglycemic mice, HDAd-LDLR significantly reduced plasma cholesterol levels, decreased atherosclerotic lesion size, reduced macrophage area and lipid content, and increased collagen content of plaque in the aortic sinus. However, reductions in anti-inflammatory and ER stress-related genes were less pronounced in STZ-diabetic mice compared to non-diabetic mice. In conclusion, HDAd-mediated Ldlr gene therapy is an effective and simple method to induce atherosclerosis regression in Ldlr-/- mice in different metabolic states.

  10. 12/15-lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice.

    Directory of Open Access Journals (Sweden)

    Dorothy D Sears

    2009-09-01

    Full Text Available Recent understanding that insulin resistance is an inflammatory condition necessitates searching for genes that regulate inflammation in insulin sensitive tissues. 12/15-lipoxygenase (12/15LO regulates the expression of proinflammatory cytokines and chemokines and is implicated in the early development of diet-induced atherosclerosis. Thus, we tested the hypothesis that 12/15LO is involved in the onset of high fat diet (HFD-induced insulin resistance.Cells over-expressing 12/15LO secreted two potent chemokines, MCP-1 and osteopontin, implicated in the development of insulin resistance. We assessed adipose tissue inflammation and whole body insulin resistance in wild type (WT and 12/15LO knockout (KO mice after 2-4 weeks on HFD. In adipose tissue from WT mice, HFD resulted in recruitment of CD11b(+, F4/80(+ macrophages and elevated protein levels of the inflammatory markers IL-1beta, IL-6, IL-10, IL-12, IFNgamma, Cxcl1 and TNFalpha. Remarkably, adipose tissue from HFD-fed 12/15LO KO mice was not infiltrated by macrophages and did not display any increase in the inflammatory markers compared to adipose tissue from normal chow-fed mice. WT mice developed severe whole body (hepatic and skeletal muscle insulin resistance after HFD, as measured by hyperinsulinemic euglycemic clamp. In contrast, 12/15LO KO mice exhibited no HFD-induced change in insulin-stimulated glucose disposal rate or hepatic glucose output during clamp studies. Insulin-stimulated Akt phosphorylation in muscle tissue from HFD-fed mice was significantly greater in 12/15LO KO mice than in WT mice.These results demonstrate that 12/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding.

  11. Altered fibre types in gastrocnemius muscle of high wheel-running selected mice with mini-muscle phenotypes.

    Science.gov (United States)

    Guderley, Helga; Joanisse, Denis R; Mokas, Sophie; Bilodeau, Geneviève M; Garland, Theodore

    2008-03-01

    Selective breeding of mice for high voluntary wheel running has favoured characteristics that facilitate sustained, aerobically supported activity, including a "mini-muscle" phenotype with markedly reduced hind limb muscle mass, increased mass-specific activities of oxidative enzymes, decreased % myosin heavy chain IIb, and, in the medial gastrocnemius, reduced twitch speed, reduced mass-specific isotonic power, and increased fatigue resistance. To evaluate whether selection has altered fibre type expression in mice with either "mini" or normal muscle phenotypes, we examined fibre types of red and white gastrocnemius. In both the medial and lateral gastrocnemius, the mini-phenotype increased activities of oxidative enzymes and decreased activities of glycolytic enzymes. In red muscle samples, the mini-phenotype markedly changed fibre types, with the % type I and type IIA fibres and the surface area of type IIA fibres increasing; in addition, mice from selected lines in general had an increased % type IIA fibres and larger type I fibres as compared with mice from control lines. White muscle samples from mini-mice showed dramatic structural alterations, with an atypical distribution of extremely small, unidentifiable fibres surrounded by larger, more oxidative fibres than normally present in white muscle. The increased proportion of oxidative fibres and these atypical small fibres together may explain the reduced mass and increased mitochondrial enzyme activities in mini-muscles. These and previous results demonstrate that extension of selective breeding beyond the time when the response of the selected trait (i.e. distance run) has levelled off can still modify the mechanistic underpinnings of this behaviour.

  12. Green tea extracts ameliorate high-fat diet-induced muscle atrophy in senescence-accelerated mouse prone-8 mice.

    Science.gov (United States)

    Onishi, Shintaro; Ishino, Mayu; Kitazawa, Hidefumi; Yoto, Ai; Shimba, Yuki; Mochizuki, Yusuke; Unno, Keiko; Meguro, Shinichi; Tokimitsu, Ichiro; Miura, Shinji

    2018-01-01

    Muscle atrophy (loss of skeletal muscle mass) causes progressive deterioration of skeletal function. Recently, excessive intake of fats was suggested to induce insulin resistance, followed by muscle atrophy. Green tea extracts (GTEs), which contain polyphenols such as epigallocatechin gallate, have beneficial effects on obesity, hyperglycemia, and insulin resistance, but their effects against muscle atrophy are still unclear. Here, we found that GTEs prevented high-fat (HF) diet-induced muscle weight loss in senescence-accelerated mouse prone-8 (SAMP8), a murine model of senescence. SAMP8 mice were fed a control diet, an HF diet, or HF with 0.5% GTEs (HFGT) diet for 4 months. The HF diet induced muscle weight loss with aging (measured as quadriceps muscle weight), whereas GTEs prevented this loss. In HF diet-fed mice, blood glucose and plasma insulin concentrations increased in comparison with the control group, and these mice had insulin resistance as determined by homeostasis model assessment of insulin resistance (HOMA-IR). In these mice, serum concentrations of leukocyte cell-derived chemotaxin 2 (LECT2), which is known to induce insulin resistance in skeletal muscle, were elevated, and insulin signaling in muscle, as determined by the phosphorylation levels of Akt and p70 S6 kinases, tended to be decreased. In HFGT diet-fed mice, these signs of insulin resistance and elevation of serum LECT2 were not observed. Although our study did not directly show the effect of serum LECT2 on muscle weight, insulin resistance examined using HOMA-IR indicated an intervention effect of serum LECT2 on muscle weight, as revealed by partial correlation analysis. Accordingly, GTEs might have beneficial effects on age-related and HF diet-induced muscle weight loss, which correlates with insulin resistance and is accompanied by a change in serum LECT2.

  13. Consumption of a low-carbohydrate and high-fat diet (the ketogenic diet) exaggerates biotin deficiency in mice.

    Science.gov (United States)

    Yuasa, Masahiro; Matsui, Tomoyoshi; Ando, Saori; Ishii, Yoshie; Sawamura, Hiromi; Ebara, Shuhei; Watanabe, Toshiaki

    2013-10-01

    Biotin is a water-soluble vitamin that acts as a cofactor for several carboxylases. The ketogenic diet, a low-carbohydrate, high-fat diet, is used to treat drug-resistant epilepsy and promote weight loss. In Japan, the infant version of the ketogenic diet is known as the "ketone formula." However, as the special infant formulas used in Japan, including the ketone formula, do not contain sufficient amounts of biotin, biotin deficiency can develop in infants who consume the ketone formula. Therefore, the aim of this study was to evaluate the effects of the ketogenic diet on biotin status in mice. Male mice (N = 32) were divided into the following groups: control diet group, biotin-deficient (BD) diet group, ketogenic control diet group, and ketogenic biotin-deficient (KBD) diet group. Eight mice were used in each group. At 9 wk, the typical symptoms of biotin deficiency such as hair loss and dermatitis had only developed in the KBD diet group. The total protein expression level of biotin-dependent carboxylases and the total tissue biotin content were significantly decreased in the KBD and BD diet groups. However, these changes were more severe in the KBD diet group. These findings demonstrated that the ketogenic diet increases biotin bioavailability and consumption, and hence, promotes energy production by gluconeogenesis and branched-chain amino acid metabolism, which results in exaggerated biotin deficiency in biotin-deficient mice. Therefore, biotin supplementation is important for mice that consume the ketogenic diet. It is suggested that individuals that consume the ketogenic diet have an increased biotin requirement. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Elevated mRNA-levels of distinct mitochondrial and plasma membrane Ca2+ transporters in individual hypoglossal motor neurons of endstage SOD1 transgenic mice.

    Directory of Open Access Journals (Sweden)

    Tobias eMühling

    2014-11-01

    Full Text Available Disturbances in Ca2+ homeostasis and mitochondrial dysfunction have emerged as major pathogenic features in familial and sporadic forms of Amyotrophic Lateral Sclerosis (ALS, a fatal degenerative motor neuron disease. However, the distinct molecular ALS-pathology remains unclear. Recently, an activity-dependent Ca2+ homeostasis deficit, selectively in highly vulnerable cholinergic motor neurons in the hypoglossal nucleus (hMNs from a common ALS mouse model, endstage superoxide dismutase SOD1G93A transgenic mice, was described. This functional deficit was defined by a reduced hMN mitochondrial Ca2+ uptake capacity and elevated Ca2+ extrusion across the plasma membrane. To address the underlying molecular mechanisms, here we quantified mRNA-levels of respective potential mitochondrial and plasma membrane Ca2+ transporters in individual, choline-acetyltransferase (ChAT positive hMNs from wildtype (WT and endstage SOD1G93A mice, by combining UV laser microdissection with RT-qPCR techniques, and specific data normalization. As ChAT cDNA levels as well as cDNA and genomic DNA levels of the mitochondrially encoded NADH dehydrogenase ND1 were not different between hMNs from WT and endstage SOD1G93A mice, these genes were used to normalize hMN-specific mRNA-levels of plasma membrane and mitochondrial Ca2+ transporters, respectively. We detected about 2-fold higher levels of the mitochondrial Ca2+ transporters MCU/MICU1, Letm1 and UCP2 in remaining hMNs from endstage SOD1G93A mice. These higher expression-levels of mitochondrial Ca2+ transporters in individual hMNs were not associated with a respective increase in number of mitochondrial genomes, as evident from hMN specific ND1 DNA quantification. Normalized mRNA-levels for the plasma membrane Na2+/Ca2+exchanger NCX1 was also about 2-fold higher in hMNs from SOD1G93A mice. Thus, pharmacological stimulation of Ca2+ transporters in highly vulnerable hMNs might offer a novel neuroprotective strategy for ALS.

  15. Inability of naloxone to change brain morphine levels in tolerant mice

    International Nuclear Information System (INIS)

    Dum, J.; Meyer, G.; Hoellt, V.; Herz, A.; Catlin, D.H.

    1977-01-01

    The effect of naloxone on brain morphine concentrations was measured in naive and morphine-dependent mice using radioimmunoassay and gas-liquid chromatography. No displacement of morphine from the brain by naloxone could be observed in naive mice acutely injected with morphine or in pellet-implanted mice at increasing intervals after removal of the morphine pellets. The suggestion of a change in affinity of opiate receptors during the development of tolerance/dependence, which had been made on the basis of the displacement of morphine by naloxone found by other workers, is thus not supported by the present results

  16. Locomotor trade-offs in mice selectively bred for high voluntary wheel running.

    Science.gov (United States)

    Dlugosz, Elizabeth M; Chappell, Mark A; McGillivray, David G; Syme, Douglas A; Garland, Theodore

    2009-08-01

    We investigated sprint performance and running economy of a unique ;mini-muscle' phenotype that evolved in response to selection for high voluntary wheel running in laboratory mice (Mus domesticus). Mice from four replicate selected (S) lines run nearly three times as far per day as four control lines. The mini-muscle phenotype, resulting from an initially rare autosomal recessive allele, has been favoured by the selection protocol, becoming fixed in one of the two S lines in which it occurred. In homozygotes, hindlimb muscle mass is halved, mass-specific muscle oxidative capacity is doubled, and the medial gastrocnemius exhibits about half the mass-specific isotonic power, less than half the mass-specific cyclic work and power, but doubled fatigue resistance. We hypothesized that mini-muscle mice would have a lower whole-animal energy cost of transport (COT), resulting from lower costs of cycling their lighter limbs, and reduced sprint speed, from reduced maximal force production. We measured sprint speed on a racetrack and slopes (incremental COT, or iCOT) and intercepts of the metabolic rate versus speed relationship during voluntary wheel running in 10 mini-muscle and 20 normal S-line females. Mini-muscle mice ran faster and farther on wheels, but for less time per day. Mini-muscle mice had significantly lower sprint speeds, indicating a functional trade-off. However, contrary to predictions, mini-muscle mice had higher COT, mainly because of higher zero-speed intercepts and postural costs (intercept-resting metabolic rate). Thus, mice with altered limb morphology after intense selection for running long distances do not necessarily run more economically.

  17. A high-fat diet induces bone loss in mice lacking the Alox5 gene.

    Science.gov (United States)

    Le, Phuong; Kawai, Masanobu; Bornstein, Sheila; DeMambro, Victoria E; Horowitz, Mark C; Rosen, Clifford J

    2012-01-01

    5-Lipoxygenase catalyzes leukotriene generation from arachidonic acid. The gene that encodes 5-lipoxygenase, Alox5, has been identified in genome-wide association and mouse Quantitative Trait Locus studies as a candidate gene for obesity and low bone mass. Thus, we tested the hypothesis that Alox5(-/-) mice would exhibit metabolic and skeletal changes when challenged by a high-fat diet (HFD). On a regular diet, Alox5(-/-) mice did not differ in total body weight, percent fat mass, or bone mineral density compared with wild-type (WT) controls (P < 0.05). However, when placed on a HFD, Alox5(-/-) gained more fat mass and lost greater areal bone mass vs. WT (P < 0.05). Microarchitectural analyses revealed that on a HFD, WT showed increases in cortical area (P < 0.01) and trabecular thickness (P < 0.01), whereas Alox5(-/-) showed no change in cortical parameters but a decrease in trabecular number (P < 0.05) and bone volume fraction compared with WT controls (P < 0.05). By histomorphometry, a HFD did not change bone formation rates of either strain but produced an increase in osteoclast number per bone perimeter in Alox5(-/-) mice (P < 0.03). In vitro, osteoclastogenesis of marrow stromal cells was enhanced in mutant but not WT mice fed a HFD. Gene expression for Rankl, Pparg, and Cox-2 was greater in the femur of Alox5(-/-) than WT mice on a HFD (P < 0.01), but these increases were suppressed in the Alox5(-/-) mice after 8 wk of treatment with celecoxib, a cyclooxygenase-2 inhibitor. In sum, there is a strong gene by environmental interaction for bone mass when mice lacking the Alox5 gene are fed a HFD.

  18. High bicarbonate levels in narcoleptic children.

    Science.gov (United States)

    Franco, Patricia; Junqua, Aurelie; Guignard-Perret, Anne; Raoux, Aude; Perier, Magali; Raverot, Veronique; Claustrat, Bruno; Gustin, Marie-Paule; Inocente, Clara Odilia; Lin, Jian-Sheng

    2016-04-01

    The objective of this study was to evaluate the levels of plasma bicarbonate levels in narcoleptic children. Clinical, electrophysiological data and bicarbonate levels were evaluated retrospectively in children seen in our paediatric national reference centre for hypersomnia. The cohort included 23 control subjects (11.5 ± 4 years, 43% boys) and 51 patients presenting de-novo narcolepsy (N) (12.7 ± 3.7 years, 47% boys). In narcoleptic children, cataplexy was present in 78% and DQB1*0602 was positive in 96%. The control children were less obese (2 versus 47%, P = 0.001). Compared with control subjects, narcoleptic children had higher bicarbonate levels (P = 0.02) as well as higher PCO2 (P < 0.01) and lower venous pH gas (P < 0.01). Bicarbonate levels higher than 27 mmol L(-1) were found in 41.2% of the narcoleptic children and 4.2% of the controls (P = 0.001). Bicarbonate levels were correlated with the Adapted Epworth Sleepiness Scale (P = 0.01). Narcoleptic patients without obesity often had bicarbonate levels higher than 27 mmol L (-1) (55 versus 25%, P = 0.025). No differences were found between children with and without cataplexy. In conclusion, narcoleptic patients had higher bicarbonate plasma levels compared to control children. This result could be a marker of hypoventilation in this pathology, provoking an increase in PCO2 and therefore a respiratory acidosis, compensated by an increase in plasma bicarbonates. This simple screening tool could be useful for prioritizing children for sleep laboratory evaluation in practice. © 2015 European Sleep Research Society.

