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Sample records for palmitate exposure inhibits

  1. Stevioside counteracts the alpha cell hypersecretion caused by long-term palmitate exposure

    DEFF Research Database (Denmark)

    Hong, Jing; Chen, Jianguo; Jeppesen, Per Bendix

    2006-01-01

    Long-term exposure to fatty acids impairs beta-cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on alpha-cells. We therefore studied the prolonged impact of palmitate on alpha-cell function and on the expression of genes related to fuel metabolism. We......-activated receptor-gamma, and stearoyl-CoA desaturase gene expressions in the presence of palmitate (Pacids leads to a hypersecretion of glucagon and an accumulation of TG content in clonal alpha-TC1-6 cells. Stevioside was able to counteract the alpha......-cell hypersecretion caused by palmitate and enhanced the expression of genes involved in fatty acid metabolism. This indicates that stevioside may be a promising antidiabetic agent in treatment of type 2 diabetes....

  2. High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes.

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    Nazli, S A; Loeser, R F; Chubinskaya, S; Willey, J S; Yammani, R R

    2017-09-01

    Insulin-like growth factor-1 (IGF-1) promotes matrix synthesis and cell survival in cartilage. Chondrocytes from aged and osteoarthritic cartilage have a reduced response to IGF-1. The purpose of this study was to determine the effect of free fatty acids (FFA) present in a high-fat diet on IGF-1 function in cartilage and the role of endoplasmic reticulum (ER) stress. C57BL/6 male mice were maintained on either a high-fat (60% kcal from fat) or a low-fat (10% kcal from fat) diet for 4 months. Mice were then sacrificed; femoral head cartilage caps were collected and treated with IGF-1 to measure proteoglycan (PG) synthesis. Cultured human chondrocytes were treated with 500 μM FFA palmitate or oleate, followed by stimulation with (100 ng/ml) IGF-1 overnight to measure CHOP (a protein marker for ER stress) and PG synthesis. Human chondrocytes were pre-treated with palmitate or 1 mM 4-phenyl butyric acid (PBA) or 1 μM C-Jun N terminal Kinase (JNK) inhibitor, and IGF-1 function (PG synthesis and signaling) was measured. Cartilage explants from mice on the high fat-diet showed reduced IGF-1 mediated PG synthesis compared to a low-fat group. Treatment of human chondrocytes with palmitate induced expression of CHOP, activated JNK and inhibited IGF-1 function. PBA, a small molecule chemical chaperone that alleviates ER stress rescued IGF-1 function and a JNK inhibitor rescued IGF-1 signaling. Palmitate-induced ER stress inhibited IGF-1 function in chondrocytes/cartilage via activating the mitogen-activated protein (MAP) kinase JNK. This is the first study to demonstrate that ER stress is metabolic factor that regulates IGF-1 function in chondrocytes. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  3. Astragalus Polysaccharide Improves Palmitate-Induced Insulin Resistance by Inhibiting PTP1B and NF-κB in C2C12 Myotubes

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    Yong Li

    2012-06-01

    Full Text Available We investigated the effects of Astragalus polysaccharide (APS on palmitate-induced insulin resistance in C2C12 skeletal muscle myotubes. Palmitate-reduced glucose uptake was restored by APS. APS prevented palmitate-induced C2C12 myotubes from impaired insulin signaling by inhibiting Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 and increasing Ser473 phosphorylation of Akt. Moreover, the increases in protein-tyrosine phosphatase-1B (PTP1B protein level and NF-κB activation associated with palmitate treatment were also prevented by APS. However the treatment with APS didn’t change AMP-activated protein kinase (AMPK activation in palmitate-induced myotubes. The results of the present study suggest that Astragalus polysaccharide inhibits palmitate-induced insulin resistance in C2C12 myotubes by inhibiting expression of PTP1B and regulating NF-κB but not AMPK pathway.

  4. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

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    Nishiwaki, Satoshi; Nakayama, Takayuki; Murata, Makoto; Nishida, Tetsuya; Terakura, Seitaro; Saito, Shigeki; Kato, Tomonori; Mizuno, Hiroki; Imahashi, Nobuhiko; Seto, Aika; Ozawa, Yukiyasu; Miyamura, Koichi; Ito, Masafumi; Takeshita, Kyosuke; Kato, Hidefumi; Toyokuni, Shinya; Nagao, Keisuke; Ueda, Ryuzo; Naoe, Tomoki

    2014-01-01

    Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.

  5. Effects of inhibition of serine palmitoyltransferase (SPT and sphingosine kinase 1 (SphK1 on palmitate induced insulin resistance in L6 myotubes.

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    Agnieszka Mikłosz

    Full Text Available BACKGROUND: The objective of this study was to examine the effects of short (2 h and prolonged (18 h inhibition of serine palmitoyltransferase (SPT and sphingosine kinase 1 (SphK1 on palmitate (PA induced insulin resistance in L6 myotubes. METHODS: L6 myotubes were treated simultaneously with either PA and myriocin (SPT inhibitor or PA and Ski II (SphK1inhibitor for different time periods (2 h and 18 h. Insulin stimulated glucose uptake was measured using radioactive isotope. Expression of insulin signaling proteins was determined using Western blot analyses. Intracellular sphingolipids content [sphinganine (SFA, ceramide (CER, sphingosine (SFO, sphingosine-1-phosphate (S1P] were estimated by HPLC. RESULTS: Our results revealed that both short and prolonged time of inhibition of SPT by myriocin was sufficient to prevent ceramide accumulation and simultaneously reverse palmitate induced inhibition of insulin-stimulated glucose transport. In contrast, prolonged inhibition of SphK1 intensified the effect of PA on insulin-stimulated glucose uptake and attenuated further the activity of insulin signaling proteins (pGSK3β/GSK3β ratio in L6 myotubes. These effects were related to the accumulation of sphingosine in palmitate treated myotubes. CONCLUSION: Myriocin is more effective in restoration of palmitate induced insulin resistance in L6 myocytes, despite of the time of SPT inhibition, comparing to SKII (a specific SphK1 inhibitor. Observed changes in insulin signaling proteins were related to the content of specific sphingolipids, namely to the reduction of ceramide. Interestingly, inactivation of SphK1 augmented the effect of PA induced insulin resistance in L6 myotubes, which was associated with further inhibition of insulin stimulated PKB and GSK3β phosphorylation, glucose uptake and the accumulation of sphingosine.

  6. Inhibition of HIV-1 infection in ex vivo cervical tissue model of human vagina by palmitic acid; implications for a microbicide development.

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    Xudong Lin

    Full Text Available BACKGROUND: Approximately 80% of all new HIV-1 infections are acquired through sexual contact. Currently, there is no clinically approved microbicide, indicating a clear and urgent therapeutic need. We recently reported that palmitic acid (PA is a novel and specific inhibitor of HIV-1 fusion and entry. Mechanistically, PA inhibits HIV-1 infection by binding to a novel pocket on the CD4 receptor and blocks efficient gp120-to-CD4 attachment. Here, we wanted to assess the ability of PA to inhibit HIV-1 infection in cervical tissue ex vivo model of human vagina, and determine its effect on Lactobacillus (L species of probiotic vaginal flora. PRINCIPAL FINDINGS: Our results show that treatment with 100-200 µM PA inhibited HIV-1 infection in cervical tissue by up to 50%, and this treatment was not toxic to the tissue or to L. crispatus and jensenii species of vaginal flora. In vitro, in a cell free system that is independent of in vivo cell associated CD4 receptor; we determined inhibition constant (Ki to be ∼2.53 µM. SIGNIFICANCE: These results demonstrate utility of PA as a model molecule for further preclinical development of a safe and potent HIV-1 entry microbicide inhibitor.

  7. Inhibition of SH2-domain-containing inositol 5-phosphatase (SHIP2) ameliorates palmitate induced-apoptosis through regulating Akt/FOXO1 pathway and ROS production in HepG2 cells

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    Gorgani-Firuzjaee, Sattar [Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran (Iran, Islamic Republic of); Adeli, Khosrow [Division of Clinical Biochemistry, The Hospital for Sick Children, University of Toronto, Toronto (Canada); Meshkani, Reza, E-mail: rmeshkani@tums.ac.ir [Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran (Iran, Islamic Republic of)

    2015-08-21

    The serine–threonine kinase Akt regulates proliferation and survival by phosphorylating a network of protein substrates; however, the role of a negative regulator of the Akt pathway, the SH2-domain-containing inositol 5-phosphatase (SHIP2) in apoptosis of the hepatocytes, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to apoptosis using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to palmitate (0.5 mM). Overexpression of the dominant negative mutant SHIP2 (SHIP2-DN) significantly reduced palmitate-induced apoptosis in HepG2 cells, as these cells had increased cell viability, decreased apoptotic cell death and reduced the activity of caspase-3, cytochrome c and poly (ADP-ribose) polymerase. Overexpression of the wild-type SHIP2 gene led to a massive apoptosis in HepG2 cells. The protection from palmitate-induced apoptosis by SHIP2 inhibition was accompanied by a decrease in the generation of reactive oxygen species (ROS). In addition, SHIP2 inhibition was accompanied by an increased Akt and FOXO-1 phosphorylation, whereas overexpression of the wild-type SHIP2 gene had the opposite effects. Taken together, these findings suggest that SHIP2 expression level is an important determinant of hepatic lipoapotosis and its inhibition can potentially be a target in treatment of hepatic lipoapoptosis in diabetic patients. - Highlights: • Lipoapoptosis is the major contributor to the development of NAFLD. • The PI3-K/Akt pathway regulates apoptosis in different cells. • The role of negative regulator of this pathway, SHIP2 in lipoapoptosis is unknown. • SHIP2 inhibition significantly reduces palmitate-induced apoptosis in HepG2 cells. • SHIP2 inhibition prevents palmitate induced-apoptosis by regulating Akt/FOXO1 pathway.

  8. Inhibition of SH2-domain-containing inositol 5-phosphatase (SHIP2) ameliorates palmitate induced-apoptosis through regulating Akt/FOXO1 pathway and ROS production in HepG2 cells

    International Nuclear Information System (INIS)

    Gorgani-Firuzjaee, Sattar; Adeli, Khosrow; Meshkani, Reza

    2015-01-01

    The serine–threonine kinase Akt regulates proliferation and survival by phosphorylating a network of protein substrates; however, the role of a negative regulator of the Akt pathway, the SH2-domain-containing inositol 5-phosphatase (SHIP2) in apoptosis of the hepatocytes, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to apoptosis using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to palmitate (0.5 mM). Overexpression of the dominant negative mutant SHIP2 (SHIP2-DN) significantly reduced palmitate-induced apoptosis in HepG2 cells, as these cells had increased cell viability, decreased apoptotic cell death and reduced the activity of caspase-3, cytochrome c and poly (ADP-ribose) polymerase. Overexpression of the wild-type SHIP2 gene led to a massive apoptosis in HepG2 cells. The protection from palmitate-induced apoptosis by SHIP2 inhibition was accompanied by a decrease in the generation of reactive oxygen species (ROS). In addition, SHIP2 inhibition was accompanied by an increased Akt and FOXO-1 phosphorylation, whereas overexpression of the wild-type SHIP2 gene had the opposite effects. Taken together, these findings suggest that SHIP2 expression level is an important determinant of hepatic lipoapotosis and its inhibition can potentially be a target in treatment of hepatic lipoapoptosis in diabetic patients. - Highlights: • Lipoapoptosis is the major contributor to the development of NAFLD. • The PI3-K/Akt pathway regulates apoptosis in different cells. • The role of negative regulator of this pathway, SHIP2 in lipoapoptosis is unknown. • SHIP2 inhibition significantly reduces palmitate-induced apoptosis in HepG2 cells. • SHIP2 inhibition prevents palmitate induced-apoptosis by regulating Akt/FOXO1 pathway

  9. Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

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    Perry, Ben D; Rahnert, Jill A; Xie, Yang; Zheng, Bin; Woodworth-Hobbs, Myra E; Price, S Russ

    2018-01-01

    Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4). Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory indicators of TLR4 activation (IL-6 and TNFα) and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

  10. Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

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    Ben D Perry

    Full Text Available Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4. Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides, palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242. Inflammatory indicators of TLR4 activation (IL-6 and TNFα and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

  11. Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

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    Luo, Yi, E-mail: yi.luo@pfizer.com; Rana, Payal; Will, Yvonne

    2012-06-01

    Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ► Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ► The impairment of mitochondrial functions may contribute to the enhanced toxicity. ► Inhibition of JNK activity attenuated

  12. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells.

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    Yeh, Lee-Chuan C; Ford, Jeffery J; Lee, John C; Adamo, Martin L

    2014-07-18

    Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. ShenFu Preparation Protects AML12 Cells Against Palmitic Acid-Induced Injury Through Inhibition of Both JNK/Nox4 and JNK/NFκB Pathways

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    Jia-Fu Ji

    2018-02-01

    Full Text Available Background/Aims: Nonalcoholic steatohepatitis includes steatosis along with liver inflammation, hepatocyte injury and fibrosis. In this study, we investigated the protective role and the potential mechanisms of a traditional Chinese medicine ShenFu (SF preparation in an in vitro hepatic steatosis model. Methods: In palmitic acid (PA-induced murine hepatic AML12 cell injury, effects of SF preparation on cellular apoptosis and intracellular triglyceride (iTG level were assessed using TUNEL and TG Colorimetric Assay. Reactive oxygen species (ROS and mitochondrial membrane potential (MMP levels were measured using DCF and JC-1 assay. Cytokine levels were evaluated using ELISA assay. Immunoblot was used to compare the activation level of c-Jun N terminal kinase (JNK, NADPH oxidase (Nox4, and NFκB pathways. Results: Addition of SF preparation prevented PA-mediated increase of apoptosis and iTG as well as IL-8 and IL-6. In PA-treated cell, SF preparation reduced the level of Nox4 and ROS, while increasing the level of MMP and the expression of manganese superoxide dismutase (MnSOD and catalase, indicating emendation of mitochondrial dysfunction. Nox4 inhibitor GKT137381 prevented PA-induced increase of ROS and apoptosis, while decreasing iTG slightly and not influencing the level of IL-8 and IL-6. SF preparation prevented PA-induced upregulation of phospho-JNK. JNK inhibitor SP600125 prevented PA-mediated increase of Nox4, IL-8, IL-6 and iTG. Nuclear translocation of NFκB/p65 was detected in PA-treated cells, which was prevented by SF preparation. An IκB degradation inhibitor, BAY11-7082, prevented PA-induced increase of IL-8 and IL-6 as well as iTG, whereas it only decreased ROS levels slightly and showed no influence on cellular apoptosis. Conclusion: SF preparation shows a beneficial role in prevention of hepatocyte injury by attenuating oxidative stress and cytokines production at least partially through inhibition of JNK/Nox4 and JNK

  14. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells

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    Yeh, Lee-Chuan C.; Ford, Jeffery J. [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); Lee, John C. [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX (United States); Adamo, Martin L., E-mail: adamo@biochem.uthscsa.edu [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX (United States)

    2014-07-18

    Highlights: • Palmitate inhibits osteoblast differentiation. • Fatty acid synthase. • PPARγ. • Acetyl Co-A carboxylase inhibitor TOFA. • Fetal rat calvarial cell culture. - Abstract: Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects.

  15. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells

    International Nuclear Information System (INIS)

    Yeh, Lee-Chuan C.; Ford, Jeffery J.; Lee, John C.; Adamo, Martin L.

    2014-01-01

    Highlights: • Palmitate inhibits osteoblast differentiation. • Fatty acid synthase. • PPARγ. • Acetyl Co-A carboxylase inhibitor TOFA. • Fetal rat calvarial cell culture. - Abstract: Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects

  16. Paliperidone palmitate-induced sialorrhoea

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    Cengiz Cengisiz

    2016-03-01

    Full Text Available Extrapyramidal, metabolic, and cardiac side effects were reported for atypical antipsychotics; although a few resources show paliperidone-induced sialorrhea, there are no resources that show paliperidone palmitate-induced sialorrhea. In this paper, we present the paliperidone palmitate-induced sialorrhea side effects of a patient who applied on our clinic [Cukurova Med J 2016; 41(0.100: 8-13

  17. Jinlida granule inhibits palmitic acid induced-intracellular lipid accumulation and enhances autophagy in NIT-1 pancreatic β cells through AMPK activation.

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    Wang, Dingkun; Tian, Min; Qi, Yuan; Chen, Guang; Xu, Lijun; Zou, Xin; Wang, Kaifu; Dong, Hui; Lu, Fuer

    2015-02-23

    TOR and the up-regulation of TSC1 and LC3-II proteins expression. However, when AMPK phosphorylation was inhibited by Compound C, JLDG supplementation did not exhibit any effect on the expression of these AMPK downstream molecules in NIT-1 cells. The results suggest that JLDG could reduce intracellular lipid accumulation and enhance the autophagy in NIT-1 pancreatic β cells cultured with PA. The mechanism is possibly mediated by AMPK activation. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  18. Inhibition of cardiac sodium currents by toluene exposure

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    Cruz, Silvia L; Orta-Salazar, Gerardo; Gauthereau, Marcia Y; Millan-Perez Peña, Lourdes; Salinas-Stefanón, Eduardo M

    2003-01-01

    Toluene is an industrial solvent widely used as a drug of abuse, which can produce sudden sniffing death due to cardiac arrhythmias. In this paper, we tested the hypothesis that toluene inhibits cardiac sodium channels in Xenopus laevis oocytes transfected with Nav1.5 cDNA and in isolated rat ventricular myocytes. In oocytes, toluene inhibited sodium currents (INa+) in a concentration-dependent manner, with an IC50 of 274 μM (confidence limits: 141–407μM). The inhibition was complete, voltage-independent, and slowly reversible. Toluene had no effect on: (i) the shape of the I–V curves; (ii) the reversal potential of Na+; and (iii) the steady-state inactivation. The slow recovery time constant from inactivation of INa+ decreased with toluene exposure, while the fast recovery time constant remained unchanged. Block of INa+ by toluene was use- and frequency-dependent. In rat cardiac myocytes, 300 μM toluene inhibited the sodium current (INa+) by 62%; this inhibition was voltage independent. These results suggest that toluene binds to cardiac Na+ channels in the open state and unbinds either when channels move between inactivated states or from an inactivated to a closed state. The use- and frequency-dependent block of INa+ by toluene might be responsible, at least in part, for its arrhythmogenic effect. PMID:14534149

  19. Mechanisms of palmitate-induced cell death in human osteoblasts

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    Gunaratnam, Krishanthi; Vidal, Christopher; Boadle, Ross; Thekkedam, Chris; Duque, Gustavo

    2013-01-01

    Summary Lipotoxicity is an overload of lipids in non-adipose tissues that affects function and induces cell death. Lipotoxicity has been demonstrated in bone cells in vitro using osteoblasts and adipocytes in coculture. In this condition, lipotoxicity was induced by high levels of saturated fatty acids (mostly palmitate) secreted by cultured adipocytes acting in a paracrine manner. In the present study, we aimed to identify the underlying mechanisms of lipotoxicity in human osteoblasts. Palmitate induced autophagy in cultured osteoblasts, which was preceded by the activation of autophagosomes that surround palmitate droplets. Palmitate also induced apoptosis though the activation of the Fas/Jun kinase (JNK) apoptotic pathway. In addition, osteoblasts could be protected from lipotoxicity by inhibiting autophagy with the phosphoinositide kinase inhibitor 3-methyladenine or by inhibiting apoptosis with the JNK inhibitor SP600125. In summary, we have identified two major molecular mechanisms of lipotoxicity in osteoblasts and in doing so we have identified a new potential therapeutic approach to prevent osteoblast dysfunction and death, which are common features of age-related bone loss and osteoporosis. PMID:24285710

  20. Reduced levels of SCD1 accentuate palmitate-induced stress in insulin-producing β-cells

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    Hovsepyan Meri

    2010-09-01

    Full Text Available Abstract Background Stearoyl-CoA desaturase 1 (SCD1 is an ER resident enzyme introducing a double-bond in saturated fatty acids. Global knockout of SCD1 in mouse increases fatty acid oxidation and insulin sensitivity which makes the animal resistant to diet-induced obesity. Inhibition of SCD1 has therefore been proposed as a potential therapy of the metabolic syndrome. Much of the work has focused on insulin target tissue and very little is known about how reduced levels of SCD1 would affect the insulin-producing β-cell, however. The aim of the present study was therefore to investigate how reduced levels of SCD1 affect the β-cell. Results Insulin-secreting MIN6 cells with reduced levels of SCD1 were established by siRNA mediated knockdown. When fatty acid oxidation was measured, no difference between cells with reduced levels of SCD1 and mock-transfected cells were found. Also, reducing levels of SCD1 did not affect insulin secretion in response to glucose. To investigate how SCD1 knockdown affected cellular mechanisms, differentially regulated proteins were identified by a proteomic approach. Cells with reduced levels of SCD1 had higher levels of ER chaperones and components of the proteasome. The higher amounts did not protect the β-cell from palmitate-induced ER stress and apoptosis. Instead, rise in levels of p-eIF2α and CHOP after palmitate exposure was 2-fold higher in cells with reduced levels of SCD1 compared to mock-transfected cells. Accordingly, apoptosis rose to higher levels after exposure to palmitate in cells with reduced levels of SCD1 compared to mock-transfected cells. Conclusions In conclusion, reduced levels of SCD1 augment palmitate-induced ER stress and apoptosis in the β-cell, which is an important caveat when considering targeting this enzyme as a treatment of the metabolic syndrome.

  1. Protective Effect of 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione, Isolated from Averrhoa Carambola L., Against Palmitic Acid-Induced Inflammation and Apoptosis in Min6 Cells by Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway

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    Qiuqiao Xie

    2016-09-01

    Full Text Available Background/Aims: Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD, isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic β-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. Methods: Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Results: Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. Conclusions: DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway.

  2. Protective Effect of 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione, Isolated from Averrhoa Carambola L., Against Palmitic Acid-Induced Inflammation and Apoptosis in Min6 Cells by Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway.

    Science.gov (United States)

    Xie, Qiuqiao; Zhang, Shijun; Chen, Chunxia; Li, Juman; Wei, Xiaojie; Xu, Xiaohui; Xuan, Feifei; Chen, Ning; Pham, Thithaihoa; Qin, Ni; He, Junhui; Ye, Fangxing; Huang, Wansu; Huang, Renbin; Wen, Qingwei

    2016-01-01

    Studies have demonstrated that 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione (DMDD), isolated from the roots of Averrhoa carambola L., has significant therapeutic potential for the treatment of diabetes. However, the protective effect of DMDD against pancreatic beta cell dysfunction has never been reported. We investigated whether DMDD protected against palmitic acid-induced dysfunction in pancreatic β-cell line Min6 cells by attenuating the inflammatory response and apoptosis and to shed light on its possible mechanism. Cell viability was assessed by CCK-8. Glucose-stimulated insulin secretion levels and inflammatory cytokines levels were examined by ELISA. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay, Hoechst 33342/PI double-staining assay, and Transmission electron microscopy assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Cell viability and glucose-stimulated insulin secretion levels were increased in DMDD-pretreated Min6 cells. DMDD inhibited inflammatory cytokines IL-6, TNF-α and MCP-1 generations in palmitic acid (PA)-induced Min6 cells. Moreover, DMDD protected against PA-induced Min6 cells apoptosis and the expression of Cleaved-Caspase-3, -8 and -9 were down-regulated and the Bcl-2/Bax ratio was increased in DMDD-pretreated Min6 cells. In addition, the expression of TLR4, MyD88 and NF-κB were down-regulated in DMDD-pretreated Min6 cells and TAK-242-pretreated group cells. DMDD protected Min6 cells against PA-induced dysfunction by attenuating the inflammatory response and apoptosis, and its mechanism of this protection was associated with inhibiting the TLR4-MyD88-NF-κB signaling pathway. © 2016 The Author(s) Published by S. Karger AG, Basel.

  3. Enzymatic Cellulose Palmitate Synthesis Using Immobilized Lipase

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    Anna Roosdiana

    2017-06-01

    Full Text Available Bacterial cellulose can be modified by esterification using palmitic acid and Mucor miehei  lipase  as catalyst. The purpose of this research was to determine the optimum conditions of esterification reaction of cellulose and palmitic acid . The esterification reaction was carried out at the time variation  of  6, 12, 18, 24 and 30 hours and the mass ratio of cellulose: palmitic acid (1: 11: 2, 1: 3, 1: 4, 1: 5,1:6 at 50 °C. The   cellulose palmitate  was examined  its  physical and chemical properties by using FTIR spectrophotometer, XRD, bubble point test and saponification  apparatus. The results showed that the optimum reaction time of esterification reaction of cellulose and palmitic acid occurred within 24 hours and the mass ratio of cellulose: palmitic acid was 1: 3 resulting in DS of  0.376 with  swelling index of 187 %, crystallinity index of 61.95%,  and Φ porous of 2.40 μm. Identification of functional groups using FTIR spectrophotometer showed that C=O ester group  was observed at 1737.74 cm-1 and strengthened  by  the appearance of C-O ester peak at 1280 cm-1. The conclusion of this study is reaction time and reactant ratio influence significantly the DS of cellulose ester.

  4. Identification of Lipoproteins Using Globomycin and Radioactive Palmitate.

    Science.gov (United States)

    Buddelmeijer, Nienke

    2017-01-01

    Bacterial lipoproteins are characterized by fatty acids that are covalently attached to their amino terminus via posttranslational modification in the cytoplasmic membrane. Three enzymatic steps are involved in the synthesis of mature triacylated lipoprotein: prolipoprotein converts into diacylglyceryl-prolipoprotein that in turn converts into apolipoprotein, which is finally converted into mature triacylated lipoprotein. Here we describe the detection of one of these intermediate forms of lipoprotein, diacylglyceryl-prolipoprotein, using 3 H-palmitate labeling and inhibition by globomycin and detection by fluorography.

  5. Palmitate induces VSMC apoptosis via toll like receptor (TLR)4/ROS/p53 pathway.

    Science.gov (United States)

    Zhang, Yuanjun; Xia, Guanghao; Zhang, Yaqiong; Liu, Juxiang; Liu, Xiaowei; Li, Weihua; Lv, Yaya; Wei, Suhong; Liu, Jing; Quan, Jinxing

    2017-08-01

    Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway. VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA. Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression. Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Isosteviol has beneficial effects on palmitate-induced α-cell dysfunction and gene expression.

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    Xiaoping Chen

    Full Text Available BACKGROUND: Long-term exposure to high levels of fatty acids impairs insulin secretion and exaggerates glucagon secretion. The aim of this study was to explore if the antihyperglycemic agent, Isosteviol (ISV, is able to counteract palmitate-induced α-cell dysfunction and to influence α-cell gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Long-term incubation studies with clonal α-TC1-6 cells were performed in the presence of 0.5 mM palmitate with or without ISV. We investigated effects on glucagon secretion, glucagon content, cellular triglyceride (TG content, cell proliferation, and expression of genes involved in controlling glucagon synthesis, fatty acid metabolism, and insulin signal transduction. Furthermore, we studied effects of ISV on palmitate-induced glucagon secretion from isolated mouse islets. Culturing α-cells for 72-h with 0.5 mM palmitate in the presence of 18 mM glucose resulted in a 56% (p<0.01 increase in glucagon secretion. Concomitantly, the TG content of α-cells increased by 78% (p<0.01 and cell proliferation decreased by 19% (p<0.05. At 18 mM glucose, ISV (10(-8 and 10(-6 M reduced palmitate-stimulated glucagon release by 27% (p<0.05 and 27% (p<0.05, respectively. ISV (10(-6 M also counteracted the palmitate-induced hypersecretion of glucagon in mouse islets. ISV (10(-6 M reduced α-TC1-6 cell proliferation rate by 25% (p<0.05, but ISV (10(-8 and 10(-6 M had no effect on TG content in the presence of palmitate. Palmitate (0.5 mM increased Pcsk2 (p<0.001, Irs2 (p<0.001, Fasn (p<0.001, Srebf2 (p<0.001, Acaca (p<0.01, Pax6 (p<0.05 and Gcg mRNA expression (p<0.05. ISV significantly (p<0.05 up-regulated Insr, Irs1, Irs2, Pik3r1 and Akt1 gene expression in the presence of palmitate. CONCLUSIONS/SIGNIFICANCE: ISV counteracts α-cell hypersecretion and apparently contributes to changes in expression of key genes resulting from long-term exposure to palmitate. ISV apparently acts as a glucagonostatic drug with potential as a

  7. PERIPUBERTAL PROCHLORAZ EXPOSURE STRONGLY INHIBITS TESTOSTERONE PRODUCTION, BUT HAS WEAK EFFECTS ON PUBERTY

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    Prochloraz (PCZ) is an imidazole fungicide that inhibits steroidogenesis and acts as an androgen receptor antagonist. We hypothesized that pubertal exposure to prochloraz would delay preputial separation and development of reproductive organs. Sprague Dawley rats were dosed wit...

  8. Bitter melon extract ameliorates palmitate-induced apoptosis via inhibition of endoplasmic reticulum stress in HepG2 cells and high-fat/high-fructose-diet-induced fatty liver

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    Hwa Joung Lee

    2018-03-01

    Full Text Available Background: Bitter melon (BM improves glucose level, lipid homeostasis, and insulin resistance in vivo. However, the preventive mechanism of BM in nonalcoholic fatty liver disease (NAFLD has not been elucidated yet. Aim & Design: To determine the protective mechanism of bitter melon extract (BME, we performed experiments in vitro and in vivo. BME were treated palmitate (PA-administrated HepG2 cells. C57BL/6J mice were divided into two groups: high-fat/high-fructose (HF/HFr without or with BME supplementation (100 mg/kg body weight. Endoplasmic reticulum (ER stress, apoptosis, and biochemical markers were then examined by western blot and real-time PCR analyses. Results: BME significantly decreased expression levels of ER-stress markers (including phospho-eIF2α, CHOP, and phospho-JNK [Jun N-terminal kinases] in PA-treated HepG2 cells. BME also significantly decreased the activity of cleaved caspase-3 (a well known apoptotic-induced molecule and DNA fragmentation. The effect of BME on ER stress–mediated apoptosis in vitro was similarly observed in HF/HFr-fed mice in vivo. BME significantly reduced HF/HFr-induced hepatic triglyceride (TG and serum alanine aminotransferase (ALT as markers of hepatic damage in mice. In addition, BME ameliorated HF/HFr-induced serum TG and serum-free fatty acids. Conclusion: These data indicate that BME has protective effects against ER stress mediated apoptosis in HepG2 cells as well as in HF/HFr-induced fatty liver of mouse. Therefore, BME might be useful for preventing and treating NAFLD.

  9. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

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    Patel, Shreya, E-mail: Shreya.patel214@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Peretz, Jackye, E-mail: Jackye.peretz@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Pan, Yuan-Xiang, E-mail: yxpan@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Helferich, William G., E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

    2016-02-15

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes.

  10. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

    International Nuclear Information System (INIS)

    Patel, Shreya; Peretz, Jackye; Pan, Yuan-Xiang; Helferich, William G.; Flaws, Jodi A.

    2016-01-01

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes.