  19. Vision in high-level football officials.

    Science.gov (United States)

    Baptista, António Manuel Gonçalves; Serra, Pedro M; McAlinden, Colm; Barrett, Brendan T

    2017-01-01

    Officiating in football depends, at least to some extent, upon adequate visual function. However, there is no vision standard for football officiating and the nature of the relationship between officiating performance and level of vision is unknown. As a first step in characterising this relationship, we report on the clinically-measured vision and on the perceived level of vision in elite-level, Portuguese football officials. Seventy-one referees (R) and assistant referees (AR) participated in the study, representing 92% of the total population of elite level football officials in Portugal in the 2013/2014 season. Nine of the 22 Rs (40.9%) and ten of the 49 ARs (20.4%) were international-level. Information about visual history was also gathered. Perceived vision was assessed using the preference-values-assigned-to-global-visual-status (PVVS) and the Quality-of-Vision (QoV) questionnaire. Standard clinical vision measures (including visual acuity, contrast sensitivity and stereopsis) were gathered in a subset (n = 44, 62%) of the participants. Data were analysed according to the type (R/AR) and level (international/national) of official, and Bonferroni corrections were applied to reduce the risk of type I errors. Adopting criterion for statistical significance of pfootball officials were similar to published normative values for young, adult populations and similar between R and AR. Clinically-measured vision did not differ according to officiating level. Visual acuity measured with and without a pinhole disc indicated that around one quarter of participants may be capable of better vision when officiating, as evidenced by better acuity (≥1 line of letters) using the pinhole. Amongst the clinical visual tests we used, we did not find evidence for above-average performance in elite-level football officials. Although the impact of uncorrected mild to moderate refractive error upon officiating performance is unknown, with a greater uptake of eye examinations, visual

  20. Effects of Enzymatically Synthesized Glycogen and Exercise on Abdominal Fat Accumulation in High-Fat Diet-Fed Mice.

    Science.gov (United States)

    Tamura, Shohei; Honda, Kazuhisa; Morinaga, Ryoji; Saneyasu, Takaoki; Kamisoyama, Hiroshi

    2017-01-01

    The combination of diet and exercise is the first choice for the treatment of obesity and metabolic syndrome. We previously reported that enzymatically synthesized glycogen (ESG) suppresses abdominal fat accumulation in obese rats. However, the effect of the combination of ESG and exercise on abdominal fat accumulation has not yet been investigated. Our goal in this study was therefore to evaluate the effects of dietary ESG and its combination with exercise on abdominal fat accumulation in high-fat diet (HFD)-fed mice. Male ICR mice were assigned to four groups: HFD, HFD containing 20% ESG, HFD with exercise, HFD containing 20% ESG with exercise. Treadmill exercise was performed for 3 wk (25 m/min, 30 min/d, 3 d/wk) after 5-d adaption to running at that speed. Both ESG and exercise significantly reduced the weights of abdominal adipose tissues. In addition, the combination of ESG and exercise significantly suppressed abdominal fat accumulation, suggesting that ESG and exercise showed an additive effect. Exercise significantly increased the mRNA levels of lipid metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor delta; factor-delta (PPARδ), carnitin palmitoyltransferase b, adipose triglyceride lipase (ATGL), and uncoupling protein-3 in the gastrocnemius muscle. On the other hand, dietary ESG significantly decreased the mRNA levels of PPARδ and ATGL in the gastrocnemius muscle. These results suggest that the combined treatment of ESG and exercise effectively suppresses abdominal fat accumulation in HFD-fed mice by different mechanisms.

  1. Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high-fat diet.

    Science.gov (United States)

    Ferreira, Paula S; Spolidorio, Luis C; Manthey, John A; Cesar, Thais B

    2016-06-15

    The flavanones hesperidin, eriocitrin and eriodictyol were investigated for their prevention of the oxidative stress and systemic inflammation caused by high-fat diet in C57BL/6J mice. The mice received a standard diet (9.5% kcal from fat), high-fat diet (45% kcal from fat) or high-fat diet supplemented with hesperidin, eriocitrin or eriodictyol for a period of four weeks. Hesperidin, eriocitrin and eriodictyol increased the serum total antioxidant capacity, and restrained the elevation of interleukin-6 (IL-6), macrophage chemoattractant protein-1 (MCP-1), and C-reactive protein (hs-CRP). In addition, the liver TBARS levels and spleen mass (g per kg body weight) were lower for the flavanone-treated mice than in the unsupplemented mice. Eriocitrin and eriodictyol reduced TBARS levels in the blood serum, and hesperidin and eriodictyol also reduced fat accumulation and liver damage. The results showed that hesperidin, eriocitrin and eriodictyol had protective effects against inflammation and oxidative stress caused by high-fat diet in mice, and may therefore prevent metabolic alterations associated with the development of cardiovascular diseases in other animals.

  2. Effects of sleep disruption and high fat intake on glucose metabolism in mice.

    Science.gov (United States)

    Ho, Jacqueline M; Barf, R Paulien; Opp, Mark R

    2016-06-01

    Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this

  3. 7-Alkylguanine adduct levels in urine, lungs and liver of mice exposed to styrene by inhalation

    International Nuclear Information System (INIS)

    Vodicka, Pavel Erik; Linhart, Igor; Novak, Jan; Koskinen, Mikko; Vodickova, Ludmila; Hemminki, Kari

    2006-01-01

    This study describes urinary excretion of two nucleobase adducts derived from styrene 7,8-oxide (SO), i.e., 7-(2-hydroxy-1-phenylethyl)guanine (N7αG) and 7-(2-hydroxy-2-phenylethyl)guanine (N7βG), as well as a formation of N7-SO-guanine adducts in lungs and liver of two month old male NMRI mice exposed to styrene by inhalation in a 3-week subacute study. Strikingly higher excretion of both isomeric nucleobase adducts in the first day of exposure was recorded, while the daily excretion of nucleobase adducts in following time intervals reached the steady-state level at 4.32 + 1.14 and 6.91 + 1.17 pmol/animal for lower and higher styrene exposure, respectively. β-SO-guanine DNA adducts in lungs increased with exposure in a linear way (F = 13.7 for linearity and 0.17 for non-linearity, respectively), reaching at the 21st day the level of 23.0 adducts/10 8 normal nucleotides, i.e., 0.74 fmol/μg DNA of 7-alkylguanine DNA adducts for the concentration of 1500 mg/m 3 , while no 7-SO-guanine DNA adducts were detected in the liver after 21 days of inhalation exposure to both of styrene concentrations. A comparison of 7-alkylguanines excreted in urine with 7-SO-guanines in lungs (after correction for depurination and for missing α-isomers) revealed that persisting 7-SO-guanine DNA adducts in lungs account for about 0.5% of the total alkylation at N7 of guanine. The total styrene-specific 7-guanine alkylation accounts for about 1.0 x 10 -5 % of the total styrene uptake, while N1-adenine alkylation contributes to this percentage only negligibly

  4. Heterozygous deficiency of endoglin decreases insulin and hepatic triglyceride levels during high fat diet.

    Directory of Open Access Journals (Sweden)

    Daniel Beiroa

    Full Text Available Endoglin is a transmembrane auxiliary receptor for transforming growth factor-beta (TGF-beta that is predominantly expressed on proliferating endothelial cells. It plays a wide range of physiological roles but its importance on energy balance or insulin sensitivity has been unexplored. Endoglin deficient mice die during midgestation due to cardiovascular defects. Here we report for first time that heterozygous endoglin deficiency in mice decreases high fat diet-induced hepatic triglyceride content and insulin levels. Importantly, these effects are independent of changes in body weight or adiposity. At molecular level, we failed to detect relevant changes in the insulin signalling pathway at basal levels in liver, muscle or adipose tissues that could explain the insulin-dependent effect. However, we found decreased triglyceride content in the liver of endoglin heterozygous mice fed a high fat diet in comparison to their wild type littermates. Overall, our findings indicate that endoglin is a potentially important physiological mediator of insulin levels and hepatic lipid metabolism.

  5. Vision in high-level football officials.

    Directory of Open Access Journals (Sweden)

    António Manuel Gonçalves Baptista

    Full Text Available Officiating in football depends, at least to some extent, upon adequate visual function. However, there is no vision standard for football officiating and the nature of the relationship between officiating performance and level of vision is unknown. As a first step in characterising this relationship, we report on the clinically-measured vision and on the perceived level of vision in elite-level, Portuguese football officials. Seventy-one referees (R and assistant referees (AR participated in the study, representing 92% of the total population of elite level football officials in Portugal in the 2013/2014 season. Nine of the 22 Rs (40.9% and ten of the 49 ARs (20.4% were international-level. Information about visual history was also gathered. Perceived vision was assessed using the preference-values-assigned-to-global-visual-status (PVVS and the Quality-of-Vision (QoV questionnaire. Standard clinical vision measures (including visual acuity, contrast sensitivity and stereopsis were gathered in a subset (n = 44, 62% of the participants. Data were analysed according to the type (R/AR and level (international/national of official, and Bonferroni corrections were applied to reduce the risk of type I errors. Adopting criterion for statistical significance of p<0.01, PVVS scores did not differ between R and AR (p = 0.88, or between national- and international-level officials (p = 0.66. Similarly, QoV scores did not differ between R and AR in frequency (p = 0.50, severity (p = 0.71 or bothersomeness (p = 0.81 of symptoms, or between international-level vs national-level officials for frequency (p = 0.03 or bothersomeness (p = 0.07 of symptoms. However, international-level officials reported less severe symptoms than their national-level counterparts (p<0.01. Overall, 18.3% of officials had either never had an eye examination or if they had, it was more than 3 years previously. Regarding refractive correction, 4.2% had undergone refractive surgery and

  6. Effect of high sugar intake on glucose transporter and weight regulating hormones in mice and humans.

    Directory of Open Access Journals (Sweden)

    Yvonne Ritze

    Full Text Available OBJECTIVE: Sugar consumption has increased dramatically over the last decades in Western societies. Especially the intake of sugar-sweetened beverages seems to be a major risk for the development of obesity. Thus, we compared liquid versus solid high-sugar diets with regard to dietary intake, intestinal uptake and metabolic parameters in mice and partly in humans. METHODS: Five iso-caloric diets, enriched with liquid (in water 30% vol/vol or solid (in diet 65% g/g fructose or sucrose or a control diet were fed for eight weeks to C57bl/6 mice. Sugar, liquid and caloric intake, small intestinal sugar transporters (GLUT2/5 and weight regulating hormone mRNA expression, as well as hepatic fat accumulation were measured. In obese versus lean humans that underwent either bariatric surgery or small bowel resection, we analyzed small intestinal GLUT2, GLUT5, and cholecystokinin expression. RESULTS: In mice, the liquid high-sucrose diet caused an enhancement of total caloric intake compared to the solid high-sucrose diet and the control diet. In addition, the liquid high-sucrose diet increased expression of GLUT2, GLUT5, and cholecystokinin expression in the ileum (P<0.001. Enhanced liver triglyceride accumulation was observed in mice being fed the liquid high-sucrose or -fructose, and the solid high-sucrose diet compared to controls. In obese, GLUT2 and GLUT5 mRNA expression was enhanced in comparison to lean individuals. CONCLUSIONS: We show that the form of sugar intake (liquid versus solid is presumably more important than the type of sugar, with regard to feeding behavior, intestinal sugar uptake and liver fat accumulation in mice. Interestingly, in obese individuals, an intestinal sugar transporter modulation also occurred when compared to lean individuals.

  7. Investigation of the antioxidant activity of chitooligosaccharides on mice with high-fat diet

    Directory of Open Access Journals (Sweden)

    Daofeng Qu

    Full Text Available ABSTRACT The objective of this study was to analyze the antioxidant activities of chitooligosaccharides (COS both in vitro and in high-fat diet (HFD-mouse model. In antioxidant assays in HFD-mouse model, mice were administered with normal diet, HFD, or HFD with 0.5% COS for six weeks. The administration of HFD with 0.5% COS resulted in significant increase in the activity of superoxide dismutase, catalase, and glutathione peroxidase in stomach, liver, and serum of mice as compared with the HFD-fed group, which means that COS may have certain antioxidant activity and can restore the activity of the enzymes affected by the HFD. Through morphological measurements of the small intestinal mucosa, mice fed HFD showed decreased villus height compared with other groups. On the other hand, HFD with 0.5% COS group showed similar ratio of villus height to depth compared with control mice, indicating that intestinal integrity was improved when COS was added. Chitooligosaccharides have potent antioxidant activity that can protect mice from oxidative stress.

  8. [Alterations in the protein content and dysfunction of high-density lipoproteins from hyperhomocysteinemic mice].

    Science.gov (United States)

    Julve, Josep; Errico, Teresa Laura; Chen, Xiangyu; Santos, David; Freixa, Júlia; Porcel, Inmaculada; Cubero, Esther; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2013-01-01

    The aim of this study was to evaluate the proteic changes in high-density lipoproteins (HDL) induced by methionine-induced hyperhomocysteinemia in mice and its relationship with two of their main antiatherogenic properties. The oral administration of methionine resulted in an elevation (~8 times) in the plasma concentration of homocysteine. Hyperhomocysteinemia was inversely correlated with the plasma concentration of HDL cholesterol and its main protein component of HDL, apolipoprotein (apo) A-I, respectively. The cholesterol efflux in vivo from macrophages to HDL was decreased in hyperhomocysteinemic mice compared with the control mice. However, the reverse cholesterol transport from macrophages to feces remained unchanged. On the other hand, the ability of HDL from hyperhomocysteinemic mice to prevent the oxidative modification of low-density lipoproteins (LDL) was found decreased and associated with a concomitant reduction in the plasma activity of paraoxonase-1 (PON1) and the plasma concentration of apoA-I, and with a relative reduction in the apoA-IV content (~1.5 times) in the hyperhomocysteinemic HDL, respectively. The decrease in the ability of HDL from hyperhomocysteinemic mice to prevent LDL from oxidation was associated with a decrease in the apoA-I, PON1 and apoA-IV. Copyright © 2013 Elsevier España, S.L. and SEA. All rights reserved.