  11. Palmitate-induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis.

    Science.gov (United States)

    Pillon, Nicolas J; Azizi, Paymon M; Li, Yujin E; Liu, Jun; Wang, Changsen; Chan, Kenny L; Hopperton, Kathryn E; Bazinet, Richard P; Heit, Bryan; Bilan, Philip J; Lee, Warren L; Klip, Amira

    2015-07-01

    Obesity is associated with inflammation and immune cell recruitment to adipose tissue, muscle and intima of atherosclerotic blood vessels. Obesity and hyperlipidemia are also associated with tissue insulin resistance and can compromise insulin delivery to muscle. The muscle/fat microvascular endothelium mediates insulin delivery and facilitates monocyte transmigration, yet its contribution to the consequences of hyperlipidemia is poorly understood. Using primary endothelial cells from human adipose tissue microvasculature (HAMEC), we investigated the effects of physiological levels of fatty acids on endothelial inflammation and function. Expression of cytokines and adhesion molecules was measured by RT-qPCR. Signaling pathways were evaluated by pharmacological manipulation and immunoblotting. Surface expression of adhesion molecules was determined by immunohistochemistry. THP1 monocyte interaction with HAMEC was measured by cell adhesion and migration across transwells. Insulin transcytosis was measured by total internal reflection fluorescence microscopy. Palmitate, but not palmitoleate, elevated the expression of IL-6, IL-8, TLR2 (Toll-like receptor 2), and intercellular adhesion molecule 1 (ICAM-1). HAMEC had markedly low fatty acid uptake and oxidation, and CD36 inhibition did not reverse the palmitate-induced expression of adhesion molecules, suggesting that inflammation did not arise from palmitate uptake/metabolism. Instead, inhibition of TLR4 to NF-κB signaling blunted palmitate-induced ICAM-1 expression. Importantly, palmitate-induced surface expression of ICAM-1 promoted monocyte binding and transmigration. Conversely, palmitate reduced insulin transcytosis, an effect reversed by TLR4 inhibition. In summary, palmitate activates inflammatory pathways in primary microvascular endothelial cells, impairing insulin transport and increasing monocyte transmigration. This behavior may contribute in vivo to reduced tissue insulin action and enhanced tissue

  12. Anti-inflammatory and antifibrotic effects of methyl palmitate

    International Nuclear Information System (INIS)

    El-Demerdash, Ebtehal

    2011-01-01

    Methyl palmitate (MP) has been shown earlier to inhibit Kupffer cells and rat peritoneal macrophages. To evaluate the potential of MP to inhibit the activation of other macrophages, RAW cells (macrophages of alveolar origin) were treated with varying concentrations of MP (0.25, 0.5, 1 mM). Assessment of cytotoxicity using MTT assay revealed that 0.25 and 0.5 mM are not toxic to RAW cells. MP was able to inhibit the phagocytic function of RAW cells. Treatment of cells with MP 24 hours prior to LPS stimulation significantly decreased nitric oxide release and altered the pattern of cytokines release; there was a significant decrease in TNF-α and a significant increase in IL-10 compared to the controls. However, there is a non-significant change in IL-6 level. Furthermore, phosphorylation of inhibitory kappa B (IκBα) protein was significantly decreased in RAW cells treated with 0.5 mM MP after LPS stimulation. Based upon the in-vitro results, it was examined whether MP treatment will be effective in preventing bleomycin-induced lung inflammation and fibrosis in-vivo. Bleomycin given by itself caused destruction of the lung architecture characterized by pulmonary fibrosis with collapse of air alveoli and emphysematous. Bleomycin induced a significant increase in hydroxyproline level and activated NF-κB, p65 expression in the lung. MP co-treatment significantly ameliorated bleomycin effects. These results suggest that MP has a potential of inhibiting macrophages in general. The present study demonstrated for the first time that MP has anti-inflammatory and antifibrotic effect that could be through NF-kB inhibition. Thus MP like molecule could be a promising anti-inflammatory and antifibrotic drug. - Research highlights: →Methyl palmitate is a universal macrophage inhibitor. →It could be a promising nucleus of anti-inflammatory and antifibrotic drugs. →The underlying mechanism of these effects could be through NF-kB inhibition.

  13. Saturated fatty acid palmitate negatively regulates autophagy by promoting ATG5 protein degradation in meniscus cells.

    Science.gov (United States)

    Mallik, Aritra; Yammani, Raghunatha R

    2018-07-20

    Obesity and associated metabolic factors are major risk factors for the development of osteoarthritis. Previously, we have shown that the free fatty acid palmitate induces endoplasmic reticulum (ER) stress and induces apoptosis in meniscus cells. However, the molecular mechanisms involved in these effects are not clearly understood. In our current study, we found that palmitate inhibits autophagy by modulating the protein levels of autophagy-related genes-5 (ATG5) that is associated with decreased lipidation of LC3 and increased activation of cleaved caspase 3. Pretreatment of meniscus cells with 4-phenyl butyric acid, a small molecule chemical chaperone that alleviates ER stress, or with MG-132, a proteasome inhibitor, restored normal levels of ATG5 and autophagosome formation, and decreased expression of cleaved caspase 3. Thus, our data suggest that palmitate downregulates autophagy in meniscus cells by degrading ATG5 protein via ER-associated protein degradation, and thus promotes apoptosis. This is the first study to demonstrate that palmitate-induced endoplasmic reticulum stress negatively regulates autophagy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Esterification of Palmitic Acid with Methanol in the Presence of Macroporous Ion Exchange Resin as Catalyst

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    Amelia Qarina Yaakob and Subhash Bhatia

    2012-10-01

    Full Text Available The esterification of palmitic acid with methanol was studied in a batch reactor using macro porous ion exchange resin Amberlyst 15 as a catalyst. Methyl palmitate was produced from the reaction between palmitic acid and methanol in the presence of catalyst. The effects of processing parameters, molar ratio of alcohol to acid M, (4-10, catalyst loading (0-10 g cat/liter, water inhibition (0-2 mol/liter, agitator speed (200-800 rpm and reaction temperature (343-373K were studied. The experimental kinetic data were correlated using homogenous as well as heterogeneous models (based on single as well as dual site mechanisms. The activation energy of the reaction was 11.552 kJ/mol for forward reaction whilst 5.464 kJ/mol for backward reaction. The experimental data fitted well with the simulated data obtained from the kinetic models. Keywords: Palmitic Acid, Methanol, Esterification, Ion Exchange Resin, Kinetics.

  15. Exposure of nonbreeding migratory shorebirds to cholinesterase-inhibiting contaminants in the western hemisphere

    Science.gov (United States)

    Strum, K.M.; Hooper, M.J.; Johnson, K.A.; Lanctot, Richard B.; Zaccagnini, M.E.; Sandercock, B.K.

    2010-01-01

    Migratory shorebirds frequently forage and roost in agricultural habitats, where they may be exposed to cholinesterase-inhibiting pesticides. Exposure to organophosphorus and carbamate compounds, common anti-cholinesterases, can cause sublethal effects, even death. To evaluate exposure of migratory shorebirds to organophosphorus and carbamates, we sampled birds stopping over during migration in North America and wintering in South America. We compared plasma cholinesterase activities and body masses of individuals captured at sites with no known sources of organophosphorus or carbamates to those captured in agricultural areas where agrochemicals were recommended for control of crop pests. In South America, plasma acetylcholinesterase and butyrylcholinesterase activity in Buff-breasted Sandpipers was lower at agricultural sites than at reference sites, indicating exposure to organophosphorus and carbamates. Results of plasma cholinesterase reactivation assays and foot-wash analyses were inconclusive. A meta-analysis of six species revealed no widespread effect of agricultural chemicals on cholinesterase activity. however, four of six species were negative for acetylcholinesterase and one of six for butyrylcholinesterase, indicating negative effects of pesticides on cholinesterase activity in a subset of shorebirds. Exposure to cholinesterase inhibitors can decrease body mass, but comparisons between treatments and hemispheres suggest that agrochemicals did not affect migratory shorebirds' body mass. Our study, one of the first to estimate of shorebirds' exposure to cholinesterase-inhibiting pesticides, suggests that shorebirds are being exposed to cholinesterase- inhibiting pesticides at specific sites in the winter range but not at migratory stopover sites. future research should examine potential behavioral effects of exposure and identify other potential sitesand levels of exposure. ?? The Cooper Ornithological Society 2010.

  16. Avoidance behaviour response and esterase inhibition in the earthworm, Lumbricus terrestris, after exposure to chlorpyrifos.

    Science.gov (United States)

    Martínez Morcillo, S; Yela, J L; Capowiez, Y; Mazzia, C; Rault, M; Sanchez-Hernandez, Juan C

    2013-05-01

    The avoidance response of earthworms to polluted soils has been standardised using a simple and low-cost test, which facilitates soil toxicity screening. In this study, the avoidance response of Lumbricus terrestris was quantified in chlorpyrifos-spiked soils, depending on the pesticide concentration and exposure duration. The inhibition of acetylcholinesterase (AChE) and carboxylesterase (CbE) activities was also determined as indirect measures of pesticide bioavailability. The effects of different chlorpyrifos concentrations were examined in a standardised test (two-chamber system) with 0.6, 3 and 15 mg/kg chlorpyrifos. A modification of the test involved a pre-exposure step (24, 48 or 72 h) in soils spiked with 15 mg/kg. In both protocols, earthworms were unable to avoid the contaminated soils. However, the esterase activities showed that all earthworms were exposed to chlorpyrifos. Acetylcholinesterase activity did not change in earthworms in the standardised behavioural test (0.58 ± 0.20 U/mg protein, mean ± SD; n = 72), whereas the CbE activity was significantly inhibited (62-87 % inhibition) in earthworms exposed to 3 and 15 mg/kg. In the modified test, earthworms had greatly inhibited AChE activity (0.088 ± 0.034 U/mg protein, n = 72), which was supported by reactivation of the inhibited enzyme activity in the presence of pralidoxime (2-PAM). Similarly, the CbE activity was significantly inhibited in earthworms with all treatments. This study suggests that the avoidance behaviour test for organophosphorus-contaminated soils could be supported by specific biomarkers to facilitate a better understanding of pesticide exposure and toxicity during this test.

  17. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

    Science.gov (United States)

    Benoit, Stephen C.; Kemp, Christopher J.; Elias, Carol F.; Abplanalp, William; Herman, James P.; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G.; Holland, William L.; Clegg, Deborah J.

    2009-01-01

    Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-θ to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-θ nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-θ attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-θ activation, resulting in reduced insulin activity. PMID:19726875

  18. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents.

    Science.gov (United States)

    Benoit, Stephen C; Kemp, Christopher J; Elias, Carol F; Abplanalp, William; Herman, James P; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G; Holland, William L; Clegg, Deborah J

    2009-09-01

    Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-theta, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-theta was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-theta to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-theta nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-theta attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-theta activation, resulting in reduced insulin activity.

  19. Covalent modification of platelet proteins by palmitate

    International Nuclear Information System (INIS)

    Muszbek, L.; Laposata, M.

    1989-01-01

    Covalent attachment of fatty acid to proteins plays an important role in association of certain proteins with hydrophobic membrane structures. In platelets, the structure of many membrane glycoproteins (GPs) has been examined in detail, but the question of fatty acid acylation of platelet proteins has not been addressed. In this study, we wished to determine (a) whether platelet proteins could be fatty acid acylated; and, if so, (b) whether these modified proteins were present in isolated platelet membranes and cytoskeletal fractions; and (c) if the pattern of fatty acid acylated proteins changed on stimulation of the platelets with the agonist thrombin. We observed that in platelets allowed to incorporate 3H-palmitate, a small percentage (1.37%) of radioactivity incorporated into the cells became covalently bound to protein. Selective cleavage of thioester, thioester plus O-ester, and amide-linked 3H-fatty acids from proteins, and their subsequent analysis by high-performance liquid chromatography (HPLC) indicated that the greatest part of 3H-fatty acid covalently bound to protein was thioester-linked 3H-palmitate. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography, at least ten major radiolabeled proteins were detected. Activation of platelets by thrombin greatly increased the quantity of 3H-palmitoylated proteins associated with the cytoskeleton. Nearly all radiolabeled proteins were recovered in the membrane fraction, indicating that these proteins are either integral or peripheral membrane proteins or proteins tightly associated to membrane constituents. Components of the GPIIb-IIIa complex were not palmitoylated. Thus, platelet proteins are significantly modified posttranslationally by 3H-palmitate, and incorporation of palmitoylated proteins into the cytoskeleton is a prominent component of the platelet response to thrombin stimulation

  20. Prolonged exposure to particulate chromate inhibits RAD51 nuclear import mediator proteins.

    Science.gov (United States)

    Browning, Cynthia L; Wise, John Pierce

    2017-09-15

    Particulate hexavalent chromium (Cr(VI)) is a human lung carcinogen and a human health concern. The induction of structural chromosome instability is considered to be a driving mechanism of Cr(VI)-induced carcinogenesis. Homologous recombination repair protects against Cr(VI)-induced chromosome damage, due to its highly accurate repair of Cr(VI)-induced DNA double strand breaks. However, recent studies demonstrate Cr(VI) inhibits homologous recombination repair through the misregulation of RAD51. RAD51 is an essential protein in HR repair that facilitates the search for a homologous sequence. Recent studies show prolonged Cr(VI) exposure prevents proper RAD51 subcellular localization, causing it to accumulate in the cytoplasm. Since nuclear import of RAD51 is crucial to its function, this study investigated the effect of Cr(VI) on the RAD51 nuclear import mediators, RAD51C and BRCA2. We show acute (24h) Cr(VI) exposure induces the proper localization of RAD51C and BRCA2. In contrast, prolonged (120h) exposure increased the cytoplasmic localization of both proteins, although RAD51C localization was more severely impaired. These results correlate temporally with the previously reported Cr(VI)-induced RAD51 cytoplasmic accumulation. In addition, we found Cr(VI) does not inhibit interaction between RAD51 and its nuclear import mediators. Altogether, our results suggest prolonged Cr(VI) exposure inhibits the nuclear import of RAD51C, and to a lesser extent, BRCA2, which results in the cytoplasmic accumulation of RAD51. Cr(VI)-induced inhibition of nuclear import may play a key role in its carcinogenic mechanism since the nuclear import of many tumor suppressor proteins and DNA repair proteins is crucial to their function. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. In vitro atrazine-exposure inhibits human natural killer cell lytic granule release

    International Nuclear Information System (INIS)

    Rowe, Alexander M.; Brundage, Kathleen M.; Barnett, John B.

    2007-01-01

    The herbicide atrazine is a known immunotoxicant and an inhibitor of human natural killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell-mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24-h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test this hypothesis, flow cytometry and fluorescent microscopy were employed to analyze NK cell-target cell co-cultures following atrazine exposure. These assays demonstrated no significant decrease in the level of target cell binding. However, the levels of NK intracellular lytic protein retained and the amount of lytic protein released were assessed following a 4-h incubation with K562 target cells. The relative level of intracellular lytic protein was 25-50% higher, and the amount of lytic protein released was 55-65% less in atrazine-treated cells than vehicle-treated cells following incubation with the target cells. These results indicate that ATR exposure inhibits the ability of NK cells to lyse target cells by blocking lytic granule release without affecting the ability of the NK cell to form stable conjugates with target cells

  2. The effect of cetyl palmitate crystallinity on physical properties of gamma-oryzanol encapsulated in solid lipid nanoparticles.

    Science.gov (United States)

    Ruktanonchai, Uracha; Limpakdee, Surachai; Meejoo, Siwaporn; Sakulkhu, Usawadee; Bunyapraphatsara, Nuntavan; Junyaprasert, Varaporn; Puttipipatkhachorn, Satit

    2008-03-05

    This present study was aimed at investigating the effect of the crystallinity of cetyl palmitate based solid lipid nanoparticles (SLNs) on the physical properties of γ-oryzanol-loaded SLNs. SLNs consisting of varying ratios of cetyl palmitate and γ-oryzanol were prepared. Their hydrodynamic diameters were in the range 210-280 nm and the zeta potentials were in the range -27 to -35 mV. The size of SLNs increased as the amount of cetyl palmitate decreased whereas no significant change of zeta potentials was found. Atomic force microscopy pictures indicated the presence of disc-like particles. The crystallinity of SLNs, determined by differential scanning calorimetry and powder x-ray diffraction, was directly dependent on the ratio of cetyl palmitate to γ-oryzanol and decreased with decreasing cetyl palmitate content in the lipid matrix. Varying this ratio in the lipid mix resulted in a shift in the melting temperature and enthalpy, although the SLN structure remained unchanged as an orthorhombic lamellar lattice. This has been attributed to a potential inhibition by γ-oryzanol during lipid crystal growth as well as a less ordered structure of the SLNs. The results revealed that the crystallinity of the SLNs was mainly dependent on the solid lipid, and that the crystallinity has an important impact on the physical characteristics of active-loaded SLNs.

  3. The effect of cetyl palmitate crystallinity on physical properties of gamma-oryzanol encapsulated in solid lipid nanoparticles

    International Nuclear Information System (INIS)

    Ruktanonchai, Uracha; Sakulkhu, Usawadee; Limpakdee, Surachai; Meejoo, Siwaporn; Bunyapraphatsara, Nuntavan; Junyaprasert, Varaporn; Puttipipatkhachorn, Satit

    2008-01-01

    This present study was aimed at investigating the effect of the crystallinity of cetyl palmitate based solid lipid nanoparticles (SLNs) on the physical properties of γ-oryzanol-loaded SLNs. SLNs consisting of varying ratios of cetyl palmitate and γ-oryzanol were prepared. Their hydrodynamic diameters were in the range 210-280 nm and the zeta potentials were in the range -27 to -35 mV. The size of SLNs increased as the amount of cetyl palmitate decreased whereas no significant change of zeta potentials was found. Atomic force microscopy pictures indicated the presence of disc-like particles. The crystallinity of SLNs, determined by differential scanning calorimetry and powder x-ray diffraction, was directly dependent on the ratio of cetyl palmitate to γ-oryzanol and decreased with decreasing cetyl palmitate content in the lipid matrix. Varying this ratio in the lipid mix resulted in a shift in the melting temperature and enthalpy, although the SLN structure remained unchanged as an orthorhombic lamellar lattice. This has been attributed to a potential inhibition by γ-oryzanol during lipid crystal growth as well as a less ordered structure of the SLNs. The results revealed that the crystallinity of the SLNs was mainly dependent on the solid lipid, and that the crystallinity has an important impact on the physical characteristics of active-loaded SLNs

  4. ORIGIN OF PALMITIC ACID CARBON IN PALMITATES FORMED FROM HEXADECANE-1-C14 AND TETRADECANE-1-C14 BY MICROCOCCUS CERIFICANS

    Science.gov (United States)

    Finnerty, W. R.; Kallio, R. E.