  9. Effects of bixin in high-fat diet-fed-induced fatty liver in C57BL/6J mice

    Institute of Scientific and Technical Information of China (English)

    Rosa; Martha; Perez; Gutierrez; Rita; Valadez; Romero

    2016-01-01

    Objective:To evaluate the anti-obesity activity of bixin(BIX) on C57BL/6J mice which were fed a high-fat diet(HFD) and to determine the mechanism of this effect.Methods:C57BL/6J mice were separately fed a high-calorie diet or a normal diet for 8weeks,then they were treated with BIX for another 13 weeks.After administration for 13 weeks,the animals were sacrificed.Body adiposity,serum lipid level,and insulin resistance were evaluated.In addition,a histological assay of pancreas and liver,an evaluation of the inhibitory properties on pancreatic lipase,and a-amylase were conducted.Results:Administration of BIX significantly decreased the body weight gain,adipocyte size,fat pad weights,hepatic lipid levels in HFD-induced obese mice.In addition,reduced liver weight exhibited decreased serum leptin levels,malic enzyme,glucose-6-phosphate dehydrogenase,hepatic fatty acid synthase,aspartate aminotransferase,alanine aminotransferase and hepatic phosphatidate phosphohydrolase activity.However,superoxide dismutase,catalase,glutathione peroxidase,and glutathione levels were increased in hepatic tissue.BIX also decreased lipid and carbohydrates absorption due to inhibition of pancreatic lipase and a-amylase.Long term supplementation of BIX significantly decreased hyperlipidemia,insulin resistance and glucose level.Decreased levels of hepatic steatosis and the islets of Langerhans appeared less shrunken in HFD-fed mice.Conclusions:The antiobesity effect of BIX appears to be associated at least in part,to its inhibitory effect on lipids and carbohydrate digestion enzymes such as pancreatic lipase,a-glucosidase,and a-amylase.The results suggested that BIX also act as an antioxidant and may treat visceral obesity normalizing glucose levels,improving insulin resistance and increasing energy expenditure.Therefore,achiote which has a main component,the carotenoid BIX,could be a viable food for the treatment of obesity and diabetes.

  10. Statistics of high-level scene context.

    Science.gov (United States)

    Greene, Michelle R

    2013-01-01

    CONTEXT IS CRITICAL FOR RECOGNIZING ENVIRONMENTS AND FOR SEARCHING FOR OBJECTS WITHIN THEM: contextual associations have been shown to modulate reaction time and object recognition accuracy, as well as influence the distribution of eye movements and patterns of brain activations. However, we have not yet systematically quantified the relationships between objects and their scene environments. Here I seek to fill this gap by providing descriptive statistics of object-scene relationships. A total of 48, 167 objects were hand-labeled in 3499 scenes using the LabelMe tool (Russell et al., 2008). From these data, I computed a variety of descriptive statistics at three different levels of analysis: the ensemble statistics that describe the density and spatial distribution of unnamed "things" in the scene; the bag of words level where scenes are described by the list of objects contained within them; and the structural level where the spatial distribution and relationships between the objects are measured. The utility of each level of description for scene categorization was assessed through the use of linear classifiers, and the plausibility of each level for modeling human scene categorization is discussed. Of the three levels, ensemble statistics were found to be the most informative (per feature), and also best explained human patterns of categorization errors. Although a bag of words classifier had similar performance to human observers, it had a markedly different pattern of errors. However, certain objects are more useful than others, and ceiling classification performance could be achieved using only the 64 most informative objects. As object location tends not to vary as a function of category, structural information provided little additional information. Additionally, these data provide valuable information on natural scene redundancy that can be exploited for machine vision, and can help the visual cognition community to design experiments guided by statistics

  11. The influence of blood glucose level on distribution of 18F-FDG in mice with tumor

    International Nuclear Information System (INIS)

    Fu Zhanli; Lin Jinghui; Wang Rongfu; Zhu Shaoli; Zhang Chunli; Pan Zhongyun

    2003-01-01

    To explore the influence of blood glucose level on 18 F-FDG uptake in tumor and normal tissues of mice, thirty five mice carrying Ehrlich ascitic cancer (EAC) are fasted 20 h and divided into four groups. The glucose loading group (n=12) and the control group (n=11) is given a solution of 50% glucose and distilled water orally just one hour before the 18 F FDG injection. Another two groups (n=5, n=7) is given a solution of 10%, 30% glucose respectively. Before 18 F-FDG intravenous injection, blood glucose levels are measured. The mice are killed one hour after the 18 F FDG injection. The tumor and normal tissues are excised, weighed, and counted by a γ well counter. The quantity of 18 F-FDG uptake is expressed as standardized uptake value (SUV). Blood glucose levels of the mice with EAC in the glucose loading group are significantly elevated than the control group (11.98 ± 3.01 mmol/L vs. 3.95 ± 1. 11 mmol/L, P 18 F-FDG uptake ratios of tumor and muscle in the glucose-loading group (1.34, 0.86, 0.48, 0.09, 1.38 respectively) are significantly lower than those in the control group (3.02, 2.62, 0.80, 0.16, 5.38 respectively) (P 18 F-FDG uptake ratios of tumor and brain, heart and blood in the glucose loading group (8.31. 1.05, 1.58, 103.00 respectively) are significantly higher than those in the control group (1.57, 0.64, 1.20, 9.73 respectively) (P 18 F-FDG distribution in mice. suggesting the blood glucose level should be controlled during clinically 18 F-FDG imaging

  12. The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice.

    Science.gov (United States)

    Kim, Jaeyeon; Coffey, Donna M; Ma, Lang; Matzuk, Martin M

    2015-06-01

    Although named "ovarian cancer," it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53(R172H), into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53(R172H)-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice.

  13. Progress in the High Level Trigger Integration

    CERN Multimedia

    Cristobal Padilla

    2007-01-01

    During the week from March 19th to March 23rd, the DAQ/HLT group performed another of its technical runs. On this occasion the focus was on integrating the Level 2 and Event Filter triggers, with a much fuller integration of HLT components than had been done previously. For the first time this included complete trigger slices, with a menu to run the selection algorithms for muons, electrons, jets and taus at the Level-2 and Event Filter levels. This Technical run again used the "Pre-Series" system (a vertical slice prototype of the DAQ/HLT system, see the ATLAS e-news January issue for details). Simulated events, provided by our colleagues working in the streaming tests, were pre-loaded into the ROS (Read Out System) nodes. These are the PC's where the data from the detector is stored after coming out of the front-end electronics, the "first part of the TDAQ system" and the interface to the detectors. These events used a realistic beam interaction mixture and had been subjected to a Level-1 selection. The...

  14. Curcumin suppresses intestinal polyps in APC Min mice fed a high fat diet

    Directory of Open Access Journals (Sweden)

    Christina Pettan-Brewer

    2011-06-01

    Full Text Available Colorectal cancer (CRC is a leading cause of cancer deaths in the United States. Various risk factors have been associated with CRC including increasing age and diet. Epidemiological and experimental studies have implicated a diet high in fat as an important risk factor for colon cancer. High fat diets can promote obesity resulting in insulin resistance and inflammation and the development of oxidative stress, increased cell proliferation, and suppression of apoptosis. Because of the high consumption of dietary fats, especially saturated fats, by Western countries, it is of interest to see if non-nutrient food factors might be effective in preventing or delaying CRC in the presence of high saturated fat intake. Curcumin (Curcuma longa, the main yellow pigment in turmeric, was selected to test because of its reported anti-tumor activity. APC Min mice, which develop intestinal polyps and have many molecular features of CRC, were fed a diet containing 35% pork fat, 33% sucrose, and a protein and vitamin mineral mixture (HFD with or without 0.5% curcumin. These cohorts were compared to APC Min mice receiving standard rodent chow (RC with 8% fat. APC Min mice fed the HFD for 3 months had a 23% increase in total number of polyps compared to APC Min mice on RC. Curcumin was able to significantly reverse the accelerated polyp development associated with the HFD suggesting it may be effective clinically in helping prevent colon cancer even when ingesting high amounts of fatty foods. The anti-tumor effect of curcumin was shown to be associated with enhanced apoptosis and increased efficiency of DNA repair. Since curcumin prevented the gain in body weight seen in APC Min mice ingesting the HFD, modulation of energy metabolism may also be a factor.

  15. Refeeding with a high-protein diet after a 48 h fast causes acute hepatocellular injury in mice.

    Science.gov (United States)

    Oarada, Motoko; Tsuzuki, Tsuyoshi; Nikawa, Takeshi; Kohno, Shohei; Hirasaka, Katsuya; Gonoi, Tohru

    2012-05-01

    Elucidating the effects of refeeding a high-protein diet after fasting on disease development is of interest in relation to excessive protein ingestion and irregular eating habits in developed countries. The objective of the present study was to address the hepatic effects of refeeding a high-protein diet after fasting. Mice were fasted for 48 h and then refed with a test diet containing 3, 15, 35, 40, 45 or 50 % casein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and liver immediate-early gene expression levels were sequentially measured for the first 24 h after initiation of refeeding. Refeeding with a 50 % casein diet after 48 h of fasting led to a rapid (within 2-3 h) and abnormal elevation in serum ALT (P = 0·006) and AST (P = 0·001) activities and a marked increase in liver Finkel-Biskis-Jinkins (FBJ) osteosarcoma oncogene (P = 0·007) and nuclear receptor subfamily 4, group A, member 1 (P = 0·002) mRNA levels. In contrast, refeeding of the 3, 15 or 35 % casein diets produced no substantial increases in serum ALT and AST activities in mice. Refeeding of 40, 45 or 50 % casein increased serum ALT and AST activities in proportion to this dietary casein content. In mice refed the 3, 15 or 35, but not 50 %, casein diets, liver heat shock protein 72 transcript levels greatly increased. We conclude from these data that the consumption of a high-protein diet after fasting causes acute hepatocellular injury in healthy animals, and propose that careful attention should be paid to the use of such diets.

  16. High sugar and butter (HSB) diet induces obesity and metabolic syndrome with decrease in regulatory T cells in adipose tissue of mice.

    Science.gov (United States)

    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.

  17. Prevention of diet-induced obesity by safflower oil: insights at the levels of PPARalpha, orexin, and ghrelin gene expression of adipocytes in mice.

    Science.gov (United States)

    Zhang, Zhong; Li, Qiang; Liu, Fengchen; Sun, Yuqian; Zhang, Jinchao

    2010-03-15

    The aim of this study was to investigate the prevention of diet-induced obesity by a high safflower oil diet and adipocytic gene expression in mice. Forty 3-week-old C57BL/6 mice were randomly divided into three groups: control group (CON, 5% lard + 5% safflower oil), high lard group (LAR, 45% lard + 5% safflower oil), and high safflower oil group (SAF, 45% safflower oil + 5% lard). After 10 weeks, 10 mice of the LAR group were switched to high safflower oil diet (LAR-SAF). Ten weeks later, glucose tolerance tests were performed by intraperitoneal injection of glucose. Circulating levels of lipid and insulin were measured and white adipose tissues were taken for gene chip and reverse transcriptase-polymerase chain reaction analysis. The LAR group showed higher body weight, adiposity index, insulin, and lipids than the CON group (P<0.05). The body weight in the LAR-SAF group decreased after dietary reversal. The plasma biochemical profiles decreased in the LAR-SAF and SAF groups (P<0.05) compared with those of the LAR group. The blood glucose level of the LAR-SAF group was reduced during intraperitoneal glucose tolerance test compared with that of the LAR group. The LAR-SAF group had lower levels of Orexin and Ghrelin gene expression, whereas the level of PPARalpha gene expression was significantly enhanced compared with that of the LAR group. So, the SAF diet can alter adipocytic adiposity-related gene expression and result in effective amelioration of diet-induced obesity.

  18. High blood pressure in transgenic mice carrying the rat angiotensinogen gene.

    Science.gov (United States)

    Kimura, S; Mullins, J J; Bunnemann, B; Metzger, R; Hilgenfeldt, U; Zimmermann, F; Jacob, H; Fuxe, K; Ganten, D; Kaling, M

    1992-01-01

    Transgenic mice were generated by injecting the entire rat angiotensinogen gene into the germline of NMRI mice. The resulting transgenic animals were characterized with respect to hemodynamics, parameters of the renin angiotension system, and expression of the transgene. The transgenic line TGM(rAOGEN)123 developed hypertension with a mean arterial blood pressure of 158 mmHg in males and 132 mmHg in females. In contrast, the transgenic line TGM(rAOGEN)92 was not hypertensive. Rat angiotensinogen was detectable only in plasma of animals of line 123. Total plasma angiotensinogen and plasma angiotensin II concentrations were about three times as high as those of negative control mice. In TGM(rAOGEN)123 the transgene was highly expressed in liver and brain. Transcripts were also detected in heart, kidney and testis. In TGM(rAOGEN)92 the brain was the main expressing organ. In situ hybridization revealed an mRNA distribution in the brain of TGM(rAOGEN)123 similar to the one in rat. In TGM(rAOGEN)92 the expression pattern in the brain was aberrant. These data indicate that overexpression of the angiotensinogen gene in liver and brain leads to the development of hypertension in transgenic mice. The TGM(rAOGEN)123 constitutes a high angiotensin II type of hypertension and may provide a new experimental animal model to study the kinetics and function of the renin angiotensin system. Images PMID:1547785

  19. TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice.

    Directory of Open Access Journals (Sweden)

    Stephen J Kentish

    Full Text Available Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1 are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice.TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined.Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet.TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity.

  20. Serotonin augmentation therapy by escitalopram has minimal effects on amyloid-β levels in early-stage Alzheimer's-like disease in mice.

    Science.gov (United States)

    von Linstow, Christian Ulrich; Waider, Jonas; Grebing, Manuela; Metaxas, Athanasios; Lesch, Klaus Peter; Finsen, Bente

    2017-09-12

    Dysfunction of the serotonergic (5-HTergic) system has been implicated in the cognitive and behavioural symptoms of Alzheimer's disease (AD). Accumulation of toxic amyloid-β (Aβ) species is a hallmark of AD and an instigator of pathology. Serotonin (5-HT) augmentation therapy by treatment with selective serotonin reuptake inhibitors (SSRIs) in patients with AD has had mixed success in improving cognitive function, whereas SSRI administration to mice with AD-like disease has been shown to reduce Aβ pathology. The objective of this study was to investigate whether an increase in extracellular levels of 5-HT induced by chronic SSRI treatment reduces Aβ pathology and whether 5-HTergic deafferentation of the cerebral cortex could worsen Aβ pathology in the APP swe /PS1 ΔE9 (APP/PS1) mouse model of AD. We administered a therapeutic dose of the SSRI escitalopram (5 mg/kg/day) in the drinking water of 3-month-old APP/PS1 mice to increase levels of 5-HT, and we performed intracerebroventricular injections of the neurotoxin 5,7-dihydroxytryptamine (DHT) to remove 5-HTergic afferents. We validated the effectiveness of these interventions by serotonin transporter autoradiography (neocortex 79.7 ± 7.6%) and by high-performance liquid chromatography for 5-HT (neocortex 64% reduction). After 6 months of escitalopram treatment or housing after DHT-induced lesion, we evaluated brain tissue by mesoscale multiplex analysis and sections by IHC analysis. Amyloid-β-containing plaques had formed in the neocortex and hippocampus of 9-month-old APP/PS1 mice after 6 months of escitalopram treatment and 5-HTergic deafferentation. Unexpectedly, levels of insoluble Aβ42 were unaffected in the neocortex and hippocampus after both types of interventions. Levels of insoluble Aβ40 increased in the neocortex of SSRI-treated mice compared with those treated with vehicle control, but they were unaffected in the hippocampus. 5-HTergic deafferentation was without effect on the levels of

  1. Effects of Fortunella margarita fruit extract on metabolic disorders in high-fat diet-induced obese C57BL/6 mice.

    Science.gov (United States)

    Tan, Si; Li, Mingxia; Ding, Xiaobo; Fan, Shengjie; Guo, Lu; Gu, Ming; Zhang, Yu; Feng, Li; Jiang, Dong; Li, Yiming; Xi, Wanpeng; Huang, Cheng; Zhou, Zhiqin

    2014-01-01

    Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle) fruit extract (FME) on high-fat diet-induced C57BL/6 obese mice. The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow), high-fat diet (HF), and high-fat diet with 1% (w/w) extract of kumquat (HF+FME) for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay. In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC), serum low density lipoprotein cholesterol (LDL-c) levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG), serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes. Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances.