    1964-01-01

    Finnerty, W. R. (University of Iowa, Iowa City), and R. E. Kallio. Origin of palmitic acid carbon in palmitates formed from hexadecane-1-C14 and tetradecane-1-C14 by Micrococcus cerificans. J. Bacteriol. 87:1261–1265. 1964.—Degradation of the palmitic acid moiety of cetyl palmitate and myristyl palmitate formed from hexadecane-1-C14 and tetradecane-1-C14 by Micrococcus cerificans was carried out. The patterns of C14 labeling in palmitic acid from cetyl palmitate showed that hexadecane is oxidized at the C1 position, and cetyl alcohol and palmitic acid thus formed are directly esterified. Palmitic acid arising from tetradecane and esterified to tetradecanol appeared to have been synthesized by the addition of two carbon atoms to an existing 14-carbon atom skeleton. Considerable mixing of C14 occurred in the C1 and C2 positions of palmitic acid thus synthesized. PMID:14188700

  5. Resveratrol Ameliorates Palmitate-Induced Inflammation in Skeletal Muscle Cells by Attenuating Oxidative Stress and JNK/NF-κB Pathway in a SIRT1-Independent Mechanism.

    Science.gov (United States)

    Sadeghi, Asie; Seyyed Ebrahimi, Shadi Sadat; Golestani, Abolfazl; Meshkani, Reza

    2017-09-01

    Resveratrol has been shown to exert anti-inflammatory and anti-oxidant effects in a variety of cell types, however, its role in prevention of inflammatory responses mediated by palmitate in skeletal muscle cells remains unexplored. In the present study, we investigated the effects of resveratrol on palmitate-induced inflammation and elucidated the underlying mechanisms in skeletal muscle cells. The results showed that palmitate significantly enhanced TNF-α and IL-6 mRNA expression and protein secretion from C2C12 cells at 12, 24, and 36 h treatments. Increased expression of cytokines was accompanied by an enhanced phosphorylation of JNK, P38, ERK1/2, and IKKα/IKKβ. In addition, JNK and P38 inhibitors could significantly attenuate palmitate-induced mRNA expression of TNF-α and IL-6, respectively, whereas NF-κB inhibitor reduced the expression of both cytokines in palmitate-treated cells. Resveratrol pretreatment significantly prevented palmitate-induced TNF-α and IL-6 mRNA expression and protein secretion in C2C12 cells. Importantly, pre-treatment of the cells with resveratrol completely abrogated the phosphorylation of ERK1/2, JNK, and IKKα/IKKβ in palmitate treated cells. The protection from palmitate-induced inflammation by resveratrol was accompanied by a decrease in the generation of reactive oxygen species (ROS). N-acetyl cysteine (NAC), a known scavenger of ROS, could protect palmitate-induced expression of TNF-α and IL-6. Furthermore, inhibition of SIRT1 by shRNA or sirtinol demonstrated that the anti-inflammatory effect of resveratrol in muscle cells is mediated through a SIRT1-independent mechanism. Taken together, these findings suggest that resveratrol may represent a promising therapy for prevention of inflammation in skeletal muscle cells. J. Cell. Biochem. 118: 2654-2663, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Chronic ethanol exposure inhibits distraction osteogenesis in a mouse model: Role of the TNF signaling axis

    International Nuclear Information System (INIS)

    Wahl, Elizabeth C.; Aronson, James; Liu, Lichu; Liu, Zhendong; Perrien, Daniel S.; Skinner, Robert A.; Badger, Thomas M.; Ronis, Martin J.J.; Lumpkin, Charles K.

    2007-01-01

    Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that modulates osteoblastogenesis. In addition, the demonstrated inhibitory effects of chronic ethanol exposure on direct bone formation in rats are hypothetically mediated by TNF-α signaling. The effects in mice are unreported. Therefore, we hypothesized that in mice (1) administration of a soluble TNF receptor 1 derivative (sTNF-R1) would protect direct bone formation during chronic ethanol exposure, and (2) administration of recombinant mouse TNF-α (rmTNF-α) to ethanol naive mice would inhibit direct bone formation. We utilized a unique model of limb lengthening (distraction osteogenesis, DO) combined with liquid diets to measure chronic ethanol's effects on direct bone formation. Chronic ethanol exposure resulted in increased marrow TNF, IL-1, and CYP 2E1 RNA levels in ethanol-treated vs. control mice, while no significant weight differences were noted. Systemic administration of sTNF-R1 during DO (8.0 mg/kg/2 days) to chronic ethanol-exposed mice resulted in enhanced direct bone formation as measured radiologically and histologically. Systemic rmTNF-α (10 μg/kg/day) administration decreased direct bone formation measures, while no significant weight differences were noted. We conclude that chronic ethanol-associated inhibition of direct bone formation is mediated to a significant extent by the TNF signaling axis in a mouse model

  7. Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPAR{sub β/δ} in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Guanghua; Shi, Yuanping; Zhang, Jun; Mu, Qinfeng; Qin, Li; Zheng, Lu; Feng, Yuehua [Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou 213003 (China); Berggren-Söderlund, Maria; Nilsson-Ehle, Peter [Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund (Sweden); Zhang, Xiaoying, E-mail: zhangxy6689996@163.com [Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003 (China); Xu, Ning, E-mail: ning.xu@med.lu.se [Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund (Sweden)

    2014-02-28

    Highlights: • Palmitic acid significantly inhibited APOM gene expression in HepG2 cells. • Palmitic acid could obviously increase PPARB/D mRNA levels in HepG2 cells. • PPAR{sub β/δ} antagonist, GSK3787, had no effect on APOM expression. • GSK3787 could reverse the palmitic acid-induced down-regulation of APOM expression. • Palmitic acid induced suppression of APOM expression is mediated via the PPAR{sub β/δ} pathway. - Abstract: It has been demonstrated that apolipoprotein M (APOM) is a vasculoprotective constituent of high density lipoprotein (HDL), which could be related to the anti-atherosclerotic property of HDL. Investigation of regulation of APOM expression is of important for further exploring its pathophysiological function in vivo. Our previous studies indicated that expression of APOM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), leptin, hyperglycemia and etc., in vivo and/or in vitro. In the present study, we demonstrated that palmitic acid could significantly inhibit APOM gene expression in HepG2 cells. Further study indicated neither PI-3 kinase (PI3K) inhibitor LY294002 nor protein kinase C (PKC) inhibitor GFX could abolish palmitic acid induced down-regulation of APOM expression. In contrast, the peroxisome proliferator-activated receptor beta/delta (PPAR{sub β/δ}) antagonist GSK3787 could totally reverse the palmitic acid-induced down-regulation of APOM expression, which clearly demonstrates that down-regulation of APOM expression induced by palmitic acid is mediated via the PPAR{sub β/δ} pathway.

  8. Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

    International Nuclear Information System (INIS)

    Collange, B.; Wheelock, C.E.; Rault, M.; Mazzia, C.; Capowiez, Y.; Sanchez-Hernandez, J.C.

    2010-01-01

    Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg -1 chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (≤1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

  9. Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

    Energy Technology Data Exchange (ETDEWEB)

    Collange, B. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Wheelock, C.E. [Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm (Sweden); Rault, M.; Mazzia, C. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Capowiez, Y. [INRA, Unite PSH, Site AGROPARC, F-84914 Avignon Cedex 09 (France); Sanchez-Hernandez, J.C., E-mail: juancarlos.sanchez@uclm.e [Laboratory of Ecotoxicology, Faculty of Environmental Science, University of Castilla-La Mancha, Avda. Carlos III s/n, 45071, Toledo (Spain)

    2010-06-15

    Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg{sup -1} chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (<=1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

  10. Fabrication of shape memory natural rubber using palmitic acid

    Directory of Open Access Journals (Sweden)

    Jeff Sze-Hua Wee

    2017-10-01

    Full Text Available This paper investigates the practicability of fabricating a shape memory natural rubber with the use of palmitic acid as the swelling agent. Strips of natural rubber samples were swollen in molten palmitic acid at 75 °C. Equilibrium swelling of natural rubber with palmitic acid was found to occur at approximately 50 min of swelling time. Under cooling effect, the palmitic acid crystallized to form a percolated crystalline platelet network. These networks allow fabricated shape memory natural rubber (SMNR to deform and recover its shape at a temperature above the melting point of palmitic acid. Under controlled uniaxial stress, the natural rubber sample with 0 parts per hundred rubber (phr carbon black loading exhibits fixity and recovery of 80 ± 10%. Motivation of this research is primarily on practicability of palmitic acid to be used as a swelling agent for shape memory properties. Results show that palmitic acid is a relatively good swelling agent to induce shape memory properties into natural rubber.

  11. Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate.

    Science.gov (United States)

    Liu, Ning; Wu, Jichao; Zhang, Linxue; Gao, Zhaopeng; Sun, Yu; Yu, Miao; Zhao, Yajun; Dong, Shiyun; Lu, Fanghao; Zhang, Weihua

    2017-12-01

    Endothelial cell dysfunction is one of the main reasons for type II diabetes vascular complications. Hydrogen sulphide (H 2 S) has antioxidative effect, but its regulation on mitochondrial dynamics and mitophagy in aortic endothelial cells under hyperglycaemia and hyperlipidaemia is unclear. Rat aortic endothelial cells (RAECs) were treated with 40 mM glucose and 200 μM palmitate to imitate endothelium under hyperglycaemia and hyperlipidaemia, and 100 μM NaHS was used as an exogenous H 2 S donor. Firstly, we demonstrated that high glucose and palmitate decreased H 2 S production and CSE expression in RAECs. Then, the antioxidative effect of H 2 S was proved in RAECs under high glucose and palmitate to reduce mitochondrial ROS level. We also showed that exogenous H 2 S inhibited mitochondrial apoptosis in RAECs under high glucose and palmitate. Using Mito Tracker and transmission electron microscopy assay, we revealed that exogenous H 2 S decreased mitochondrial fragments and significantly reduced the expression of p-Drp-1/Drp-1 and Fis1 compared to high-glucose and high-palmitate group, whereas it increased mitophagy by transmission electron microscopy assay. We demonstrated that exogenous H 2 S facilitated Parkin recruited by PINK1 by immunoprecipitation and immunostaining assays and then ubiquitylated mitofusin 2 (Mfn2), which illuminated the mechanism of exogenous H 2 S on mitophagy. Parkin siRNA suppressed the expression of Mfn2, Nix and LC3B, which revealed that it eliminated mitophagy. In summary, exogenous H 2 S could protect RAECs against apoptosis under high glucose and palmitate by suppressing oxidative stress, decreasing mitochondrial fragments and promoting mitophagy. Based on these results, we proposed a new mechanism of H 2 S on protecting endothelium, which might provide a new strategy for type II diabetes vascular complication. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for

  12. Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways.

    Science.gov (United States)

    Hao, Feng; Kang, Jinsen; Cao, Yajun; Fan, Shengjun; Yang, Haopeng; An, Yu; Pan, Yan; Tie, Lu; Li, Xuejun

    2015-11-01

    Lipotoxicity plays a vital role in development and progression of type 2 diabetes. Prolonged elevation of free fatty acids especially the palmitate leads to pancreatic β-cell dysfunction and apoptosis. Curcumin (diferuloylmethane), a polyphenol from the curry spice turmeric, is considered to be a broadly cytoprotective agent. The present study was designed to determine the protective effect of curcumin on palmitate-induced apoptosis in β-cells and investigate underlying mechanisms. Our results showed that curcumin improved cell viability and enhanced glucose-induced insulin secretory function in MIN6 pancreatic β-cells. Palmitate incubation evoked chromatin condensation, DNA nick end labeling and activation of caspase-3 and -9. Curcumin treatment inhibited palmitate-induced apoptosis, relieved mitochondrial depolarization and up-regulated Bcl-2/Bax ratio. Palmitate induced the generation of reactive oxygen species and inhibited activities of antioxidant enzymes, which could be neutralized by curcumin treatment. Moreover, curcumin could promote rapid phosphorylation of Akt and nuclear exclusion of FoxO1 in MIN6 cells under lipotoxic condition. Phosphatidylinositol 3-kinase and Akt specific inhibitors abolished the anti-lipotoxic effect of curcumin and stimulated FoxO1 nuclear translocation. These findings suggested that curcumin protected MIN6 pancreatic β-Cells against apoptosis through activation of Akt, inhibition of nuclear translocation of FoxO1 and mitochondrial survival pathway.

  13. Systemic treatment of seborrheic dermatitis with retinol palmitate

    OpenAIRE

    O. V. Kalinina; V. I. Albanova; T. A. Belousova; V. I. Nozdrin

    2014-01-01

    The goal of the study. Evaluating of the effectiveness of treatment of men with a diagnosis «Seborrheic dermatitis of the scalp» by the system using of retinol palmitate. Material and methods. 36 patients every day for 2 months received overnight per os 200000 ME of retinol palmitate, and in the comparison group (39 people) antiseborrheic shampoos have been used. The dynamics of severity of skin oiliness, pruritis, erythema, peeling, infiltration, excoriations has been evaluated in points. Be...

  14. Enhanced eyeblink conditioning in behaviorally inhibited individuals is disrupted by proactive interference following US alone pre-exposures.

    Directory of Open Access Journals (Sweden)

    Michael Todd Allen

    2016-03-01

    Full Text Available Anxiety vulnerable individuals exhibit enhanced acquisition of conditioned eyeblinks as well as enhanced proactive interference from CS or US alone pre-exposures (Holloway et al., 2012. US alone pre-exposures disrupt subsequent CR acquisition to CS-US paired trials as compared to context pre-exposure controls. While Holloway et al., (2012 reported enhanced acquisition in high trait anxiety individuals in the context condition, anxiety vulnerability effects were not reported for the US alone pre-exposure group. It appears from the published data that there were no differences between high and low anxiety individuals in the US alone condition. In the work reported here, we sought to extend the findings of enhanced proactive interference with US alone pre-exposures to determine if the enhanced conditioning was disrupted by proactive interference procedures. We also were interested in the spontaneous eyeblinks during the pre-exposure phase of training. We categorized individuals as anxiety vulnerability or non-vulnerable individuals based scores on the Adult Measure of Behavioural Inhibition (AMBI. Sixty six participants received 60 trials consisting of 30 US alone or context alone pre-exposures followed by 30 CS-US trials. US alone pre-exposures not only disrupted CR acquisition overall, but behaviorally inhibited (BI individuals exhibited enhanced proactive interference as compared to non-inhibited (NI individuals. In addition, US alone pre-exposures disrupted the enhanced acquisition observed in BI individuals as compared to NI individuals following context alone pre-exposures. Differences were also found in rates of spontaneous eyeblinks between BI and NI individuals during context pre-exposure. Our findings will be discussed in the light of the neural substrates of eyeblink conditioning as well as possible factors such as hypervigilance in the amygdala and hippocampal systems, and possible learned helplessness. Applications of these findings of

  15. Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models

    Energy Technology Data Exchange (ETDEWEB)

    Saeed, Noha M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); El-Demerdash, Ebtehal [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); Abdel-Rahman, Hanaa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); Algandaby, Mardi M. [Department of Biology (Botany), Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Al-Abbasi, Fahad A. [Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Abdel-Naim, Ashraf B., E-mail: abnaim@pharma.asu.edu.eg [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-10-01

    Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). MP and EP decreased NF-κB expression in liver and lung tissues and ameliorated histopathological changes caused by LPS. Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ► Efficacy of MP and EP in combating inflammation was displayed in several models. ► MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ► MP and EP decreased TNF-α and IL-6 levels in experimental endotoxemia. ► MP and EP reduced NF-κB expression and histological changes in rat liver and lung. ► MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.