  2. Period analysis at high noise level

    International Nuclear Information System (INIS)

    Kovacs, G.

    1980-01-01

    Analytical expressions are derived for the variances of some types of the periodograms due to normal-distributed noise present in the data. The equivalence of the Jurkevich and the Warner and Robinson methods is proved. The optimum phase cell number of the Warner and Robinson method is given; this number depends on the data length, signal form and noise level. The results are illustrated by numerical examples. (orig.)

  3. High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice

    NARCIS (Netherlands)

    Xiao, Liang; Sonne, Si Brask; Feng, Qiang; Chen, Ning; Xia, Zhongkui; Li, Xiaoping; Fang, Zhiwei; Zhang, Dongya; Fjære, Even; Midtbø, Lisa Kolden; Derrien, Muriel; Hugenholtz, Floor; Tang, Longqing; Li, Junhua; Zhang, Jianfeng; Liu, Chuan; Hao, Qin; Vogel, Ulla Birgitte; Mortensen, Alicja; Kleerebezem, Michiel; Licht, Tine Rask; Yang, Huanming; Wang, Jian; Li, Yingrui; Arumugam, Manimozhiyan; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2017-01-01

    BACKGROUND: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those

  4. Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice.

    Science.gov (United States)

    Slijepcevic, Davor; Roscam Abbing, Reinout L P; Katafuchi, Takeshi; Blank, Antje; Donkers, Joanne M; van Hoppe, Stéphanie; de Waart, Dirk R; Tolenaars, Dagmar; van der Meer, Jonathan H M; Wildenberg, Manon; Beuers, Ulrich; Oude Elferink, Ronald P J; Schinkel, Alfred H; van de Graaf, Stan F J

    2017-11-01

    The Na + -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. Mice or healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake kinetics were determined in wild-type (WT), organic anion transporting polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1-transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic transporter mRNA levels were assessed in rat hepatoma cells and in mice by peptide injection or adeno-associated virus-mediated overexpression. NTCP inhibition using myrcludex B had only moderate effects on bile acid kinetics in WT mice, but completely inhibited active transport of conjugated bile acid species in OATP knockout mice. Cholesterol 7α-hydroxylase Cyp7a1 expression was strongly down-regulated upon prolonged inhibition of hepatic uptake of conjugated bile acids. Fgf15 (mouse counterpart of FGF19) expression was induced in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B-treated cholestatic mice, whereas plasma FGF19 was not induced in humans treated with myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte-models and mouse organoids by basolateral incubation with a high concentration (1 mM) of conjugated bile acids. NTCP and OATPs contribute to hepatic uptake of conjugated bile acids in mice, whereas the predominant uptake in humans is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile acids in the systemic circulation to induce FGF15/19, which modulates hepatic bile acid synthesis and uptake. (Hepatology 2017;66:1631-1643).

  5. Influence of infection by Toxoplasma gondii on purine levels and E-ADA activity in the brain of mice experimentally infected mice.

    Science.gov (United States)

    Tonin, Alexandre A; Da Silva, Aleksandro S; Casali, Emerson A; Silveira, Stephanie S; Moritz, Cesar E J; Camillo, Giovana; Flores, Mariana M; Fighera, Rafael; Thomé, Gustavo R; Morsch, Vera M; Schetinger, Maria Rosa C; Rue, Mario De La; Vogel, Fernanda S F; Lopes, Sonia T A

    2014-07-01

    The aim of this study was to assess the purine levels and E-ADA activity in the brain of mice (BALB/c) experimentally infected with Toxoplasma gondii. In experiment I (n=24) the mice were infected with RH strain of T. gondii, while in experiment II (n=36) they were infected with strain ME-49 of T. gondii. Our results showed that, for RH strain (acute phase), an increase in both periods in the levels of ATP, ADP, AMP, adenosine, hypoxanthine, xanthine (only on day 6 PI) and uric acid (only on day 6 PI). By the other hand, the RH strain led, on days 4 and 6 PI, to a reduction in the concentration of inosine. ME-49, a cystogenic strain, showed some differences in acute and chronic phase, since on day 6 PI the levels of ATP and ADP were increased, while on day 30 these same nucleotides were reduced. On day 60 PI, ME-49 induced a reduction in the levels of ATP, ADP, AMP, adenosine, inosine and xanthine, while uric acid was increased. A decrease of E-ADA activity was observed in brain on days 4 and 6 PI (RH), and 30 PI (ME-49); however on day 60 PI E-ADA activity was increased for infection by ME-49 strain. Therefore, it was possible to conclude that infection with T. gondii changes the purine levels and the activity of E-ADA in brain, which may be associated with neurological signs commonly observed in this disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Disposal of high-level radioactive wastes

    Energy Technology Data Exchange (ETDEWEB)

    Costello, J M [Australian Atomic Energy Commission Research Establishment, Lucas Heights

    1982-03-01

    The aims and options for the management and disposal of highly radioactive wastes contained in spent fuel from the generation of nuclear power are outlined. The status of developments in reprocessing, waste solidification and geologic burial in major countries is reviewed. Some generic assessments of the potential radiological impacts from geologic repositories are discussed, and a perspective is suggested on risks from radiation.

  7. High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Peng Lu

    Full Text Available BACKGROUND: Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate, the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate, the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha'-palmitate fat (HAPF diet and high beta-palmitate fat (HBPF diet on colitis development in Muc2 deficient (Muc2(-/- mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer. METHODS: Muc2(-/- mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed. RESULTS: Both HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2(-/- mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1, genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis. CONCLUSIONS: This study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2(-/- mice by inducing an immunosuppressive Treg cell response.

  8. High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice.

    Science.gov (United States)

    Lu, Peng; Bar-Yoseph, Fabiana; Levi, Liora; Lifshitz, Yael; Witte-Bouma, Janneke; de Bruijn, Adrianus C J M; Korteland-van Male, Anita M; van Goudoever, Johannes B; Renes, Ingrid B

    2013-01-01

    Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate), the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate), the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha'-palmitate fat (HAPF) diet and high beta-palmitate fat (HBPF) diet on colitis development in Muc2 deficient (Muc2(-/-)) mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer. Muc2(-/-) mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed. Both HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2(-/-) mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg) cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1), genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis. This study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2(-/-) mice by inducing an immunosuppressive Treg cell response.

  9. Corticosterone levels and behavioral changes induced by simultaneous exposure to chronic social stress and enriched environments in NMRI male mice.

    Science.gov (United States)

    Mesa-Gresa, Patricia; Ramos-Campos, Marta; Redolat, Rosa

    2016-05-01

    Environmental enrichment (EE) is an experimental model which is believed to counteract some of the effects induced by stressors, although few studies have exposed rodents simultaneously to EE and stress. Our aim was to compare the short- and long-term effects of different housing conditions in mice submitted to chronic stress. 128 NMRI male mice arrived at our laboratory on postnatal day (PND) 21. During Phase I (PND 28), animals were randomly assigned to four experimental conditions: 1) EE+STRESS: mice housed in EE and submitted to social stress (n=32); 2) EE+NO STRESS: mice housed in EE without stress (n=32); 3) SE+STRESS: mice maintained in standard conditions (SE) and submitted to social stress (n=32); and 4) SE+NO STRESS (n=32). At the end of Phase I (PND 77), one cohort of 32 animals was used for behavioral assessment whereas another cohort of 32 was sacrificed for corticosterone analysis. Results indicated that EE animals showed less body weight, higher water and food intake, diminished anxiety response and decreased motor and exploratory behavior than SE mice. Mice exposed to stress gained less body weight, showed higher food and fluid intake and displayed decreased exploratory behavior than non-stressed mice. Furthermore, EE+STRESS group displayed significantly higher corticosterone levels than EE+NO STRESS group whereas EE+NO STRESS group showed lower levels than SE+NO STRESS. On PND 83, Phase II of the study began. Animals (n=96) were assigned to two different housing conditions: EE (n=48) and SE (n=48). On PND 112, corticosterone analysis (n=32) and behavioral study (n=64) were done. The factor "Housing Phase II" reached statistical significance. Results indicated that EE animals showed lower body weight and higher fluid intake than SE group, as well as decreased anxiety. No clear effects on motor and exploratory behavior or learning were observed. When long-term effects were analyzed, results indicated that "Initial Housing" condition was significant

  10. C57Bl/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Desmarchelier Charles

    2012-03-01

    Full Text Available Abstract Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be determined. Methods We therefore measured cholesterol and phospholipid concentration in intestine and liver and quantified fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat Western diet containing 0.03% (w/w cholesterol. To identify the underlying mechanisms of dietary adaptations in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Mice on Western diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load.

  11. High-lying 0+ and 3- levels in 12C

    International Nuclear Information System (INIS)

    Hanna, S.S.; Feldman, W.; Suffert, M.; Kurath, D.

    1982-01-01

    The γ decays of the levels at 17.77 and 18.36 MeV in 12 C are studied by proton capture and the assignments of (0 + ,1) and (3 - ,1), respectively, are confirmed. The very great strength of the decay of the (0 + ,1) level to the lower (1 + ,0) level at 12.71 MeV is consistent with a spin- and isospin-flip deuteronlike transition. The strong decay of the (3 - ,1) level to the lower (3 - 0,) level at 9.64 MeV is fairly typical of an analog to antianalog transition. The γ-decay widths of these levels are compared with shell-model calculations

  12. Mice divergently selected for high and low basal metabolic rates evolved different cell size and organ mass.

    Science.gov (United States)

    Maciak, S; Bonda-Ostaszewska, E; Czarnołęski, M; Konarzewski, M; Kozłowski, J

    2014-03-01

    Evolution of metabolic rates of multicellular organisms is hypothesized to reflect the evolution of their cell architecture. This is likely to stem from a tight link between the sizes of cells and nuclei, which are expected to be inversely related to cell metabolism. Here, we analysed basal metabolic rate (BMR), internal organ masses and the cell/nucleus size in different tissues of laboratory mice divergently selected for high/low mass-corrected BMR and four random-bred mouse lines. Random-bred lines had intermediate levels of BMR as compared to low- and high-BMR lines. Yet, this pattern was only partly consistent with the between-line differences in cell/nucleus sizes. Erythrocytes and skin epithelium cells were smaller in the high-BMR line than in other lines, but the cells of low-BMR and random-bred mice were similar in size. On the other hand, the size of hepatocytes, kidney proximal tubule cells and duodenum enterocytes were larger in high-BMR mice than other lines. All cell and nucleus sizes were positively correlated, which supports the role of the nucleus in cell size regulation. Our results suggest that the evolution of high BMR involves a reduction in cell size in specialized tissues, whose functions are primarily dictated by surface-to-volume ratios, such as erythrocytes. High BMR may, however, also incur an increase in cell size in tissues with an intense transcription and translation, such as hepatocytes. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  13. Antidiabetic Effects of Carassius auratus Complex Formula in High Fat Diet Combined Streptozotocin-Induced Diabetic Mice

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    Zhi-Hong Wang

    2014-01-01

    Full Text Available Carassius auratus complex formula, including Carassius auratus, Rhizoma dioscoreae, Lycium chinense, and Rehmannia glutinosa Libosch, is a combination prescription of traditional Chinese medicine, which has always been used to treat diabetes mellitus in ancient China. In this study, we provided experimental evidence for the use of Carassius auratus complex formula in the treatment of high fat diet combined streptozotocin- (STZ- induced type 2 diabetes. Carassius auratus complex formula aqueous extract was prepared and the effects of it on blood glucose, serum insulin, adipose tissue weight, oral glucose tolerance test (OGTT, total cholesterol, and triglyceride (TG levels in mice were measured. Moreover, adiponectin, TG synthesis related gene expressions, and the inhibitory effect of aldose reductase (AR were performed to evaluate its antidiabetic effects. After the 8-week treatment, blood glucose, insulin levels, and adipose tissue weight were significantly decreased. OGTT and HOMA-IR index showed improved glucose tolerance. It could also lower plasma TG, TC, and liver TG levels. Furthermore, Carassius auratus complex formula could inhibit the activity of AR and restore adiponectin expression in serum. Based on these findings, it is suggested that Carassius auratus complex formula possesses potent anti-diabetic effects on high fat diet combined STZ-induced diabetic mice.

  14. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.

    Science.gov (United States)

    Bowen, T Scott; Eisenkolb, Sophia; Drobner, Juliane; Fischer, Tina; Werner, Sarah; Linke, Axel; Mangner, Norman; Schuler, Gerhard; Adams, Volker

    2017-01-01

    Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice. © FASEB.

  15. Neuropeptide Y deficiency attenuates responses to fasting and high-fat diet in obesity-prone mice.

    Science.gov (United States)

    Patel, Hiralben R; Qi, Yong; Hawkins, Evan J; Hileman, Stanley M; Elmquist, Joel K; Imai, Yumi; Ahima, Rexford S

    2006-11-01

    Neuropeptide Y (NPY) stimulates feeding and weight gain, but deletion of the NPY gene does not affect food intake and body weight in mice bred on a mixed genetic background. We reasoned that the orexigenic action of NPY would be evident in C57Bl/6J mice susceptible to obesity. NPY deficiency has no significant effect in mice fed a normal rodent diet. However, energy expenditure is elevated during fasting, and hyperphagia and weight gain are blunted during refeeding. Expression of agouti-related peptide (AGRP) in the hypothalamus is increased in NPY knockout (NPYko) than wild-type mice, but unlike wild type there is no further increase in AGRP when NPYko mice are fasted. Moreover, NPYko mice have higher oxygen consumption and uncoupling protein-1 expression in brown adipose tissue during fasting. The failure of an increase in orexigenic peptides and higher thermogenesis may contribute to attenuation of weight gain when NPYko mice are refed. C57Bl/6J mice lacking NPY are also less susceptible to diet-induced obesity (DIO) as a result of reduced feeding and increased energy expenditure. The resistance to DIO in NPYko mice is associated with a reduction in nocturnal feeding and increased expression of anorexigenic hypothalamic peptides. Insulin, leptin, and triglyceride levels increase with adiposity in both wild-type and NPYko mice.

  16. Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice

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    Soyoung Park

    2016-01-01

    Full Text Available Korean pine nut oil (PNO has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO (PC, SC or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD, for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively compared with SHFD. Hepatic triacylglycerol (TG level was significantly lower in PHFD than the SHFD (26% lower. PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response.