  16. Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice

    International Nuclear Information System (INIS)

    Yu, Lunyin; Hales, Charles A

    2011-01-01

    Hypoxia has been identified as a major negative factor for tumor progression in clinical observations and in animal studies. However, the precise role of hypoxia in tumor progression has not been fully explained. In this study, we extensively investigated the effect of long-term exposure to hypoxia on tumor progression in vivo. Rats bearing transplanted tumors consisting of A549 human lung cancer cells (lung cancer tumor) were exposed to hypoxia for different durations and different levels of oxygen. The tumor growth and metastasis were evaluated. We also treated A549 lung cancer cells (A549 cells) with chronic hypoxia and then implanted the hypoxia-pretreated cancer cells into mice. The effect of exposure to hypoxia on metastasis of Lewis lung carcinoma in mice was also investigated. We found that long-term exposure to hypoxia a) significantly inhibited lung cancer tumor growth in xenograft and orthotopic models in rats, b) significantly reduced lymphatic metastasis of the lung cancer in rats and decreased lung metastasis of Lewis lung carcinoma in mice, c) reduced lung cancer cell proliferation and cell cycle progression in vitro, d) decreased growth of the tumors from hypoxia-pretreated A549 cells, e) decreased Na + -K + ATPase α1 expression in hypoxic lung cancer tumors, and f) increased expression of hypoxia inducible factors (HIF1α and HIF2α) but decreased microvessel density in the lung cancer tumors. In contrast to lung cancer, the growth of tumor from HCT116 human colon cancer cells (colon cancer tumor) was a) significantly enhanced in the same hypoxia conditions, accompanied by b) no significant change in expression of Na + -K + ATPase α1, c) increased HIF1α expression (no HIF2α was detected) and d) increased microvessel density in the tumor tissues. This study demonstrated that long-term exposure to hypoxia repressed tumor progression of the lung cancer from A549 cells and that decreased expression of Na + -K + ATPase was involved in hypoxic

  17. Anterior cingulate cortex surface area relates to behavioral inhibition in adolescents with and without heavy prenatal alcohol exposure.

    Science.gov (United States)

    Migliorini, Robyn; Moore, Eileen M; Glass, Leila; Infante, M Alejandra; Tapert, Susan F; Jones, Kenneth Lyons; Mattson, Sarah N; Riley, Edward P

    2015-10-01

    Prenatal alcohol exposure is associated with behavioral disinhibition, yet the brain structure correlates of this deficit have not been determined with sufficient detail. We examined the hypothesis that the structure of the anterior cingulate cortex (ACC) relates to inhibition performance in youth with histories of heavy prenatal alcohol exposure (AE, n = 32) and non-exposed controls (CON, n = 21). Adolescents (12-17 years) underwent structural magnetic resonance imaging yielding measures of gray matter volume, surface area, and thickness across four ACC subregions. A subset of subjects were administered the NEPSY-II Inhibition subtest. MANCOVA was utilized to test for group differences in ACC and inhibition performance and multiple linear regression was used to probe ACC-inhibition relationships. ACC surface area was significantly smaller in AE, though this effect was primarily driven by reduced right caudal ACC (rcACC). AE also performed significantly worse on inhibition speed but not on inhibition accuracy. Regression analyses with the rcACC revealed a significant group × ACC interaction. A smaller rcACC surface area was associated with slower inhibition completion time for AE but was not significantly associated with inhibition in CON. After accounting for processing speed, smaller rcACC surface area was associated with worse (i.e., slower) inhibition regardless of group. Examining processing speed independently, a decrease in rcACC surface area was associated with faster processing speed for CON but not significantly associated with processing speed in AE. Results support the theory that caudal ACC may monitor reaction time in addition to inhibition and highlight the possibility of delayed ACC neurodevelopment in prenatal alcohol exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

    International Nuclear Information System (INIS)

    Lacorte, Livia M.; Rinaldi, Jaqueline C.; Justulin, Luis A.; Delella, Flávia K.; Moroz, Andrei; Felisbino, Sérgio L.

    2015-01-01

    Matrix metalloproteinases (MMPs) are zinc (Zn 2+ ) and calcium (Ca 2+ ) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd 2+ ) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd 2+ intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl 2 diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 μM or 2 mM cadmium chloride (CdCl 2 ) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl 2 intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd 2+ treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 μM and 2 mM of CdCl 2 , respectively, even in the presence of 10 mM of CaCl 2 within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its exposure. - Highlights: • Wistar rats were given

  19. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

    Energy Technology Data Exchange (ETDEWEB)

    Lacorte, Livia M.; Rinaldi, Jaqueline C.; Justulin, Luis A.; Delella, Flávia K. [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil); Moroz, Andrei [Univ Estadual Paulista – UNESP, School of Pharmaceutical Sciences, Department of Bioprocess and Biotechnology, Cell Culture Laboratory, Araraquara, SP (Brazil); Felisbino, Sérgio L., E-mail: felisbin@ibb.unesp.br [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil)

    2015-02-20

    exposure. - Highlights: • Wistar rats were given tap water or 15 ppm CdCl{sub 2} diluted in drinking water. • Ventral prostate, dorsal prostate, and testicles were tested for MMPs activity. • CdCl{sub 2} was also directly dissolved at the incubation buffer in another experiment. • Cadmium inhibited the activity of MMP2 and MMP9 in both experiments. • Cadmium contamination may deregulate the natural balance in the ECM turnover.

  20. Cigarette Smoke Exposure Inhibits Bacterial Killing via TFEB-Mediated Autophagy Impairment and Resulting Phagocytosis Defect

    Directory of Open Access Journals (Sweden)

    Garrett Pehote

    2017-01-01

    Full Text Available Introduction. Cigarette smoke (CS exposure is the leading risk factor for COPD-emphysema pathogenesis. A common characteristic of COPD is impaired phagocytosis that causes frequent exacerbations in patients leading to increased morbidity. However, the underlying mechanism is unclear. Hence, we investigated if CS exposure causes autophagy impairment as a mechanism for diminished bacterial clearance via phagocytosis by utilizing murine macrophages (RAW264.7 cells and Pseudomonas aeruginosa (PA01-GFP as an experimental model. Methods. Briefly, RAW cells were treated with cigarette smoke extract (CSE, chloroquine (autophagy inhibitor, TFEB-shRNA, CFTR(inh-172, and/or fisetin prior to bacterial infection for functional analysis. Results. Bacterial clearance of PA01-GFP was significantly impaired while its survival was promoted by CSE (p<0.01, autophagy inhibition (p<0.05; p<0.01, TFEB knockdown (p<0.01; p<0.001, and inhibition of CFTR function (p<0.001; p<0.01 in comparison to the control group(s that was significantly recovered by autophagy-inducing antioxidant drug, fisetin, treatment (p<0.05; p<0.01; and p<0.001. Moreover, investigations into other pharmacological properties of fisetin show that it has significant mucolytic and bactericidal activities (p<0.01; p<0.001, which warrants further investigation. Conclusions. Our data suggests that CS-mediated autophagy impairment as a critical mechanism involved in the resulting phagocytic defect, as well as the therapeutic potential of autophagy-inducing drugs in restoring is CS-impaired phagocytosis.

  1. Varying effects of calcium on the oxidation of palmitate and alpha-ketoglutarate in isolated rat liver mitochondria incubated in KCl-based and sucrose-based media.

    Science.gov (United States)

    Borrebaek, B; Dolva, K; Singh, B

    1984-01-01

    Isolated mitochondria from rat liver were incubated in the presence of [U-14C]palmitate, ATP, CoA, carnitine, EGTA (ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid) and varying amounts of calcium. When a KC1-based incubation medium was used, the oxidation of palmitate was inhibited when the concentration of free calcium was increased from about 0.1-10 microM. When a sucrose-based incubation medium was used, the basal rate of palmitate oxidation was about half of that observed with the KC1-medium and calcium had a stimulatory effect. With the KC1-medium the rate of oxygen consumption was inhibited by calcium with alpha-ketoglutarate as well as palmitate as the respiratory substrate. No inhibitory effect of calcium was observed with succinate or beta-hydroxybutyrate. With the KC1-medium and with alpha-ketoglutarate as the respiratory substrate, state 3 respiration but not state 4 respiration was inhibited by calcium. When the sucrose-medium was used, state 3 respiration was first inhibited by calcium, but this inhibition was gradually relieved and the respiratory rate finally became higher than it was before calcium addition.

  2. In Vitro Palmitate Treatment of Myotubes from Postmenopausal Women Leads to Ceramide Accumulation, Inflammation and Affected Insulin Signaling

    DEFF Research Database (Denmark)

    Abildgaard, Julie; Henstridge, Darren C; Pedersen, Anette Tønnes

    2014-01-01

    Menopause is associated with an increased incidence of insulin resistance and metabolic diseases. In a chronic palmitate treatment model, we investigated the role of skeletal muscle fatty acid exposure in relation to the metabolic deterioration observed with menopause. Human skeletal muscle......, post-myotubes showed a blunted insulin stimulated phosphorylation of AS160 in response to chronic palmitate treatment compared with pre-myotubes (p = 0.02). The increased intramyocellular ceramide content in the post-myotubes was associated with a significantly higher mRNA expression of Serine...... Palmitoyltransferase1 (SPT1) after one day of palmitate treatment (p = 0.03) in post-myotubes compared with pre-myotubes. Our findings indicate that post-myotubes are more prone to develop lipid accumulation and defective insulin signaling following chronic saturated fatty acid exposure as compared to pre-myotubes....

  3. Switching away from pipotiazine palmitate: a naturalistic study.

    Science.gov (United States)

    Mustafa, Feras Ali

    2017-01-01

    In March 2015, pipotiazine palmitate depot antipsychotic was globally withdrawn due to the shortage of its active ingredient. Thus, all patients receiving this medication had to be switched to an alternative antipsychotic drug. In this study we set to evaluate the process of switching away from pipotiazine palmitate within our clinical service, and its impact on hospitalization. Demographic and clinical data on patients who were receiving pipotiazine palmitate in Northamptonshire at the time of its withdrawal were anonymously extracted from their electronic records and analyzed using descriptive statistics. A total of 17 patients were switched away from pipotiazine palmitate at the time of its withdrawal, all of whom had a prior history of nonadherence with oral treatment. A total of 14 patients were switched to another depot antipsychotic drug, while three patients chose an oral alternative which they subsequently discontinued resulting in relapse and hospitalization. There was a five-fold increase in mean hospitalization among patients who completed a year after the switch. Switching away from pipotiazine palmitate was associated with significant clinical deterioration in patients who switched to an oral antipsychotic, whereas most patients who switched to another depot treatment maintained stability. Clinicians should exercise caution when switching patients with schizophrenia away from depot antipsychotic drugs, especially in cases of patients with a history of treatment nonadherence who prefer to switch to oral antipsychotics.

  4. Systemic treatment of seborrheic dermatitis with retinol palmitate

    Directory of Open Access Journals (Sweden)

    O. V. Kalinina

    2014-01-01

    Full Text Available The goal of the study. Evaluating of the effectiveness of treatment of men with a diagnosis «Seborrheic dermatitis of the scalp» by the system using of retinol palmitate. Material and methods. 36 patients every day for 2 months received overnight per os 200000 ME of retinol palmitate, and in the comparison group (39 people antiseborrheic shampoos have been used. The dynamics of severity of skin oiliness, pruritis, erythema, peeling, infiltration, excoriations has been evaluated in points. Before and after the treatment a histological and morphometric study of biopsy material from the affected areas has been carried.The terms of relapses have been set. Results. Retinol palmitate treatment efficiency - 91.7%, antiseborrheic shampoos - 84.6%. Along with the regression of symptoms of the disease in both groups after retinol palmitate treatment significantly declined oiliness of skin; the sizes of sebaceous glands acini and the presence of differentiated sebocytes, the squares of lymphocytic-macrophage clusters in the dermis, the number of keratinocytes with vacuolated cytoplasm have been reduced. Relapses of the disease during a year occured more rare - in 21 patients out of 32 (in the comparison group- in 25 out of 31 and at a later date (in the first 3 months in 2 patients out of 32, in comparison group in 10 out of 31. Identified effects were due to the action of retinol palmitate on the morphogenesis of the sebaceous glands.

  5. Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway.

    Directory of Open Access Journals (Sweden)

    Nathaniel Holcomb

    Full Text Available Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC, a surrogate for tobacco smoke, on the NER pathway in two different human lung cell lines; IMR-90 lung fibroblasts and BEAS-2B bronchial epithelial cells. To measure NER, we employed a slot-blot assay to quantify the introduction and removal of UV light-induced 6-4 photoproducts and cyclobutane pyrimidine dimers. We find a dose-dependent inhibition of 6-4 photoproduct repair in both cell lines treated with CSC. Additionally, the impact of CSC on the abundance of various NER proteins and their respective RNAs was investigated. The abundance of XPC protein, which is required for functional NER, is significantly reduced by treatment with CSC while the abundance of XPA protein, also required for NER, is unaffected. Both XPC and XPA RNA levels are modestly reduced by CSC treatment. Finally, treatment of cells with MG-132 abrogates the reduction in the abundance of XPC protein produced by treatment with CSC, suggesting that CSC enhances proteasome-dependent turnover of the protein that is mediated by ubiquitination. Together, these findings indicate that tobacco smoke can inhibit the same DNA repair pathway that is also essential for the removal of some of the carcinogenic DNA damage introduced by smoke itself, increasing the DNA damage burden of cells exposed to tobacco smoke.

  6. Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition.

    Science.gov (United States)

    Falgreen, Steffen; Laursen, Maria Bach; Bødker, Julie Støve; Kjeldsen, Malene Krag; Schmitz, Alexander; Nyegaard, Mette; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

    2014-06-05

    In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves' dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological

  7. Hibiscus sabdariffa polyphenols prevent palmitate-induced renal epithelial mesenchymal transition by alleviating dipeptidyl peptidase-4-mediated insulin resistance.

    Science.gov (United States)

    Huang, Chien-Ning; Wang, Chau-Jong; Yang, Yi-Sun; Lin, Chih-Li; Peng, Chiung-Huei

    2016-01-01

    Diabetic nephropathy has a significant socioeconomic impact, but its mechanism is unclear and needs to be examined. Hibiscus sabdariffa polyphenols (HPE) inhibited high glucose-induced angiotensin II receptor-1 (AT-1), thus attenuating renal epithelial mesenchymal transition (EMT). Recently, we reported HPE inhibited dipeptidyl-peptidase-4 (DPP-4, the enzyme degrades type 1 glucagon-like peptide (GLP-1)), which mediated insulin resistance signals leading to EMT. Since free fatty acids can realistically bring about insulin resistance, using the palmitate-stimulated cell model in contrast with type 2 diabetic rats, in this study we examined if insulin resistance causes renal EMT, and the preventive effect of HPE. Our findings reveal that palmitate hindered 30% of glucose uptake. Treatment with 1 mg mL(-1) of HPE and the DPP-4 inhibitor linagliptin completely recovered insulin sensitivity and palmitate-induced signal cascades. HPE inhibited DPP-4 activity without altering the levels of DPP-4 and the GLP-1 receptor (GLP-1R). HPE decreased palmitate-induced phosphorylation of Ser307 of insulin receptor substrate-1 (pIRS-1 (S307)), AT-1 and vimentin, while increasing phosphorylation of phosphatidylinositol 3-kinase (pPI3K). IRS-1 knockdown revealed its essential role in mediating downstream AT-1 and EMT. In type 2 diabetic rats, it suggests that HPE concomitantly decreased the protein levels of DPP-4, AT-1, vimentin, and fibronectin, but reversed the in vivo compensation of GLP-1R. In conclusion, HPE improves insulin sensitivity by attenuating DPP-4 and the downstream signals, thus decreasing AT-1-mediated tubular-interstitial EMT. HPE could be an adjuvant to prevent diabetic nephropathy.

  8. Motor deficits, impaired response inhibition, and blunted response to methylphenidate following neonatal exposure to decabromodiphenyl ether.