  17. Anti-obesity effect of Lactobacillus gasseri BNR17 in high-sucrose diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Ji-Hee Kang

    Full Text Available Previously, we reported that Lactobacillus gasseri BNR17 (BNR17, a probiotic strain isolated from human breast milk, inhibited increases in body weight and adipocyte tissue weight in high-sucrose diet-fed Sprague-Dawley (SD rats and reduced glucose levels in type 2 diabetes mice. In the current study, we conducted further experiments to extend these observations and elucidate the mechanism involved. C57BL/6J mice received a normal diet, high-sucrose diet or high-sucrose diet containing L. gasseri BNR17 (10(9 or 10(10 CFU for 10 weeks. The administration of L. gasseri BNR17 significantly reduced the body weight and white adipose tissue weight regardless of the dose administered. In BNR17-fed groups, mRNA levels of fatty acid oxidation-related genes (ACO, CPT1, PPARα, PPARδ were significantly higher and those of fatty acid synthesis-related genes (SREBP-1c, ACC were lower compared to the high-sucrose-diet group. The expression of GLUT4, main glucose transporter-4, was elevated in BNR17-fed groups. L. gasseri BNR17 also reduced the levels of leptin and insulin in serum. These results suggest that the anti-obesity actions of L. gasseri BNR17 can be attributed to elevated expression of fatty acid oxidation-related genes and reduced levels of leptin. Additionally, data suggested the anti-diabetes activity of L. gasseri BNR17 may be to due elevated GLUT4 and reduced insulin levels.

  18. The Effect of Curry Leaves (Murayya Koenigii L. on Blood Glucose Levels In Alloxan Diabetic Mice (Mus Musculus

    Directory of Open Access Journals (Sweden)

    Fauziah Fauziah

    2014-07-01

    Full Text Available This study was conducted to determine the effect of ethanol extract of curry leaves (Murraya koenigii L. on blood glucose levels in alloxan diabetic mice (Mus musculus. The diabetic conditions were made by giving alloxan 75 mg/kg body weight (BW and the hypoglycemic effects of extract of curry leaves given with various doses.   This study used 24 male mice strain Balb/c in four groups of treatment with six replications, namely the negative control group, the ethanol extract of curry leaf tree 50% mL/10g body weight group, 70% mL/10g body weight group and 90% mL/10g body weight group. The treatment was given orally by using a gastric sonde for 14 days. Blood samples were taken through the sinus caudalis using a scissors. Blood glucose level was measured at 1st , the 8th and the 24th of treatment using blood glucose test strips and Nesco® Multicheck apparatus. Blood glucose data were analyzed by one way ANOVA (Analysis of Variants and followed by Tuckey test at significance level of 5%. The result showed that treatment of ethanol extract of curry leaves (Murraya koenigii at various doses significantly affected the decrease on blood glucose levels of mice (Mus musculus alloxan diabetic.

  19. Potential Association of Lead Exposure During Early Development of Mice With Alteration of Hippocampus Nitric Oxide Levels and Learning Memory

    Institute of Scientific and Technical Information of China (English)

    LI SUN; ZHENG-YAN ZHAO; JIAN HU; XIE-LAI ZHOU

    2005-01-01

    Objective Chronic lead (Pb) exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains.Methods Sixty Balb/c mice aged 10 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05%,0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay. Results Compared with control groups, (1) the weight of 0.075% group was significantly reduced (P<0.05); (2) The number of times in mice attaining the required standards in T-water maze test was lower in 0.075%group (P<0.01). No significant difference was found between experimental and control groups in open field test (P>0.05); (3)NO level of mouse hippocampus tissue was decreased in 0.075% group (P<0.01). Conclusions The findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.

  20. Diet Matters: Endotoxin in the Diet Impacts the Level of Allergic Sensitization in Germ-Free Mice.

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    Martin Schwarzer

    Full Text Available Germ-free animals have been used to define the vital role of commensal bacteria on the maturation of the host immune system. However, the role of bacterial residues in diet in this setting is poorly understood. Here we investigated the effect of bacterial contamination in sterile diet on the level of allergic sensitization in germ-free mice. Sterile grain-based diets ST1 and R03 were tested for the level of bacterial contamination. ST1 contained higher amount of bacterial DNA, approximately ten times more endotoxin, and induced higher, TLR4-dependent, cytokine production in dendritic cells compared to R03. In a germ-free mouse model of sensitization to the major birch pollen allergen Bet v 1, feeding on ST1 for at least two generations was associated with decreased production of allergen-specific IgE and IgG1 antibodies in sera in comparison to R03. Furthermore, reduced levels of allergen-specific and ConA-induced cytokines IL-4, IL-5 and IL-13 accompanied by increased levels of IFN-γ were detected in splenocytes cultures of these mice. Our results show that contamination of experimental diet with bacterial residues, such as endotoxin, significantly affects the development of allergic sensitization in germ-free mice. Therefore, careful selection of sterile food is critical for the outcomes of germ-free or gnotobiotic experimental models of immune-deviated diseases.

  1. Impact of whey proteins on the systemic and local intestinal level of mice with diet induced obesity.

    Science.gov (United States)

    Swiątecka, D; Złotkowska, D; Markiewicz, L H; Szyc, A M; Wróblewska, B

    2017-04-19

    Obesity is a serious public health problem and being multifactorial is difficult to tackle. Since the intestinal ecosystem's homeostasis is, at least partially, diet-dependent, its modulation may be triggered by food components that are designed to exert a modulatory action leading to a health-promoting effect. Milk whey proteins, are considered as such promising factors since they influence satiation as well as body weight and constitute the source of biologically active peptides which may modulate health status locally and systemically. This way, whey proteins are associated with obesity. Therefore, this paper is aimed at the estimation of the impact of whey proteins using a commercially available whey protein isolate on the physiological response of mice with diet-induced obesity. The physiological response was evaluated on the local-intestinal level, scrutinizing intestinal microbiota as one of the important factors in obesity and on the systemic level, analyzing the response of the organism. Whey proteins brought about the decrease of the fat mass with a simultaneous increase of the lean mass of animals with diet induced obesity, which is a promising, health-promoting effect. Whey proteins also proved to act beneficially helping restore the number of beneficial bifidobacteria in obese animals and decreasing the calorie intake and fat mass as well as the LDL level. Overall, supplementation of the high fat diet with whey proteins acted locally by restoration of the intestinal ecosystem, thus preventing dysbiosis and its effects and also acted systemically by strengthening the organism increasing the lean mass and thus hindering obesity-related detrimental effects.

  2. Arachidonic acid metabolites in normal and autoimmune mice do not influence lymphocyte-high endothelial venule interactions.

    Science.gov (United States)

    Manolios, N; Bakiera, B; Geczy, C L; Schrieber, L

    1991-02-01

    In peripheral lymphoid organs the number of lymphocytes and the proportion of functional lymphocyte subsets are regulated by multiple factors including the control of lymphocyte migration by selective lymphocyte-high endothelial venule (HEV) interactions. In this study, prostaglandin E2 (PGE2) levels from normal and autoimmune mouse lymph node cells were measured. The contribution of eicosanoids to lymphocyte-HEV interactions in normal (CBA/T6) and autoimmune (MRL/n) mice was examined. There was no association between PGE2 production in normal or autoimmune mice and the age of onset of disease activity in the latter strains. Arachidonic acid metabolites, in particular PGE2 and leukotriene B4 (LTB4), did not have any effects on lymphocyte-HEV binding. Likewise, lymphocytes treated in vivo and/or in vitro with arachidonic acid metabolite inhibitors (acetyl salicylic acid, indomethacin, BW755C) did not alter lymphocyte-HEV binding interactions in both normal and autoimmune mice. No clinical significance could be attributed to lymph node PGE2 production and the age of onset of autoimmune disease. In summary, these findings cast doubt on the role of arachidonic acid metabolites in lymphocyte-HEV binding interactions.

  3. Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation.

    Science.gov (United States)

    Liu, Chang; Rajapakse, Angana G; Riedo, Erwin; Fellay, Benoit; Bernhard, Marie-Claire; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

    2016-02-05

    Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II(-/-) mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II(-/-) mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II(-/-) mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II(-/-)-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity.

  4. High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

    Science.gov (United States)

    Gao, Mingming; Ma, Yongjie; Liu, Dexi

    2015-01-01

    High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

  5. High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

    Directory of Open Access Journals (Sweden)

    Mingming Gao

    Full Text Available High-fat diet (HFD has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

  6. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.

    Science.gov (United States)

    Guerenne, Laura; Beurlet, Stéphanie; Said, Mohamed; Gorombei, Petra; Le Pogam, Carole; Guidez, Fabien; de la Grange, Pierre; Omidvar, Nader; Vanneaux, Valérie; Mills, Ken; Mufti, Ghulam J; Sarda-Mantel, Laure; Noguera, Maria Elena; Pla, Marika; Fenaux, Pierre; Padua, Rose Ann; Chomienne, Christine; Krief, Patricia

    2016-01-27

    In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  7. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Laura Guerenne

    2016-01-01

    Full Text Available Abstract Background In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. Methods We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS and acute myeloid leukemia (AML post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Results Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. Conclusions These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  8. EFECTO DE L-CARNITINA SOBRE EL PESO, NIVELES DE TRIGLICÉRIDOS Y COLESTEROL DE RATONES SOMETIDOS A DIETAS NORMO E HIPERCALÓRICAS | EFFECT OF L-CARNITINE ON WEIGHT, CHOLESTEROL AND TRIGLYCERIDES LEVELS OF MICE RECEIVING NORMAL AND HIGH CALORIC DIETS

    Directory of Open Access Journals (Sweden)

    Luis Ojeda

    2016-11-01

    Full Text Available An experimental study was conducted to determine the effect of L-carnitine on weight and serum lipid levels (triglycerides and total cholesterol on NMRI mice. To do so, a factorial arrangement of treatments 22 under a completely randomized design was carried out. Factors considered were the diet (normal and hypercaloric and the inclusion or not of the L-carnitine supplement. L-carnitine was orally administered at a rate of 2 mg/day. Weight [g], serum triglyceride concentrations [mg·dL-1] and total cholesterol [mg·dL-1] were evaluated. Analysis of variance test and Tukey mean comparisons were applied. Non significant differences were found between the type of diet for weight (F = 4.00; p = 0.0575, and cholesterol (F = 0.09; p = 0.7722, or for the administration of L-carnitine for the weight (F = 1.08; p = 0.3096, and cholesterol (F = 0.13; p = 0.7255. For triglycerides, significant differences between the type of diet (F = 12.73; p = 0.0016, and significant interaction between type of diet and the administration of L-carnitine (F = 5.95; p = 0.0228, were found. This effect suggests that the amino acid combined with a low calorie diet could be considered as an alternative to treat cases of hypertriglyceridemia.

  9. High level radiation dosimetry in biomedical research

    International Nuclear Information System (INIS)

    Inada, Tetsuo

    1979-01-01

    The physical and biological dosimetries relating to cancer therapy with radiation were taken up at the first place in the late intercomparison on high LET radiation therapy in Japan-US cancer research cooperative study. The biological dosimetry, the large dose in biomedical research, the high dose rate in biomedical research and the practical dosimeters for pulsed neutrons or protons are outlined with the main development history and the characteristics which were obtained in the relating experiments. The clinical neutron facilities in the US and Japan involved in the intercomparison are presented. Concerning the experimental results of dosimeters, the relation between the R.B.E. compared with Chiba (Cyclotron in National Institute of Radiological Sciences) and the energy of deuterons or protons used for neutron production, the survival curves of three cultured cell lines derived from human cancers, after the irradiation of 250 keV X-ray, cyclotron neutrons of about 13 MeV and Van de Graaff neutrons of about 2 MeV, the hatchability of dry Artemia eggs at the several depths in an absorber stack irradiated by 60 MeV proton beam of 40, 120 and 200 krad, the peak skin reaction of mouse legs observed at various sets of average and instantaneous dose rates, and the peak skin reaction versus three instantaneous dose rates at fixed average dose rate of 7,300 rad/min are shown. These actual data were evaluated numerically and in relation to the physical meaning from the viewpoint of the fundamental aspect of cancer therapy, comparing the Japanese measured values to the US data. The discussion record on the high dose rate effect of low LET particles on biological substances and others is added. (Nakai, Y.)

  10. L-ARGININE PREVENTS METABOLIC EFFECTS OF HIGH GLUCOSE IN DIABETIC MICE

    OpenAIRE

    West, Matthew B.; Ramana, Kota V.; Kaiserova, Karin; Srivastava, Satish K.; Bhatnagar, Aruni

    2008-01-01

    We tested the hypothesis that activation of the polyol pathway and protein kinase C (PKC) during diabetes is due to loss of NO. Our results show that after 4 weeks of streptozotocin-induced diabetes, treatment with L-arginine restored NO levels and prevented tissue accumulation of sorbitol in mice, which was accompanied by an increase in glutathiolation of aldose reductase. L-arginine treatment decreased superoxide generation in the aorta, total PKC activity and PKC-βII phosphorylation in the...

  11. High-glycemic index carbohydrates abrogate the antiobesity effect of fish oil in mice

    DEFF Research Database (Denmark)

    Hao, Qin; Lillefosse, Haldis Haukås; Fjære, Even

    2012-01-01

    Fish oil rich in n-3 polyunsaturated fatty acids is known to attenuate diet-induced obesity and adipose tissue inflammation in rodents. Here we aimed to investigate whether different carbohydrate sources modulated the antiobesity effects of fish oil. By feeding C57BL/6J mice isocaloric high-fat d...... metabolic effects of fish oil by demonstrating that high-GI carbohydrates attenuate the antiobesity effects of fish oil.......Fish oil rich in n-3 polyunsaturated fatty acids is known to attenuate diet-induced obesity and adipose tissue inflammation in rodents. Here we aimed to investigate whether different carbohydrate sources modulated the antiobesity effects of fish oil. By feeding C57BL/6J mice isocaloric high...

  12. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice12345

    Science.gov (United States)

    Christensen, Karen E; Mikael, Leonie G; Leung, Kit-Yi; Lévesque, Nancy; Deng, Liyuan; Wu, Qing; Malysheva, Olga V; Best, Ana; Caudill, Marie A; Greene, Nicholas DE

    2015-01-01

    Background: Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. Objective: Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism. Design: Folic acid–supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr+/+ and Mthfr+/− mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined. Results: Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr+/− mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr+/− livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr+/− mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile. Conclusions: We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2

  13. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.