    Science.gov (United States)

    Markowski, Vincent P; Miller-Rhodes, Patrick; Cheung, Randy; Goeke, Calla; Pecoraro, Vincent; Cohen, Gideon; Small, Deena J

    2017-09-01

    Decabromodiphenyl ether (decaBDE) is an applied brominated flame retardant that is widely-used in electronic equipment. After decades of use, decaBDE and other members of its polybrominated diphenyl ether class have become globally-distributed environmental contaminants that can be measured in the atmosphere, water bodies, wildlife, food staples and human breastmilk. Although it has been banned in Europe and voluntarily withdrawn from the U.S. market, it is still used in Asian countries. Evidence from epidemiological and animal studies indicate that decaBDE exposure targets brain development and produces behavioral impairments. The current study examined an array of motor and learning behaviors in a C57BL6/J mouse model to determine the breadth of the developmental neurotoxicity produced by decaBDE. Mouse pups were given a single daily oral dose of 0 or 20mg/kg decaBDE from postnatal day 1 to 21 and were tested in adulthood. Exposed male mice had impaired forelimb grip strength, altered motor output in a circadian wheel-running procedure, increased response errors during an operant differential reinforcement of low rates (DRL) procedure and a blunted response to an acute methylphenidate challenge administered before DRL testing. With the exception of altered wheel-running output, exposed females were not affected. Neither sex had altered somatic growth, motor coordination impairments on the Rotarod, gross learning deficits during operant lever-press acquisition, or impaired food motivation. The overall pattern of effects suggests that males are more sensitive to developmental decaBDE exposure, especially when performing behaviors that require effortful motor output or when learning tasks that require sufficient response inhibition for their successful completion. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Practical guidelines on the use of paliperidone palmitate in schizophrenia.

    Science.gov (United States)

    Newton, Richard; Hustig, Harry; Lakshmana, Raju; Lee, Joseph; Motamarri, Balaji; Norrie, Peter; Parker, Robert; Schreiner, Andreas

    2012-04-01

    Paliperidone palmitate is an atypical long-acting injectable (LAI) antipsychotic that has been approved for use in the US, EU, Australia and numerous other countries for acute and maintenance therapy of schizophrenia. LAI antipsychotics are often viewed as a 'last-resort' treatment for difficult-to-treat patients, however this article considers their role more broadly in the management of partial or non-adherence in schizophrenia. A search of MedLine, CTR and PsychInfo was conducted to identify relevant publications and clinical trials (search term 'paliperidone palmitate', up to December 2010). The findings were discussed in a number of teleconferences and the manuscript was finalized with a face-to-face meeting of the authors group. Relapse prevention in schizophrenia requires a comprehensive approach to treatment, which includes antipsychotic medication and psychosocial measures as well as family and/or carer involvement. Good symptom control and the interconnected issue of treatment adherence are arguably the most crucial factors for success. Carer and patient feedback should be carefully considered. Negotiation about commencing LAI therapy done early in course of disease is easier than many clinicians believe, although it is not often attempted in practice. Paliperidone palmitate is useful in both the acute and maintenance phases of treatment. A case-based approach is presented to suggest various opportunities where use of paliperidone palmitate could be considered within the disease course of schizophrenia. Paliperidone palmitate offers some advantages in terms of tolerability, simplicity of treatment initiation and long duration between injections. The consensus of the authors is that rather than reserving paliperidone palmitate for use in difficult-to-treat or refractory patients, it could be used to promote adherence and prevent relapse earlier in the course of the illness.

  10. Effects of Ursodeoxycholic Acid and Insulin on Palmitate-Induced ROS Production and Down-Regulation of PI3K/Akt Signaling Activity.

    Science.gov (United States)

    Yokoyama, Kunihiro; Tatsumi, Yasuaki; Hayashi, Kazuhiko; Goto, Hidemi; Ishikawa, Tetsuya; Wakusawa, Shinya

    2017-01-01

    In obese and diabetic patients, plasma free fatty acid (FFA) levels are often elevated and may play a causal role in insulin resistance and reactive oxygen species (ROS) production. We have previously shown that ursodeoxycholic acid (UDCA) has antioxidative activity through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling-mediated glutathione production. In this study, we investigated the effects of UDCA on insulin response by analyzing intracellular ROS and the activation of the PI3K/Akt signaling pathway in HepG2 cells treated with palmitate. The level of ROS was quantified using 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCFDA), and the activation of the PI3K/Akt signaling pathway was determined by Western blotting assay using appropriate antibodies. The intracellular ROS levels were increased by palmitate but were reduced by treatment with UDCA and insulin. Furthermore, insulin significantly stimulated the phosphorylation of Akt. When the cells were pre-treated with palmitate, insulin-induced Akt-phosphorylation was markedly inhibited. However, when the cells were treated with palmitate and UDCA, the effects of insulin were partially restored. UDCA may have protective effects against palmitate-induced decreases in responsiveness to insulin.

  11. Enhanced Eyeblink Conditioning in Behaviorally Inhibited Individuals is Disrupted by Proactive Interference Following US Alone Pre-exposures.

    Science.gov (United States)

    Allen, Michael Todd; Miller, Daniel P

    2016-01-01

    Anxiety vulnerable individuals exhibit enhanced acquisition of conditioned eyeblinks as well as enhanced proactive interference from conditioned stimulus (CS) or unconditioned stimulus (US) alone pre-exposures (Holloway et al., 2012). US alone pre-exposures disrupt subsequent conditioned response (CR) acquisition to CS-US paired trials as compared to context pre-exposure controls. While Holloway et al. (2012) reported enhanced acquisition in high trait anxiety individuals in the context condition, anxiety vulnerability effects were not reported for the US alone pre-exposure group. It appears from the published data that there were no differences between high and low anxiety individuals in the US alone condition. In the work reported here, we sought to extend the findings of enhanced proactive interference with US alone pre-exposures to determine if the enhanced conditioning was disrupted by proactive interference procedures. We also were interested in the spontaneous eyeblinks during the pre-exposure phase of training. We categorized individuals as anxiety vulnerability or non-vulnerable individuals based scores on the Adult Measure of Behavioral Inhibition (AMBI). Sixty-six participants received 60 trials consisting of 30 US alone or context alone pre-exposures followed by 30 CS-US trials. US alone pre-exposures not only disrupted CR acquisition overall, but behaviorally inhibited (BI) individuals exhibited enhanced proactive interference as compared to non-inhibited (NI) individuals. In addition, US alone pre-exposures disrupted the enhanced acquisition observed in BI individuals as compared to NI individuals following context alone pre-exposures. Differences were also found in rates of spontaneous eyeblinks between BI and NI individuals during context pre-exposure. Our findings will be discussed in the light of the neural substrates of eyeblink conditioning as well as possible factors such as hypervigilance in the amygdala and hippocampal systems, and possible

  12. Defective [U-14 C] palmitic acid oxidation in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Carroll, J.E.; Norris, B.J.; Brooke, M.H.

    1985-01-01

    Compared with normal skeletal muscle, muscle from patients with Duchenne dystrophy had decreased [U-14 C] palmitic acid oxidation. [1-14 C] palmitic acid oxidation was normal. These results may indicate a defect in intramitochondrial fatty acid oxidation

  13. Defective (U-14 C) palmitic acid oxidation in Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, J.E.; Norris, B.J.; Brooke, M.H.

    1985-01-01

    Compared with normal skeletal muscle, muscle from patients with Duchenne dystrophy had decreased (U-14 C) palmitic acid oxidation. (1-14 C) palmitic acid oxidation was normal. These results may indicate a defect in intramitochondrial fatty acid oxidation.

  14. Biosysthesis of Corn Starch Palmitate by Lipase Novozym 435

    Directory of Open Access Journals (Sweden)

    Kai Lin

    2012-06-01

    Full Text Available Esterification of starch was carried out to expand the usefulness of starch for a myriad of industrial applications. Lipase B from Candida antarctica, immobilized on macroporous acrylic resin (Novozym 435, was used for starch esterification in two reaction systems: micro-solvent system and solvent-free system. The esterification of corn starch with palmitic acid in the solvent-free system and micro-solvent system gave a degree of substitution (DS of 1.04 and 0.0072 respectively. Esterification of corn starch with palmitic acid was confirmed by UV spectroscopy and IR spectroscopy. The results of emulsifying property analysis showed that the starch palmitate with higher DS contributes to the higher emulsifying property (67.6% and emulsion stability (79.6% than the native starch (5.3% and 3.9%. Modified starch obtained by esterification that possesses emulsifying properties and has long chain fatty acids, like palmitic acid, has been widely used in the food, pharmaceutical and biomedical applications industries.

  15. Enzymatic formation of hexadecenoic acid from palmitic acid

    International Nuclear Information System (INIS)

    Nakano, Masao; Fujino, Yasuhiko

    1975-01-01

    Desaturation of palmitic acid was investigated in an enzyme system prepared from rat liver. 2-trans-Hexadecenoic acid as well as 9-cis-gexadecenoic acid (palmitoleic acid) were found to be formed as monoenoic acid in this system. (author)

  16. Sensitization of vascular smooth muscle cell to TNF-α-mediated death in the presence of palmitate

    International Nuclear Information System (INIS)

    Rho, Mun-Chual; Ah Lee, Kyeong; Mi Kim, Sun; Sik Lee, Chang; Jeong Jang, Min; Kook Kim, Young; Sun Lee, Hyun; Hyun Choi, Yung; Yong Rhim, Byung; Kim, Koanhoi

    2007-01-01

    Saturated free fatty acids (FFAs), including palmitate, can activate the intrinsic death pathway in cells. However, the relationship between FFAs and receptor-mediated death pathway is still unknown. In this study, we have investigated whether FFAs are able to trigger receptor-mediated death. In addition, to clarify the mechanisms responsible for the activation, we examined the biochemical changes in dying vascular smooth muscle cell (VSMC) and the effects of various molecules to the receptor-mediated VSMC death. Tumor necrosis factor (TNF)-α-mediated VSMC death occurred in the presence of sub-cytotoxic concentration of palmitate as determined by assessing viability and DNA degradation, while the cytokine did not influence VSMC viability in the presence of oleate. The VSMC death was inhibited by the gene transfer of a dominant-negative Fas-associated death domain-containing protein and the baculovirus p35, but not by the bcl-xL or the c-Jun N-terminal kinase (JNK) binding domain of JNK-interacting protein-1, in tests utilizing recombinant adenoviruses. The VSMC death was also inhibited by a neutralizing anti-TNF receptor 1 antibody, the caspase inhibitor z-VAD, and the cathepsin B inhibitor CA074, a finding indicative of the role of both caspases and cathepsin B in this process. Consistent with this finding, caspase-3 activation and an increase in cytosolic cathepsin B activity were detected in the dying VSMC. Palmitate inhibited an increase of TNF-α-mediated nuclear factor kappa B (NF-κB) activity, the survival pathway activated by the cytokine, by hindering the translocation of the NF-κB subunit of p65 from the cytosol into the nucleus. The gene transfer of inhibitor of NF-κB predisposed VSMC to palmitate-induced cell death. To the best of our knowledge, this study is the first report to demonstrate the activation of TNF-α-mediated cell death in the presence of palmitate. The current study proposes that FFAs would take part in deleterious vascular

  17. SIRT1 attenuates palmitate-induced endoplasmic reticulum stress and insulin resistance in HepG2 cells via induction of oxygen-regulated protein 150

    Science.gov (United States)

    Jung, T.W.; Lee, K.T.; Lee, M.W.; Ka, K.H.

    2012-01-01

    Endoplasmic reticulum (ER) stress has been implicated in the pathology of type 2 diabetes mellitus (T2DM). Although SIRT1 has a therapeutic effect on T2DM, the mechanisms by which SIRT1 ameliorates insulin resistance (IR) remain unclear. In this study, we investigated the impact of SIRT1 on palmitate-induced ER stress in HepG2 cells and its underlying signal pathway. Treatment with resveratrol, a SIRT1 activator significantly inhibited palmitate-induced ER stress, leading to the protection against palmitate-induced ER stress and insulin resistance. Resveratrol and SIRT1 overexpression induced the expression of oxygen-regulated protein (ORP) 150 in HepG2 cells. Forkhead box O1 (FOXO1) was involved in the regulation of ORP150 expression because suppression of FOXO1 inhibited the induction of ORP150 by SIRT1. Our results indicate a novel mechanism by which SIRT1 regulates ER stress by overexpression of ORP150, and suggest that SIRT1 ameliorates palmitate-induced insulin resistance in HepG2 cells via regulation of ER stress.

  18. Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

    International Nuclear Information System (INIS)

    Thomas, G.; Pepin, D.; Loriette, C.; Chambaz, J.; Bereziat, G.; Vidal, M.; Apparu, M.; Coornaert, S.

    1989-01-01

    The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be β oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be β oxidized only after an initial α oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me 2 ) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me 2 ) which cannot be β oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1- 14 C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethyl-branched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[ 125 I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1- 14 C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched palmitic acids were found in hepatocyte or secreted phospholipids as compared with palmitic acid. (orig.)

  19. Growth inhibition and recovery of Lemna gibba after pulse exposure to sulfonylurea herbicides

    DEFF Research Database (Denmark)

    Rosenkrantz, Rikke Tjørnhøj; Baun, Anders; Kusk, Kresten Ole

    2013-01-01

    The exposure of non-target aquatic organisms to pesticides often happens as short-term, high exposure events (pulses) and effects of these must be addressed in the current regulation in the EU. It is, however, questionable whether the effects of pulse exposures are adequately covered by the stand...... tests. The approach of this study enables experimentally based comparisons between observations of effects between the two exposure regimes. We propose that results obtained in this way be applied in effect assessments for intermittent releases....

  20. High Beta-Palmitate Fat Controls the Intestinal Inflammatory Response and Limits Intestinal Damage in Mucin Muc2 Deficient Mice

    NARCIS (Netherlands)

    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

    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

  1. High Beta-Palmitate Fat Controls the Intestinal Inflammatory Response and Limits Intestinal Damage in Mucin Muc2 Deficient Mice

    NARCIS (Netherlands)

    P. Lu (Peng); F. Bar-Yoseph (Fabiana); L. Levi (Liora); Y. Lifshitz (Yael); J. Witte-Bouma (Janneke); A.C.J.M. de Bruijn (Adrianus); A.M. Korteland-van Male (Anita); J.B. van Goudoever (Hans); I.B. Renes (Ingrid)

    2013-01-01

    textabstractBackground: 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

  2. A case of paliperidone-palmitate-induced tardive dyskinesia.

    LENUS (Irish Health Repository)

    Lally, John

    2012-06-13

    OBJECTIVES: This is one of the first cases reported in the literature of paliperidone-palmitate-induced prolonged dyskinesia. METHOD: Case report. RESULTS: We report the case of a 49-year-old woman with paranoid schizophrenia who developed orofacial dyskinesia some 4 months after the commencement of paliperidone long-acting injection. CONCLUSION: This case serves as a clinical reminder that dyskinesia can occur with all antipsychotic medications.

  3. Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin Uptake by Pancreatic Acinar Cells.

    Directory of Open Access Journals (Sweden)

    Padmanabhan Srinivasan

    Full Text Available Thiamin (vitamin B1, a member of the water-soluble family of vitamins, is essential for normal cellular functions; its deficiency results in oxidative stress and mitochondrial dysfunction. Pancreatic acinar cells (PAC obtain thiamin from the circulation using a specific carrier-mediated process mediated by both thiamin transporters -1 and -2 (THTR-1 and THTR-2; encoded by the SLC19A2 and SLC19A3 genes, respectively. The aim of the current study was to examine the effect of chronic exposure of mouse PAC in vivo and human PAC in vitro to nicotine (a major component of cigarette smoke that has been implicated in pancreatic diseases on thiamin uptake and to delineate the mechanism involved. The results showed that chronic exposure of mice to nicotine significantly inhibits thiamin uptake in murine PAC, and that this inhibition is associated with a marked decrease in expression of THTR-1 and THTR-2 at the protein, mRNA and hnRNAs level. Furthermore, expression of the important thiamin-metabolizing enzyme, thiamin pyrophosphokinase (TPKase, was significantly reduced in PAC of mice exposed to nicotine. Similarly, chronic exposure of cultured human PAC to nicotine (0.5 μM, 48 h significantly inhibited thiamin uptake, which was also associated with a decrease in expression of THTR-1 and THTR-2 proteins and mRNAs. This study demonstrates that chronic exposure of PAC to nicotine impairs the physiology and the molecular biology of the thiamin uptake process. Furthermore, the study suggests that the effect is, in part, mediated through transcriptional mechanism(s affecting the SLC19A2 and SLC19A3 genes.

  4. Prolonged particulate chromate exposure does not inhibit homologous recombination repair in North Atlantic right whale (Eubalaena glacialis) lung cells.