    Science.gov (United States)

    Christensen, Karen E; Mikael, Leonie G; Leung, Kit-Yi; Lévesque, Nancy; Deng, Liyuan; Wu, Qing; Malysheva, Olga V; Best, Ana; Caudill, Marie A; Greene, Nicholas D E; Rozen, Rima

    2015-03-01

    Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. Our goal was to investigate the impact of high folic acid intake on liver disease and methyl metabolism. Folic acid-supplemented diet (FASD, 10-fold higher than recommended) and control diet were fed to male Mthfr(+/+) and Mthfr(+/-) mice for 6 mo to assess gene-nutrient interactions. Liver pathology, folate and choline metabolites, and gene expression in folate and lipid pathways were examined. Liver and spleen weights were higher and hematologic profiles were altered in FASD-fed mice. Liver histology revealed unusually large, degenerating cells in FASD Mthfr(+/-) mice, consistent with nonalcoholic fatty liver disease. High folic acid inhibited MTHFR activity in vitro, and MTHFR protein was reduced in FASD-fed mice. 5-Methyltetrahydrofolate, SAM, and SAM/S-adenosylhomocysteine ratios were lower in FASD and Mthfr(+/-) livers. Choline metabolites, including phosphatidylcholine, were reduced due to genotype and/or diet in an attempt to restore methylation capacity through choline/betaine-dependent SAM synthesis. Expression changes in genes of one-carbon and lipid metabolism were particularly significant in FASD Mthfr(+/-) mice. The latter changes, which included higher nuclear sterol regulatory element-binding protein 1, higher Srepb2 messenger RNA (mRNA), lower farnesoid X receptor (Nr1h4) mRNA, and lower Cyp7a1 mRNA, would lead to greater lipogenesis and reduced cholesterol catabolism into bile. We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2-hit mechanism whereby mutant hepatocytes cannot

  14. Energy levels of highly ionized atoms

    International Nuclear Information System (INIS)

    Martin, W.C.

    1981-01-01

    Most of the data reviewed here were derived from spectra photographed in the wavelength range from 600 A down to about 20 A (approx. 20 to 600 eV). Measurements with uncertainties less than 0.001 A relative to appropriate standard wavelengths can be made with high-resolution diffraction-grating spectroscopy over most of the vacuum-ultraviolet region. Although this uncertainty corresponds to relative errors of 1 part per million (ppM) at 1000 A and 20 ppM at 50 A, measurements with uncertainties smaller than 0.001 A would generally require more effort at the shorter wavelengths, mainly because of the sparsity of accurate standards. Even where sufficiently numerous and accurate standards are available, the accuracy of measurements of the spectra of very high temperature plasmas is limited by Doppler broadening and, in some cases, other plasma effects. Several sources of error combine to give total estimated errors ranging from 10 to 1000 ppM for the experimental wavelengths of interest here. It will be seen, however, that with the possible exception of a few fine-structure splittings the experimental errors are small compared to the errors of the relevant theoretical calculations

  15. Activated Protein C Attenuates Severe Inflammation by Targeting VLA-3high Neutrophil Subpopulation in Mice.

    Science.gov (United States)

    Sarangi, Pranita P; Lee, Hyun-Wook; Lerman, Yelena V; Trzeciak, Alissa; Harrower, Eric J; Rezaie, Alireza R; Kim, Minsoo

    2017-10-15

    The host injury involved in multiorgan system failure during severe inflammation is mediated, in part, by massive infiltration and sequestration of hyperactive neutrophils in the visceral organ. A recombinant form of human activated protein C (rhAPC) has shown cytoprotective and anti-inflammatory functions in some clinical and animal studies, but the direct mechanism is not fully understood. Recently, we reported that, during endotoxemia and severe polymicrobial peritonitis, integrin VLA-3 (CD49c/CD29) is specifically upregulated on hyperinflammatory neutrophils and that targeting the VLA-3 high neutrophil subpopulation improved survival in mice. In this article, we report that rhAPC binds to human neutrophils via integrin VLA-3 (CD49c/CD29) with a higher affinity compared with other Arg-Gly-Asp binding integrins. Similarly, there is preferential binding of activated protein C (PC) to Gr1 high CD11b high VLA-3 high cells isolated from the bone marrow of septic mice. Furthermore, specific binding of rhAPC to human neutrophils via VLA-3 was inhibited by an antagonistic peptide (LXY2). In addition, genetically modified mutant activated PC, with a high affinity for VLA-3, shows significantly improved binding to neutrophils compared with wild-type activated PC and significantly reduced neutrophil infiltration into the lungs of septic mice. These data indicate that variants of activated PC have a stronger affinity for integrin VLA-3, which reveals novel therapeutic possibilities. Copyright © 2017 by The American Association of Immunologists, Inc.

  16. The High Level Vibration Test Program

    International Nuclear Information System (INIS)

    Hofmayer, C.H.; Curreri, J.R.; Park, Y.J.; Kato, W.Y.; Kawakami, S.

    1989-01-01

    As part of cooperative agreements between the United States and Japan, tests have been performed on the seismic vibration table at the Tadotsu Engineering Laboratory of Nuclear Power Engineering Test Center (NUPEC) in Japan. The objective of the test program was to use the NUPEC vibration table to drive large diameter nuclear power piping to substantial plastic strain with an earthquake excitation and to compare the results with state-of-the-art analysis of the problem. The test model was designed by modifying the 1/2.5 scale model of the PWR primary coolant loop. Elastic and inelastic seismic response behavior of the test model was measured in a number of test runs with an increasing excitation input level up to the limit of the vibration table. In the maximum input condition, large dynamic plastic strains were obtained in the piping. Crack initiation was detected following the second maximum excitation run. The test model was subjected to a maximum acceleration well beyond what nuclear power plants are designed to withstand. This paper describes the overall plan, input motion development, test procedure, test results and comparisons with pre-test analysis. 4 refs., 16 figs., 2 tabs

  17. The High Level Vibration Test program

    International Nuclear Information System (INIS)

    Hofmayer, C.H.; Curreri, J.R.; Park, Y.J.; Kato, W.Y.; Kawakami, S.

    1990-01-01

    As part of cooperative agreements between the United States and Japan, tests have been performed on the seismic vibration table at the Tadotsu Engineering Laboratory of Nuclear Power Engineering Test Center (NUPEC) in Japan. The objective of the test program was to use the NUPEC vibration table to drive large diameter nuclear power piping to substantial plastic strain with an earthquake excitation and to compare the results with state-of-the-art analysis of the problem. The test model was designed by modifying the 1/2.5 scale model of the pressurized water reactor primary coolant loop. Elastic and inelastic seismic response behavior of the test model was measured in a number of test runs with an increasing excitation input level up to the limit of the vibration table. In the maximum input condition, large dynamic plastic strains were obtained in the piping. Crack initiation was detected following the second maximum excitation run. The test model was subjected to a maximum acceleration well beyond what nuclear power plants are designed to withstand. This paper describes the overall plan, input motion development, test procedure, test results and comparisons with pre-test analysis

  18. Transcranial low-level laser therapy increases memory, learning, neuroprogenitor cells, BDNF and synaptogenesis in mice with traumatic brain injury

    Science.gov (United States)

    Xuan, Weijun; Huang, Liyi; Vatansever, Fatma; Agrawal, Tanupriya; Hamblin, Michael R.

    2015-03-01

    Increasing concern is evident over the epidemic of traumatic brain injury in both civilian and military medicine, and the lack of approved treatments. Transcranial low level laser therapy tLLLT) is a new approach in which near infrared laser is delivered to the head, penetrates the scalp and skull to reach the brain. We asked whether tLLLT at 810-nm could improve memory and learning in mice with controlled cortical impact traumatic brain injury. We investigated the mechanism of action by immunofluorescence studies in sections from brains of mice sacrificed at different times. Mice with TBI treated with 1 or 3 daily laser applications performed better on Morris Water Maze test at 28 days. Laser treated mice had increased BrdU incorporation into NeuN positive cells in the dentate gyrus and subventricular zone indicating formation of neuroprogenitor cells at 7 days and less at 28 days. Markers of neuron migration (DCX and Tuj1) were also increased, as was the neurotrophin, brain derived neurotrophic factor (BDNF) at 7 days. Markers of synaptogenesis (formation of new connections between existing neurons) were increased in the perilesional cortex at 28 days. tLLLT is proposed to be able to induce the brain to repair itself after injury. However its ability to induce neurogenesis and synaptogenesis suggests that tLLLT may have much wider applications to neurodegenerative and psychiatric disorders.

  19. Whole Body Hyperthermia in Mice Confers Delayed Radioprotection at Cellular and Tissue Levels: Inducible Heat Shock Proteins as Endogenous Radioprotectors

    International Nuclear Information System (INIS)

    Malytina, Y. V.; Sements, T. N.; Semina, O. V.; Mosin, A. F.; Kabakov, A.

    2004-01-01

    It was previously shown on heat shock protein (Hsp)-over expressing cell lines that the increased intracellular content of Hsp 70 or Hsp27 is associated with the elevated radioresistance. However, it was so far unknown whether the in vivo Fsp induction by stressful preconditioning can confer radioprotection at the tissue and cellular levels. In the present study, we examined how the in vivo up-regulation of the Hsp expression in response to mild whole body hyperthermia (42 degrees C, 10 min) in mice changes susceptibility of their bone marrow stem cells and thymocytes to subsequent gamma-irradiation. to assess the expectable contribution of stress-inducible Hsp we used injections with Quercetin, a flavonoid inhibiting the stress-responsive Hsp induction. The results demonstrate that the bone marrow stem cells and thymocytes from heat-preconditioned mice were more radioresistant than those from the non-preconditioned animals. the radioprotection was well manifested if mice or their isolated thymocytes were irradiated 18-25 h after the in vivo hyperthermia. This delayed radioprotection resulting from the heat preconditioning was suppressed in Quercetin-injected mice. The revealed correlation between the intracellular Hsp accumulation and the acquired Quercetin-sensitive radioprotection suggests a beneficial role of Hsps as of endogenous radioprotectors. Our finding discovers new ways for artificial modulation of effects of irradiation on target cells via manipulating the Hsp expression. (Author) 17 refs

  20. Dehydroepiandrosterone Supplementation Combined with Whole-Body Vibration Training Affects Testosterone Level and Body Composition in Mice.

    Science.gov (United States)

    Chen, Wen-Chyuan; Chen, Yi-Ming; Huang, Chi-Chang; Tzeng, Yen-Dun

    2016-01-01

    Dehydroepiandrosterone (DHEA), the most abundant sex steroid, is primarily secreted by the adrenal gland and a precursor hormone used by athletes for performance enhancement. Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults. However, the potential effects of DHEA supplementation combined with WBV training on to body composition, exercise performance, and hormone regulation are currently unclear. The objective of the study is to investigate the effects of DHEA supplementation combined with WBV training on body composition, exercise performance, and physical fatigue-related biochemical responses and testosterone content in young-adult C57BL/6 mice. In this study, male C57BL/6 mice were divided into four groups (n = 8 per group) for 6-weeks treatment: sedentary controls with vehicle (SC), DHEA supplementation (DHEA, 10.2 mg/kg), WBV training (WBV; 5.6 Hz, 2 mm, 0.13 g), and WBV training with DHEA supplementation (WBV+DHEA; WBV: 5.6 Hz, 2 mm, 0.13 g and DHEA: 10.2 mg/kg). Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time, as well as changes in body composition and anti-fatigue levels of serum lactate, ammonia, glucose, creatine kinase (CK), and blood urea nitrogen (BUN) after a 15-min swimming exercise. In addition, the biochemical parameters and the testosterone content were measured at the end of the experiment. Six-week DHEA supplementation alone significantly increased mice body weight (BW), muscle weight, testosterone level, and glycogen contents (liver and muscle) when compared with SC group. DHEA supplementation alone had no negative impact on all tissue and biochemical profiles, but could not improve exercise performance. However, WBV+DHEA supplementation also significantly decreased BW, testosterone level and glycogen content of liver, as well as serum

  1. Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

    Directory of Open Access Journals (Sweden)

    Joan Villarroya

    Full Text Available Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT and brown (BAT adipose tissues in thymidine kinase 2 (Tk2 H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues.

  2. Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

    Science.gov (United States)

    Villarroya, Joan; Dorado, Beatriz; Vilà, Maya R; Garcia-Arumí, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

    2011-01-01

    Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. © 2011 Villarroya et al.

  3. Treatment with constitutive androstane receptor ligand during pregnancy prevents insulin resistance in offspring from high-fat diet-induced obese pregnant mice.

    Science.gov (United States)

    Masuyama, Hisashi; Hiramatsu, Yuji

    2012-07-15

    The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.

  4. Heat transfer in high-level waste management

    International Nuclear Information System (INIS)

    Dickey, B.R.; Hogg, G.W.

    1979-01-01

    Heat transfer in the storage of high-level liquid wastes, calcining of radioactive wastes, and storage of solidified wastes are discussed. Processing and storage experience at the Idaho Chemical Processing Plant are summarized for defense high-level wastes; heat transfer in power reactor high-level waste processing and storage is also discussed

  5. Managing commercial high-level radioactive waste

    International Nuclear Information System (INIS)

    1983-01-01

    The article is a summary of issues raised during US Congress deliberations on nuclear waste policy legislation. It is suggested that, if history is not to repeat itself, and the current stalemate on nuclear waste is not to continue, a comprehensive policy is needed that addresses the near-term problems of interim storage as part of an explicit and credible program for dealing with the longer term problem of developing a final isolation system. Such a policy must: 1) adequately address the concerns and win the support of all the major interested parties, and 2) adopt a conservative technical and institutional approach - one that places high priority on avoiding the problems that have repeatedly beset the program in the past. It is concluded that a broadly supported comprehensive policy would contain three major elements, each designed to address one of the key questions concerning Federal credibility: commitment in law to the goals of a comprehensive policy; credible institutional mechanisms for meeting goals; and credible measures for addressing the specific concerns of the states and the various publics. Such a policy is described in detail. (Auth.)

  6. Bumblebee pupae contain high levels of aluminium.

    Science.gov (United States)

    Exley, Christopher; Rotheray, Ellen; Goulson, David

    2015-01-01

    The causes of declines in bees and other pollinators remains an on-going debate. While recent attention has focussed upon pesticides, other environmental pollutants have largely been ignored. Aluminium is the most significant environmental contaminant of recent times and we speculated that it could be a factor in pollinator decline. Herein we have measured the content of aluminium in bumblebee pupae taken from naturally foraging colonies in the UK. Individual pupae were acid-digested in a microwave oven and their aluminium content determined using transversely heated graphite furnace atomic absorption spectrometry. Pupae were heavily contaminated with aluminium giving values between 13.4 and 193.4 μg/g dry wt. and a mean (SD) value of 51.0 (33.0) μg/g dry wt. for the 72 pupae tested. Mean aluminium content was shown to be a significant negative predictor of average pupal weight in colonies. While no other statistically significant relationships were found relating aluminium to bee or colony health, the actual content of aluminium in pupae are extremely high and demonstrate significant exposure to aluminium. Bees rely heavily on cognitive function and aluminium is a known neurotoxin with links, for example, to Alzheimer's disease in humans. The significant contamination of bumblebee pupae by aluminium raises the intriguing spectre of cognitive dysfunction playing a role in their population decline.

  7. A role for the endocannabinoid 2-arachidonoyl-sn-glycerol for social and high-fat food reward in male mice.

    Science.gov (United States)

    Wei, Don; Lee, DaYeon; Li, Dandan; Daglian, Jennifer; Jung, Kwang-Mook; Piomelli, Daniele

    2016-05-01

    The endocannabinoid system is an important modulator of brain reward signaling. Investigations have focused on cannabinoid (CB1) receptors, because dissection of specific contributions of individual endocannabinoids has been limited by the available toolset. While we recently described an important role for the endocannabinoid anandamide in the regulation of social reward, it remains to be determined whether the other major endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), serves a similar or different function. To study the role of 2-AG in natural reward, we used a transgenic mouse model (MGL-Tg mice) in which forebrain 2-AG levels are selectively reduced. We complemented behavioral analysis with measurements of brain 2-AG levels. We tested male MGL-Tg mice in conditioned place preference (CPP) tasks for high-fat food, social contact, and cocaine. We measured 2-AG content in the brain regions of interest by liquid chromatography/mass spectrometry. Male MGL-Tg mice are impaired in developing CPP for high-fat food and social interaction, but do develop CPP for cocaine. Furthermore, compared to isolated mice, levels of 2-AG in socially stimulated wild-type mice are higher in the nucleus accumbens and ventral hippocampus (183 and 140 % of controls, respectively), but unchanged in the medial prefrontal cortex. The results suggest that reducing 2-AG-mediated endocannabinoid signaling impairs social and high-fat food reward in male mice, and that social stimulation mobilizes 2-AG in key brain regions implicated in the control of motivated behavior. The time course of this response differentiates 2-AG from anandamide, whose role in mediating social reward was previously documented.