    Science.gov (United States)

    Browning, Cynthia L; Wise, Catherine F; Wise, John Pierce

    2017-09-15

    Chromosome instability is a common feature of cancers that forms due to the misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a high fidelity DNA repair pathway that utilizes a homologous DNA sequence to accurately repair such damage and protect the genome. Prolonged exposure (>72h) to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits HR repair, resulting in increased chromosome instability in human cells. Comparative studies have shown acute Cr(VI) exposure induces less chromosome damage in whale cells than human cells, suggesting investigating the effect of this carcinogen in other species may inform efforts to prevent Cr(VI)-induced chromosome instability. Thus, the goal of this study was to determine the effect of prolonged Cr(VI) exposure on HR repair and clastogenesis in North Atlantic right whale (Eubalaena glacialis) lung cells. We show particulate Cr(VI) induces HR repair activity after both acute (24h) and prolonged (120h) exposure in North Atlantic right whale cells. Although the RAD51 response was lower following prolonged Cr(VI) exposure compared to acute exposure, the response was sufficient for HR repair to occur. In accordance with active HR repair, no increase in Cr(VI)-induced clastogenesis was observed with increased exposure time. These results suggest prolonged Cr(VI) exposure affects HR repair and genomic stability differently in whale and human lung cells. Future investigation of the differences in how human and whale cells respond to chemical carcinogens may provide valuable insight into mechanisms of preventing chemical carcinogenesis. Copyright © 2017. Published by Elsevier Inc.

  5. Deficits in response inhibition correlate with oculomotor control in children with fetal alcohol spectrum disorder and prenatal alcohol exposure.

    Science.gov (United States)

    Paolozza, Angelina; Rasmussen, Carmen; Pei, Jacqueline; Hanlon-Dearman, Ana; Nikkel, Sarah M; Andrew, Gail; McFarlane, Audrey; Samdup, Dawa; Reynolds, James N

    2014-02-01

    Children with fetal alcohol spectrum disorder (FASD) or prenatal alcohol exposure (PAE) frequently exhibit impairment on tasks measuring inhibition. The objective of this study was to determine if a performance-based relationship exists between psychometric tests and eye movement tasks in children with FASD. Participants for this dataset were aged 5-17 years and included those diagnosed with an FASD (n=72), those with PAE but no clinical FASD diagnosis (n=21), and typically developing controls (n=139). Participants completed a neurobehavioral test battery, which included the NEPSY-II subtests of auditory attention, response set, and inhibition. Each participant completed a series of saccadic eye movement tasks, which included the antisaccade and memory-guided tasks. Both the FASD and the PAE groups performed worse than controls on the subtest measures of attention and inhibition. Compared with controls, the FASD group made more errors on the antisaccade and memory-guided tasks. Among the combined FASD/PAE group, inhibition and switching errors were negatively correlated with direction errors on the antisaccade task but not on the memory-guided task. There were no significant correlations in the control group. These data suggests that response inhibition deficits in children with FASD/PAE are associated with difficulty controlling saccadic eye movements which may point to overlapping brain regions damaged by prenatal alcohol exposure. The results of this study demonstrate that eye movement control tasks directly relate to outcome measures obtained with psychometric tests that are used during FASD diagnosis, and may therefore help with early identification of children who would benefit from a multidisciplinary diagnostic assessment. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Exposure to waterborne Cu inhibits cutaneous Na⁺ uptake in post-hatch larval rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Zimmer, Alex M; Brauner, Colin J; Wood, Chris M

    2014-05-01

    In freshwater rainbow trout (Oncorhynchus mykiss), two common responses to acute waterborne copper (Cu) exposure are reductions in ammonia excretion and Na(+) uptake at the gills, with the latter representing the likely lethal mechanism of action for Cu in adult fish. Larval fish, however, lack a functional gill following hatch and rely predominantly on cutaneous exchange, yet represent the most Cu-sensitive life stage. It is not known if Cu toxicity in larval fish occurs via the skin or gills. The present study utilized divided chambers to assess cutaneous and branchial Cu toxicity over larval development, using disruptions in ammonia excretion (Jamm) and Na(+) uptake (Jin(Na)) as toxicological endpoints. Early in development (early; 3 days post-hatch; dph), approximately 95% of Jamm and 78% of Jin(Na) occurred cutaneously, while in the late developmental stage (late; 25 dph), the gills were the dominant site of exchange (83 and 87% of Jamm and Jin(Na), respectively). Exposure to 50 μg/l Cu led to a 49% inhibition of Jamm in the late developmental stage only, while in the early and middle developmental (mid; 17 dph) stages, Cu had no effect on Jamm. Jin(Na), however, was significantly inhibited by Cu exposure at the early (53% reduction) and late (47% reduction) stages. Inhibition at the early stage of development was mediated by a reduction in cutaneous uptake, representing the first evidence of cutaneous metal toxicity in an intact aquatic organism. The inhibitions of both Jamm and Jin(Na) in the late developmental stage occurred via a reduction in branchial exchange only. The differential responses of the skin and gills to Cu exposure suggest that the mechanisms of Jamm and Jin(Na) and/or Cu toxicity differ between these tissues. Exposure to 20μg/l Cu revealed that Jamm is the more Cu-sensitive process. The results presented here have important implications in predicting metal toxicity in larval fish. The Biotic Ligand Model (BLM) is currently used to predict

  7. Inhibition and recovery of DNA synthesis in human cells after exposure to ultraviolet light

    International Nuclear Information System (INIS)

    Painter, R.B.

    1985-01-01

    The inhibition of DNA synthesis in normal human cells by UV is a complex function of fluence because it has several causes. At low fluences, inhibition of replicon initiation is most important. This is made clear by the fact that it occurs to a lesser degree in cells from patients with ataxia telangiectasia (AT). Assuming that only leading strand synthesis is blocked by UV-induced lesions, single lesions between replicons in parental strands for leading strand synthesis inhibit DNA synthesis by acting as temporary blocks until they are replicated by extension of the lagging strand of the adjacent replicon. A more severe inhibition occurs when two lesions are induced between adjacent growing replicons, because one in four possible configurations may result in a long-lived unreplicated region (LLUR). In the absence of excision repair, these may eventually be replicated by activation of an otherwise unused origin within the LLUR. The frequency of LLURs increases steeply with fluence. Activation of normally unused origins to replicate LLURs may facilitate recovery from inhibition of DNA synthesis, but repair of lesions is probably more important. In excision-repair-defective cells, an LLUR without an origin to initiate its replication may be a lethal lesion. (orig.)

  8. Inhibition of vicariously learned fear in children using positive modeling and prior exposure.

    Science.gov (United States)

    Askew, Chris; Reynolds, Gemma; Fielding-Smith, Sarah; Field, Andy P

    2016-02-01

    One of the challenges to conditioning models of fear acquisition is to explain how different individuals can experience similar learning events and only some of them subsequently develop fear. Understanding factors moderating the impact of learning events on fear acquisition is key to understanding the etiology and prevention of fear in childhood. This study investigates these moderators in the context of vicarious (observational) learning. Two experiments tested predictions that the acquisition or inhibition of fear via vicarious learning is driven by associative learning mechanisms similar to direct conditioning. In Experiment 1, 3 groups of children aged 7 to 9 years received 1 of 3 inhibitive information interventions-psychoeducation, factual information, or no information (control)-prior to taking part in a vicarious fear learning procedure. In Experiment 2, 3 groups of children aged 7 to 10 years received 1 of 3 observational learning interventions-positive modeling (immunization), observational familiarity (latent inhibition), or no prevention (control)-before vicarious fear learning. Results indicated that observationally delivered manipulations inhibited vicarious fear learning, while preventions presented via written information did not. These findings confirm that vicarious learning shares some of the characteristics of direct conditioning and can explain why not all individuals will develop fear following a vicarious learning event. They also suggest that the modality of inhibitive learning is important and should match the fear learning pathway for increased chances of inhibition. Finally, the results demonstrate that positive modeling is likely to be a particularly effective method for preventing fear-related observational learning in children. (c) 2016 APA, all rights reserved).

  9. Cellular recovery from exposure to sub-optimal concentrations of AB toxins that inhibit protein synthesis

    Science.gov (United States)

    Shiga toxin 1, exotoxin A, diphtheria toxin and ricin are all AB-type protein toxins that act within the host cytosol to kill the host cell through a pathway involving the inhibition of protein synthesis. It is thought that a single molecule of cytosolic toxin is sufficient to kill the host cell. In...

  10. The effect of chronic exposure to fatty acids

    DEFF Research Database (Denmark)

    Xiao, J.; Gregersen, S.; Kruhøffer, Mogens

    2001-01-01

    Fatty acids affect insulin secretion of pancreatic beta-cells. Investigating gene expression profiles may help to characterize the underlying mechanism. INS-1 cells were cultured with palmitate (0, 50, and 200 microM) for up to 44 d. Insulin secretion and expressions of 8740 genes were studied. We...... 44, respectively. Genes involved in fatty acid oxidation were up-regulated, whereas those involved in glycolysis were down-regulated with 200 microM palmitate. A suppression of insulin receptor and insulin receptor substate-2 gene expression was found on d 44 in cells cultured at 200 microM palmitate....... In conclusion, chronic exposure to low palmitate alters insulin secretion as well as gene expression. The number of genes that changed expression was palmitate dose and exposure time dependent. Randle's fatty acid-glucose cycle seems to be operative on the gene transcription level. A modification of expression...

  11. Inhibition of murine splenic B lymphocyte activation following oral exposure to 7,12-dimethylbenz(a)anthracene (DMBA)

    International Nuclear Information System (INIS)

    Davis, D.P.; Burchiel, S.W.; Montano, R.M.; Seamer, L.C.

    1991-01-01

    Previous results from this laboratory have demonstrated that oral exposure of B6C3F1 mice to DMBA inhibited mitogen-stimulated lymphocyte activation in cells recovered from several lymphoid organs. These studies showed that both LPS and PHA-stimulated lymphocyte proliferation and PHA-induced Ca +2 mobilization were significantly inhibited by DMBA exposure, supporting the hypothesis that DMBA inhibits early events associated with lymphocyte activation. The purpose of the current studies was to test this hypothesis directly for B cell activation. B6C3F1 mice were treated with 0, 1.0, or 10 mg/kg/day doses of DMBA for 14 days (total cumulative doses of 0, 14, or 140 mg/kg). B lymphocyte populations were then selected on the flow cytometer by direct positive staining of spleen cells with phycoerythrin-labeled anti-Ly5 (B lymphocyte marker) antibodies. Ca +2 mobilization studies were performed using affinity-purified goat anti-mouse IgD antibodies as the stimulant and Indo-1 as the intracellular Ca +2 indicator. Cell proliferation studies were also performed using 3 H-thymidine and insoluble anti-IgD antibodies. Anti-IgD stimulated Ca +2 mobilization was significantly reduced at the 140 mg/kg dose of DMBA. A statistically significant decrease in anti-IgD stimulated B lymphocyte proliferation at the 14 mg/kg and 140 mg/kg doses of DMBA was found. These results suggest that B lymphocytes may be important targets for DMBA-mediated immunosuppression

  12. DNA Topoisomerase-I Inhibition due to Exposure to X-Rays

    International Nuclear Information System (INIS)

    Daudee, R.; Gonen, R.; German, U.; Orion, I.; Priel, E.

    2014-01-01

    In events such as radiological terrorism, accidents involving radioactive materials and occupational exposures, there is a great need to identify exposures to relatively low radiation levels. In many situations, the evaluation of radiation doses is not possible using physical dosimeters as they are not worn, and it is desirable to achieve this based on sensitive biomarkers (1, 2, 3). DNA Topoisomerase-I (Topo-I) is an essential nuclear enzyme that is responsible for the topological state of the DNA. The enzyme is involved in a variety of DNA transactions, including replication, transcription, recombination and DNA repair (4,5). The aim of the present work was to investigate the influence of X-ray radiation on the catalytic activity of this enzyme, and to evaluate its applicability as a biological dosimeter

  13. Exposure to polystyrene nanoplastic leads to inhibition of anaerobic digestion system.

    Science.gov (United States)

    Fu, Shan-Fei; Ding, Jian-Nan; Zhang, Yun; Li, Yi-Fei; Zhu, Rong; Yuan, Xian-Zheng; Zou, Hua

    2018-06-01

    In this study, impacts of nanoplastic on the pure and mixed anaerobic digestion systems were investigated. Results showed the growth and metabolism of Acetobacteroides hydrogenigenes were partly inhibited by nanoplastic existed in the pure anaerobic digestion system. The anaerobic digestion of sewage sludge was also obviously inhibited by nanoplastic existed in the mixed anaerobic digestion system. Both the methane yield and methane production rate of the mixed anaerobic digestion system showed negative correlation with the nanoplastic concentration. Compared with anaerobic digestion system without nanoplastic, methane yield and maximum daily methane yield at the nanoplastic concentration of 0.2g/L decreased for 14.4% and 40.7%, respectively. In addition, the start-up of mixed anaerobic digestion system was prolonged by addition of nanoplastic. Microbial community structure analysis indicated the microbial community structures were also affected by nanoplastic existed in the system. At the nanoplastic concentration of 0.2g/L, the relative abundances of family Cloacamonaceae, Porphyromonadaceae, Anaerolinaceae and Gracilibacteraceae decreased partly. Conversely, the relative abundances of family Anaerolinaceae, Clostridiaceae, Geobacteraceae, Dethiosulfovibrionaceae and Desulfobulbaceae improved partly. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Extremely weak magnetic field exposure may inhibit hippocampal neurogenesis of Sprague Dawley rats

    Science.gov (United States)

    Zhang, B.; Tian, L.; Cai, Y.; Xu, H.; Pan, Y.

    2016-12-01

    Hippocampal neurogenesis occurs throughout life in mammals brains and can be influenced by animals' age as well as environmental factors. Lines of evidences have shown that the magnetic field is an important physics environmental factor influencing many animals' growth and development, and extremely weak magnetic field exposures have been proved having serious adverse effects on the metabolism and behaviors in some animals, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we experimentally examined the extremely weak magnetic field effects on neurogenesis of the dentate gyrus (DG) of hippocampus of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, an extremely weak magnetic field (≤ 0.5μT) and the geomagnetic fields (strength 31-58μT) as controls. Thirty-two SD rats (3-weeks old) were used in this study. New cell survival in hippocampus was assessed at 0, 14, 28, and 42 days after a 7-day intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Meanwhile, the amounts of immature neurons and mature neurons which are both related to hippocampal neurogenesis, as documented by labeling with doublecortin (DCX) and neuron (NeuN), respectively, were also analyzed at 0, 14, 28, and 42 days. Compared with geomagnetic field exposure groups, numbers of BrdU-, DCX-positive cells of DG of hippocampus in tested rats reduces monotonously and more rapidly after 14 days, and NeuN-positive cells significantly decreases after 28days when exposed in the extremely weak magnetic field condition. Our data suggest that the exposure to an extremely weak magnetic field may suppress the neurogenesis in DG of SD rats.

  15. Cigarette smoke exposure inhibits extracellular MMP-2 (gelatinase A activity in human lung fibroblasts

    Directory of Open Access Journals (Sweden)

    Cappello Francesco

    2007-03-01

    Full Text Available Abstract Background Exposure to cigarette smoke is considered a major risk factor for the development of lung diseases, since its causative role has been assessed in the induction and maintenance of an inflamed state in the airways. Lung fibroblasts can contribute to these processes, due to their ability to produce proinflammatory chemotactic molecules and extracellular matrix remodelling proteinases. Among proteolytic enzymes, gelatinases A and B have been studied for their role in tissue breakdown and mobilisation of matrix-derived signalling molecules. Multiple reports linked gelatinase deregulation and overexpression to the development of inflammatory chronic lung diseases such as COPD. Methods In this study we aimed to determine variations in the gelatinolytic pattern of human lung fibroblasts (HFL-1 cell line exposed to cigarette smoke extract (CSE. Gelatinolytic activity levels were determined by using gelatin zymography for the in-gel detection of the enzymes (proenzyme and activated forms, and the subsequent semi-quantitative densitometric evaluation of lytic bands. Expression of gelatinases was evaluated also by RT-PCR, zymography of the cell lysates and by western blotting. Results CSE exposure at the doses used (1–10% did not exert any significant cytotoxic effects on fibroblasts. Zymographic analysis showed that CSE exposure resulted in a linear decrease of the activity of gelatinase A. Control experiments allowed excluding a direct inhibitory effect of CSE on gelatinases. Zymography of cell lysates confirmed the expression of MMP-2 in all conditions. Semi-quantitative evaluation of mRNA expression allowed assessing a reduced transcription of the enzyme, as well as an increase in the expression of TIMP-2. Statistical analyses showed that the decrease of MMP-2 activity in conditioned media reached the statistical significance (p = 0.0031 for 24 h and p = 0.0012 for 48 h, while correlation analysis showed that this result was

  16. Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

    Directory of Open Access Journals (Sweden)

    Paolo eBotta

    2014-02-01

    Full Text Available Golgi cells (GoCs are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na+/K+ pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABAA receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.