  8. Chitin Oligosaccharide Modulates Gut Microbiota and Attenuates High-Fat-Diet-Induced Metabolic Syndrome in Mice

    Directory of Open Access Journals (Sweden)

    Junping Zheng

    2018-02-01

    Full Text Available Gut microbiota has been proved to be an indispensable link between nutrient excess and metabolic syndrome, and chitin oligosaccharide (NACOS has displayed therapeutic effects on multiple diseases such as cancer and gastritis. In this study, we aim to confirm whether NACOS can ameliorate high-fat diet (HFD-induced metabolic syndrome by rebuilding the structure of the gut microbiota community. Male C57BL/6J mice fed with HFD were treated with NACOS (1 mg/mL in drinking water for five months. The results indicate that NACOS improved glucose metabolic disorder in HFD-fed mice and suppressed mRNA expression of the protein regulators related to lipogenesis, gluconeogenesis, adipocyte differentiation, and inflammation in adipose tissues. Additionally, NACOS inhibited the destruction of the gut barrier in HFD-treated mice. Furthermore, 16S ribosome RNA sequencing of fecal samples demonstrates that NACOS promoted the growth of beneficial intestinal bacteria remarkably and decreased the abundance of inflammogenic taxa. In summary, NACOS partly rebuilt the microbial community and improved the metabolic syndrome of HFD-fed mice. These data confirm the preventive effects of NACOS on nutrient excess-related metabolic diseases.

  9. ATP Synthase β-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level

    Directory of Open Access Journals (Sweden)

    Kexiu Song

    2014-01-01

    Full Text Available HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase β-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase β-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase β-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of β-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL-HDL uptake in primary hepatocytes. In response to hepatic overexpression of β-chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase β-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C.

  10. Comparative stochastic effects from low level exposure of mice to tritiated water

    International Nuclear Information System (INIS)

    Mewissen, D.J.; Ugarte, A.S.; Rust, J.H.

    1987-01-01

    A total of 1,133 C57 Black/6M mick of both sexes were randomly assigned to 5 experimental groups. In the first group, mice received a single injection of tritiated water (HTO) at weaning time. In the second group, weaned mice were exposed to tritated drinking water for the entire lifespan. In the third group the female parent received one single injection of HTO following delivery. In the fourth group, the female parent and her progeny were exposed to tritiated drinking water for the entire lifespan. In the fifth group, dams were exposed to tritiated drinking water from the beginning of pregnancy for the entire lifespan. (Drinking HTO 1 μCi/ml; single dose of HTO 1 μCi). Data from experimental groups were statistically evaluated vis a vis extensive control groups (+- 1,000 control mice of either sex). All mice were autopsied as moribund or soon after death and tissues were microscopically examined. A significantly increased incidence of reticulum cell sarcomas was observed in female offspring from dams in the third and fifth groups. A significantly increased incidence of hepatic tumors was observed in male offspring in the fourth group. Mean survival times did not significantly differ within experimental groups but were significantly different from controls

  11. The cre-inducer doxycycline lowers cytokine and chemokine transcript levels in the gut of mice

    DEFF Research Database (Denmark)

    Hansen, Axel Kornerup; Malm, Sara Astrup; Metzdorff, Stine B.

    2017-01-01

    The antibiotic doxycycline is used as an inducer of recombinase (cre)-based conditional gene knockout in mice, which is a common tool to show the effect of disrupted gene functions only in one period of a research animal’s life. However, other types of such antibiotics have been shown to have...

  12. Therapeutic levels of erythropoietin (EPO) achieved after gene electrotransfer to skin in mice

    DEFF Research Database (Denmark)

    Gothelf, A; Hojman, P; Gehl, Julie

    2010-01-01

    Gene electrotransfer refers to gene transfection by electroporation and is an effective non-viral method for delivering naked DNA into cells and tissues. This study presents data from gene electrotransfer with erythropoietin (EPO) to mouse skin. Nine-week-old female NMRI mice received one, two...

  13. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent

    OpenAIRE

    Tetri, Laura H.; Basaranoglu, Metin; Brunt, Elizabeth M.; Yerian, Lisa M.; Neuschwander-Tetri, Brent A.

    2008-01-01

    The aims of this study were to determine whether combining features of a western lifestyle in mice with trans fats in a high-fat diet, high-fructose corn syrup in the water, and interventions designed to promote sedentary behavior would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH). Male C57BL/6 mice fed ad libitum high-fat chow containing trans fats (partially hydrogenated vegetable oil) and relevant amounts of a high-fr...

  14. Whey protein reduces early life weight gain in mice fed a high-fat diet

    DEFF Research Database (Denmark)

    Tranberg, Britt; Hellgren, Lars; Lykkesfeldt, Jens

    2013-01-01

    An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would...... be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel...... electrophoresis analyses of PCR-derived 16S rRNA gene (V3-region) amplicons. At the end of the study, plasma samples were collected and assayed for glucose, insulin and lipids. Whey significantly reduced body weight gain during the first four weeks of the study compared with casein (P

  15. The Resin from Protium heptaphyllum Prevents High-Fat Diet-Induced Obesity in Mice: Scientific Evidence and Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    Karine Maria Martins Bezerra Carvalho

    2015-01-01

    Full Text Available Herbal compounds rich in triterpenes are well known to regulate glucose and lipid metabolism and to have beneficial effects on metabolic disorders. The present study investigated the antiobesity properties of resin from Protium heptaphyllum (RPH and the possible mechanisms in mice fed a high-fat diet (HFD for 15 weeks. Mice treated with RPH showed decreases in body weight, net energy intake, abdominal fat accumulation, plasma glucose, amylase, lipase, triglycerides, and total cholesterol relative to their respective controls, which were RPH unfed. Additionally, RPH treatment, while significantly elevating the plasma level of ghrelin hormone, decreased the levels of insulin, leptin, and resistin. Besides, HFD-induced increases in plasma levels of proinflammatory mediators TNF-α, IL-6, and MCP-1 were significantly lowered by RPH. Furthermore, in vitro studies revealed that RPH could significantly inhibit the lipid accumulation in 3T3-L1 adipocytes (measured by Oil-Red O staining at concentrations up to 50 μg/mL. These findings suggest that the antiobese potential of RPH is largely due to its modulatory effects on various hormonal and enzymatic secretions related to fat and carbohydrate metabolism and to the regulation of obesity-associated inflammation.

  16. Serotonin augmentation therapy by escitalopram has minimal effects on amyloid-β levels in early-stage Alzheimer's-like disease in mice

    DEFF Research Database (Denmark)

    von Linstow, Christian Ulrich; Waider, Jonas; Grebing, Manuela

    2017-01-01

    /kg/day) in the drinking water of 3-month-old APP/PS1 mice to increase levels of 5-HT, and we performed intracerebroventricular injections of the neurotoxin 5,7-dihydroxytryptamine (DHT) to remove 5-HTergic afferents. We validated the effectiveness of these interventions by serotonin transporter autoradiography (neocortex...... 79.7 ± 7.6%) and by high-performance liquid chromatography for 5-HT (neocortex 64% reduction). After 6 months of escitalopram treatment or housing after DHT-induced lesion, we evaluated brain tissue by mesoscale multiplex analysis and sections by IHC analysis. RESULTS: Amyloid-β-containing plaques...

  17. A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice

    Directory of Open Access Journals (Sweden)

    Kanokwan Jarukamjorn

    2016-01-01

    Full Text Available Excessive fat liver is an important manifestation of nonalcoholic fatty liver disease (NAFLD, associated with obesity, insulin resistance, and oxidative stress. In the present study, the effects of a high-fat, high-fructose diet (HFFD on mRNA levels and activities of the antioxidant enzymes, including superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx, were determined in mouse livers and brains. The histomorphology of the livers was examined and the state of nonenzymatic reducing system was evaluated by measuring the glutathione system and the lipid peroxidation. Histopathology of the liver showed that fat accumulation and inflammation depended on the period of the HFFD-consumption. The levels of mRNA and enzymatic activities of SOD, CAT, and GPx were raised, followed by the increases in malondialdehyde levels in livers and brains of the HFFD mice. The oxidized GSSG content was increased while the total GSH and the reduced GSH were decreased, resulting in the increase in the GSH/GSSG ratio in both livers and brains of the HFFD mice. These observations suggested that liver damage and oxidative stress in the significant organs were generated by continuous HFFD-consumption. Imbalance of antioxidant condition induced by long-term HFFD-consumption might increase the risk and progression of NAFLD.

  18. SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice

    DEFF Research Database (Denmark)

    Zadjali, Fahad; Santana-Farre, Ruyman; Vesterlund, Mattias

    2012-01-01

    in the development of diet-induced hepatic steatosis and insulin resistance. SOCS2-knockout (SOCS2(-/-)) mice and wild-type littermates were fed for 4 mo with control or high-fat diet, followed by assessment of insulin sensitivity, hepatic lipid content, and expression of inflammatory cytokines. SOCS2(-/-) mice...

  19. Potential utility of eGFP-expressing NOG mice (NOG-EGFP as a high purity cancer sampling system

    Directory of Open Access Journals (Sweden)

    Shima Kentaro

    2012-06-01

    Full Text Available Abstract Purpose It is still technically difficult to collect high purity cancer cells from tumor tissues, which contain noncancerous cells. We hypothesized that xenograft models of NOG mice expressing enhanced green fluorescent protein (eGFP, referred to as NOG-EGFP mice, may be useful for obtaining such high purity cancer cells for detailed molecular and cellular analyses. Methods Pancreato-biliary cancer cell lines were implanted subcutaneously to compare the tumorigenicity between NOG-EGFP mice and nonobese diabetic/severe combined immunodeficiency (NOD/SCID mice. To obtain high purity cancer cells, the subcutaneous tumors were harvested from the mice and enzymatically dissociated into single-cell suspensions. Then, the cells were sorted by fluorescence-activated cell sorting (FACS for separation of the host cells and the cancer cells. Thereafter, the contamination rate of host cells in collected cancer cells was quantified by using FACS analysis. The viability of cancer cells after FACS sorting was evaluated by cell culture and subsequent subcutaneous reimplantation in NOG-EGFP mice. Results The tumorigenicity of NOG-EGFP mice was significantly better than that of NOD/SCID mice in all of the analyzed cell lines (p  Conclusions This method provides a novel cancer sampling system for molecular and cellular analysis with high accuracy and should contribute to the development of personalized medicine.

  20. High-density lipoproteins inhibit urate crystal-induced inflammation in mice

    OpenAIRE

    Scanu Anna; Luisetto Roberto; Oliviero Francesca; Gruaz Lyssia; Sfriso Paolo; Burger Danielle; Punzi Leonardo

    2015-01-01

    Objectives To investigate the effects and mechanisms of action of high density lipoproteins (HDL) in monosodium urate (MSU) crystal induced inflammation—that is gouty inflammation in vivo. Methods Air pouches raised on the backs of mice were injected with MSU crystals or tumour necrosis factor (TNF) in the presence or absence of HDL and/or interleukin (IL) 1 receptor antagonist (IL 1Ra) for 3 h. Leucocyte count and neutrophil percentage in pouch fluids were measured using a haemocytometer an...

  1. High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses.

    Science.gov (United States)

    Clark, Erica S; Flannery, Brenna M; Gardner, Elizabeth M; Pestka, James J

    2015-10-19

    Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

  2. High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses

    Directory of Open Access Journals (Sweden)

    Erica S. Clark

    2015-10-01

    Full Text Available Deoxynivalenol (DON, a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos and adult (3 mos mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg and dietary (1, 2.5, 10 ppm DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

  3. Features of pathology in mice experimentally infected with highly pathogenic H5N1 influenza virus

    International Nuclear Information System (INIS)

    Ryabchikova, E. I.; Taranov, O. S.; Malkova, E. M.; Gritsyk, O. B.; Demina, O. K.

    2009-01-01

    Avian influenza became a new threat and has set people thinking about possibility of new influenza pandemic which may be caused by highly pathogenic H5N1 influenza virus. The virus could acquire ability of fast spreading between the humans and new pandemics could kill millions. Influenza virus H5N1 exhibited its deadly essence by taking out many millions of birds in nature and aviculture; other millions of chicks and ducks were killed to prevent spread of the epizootic. The strains isolated in Russia belong to Qinghai group of H5N1 influenza virus, and were imported to Russia by migratory birds. We examined time-course changes in mice blood and lungs after intranasal infection with strains A /Chicken/ Kurgan/ 05/2005, A/ Duck/ Kurgan/08/ 2005 and A/ Chicken/ Suzdalka/ Nov-11/2005 differing in virulence for this animal species. Development of leucopenia and severe damage of hemopoiesis were found in mice infected with all H5N1 influenza virus strains. Pathological changes in mice lungs during the infection with above mentioned strains, and strain-specific features have been examined. Main characteristics of lung pathology in all mice were focal nature of the alterations, severe damage of bronchial epithelium and pronounced alteration of lung vasculature. Strain A/Chicken/Suzdalka/Nov-11/2005 induced massive apoptosis of infected bronchial cells which may be a part of mechanism responsible for avirulent properties of this strain. The most interesting finding was absence of serious direct virus damage of the lung evidencing for principal role of the host humoral mechanisms in pathogenesis of H5N1 influenza in mice.(author)

  4. Novel method for high-throughput phenotyping of sleep in mice.

    Science.gov (United States)

    Pack, Allan I; Galante, Raymond J; Maislin, Greg; Cater, Jacqueline; Metaxas, Dimitris; Lu, Shan; Zhang, Lin; Von Smith, Randy; Kay, Timothy; Lian, Jie; Svenson, Karen; Peters, Luanne L

    2007-01-17

    Assessment of sleep in mice currently requires initial implantation of chronic electrodes for assessment of electroencephalogram (EEG) and electromyogram (EMG) followed by time to recover from surgery. Hence, it is not ideal for high-throughput screening. To address this deficiency, a method of assessment of sleep and wakefulness in mice has been developed based on assessment of activity/inactivity either by digital video analysis or by breaking infrared beams in the mouse cage. It is based on the algorithm that any episode of continuous inactivity of > or =40 s is predicted to be sleep. The method gives excellent agreement in C57BL/6J male mice with simultaneous assessment of sleep by EEG/EMG recording. The average agreement over 8,640 10-s epochs in 24 h is 92% (n = 7 mice) with agreement in individual mice being 88-94%. Average EEG/EMG determined sleep per 2-h interval across the day was 59.4 min. The estimated mean difference (bias) per 2-h interval between inactivity-defined sleep and EEG/EMG-defined sleep was only 1.0 min (95% confidence interval for mean bias -0.06 to +2.6 min). The standard deviation of differences (precision) was 7.5 min per 2-h interval with 95% limits of agreement ranging from -13.7 to +15.7 min. Although bias significantly varied by time of day (P = 0.0007), the magnitude of time-of-day differences was not large (average bias during lights on and lights off was +5.0 and -3.0 min per 2-h interval, respectively). This method has applications in chemical mutagenesis and for studies of molecular changes in brain with sleep/wakefulness.

  5. Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.

    Science.gov (United States)

    Mercer, Kelly E; Pulliam, Casey F; Pedersen, Kim B; Hennings, Leah; Ronis, Martin Jj

    2017-03-01

    Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein

  6. High-fat diet exacerbates pain-like behaviors and periarticular bone loss in mice with CFA-induced knee arthritis.

    Science.gov (United States)

    Loredo-Pérez, Aleyda A; Montalvo-Blanco, Carlos E; Hernández-González, Luis I; Anaya-Reyes, Maricruz; Fernández Del Valle-Laisequilla, Cecilia; Reyes-García, Juan G; Acosta-González, Rosa I; Martínez-Martínez, Arisai; Villarreal-Salcido, Jaira C; Vargas-Muñoz, Virginia M; Muñoz-Islas, Enriqueta; Ramírez-Rosas, Martha B; Jiménez-Andrade, Juan M

    2016-05-01

    Our aim was to quantify nociceptive spontaneous behaviors, knee edema, proinflammatory cytokines, bone density, and microarchitecture in high-fat diet (HFD)-fed mice with unilateral knee arthritis. ICR male mice were fed either standard diet (SD) or HFD starting at 3 weeks old. At 17 weeks, HFD and SD mice received intra-articular injections either with Complete Freund's Adjuvant (CFA) or saline into the right knee joint every 7 days for 4 weeks. Spontaneous pain-like behaviors and knee edema were assessed for 26 days. At day 26 post-first CFA injection, serum levels of IL-1β, IL-6, and RANKL were measured by ELISA, and microcomputed tomography analysis of knee joints was performed. HFD-fed mice injected with CFA showed greater spontaneous pain-like behaviors of the affected extremity as well as a decrease in the weight-bearing index compared to SD-fed mice injected with CFA. Knee edema was not significantly different between diets. HFD significantly exacerbated arthritis-induced bone loss at the distal femoral metaphysis but had no effect on femoral diaphyseal cortical bone. HFD did not modify serum levels of proinflammatory cytokines. HFD exacerbates pain-like behaviors and significantly increases the magnitude of periarticular trabecular bone loss in a murine model of unilateral arthritis. © 2016 The Obesity Society.

  7. High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice.

    Science.gov (United States)

    Xiao, Liang; Sonne, Si Brask; Feng, Qiang; Chen, Ning; Xia, Zhongkui; Li, Xiaoping; Fang, Zhiwei; Zhang, Dongya; Fjære, Even; Midtbø, Lisa Kolden; Derrien, Muriel; Hugenholtz, Floor; Tang, Longqing; Li, Junhua; Zhang, Jianfeng; Liu, Chuan; Hao, Qin; Vogel, Ulla Birgitte; Mortensen, Alicja; Kleerebezem, Michiel; Licht, Tine Rask; Yang, Huanming; Wang, Jian; Li, Yingrui; Arumugam, Manimozhiyan; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

    2017-04-08

    It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity. Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice. The changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.

  8. Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice.

    Science.gov (United States)

    Zhu, Ru-Gang; Sun, Yan-Di; Hou, Yu-Ting; Fan, Jun-Gang; Chen, Gang; Li, Tuo-Ping

    2017-06-25

    Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD. BA analysis showed that HPPS markedly decreased hepatic and small intestine BA levels but increased the gallbladder BA levels, and finally decreased the total BA pool size, compared to HCD. Studies of molecular mechanism revealed that HPPS promoted hepatic ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) expression but did not affect ATB binding cassette transporter G5/G8 (ABCG5/8) expression. HPPS inactivated hepatic farnesoid X receptor (FXR) and target genes expression, which resulted in significant increase of cholesterol 7α-hydroxylase 1 (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) expression, with up-regulations of 204.2% and 33.5% for mRNA levels, respectively, compared with HCD. In addition, HPPS markedly enhanced bile salt export pump (BSEP) expression but didn't affect the sodium/taurocholate co-transporting polypeptide (NTCP) expression. In conclusion, the study revealed that HPPS reduced cholesterol accumulation by promoting BA synthesis in the liver and excretion in the feces, and might promote macrophage-to-liver reverse cholesterol transport (RCT) but did not liver-to-fecal RCT. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Tartary buckwheat flavonoids ameliorate high fructose-induced insulin resistance and oxidative stress associated with the insulin signaling and Nrf2/HO-1 pathways in mice.

    Science.gov (United States)

    Hu, Yuanyuan; Hou, Zuoxu; Yi, Ruokun; Wang, Zhongming; Sun, Peng; Li, Guijie; Zhao, Xin; Wang, Qiang

    2017-08-01

    The present study was conducted to explore the effects of a purified tartary buckwheat flavonoid fraction (TBF) on insulin resistance and hepatic oxidative stress in mice fed high fructose in drinking water (20%) for 8 weeks. The results indicated that continuous administration of TBF dose-dependently improved the insulin sensitivity and glucose intolerance in high fructose-fed mice. TBF treatment also reversed the reduced level of insulin action on the phosphorylation of insulin receptor substrate-1 (IRS-1), protein kinase B (Akt) and phosphatidylinositol 3-kinase (PI3K), as well as the translocation of glucose transporter type 4 (GLUT4) in the insulin-resistant liver. Furthermore, TBF was found to exert high antioxidant capacity as it acts as a shield against oxidative stress induced by high fructose by restoring the antioxidant status, and modulating nuclear factor E2 related factor 2 (Nrf2) translocation to the nucleus with subsequently up-regulated antioxidative enzyme protein expression. Histopathological examinations revealed that impaired pancreatic/hepatic tissues were effectively restored in high fructose-fed mice following TBF treatment. Our results show that TBF intake is effective in preventing the conversion of high fructose-induced insulin resistance and hepatic oxidative stress in mice by improving the insulin signaling molecules and the Nrf2 signal pathway in the liver.

  10. Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety

    OpenAIRE

    Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T.

    2013-01-01

    We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique an...

  11. Effect of voluntary exercise and dietary protein levels on incorporation of 14C-leucine into protein by mice liver slices in vitro

    International Nuclear Information System (INIS)

    Yashiro, Masanori; Kimura, Shuichi

    1983-01-01

    The effect of voluntary exercise on incorporation of 14 C-leucine into protein by mice liver slices in vitro were examined with mice fed 4 %, 6 % and 20 % protein diets. The incorporation of 14 C-leucine increased as dietary protein levels decreased and was significantly higher in liver slices of exercise groups than in slices of non-exercise groups. (author)

  12. Modulation of total IgE levels in serum of normal and athymic nude BALB/c mice by cells and exogenous antigenic stimulation

    NARCIS (Netherlands)

    Savelkoul, H.F.J.; Akker, van den T.W.; Soeting, P.W.C.; Oudenaren, van A.; Benner, R.

    1989-01-01

    Several different grades of T-system impairment were studied for their effects on the total serum IgE concentration in BALB/c mice. Homozygous athymic nu/nu mice and their heterozygous nu/ littermates were compared for serum IgE levels while kept under either barrier-maintained or conventional

  13. Antioxidative Diet Supplementation Reverses High-Fat Diet-Induced Increases of Cardiovascular Risk Factors in Mice

    Directory of Open Access Journals (Sweden)

    Hilda Vargas-Robles

    2015-01-01

    Full Text Available Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD. Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.

  14. Effect of asoka on the intracellular glutathione levels and skin tumour promotion in mice.

    Science.gov (United States)

    Varghese, C D; Nair, S C; Panikkar, B; Panikkar, K R

    1993-04-15

    The bark of Saraka asoca (asoka) is commonly used to treat various diseases by the Indian system of medicine and in Sri Lanka. Further purification and chemical analysis of the active compound from the bark extract of asoka showed that (-)-epicatechin was responsible for the observed antitumour/anticarcinogenic activity. Papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil was inhibited by the topical application of 100 mg/kg body weight (b.w.) of (-)-epicatechin isolated from asoka bark extract. Oral administration of the same dose restricted the growth of s.c. injected 20 methylcholanthrene (MCA) induced soil tissue fibrosarcomas significantly in mice. Elevations of almost 2-4-fold in the intracellular reduced glutathione and related enzymes viz., glutathione reductase and glutathione S-transferase of sarcoma-180 tumour cells were noted in the presence of 1 microgram/ml of (-)-epicatechin, further highlighting its antiproliferative effect.

  15. The protective role of low-concentration alcohol in high-fructose induced adverse cardiovascular events in mice.

    Science.gov (United States)

    Wu, Xiaoqi; Pan, Bo; Wang, Ying; Liu, Lingjuan; Huang, Xupei; Tian, Jie

    2018-01-01

    Cardiovascular disease remains a worldwide public health issue. As fructose consumption is dramatically increasing, it has been demonstrated that a fructose-rich intake would increase the risk of cardiovascular disease. In addition, emerging evidences suggest that low concentration alcohol intake may exert a protective effect on cardiovascular system. This study aimed to investigate whether low-concentration alcohol consumption would prevent the adverse effects on cardiovascular events induced by high fructose in mice. From the results of hematoxylin-eosin staining, echocardiography, heart weight/body weight ratio and the expression of hypertrophic marker ANP, we found high-fructose result in myocardial hypertrophy and the low-concentration alcohol consumption would prevent the cardiomyocyte hypertrophy from happening. In addition, we observed low-concentration alcohol consumption could inhibit mitochondria swollen induced by high-fructose. The elevated levels of glucose, triglyceride, total cholesterol in high-fructose group were reduced by low concentration alcohol. Low expression levels of SIRT1 and PPAR-γ induced by high-fructose were significantly elevated when fed with low-concentration alcohol. The histone lysine 9 acetylation (acH3K9) level was decreased in PPAR-γ promoter in high-fructose group but elevated when intake with low concentration alcohol. The binding levels of histone deacetylase SIRT1 were increased in the same region in high-fructose group, while the low concentration alcohol can prevent the increased binding levels. Overall, our study indicates that low-concentration alcohol consumption could inhibit high-fructose related myocardial hypertrophy, cardiac mitochondria damaged and disorders of glucose-lipid metabolism. Furthermore, these findings also provide new insights into histone acetylation-deacetylation mechanisms of low-concentration alcohol treatment that may contribute to the prevention of cardiovascular disease induced by high

  16. Dynamic PET evaluation of elevated FLT level after sorafenib treatment in mice bearing human renal cell carcinoma xenograft.

    Science.gov (United States)

    Ukon, Naoyuki; Zhao, Songji; Yu, Wenwen; Shimizu, Yoichi; Nishijima, Ken-Ichi; Kubo, Naoki; Kitagawa, Yoshimasa; Tamaki, Nagara; Higashikawa, Kei; Yasui, Hironobu; Kuge, Yuji

    2016-12-01

    Sorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl- 3 H(N)]-3'-fluoro-3'-deoxythythymidine ([ 3 H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3'-[ 18 F]fluoro-3'-deoxythymidine ([ 18 F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498). The A498 xenograft was established in nude mice, and the mice were assigned to the control (n = 5) and treatment (n = 5) groups. The mice in the treatment group were orally given sorafenib (20 mg/kg/day p.o.) once daily for 3 days. Twenty-four hours after the treatment, dynamic [ 18 F]FLT PET was performed by small-animal PET. Three-dimensional regions of interest (ROIs) were manually defined for the tumors. A three-compartment model fitting was carried out to estimate four rate constants using the time activity curve (TAC) in the tumor and the blood clearance rate of [ 18 F]FLT. The dynamic pattern of [ 18 F]FLT levels in the tumor significantly changed after the treatment. The rate constant of [ 18 F]FLT phosphorylation (k 3 ) was significantly higher in the treatment group (0.111 ± 0.027 [1/min]) than in the control group (0.082 ± 0.009 [1/min]). No significant changes were observed in the distribution volume, the ratio of [ 18 F]FLT forward transport (K 1 ) to reverse transport (k 2 ), between the two groups (0.556 ± 0.073 and 0.641 ± 0.052 [mL/g] in the control group). Our dynamic PET studies indicated that the increase in FLT level may be caused by the phosphorylation of FLT in the tumor after the sorafenib treatment in the mice bearing a RCC xenograft. Dynamic PET studies with kinetic

  17. High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice

    DEFF Research Database (Denmark)

    Xiao, Liang; Sonne, Si Brask; Feng, Qiang

    2017-01-01

    feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF......Background: It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those......-induced obesity, but in Sv129 mice accentuates obesity.Results: Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF...

  18. A High-Voltage Level Tolerant Transistor Circuit

    NARCIS (Netherlands)

    Annema, Anne J.; Geelen, Godefridus Johannes Gertrudis Maria

    2001-01-01

    A high-voltage level tolerant transistor circuit, comprising a plurality of cascoded transistors, including a first transistor (T1) operatively connected to a high-voltage level node (3) and a second transistor (T2) operatively connected to a low-voltage level node (2). The first transistor (T1)

  19. 40 CFR 227.30 - High-level radioactive waste.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false High-level radioactive waste. 227.30...-level radioactive waste. High-level radioactive waste means the aqueous waste resulting from the operation of the first cycle solvent extraction system, or equivalent, and the concentrated waste from...

  20. Protective effects of Astragalus-Lilygranules on intestinal mucosal barrier of mice in high altitude hypoxia

    Directory of Open Access Journals (Sweden)

    Ling LI

    2016-10-01

    Full Text Available Objective  To investigate the protective effect of Astragalus-Lily Granules on intestinal mucosa and intestinal flora homeostasis in mice under high altitude hypoxia condition. Methods  We put mice into high altitude hypoxia cabin to establish high altitude hypoxia model mice. Sixty Kunming mice were randomly divided into control group, model group, Astragalus-Lily particles (ALP low, medium and high dose groups [1.75, 3.5, 7g/(kg•d] respectively. After three days of routine feeding, the ALP mice received drug by intragastric administration, once a day for continuous 17 days,control group and model group were given double distilled water in same volume. From the 15th day, all the mice but control group were exposed to simulated high altitude hypoxia condition for 3 days in a high altitude hypoxia cabin after they were gavaged for half an hour daily. By the 18th day, the fresh mouse feces were collected and smeared to observe the changes of microflora. The pathological changes of intestinal tissues were observed by HE staining and the expression of HIF-1αprotein in intestines was detected by immunohistochemistry. Results  The enterococci and gram negative bacteria showed a higher proportion (65.2%±2.4% and 56.7%±3.3%, respectively in the model group compared with the control group (24.7%±1.2%, 23.2%±1.5%, respectively, P<0.05. The pathological score of intestinal mucosal necrosis and edema (3.10±0.99, 3.30±0.67 respectively and inflammatory cell count (15.93±3.30, 16.40±3.97/ HP respectively was higher compared with the model group (0.70±0.67, 0.80±0.78; 4.07±2.12, 4.28±2.16/HP respectively; P<0.05. HIF-1αexpression increased significantly compared with the model group (P<0.0