  17. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2010-07-01

    Full Text Available Dopamine (phasic release is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function was measured with PET and (18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg. The Cocaine-cues video increased craving to the same extent with placebo (68% and with methylphenidate (64%. In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005 in left limbic regions (insula, orbitofrontal, accumbens and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005, amygdala, striatum and middle insula (p<0.05. This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes, which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

  18. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Telang, F.; Fowler, J.S.; Pradhan, K.; Jayne, M.; Logan, J.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2010-01-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18 FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

  19. Estimation of transcapillary transport of palmitate by the multiple indicator dilution technique

    International Nuclear Information System (INIS)

    Little, S.E.; van der Vusse, G.J.; Bassingthwaighte, J.B.

    1986-01-01

    From the outflow concentration-time curves for 14 C-palmitate, intravascular ( 131 I-albumin) and extracellular ( 3 H-sucrose) tracers, palmitate extraction was estimated in rabbit hearts Langendorff-perfused at a constant flow with nonrecirculated palmitate-albumin Kreb's Ringer buffer. Contamination of 131 I-albumin with free 13 $ 1 I - (typically 1%) or aggregated albumin (typically 0.1 to 0.5%) greatly alters the shapes of the tails of the curves after 2 albumin transit times, vitiating accurate estimation of cellular permeability or reactions. Buffers were prepared by adding K + -palmitate (made using K 2 CO 3 ) to albumin solutions. The final concentrations (after dialysing twice and filtering through a 1.2 μ filter) of K + , HCO 3 , and CO 3 were 5.0 mM, 23.5 mM and 0.5 mM respectively, pH was between 7.35 and 7.40 for several hours. The bolus of tracers was prepared by mixing 131 I-albumin (dialysed to remove I - , and filtered through a 0.2 μM filter to remove aggregates), K + [U- 14 C]palmitate (high specific activity) and 3 H-sucrose. Before injection the radioactive bolus is preequilibrated with the perfusate at bolus:perfusate ratio of 1:10. Glacial acetic acid is added to the outflow samples to remove the 14 CO 2 which, if present in the sample, would be interpreted as increased palmitate back diffusion. The peak extractions of palmitate were about 40% at perfusate palmitate concentrations of 0.02 to 1.0 mM, 0.4 mM albumin, at a flow of 5 mlg -1 2] 1 , showing capillary permeability-surface area product to be roughly constant. This suggests either than transcapillary palmitate transport is passive or that a transporter interacts with the albumin-palmitate complex

  20. Effects of acute or chronic ethanol exposure during adolescence on behavioral inhibition and efficiency in a modified water maze task.

    Directory of Open Access Journals (Sweden)

    Shawn K Acheson

    Full Text Available Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape and a new hidden platform was added in the opposite quadrant. The hidden platform was the only means of escape during the test phase. In experiment 1, adolescent animals received ethanol (1.0 g/kg 30 min before each session during the test phase. In experiment 2, adolescent animals received chronic intermittent ethanol (5.0 g/kg for 16 days (PND30 To PND46 prior to any training in the maze. At PND72, training was initiated in the same modified water maze task. Results from experiment 1 indicated that acute ethanol promoted behavioral disinhibition and inefficiency. Experiment 2 showed that chronic intermittent ethanol during adolescence appeared to have no lasting effect on behavioral disinhibition or new spatial learning during adulthood. However, chronic ethanol did promote behavioral inefficiency. In summary, results indicate that ethanol-induced promotion of perseverative behavior may contribute to the many adverse behavioral sequelae of alcohol intoxication in adolescents and young adults. Moreover, the long-term effect of adolescent chronic ethanol exposure on behavioral efficiency is similar to that observed after chronic exposure in humans.

  1. β-Adrenergic induction of lipolysis in hepatocytes is inhibited by ethanol exposure.

    Science.gov (United States)

    Schott, Micah B; Rasineni, Karuna; Weller, Shaun G; Schulze, Ryan J; Sletten, Arthur C; Casey, Carol A; McNiven, Mark A

    2017-07-14

    In liver steatosis ( i.e. fatty liver), hepatocytes accumulate many large neutral lipid storage organelles known as lipid droplets (LDs). LDs are important in the maintenance of energy homeostasis, but the signaling mechanisms that stimulate LD metabolism in hepatocytes are poorly defined. In adipocytes, catecholamines target the β-adrenergic (β-AR)/cAMP pathway to activate cytosolic lipases and induce their recruitment to the LD surface. Therefore, the goal of this study was to determine whether hepatocytes, like adipocytes, also undergo cAMP-mediated lipolysis in response to β-AR stimulation. Using primary rat hepatocytes and human hepatoma cells, we found that treatment with the β-AR agent isoproterenol caused substantial LD loss via activation of cytosolic lipases adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). β-Adrenergic stimulation rapidly activated PKA, which led to the phosphorylation of ATGL and HSL and their recruitment to the LD surface. To test whether this β-AR-dependent lipolysis pathway was altered in a model of alcoholic fatty liver, primary hepatocytes from rats fed a 6-week EtOH-containing Lieber-DeCarli diet were treated with cAMP agonists. Compared with controls, EtOH-exposed hepatocytes showed a drastic inhibition in β-AR/cAMP-induced LD breakdown and the phosphorylation of PKA substrates, including HSL. This observation was supported in VA-13 cells, an EtOH-metabolizing human hepatoma cell line, which displayed marked defects in both PKA activation and isoproterenol-induced ATGL translocation to the LD periphery. In summary, these findings suggest that β-AR stimulation mobilizes cytosolic lipases for LD breakdown in hepatocytes, and perturbation of this pathway could be a major consequence of chronic EtOH insult leading to fatty liver.

  2. Embryonic Methamphetamine Exposure Inhibits Methamphetamine Cue Conditioning and Reduces Dopamine Concentrations in Adult N2 Caenorhabditis elegans.

    Science.gov (United States)

    Katner, Simon N; Neal-Beliveau, Bethany S; Engleman, Eric A

    2016-01-01

    for that ion (CS+) in worms that were not pre-exposed to MAP. However, worms embryonically exposed to MAP did not exhibit significant drug cue conditioning. The inability of MAP-exposed worms to condition to MAP was not associated with deficits in food conditioning, as MAP-exposed worms exhibited a significant cue preference associated with food. Furthermore, our results found that embryonic MAP exposure reduced DA levels in adult C. elegans, which could be a key mechanism contributing to the long-term effects of embryonic MAP exposure. It is possible that embryonic MAP exposure may be impairing the ability of C. elegans to learn associations between MAP and the CS+ or inhibiting the reinforcing properties of MAP. However, our food conditioning data suggest that MAP-exposed animals can form associations between cues and food. The depletion of DA levels during embryonic exposure to MAP could be responsible for driving either of these processes during adulthood. © 2016 S. Karger AG, Basel.

  3. An extensive cocktail approach for rapid risk assessment of in vitro CYP450 direct reversible inhibition by xenobiotic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Spaggiari, Dany, E-mail: dany.spaggiari@unige.ch [School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Boulevard d' Yvoy 20, 1211 Geneva 4 (Switzerland); Daali, Youssef, E-mail: youssef.daali@hcuge.ch [Clinical Pharmacology and Toxicology Service, Geneva University Hospitals, Rue Gabrielle Perret-Gentil, 1211 Genève 14 (Switzerland); Rudaz, Serge, E-mail: serge.rudaz@unige.ch [School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Boulevard d' Yvoy 20, 1211 Geneva 4 (Switzerland); Swiss Centre for Applied Human Toxicology, University of Geneva, Boulevard d' Yvoy 20, 1211 Geneva 4 (Switzerland)

    2016-07-01

    Acute exposure to environmental factors strongly affects the metabolic activity of cytochrome P450 (P450). As a consequence, the risk of interaction could be increased, modifying the clinical outcomes of a medication. Because toxic agents cannot be administered to humans for ethical reasons, in vitro approaches are therefore essential to evaluate their impact on P450 activities. In this work, an extensive cocktail mixture was developed and validated for in vitro P450 inhibition studies using human liver microsomes (HLM). The cocktail comprised eleven P450-specific probe substrates to simultaneously assess the activities of the following isoforms: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2 and subfamily 3A. The high selectivity and sensitivity of the developed UHPLC-MS/MS method were critical for the success of this methodology, whose main advantages are: (i) the use of eleven probe substrates with minimized interactions, (ii) a low HLM concentration, (iii) fast incubation (5 min) and (iv) the use of metabolic ratios as microsomal P450 activities markers. This cocktail approach was successfully validated by comparing the obtained IC{sub 50} values for model inhibitors with those generated with the conventional single probe methods. Accordingly, reliable inhibition values could be generated 10-fold faster using a 10-fold smaller amount of HLM compared to individual assays. This approach was applied to assess the P450 inhibition potential of widespread insecticides, namely, chlorpyrifos, fenitrothion, methylparathion and profenofos. In all cases, P450 2B6 was the most affected with IC{sub 50} values in the nanomolar range. For the first time, mixtures of these four insecticides incubated at low concentrations showed a cumulative inhibitory in vitro effect on P450 2B6. - Highlights: • Ten P450 isoforms activities assessed simultaneously with only one incubation. • P450 activity levels measured using the metabolic ratio approach. • IC{sub 50} values generated 10

  4. An extensive cocktail approach for rapid risk assessment of in vitro CYP450 direct reversible inhibition by xenobiotic exposure

    International Nuclear Information System (INIS)

    Spaggiari, Dany; Daali, Youssef; Rudaz, Serge

    2016-01-01

    Acute exposure to environmental factors strongly affects the metabolic activity of cytochrome P450 (P450). As a consequence, the risk of interaction could be increased, modifying the clinical outcomes of a medication. Because toxic agents cannot be administered to humans for ethical reasons, in vitro approaches are therefore essential to evaluate their impact on P450 activities. In this work, an extensive cocktail mixture was developed and validated for in vitro P450 inhibition studies using human liver microsomes (HLM). The cocktail comprised eleven P450-specific probe substrates to simultaneously assess the activities of the following isoforms: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2 and subfamily 3A. The high selectivity and sensitivity of the developed UHPLC-MS/MS method were critical for the success of this methodology, whose main advantages are: (i) the use of eleven probe substrates with minimized interactions, (ii) a low HLM concentration, (iii) fast incubation (5 min) and (iv) the use of metabolic ratios as microsomal P450 activities markers. This cocktail approach was successfully validated by comparing the obtained IC 50 values for model inhibitors with those generated with the conventional single probe methods. Accordingly, reliable inhibition values could be generated 10-fold faster using a 10-fold smaller amount of HLM compared to individual assays. This approach was applied to assess the P450 inhibition potential of widespread insecticides, namely, chlorpyrifos, fenitrothion, methylparathion and profenofos. In all cases, P450 2B6 was the most affected with IC 50 values in the nanomolar range. For the first time, mixtures of these four insecticides incubated at low concentrations showed a cumulative inhibitory in vitro effect on P450 2B6. - Highlights: • Ten P450 isoforms activities assessed simultaneously with only one incubation. • P450 activity levels measured using the metabolic ratio approach. • IC 50 values generated 10-fold faster

  5. Inhibition in fertilisation of coral gametes following exposure to nickel and copper.

    Science.gov (United States)

    Gissi, Francesca; Stauber, Jenny; Reichelt-Brushett, Amanda; Harrison, Peter L; Jolley, Dianne F

    2017-11-01

    The mining and production of nickel in tropical regions have the potential to impact on ecologically valuable tropical marine ecosystems. Currently, few data exist to assess the risks of nickel exposure to tropical ecosystems and to derive ecologically relevant water quality guidelines. In particular, data are lacking for keystone species such as scleractinian corals, which create the complex structural reef habitats that support many other marine species. As part of a larger study developing risk assessment tools for nickel in the tropical Asia-Pacific region, we investigated the toxicity of nickel on fertilisation success in three species of scleractinian corals: Acropora aspera, Acropora digitifera and Platygyra daedalea. In the literature, more data are available on the effects of copper on coral fertilisation, so to allow for comparisons with past studies, the toxicity of copper to A. aspera and P. daedalea was also determined. Overall, copper was more toxic than nickel to the fertilisation success of the species tested. Acropora aspera was the most sensitive species to nickel (NOEC 4610µg Ni/L). Acropora aspera was also the more sensitive species to copper with an EC10 of 5.8µg Cu/L. The EC10 for P. daedalea was 16µg Cu/L, similar to previous studies. This is the first time that the toxicity of nickel on fertilisation success in Acropora species has been reported, and thus provides valuable data that can contribute to the development of reliable water quality guidelines for nickel in tropical marine waters. Copyright © 2017. Published by Elsevier Inc.

  6. Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

    Directory of Open Access Journals (Sweden)

    Carly A Buckner

    Full Text Available Electromagnetic field (EMF exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca(2+ influx which could be blocked by inhibitors of voltage-gated T-type Ca(2+ channels. Blocking Ca(2+ uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca(2+ influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.

  7. Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

    Science.gov (United States)

    Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

    2015-01-01

    Electromagnetic field (EMF) exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz) EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca(2+) influx which could be blocked by inhibitors of voltage-gated T-type Ca(2+) channels. Blocking Ca(2+) uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca(2+) influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.

  8. Monocyte adhesion induced by multi-walled carbon nanotubes and palmitic acid in endothelial cells and alveolar-endothelial co-cultures

    DEFF Research Database (Denmark)

    Cao, Yi; Roursgaard, Martin; Jacobsen, Nicklas Raun

    2016-01-01

    Free palmitic acid (PA) is a potential pro-atherogenic stimulus that may aggravate particle-mediated cardiovascular health effects. We hypothesized that the presence of PA can aggravate oxidative stress and endothelial activation induced by multi-walled carbon nanotube (MWCNT) exposure in vitro. We...... measured in the lower chamber on HUVECs and THP-1 cells. The exposure to MWCNTs, including a short (NM400) and long (NM402) type of entangled fibers, was associated with elevated levels of reactive oxygen species as well as a decrease in the intracellular glutathione concentration in HUVEC and A549...

  9. Mitochondrial electron transport is inhibited by disappearance of metallothionein in human bronchial epithelial cells following exposure to silver nitrate.

    Science.gov (United States)

    Miyayama, Takamitsu; Arai, Yuta; Suzuki, Noriyuki; Hirano, Seishiro

    2013-03-08

    Silver (Ag) possesses antibacterial activity and has been used in wound dressings and deodorant powders worldwide. However, the metabolic behavior and biological roles of Ag in mammals have not been well characterized. In the present study, we exposed human bronchial epithelial cells (BEAS-2B) to AgNO3 and investigated uptake and intracellular distribution of Ag, expression of metallothionein (MT), generation of reactive oxygen species (ROS), and changes in mitochondrial respiration. The culture medium concentration of Ag decreased with time and stabilized at 12h. The concentration of both Ag and MT in the soluble cellular fraction increased up to 3h and then decreased, indicating that cytosolic Ag relocated to the insoluble fraction of the cells. The levels of mRNAs for the major human MT isoforms MT-I and MT-II paralleled with the protein levels of Ag-MT. The intensity of fluorescence derived from ROS was elevated in the mitochondrial region at 24h. Ag decreased mitochondrial oxygen consumption in a dose-dependent manner and the activity of mitochondrial complex I-IV enzymes was significantly inhibited following exposure to Ag. In a separate experiment, we found that hydrogen peroxide (H2O2) at concentrations as low as 0.001% (equivalent to the concentration of H2O2 in Ag-exposed cells) removed Ag from MT. These results suggest MT was decomposed by cytosolic H2O2, and then Ag released from MT relocated to insoluble cellular fractions and inhibited electron chain transfer of mitochondrial complexes, which eventually led to cell damage. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Effects of methyl palmitate on cytokine release, liver injury and survival in mice with sepsis.

    Science.gov (United States)

    Villa, P; Demitri, M T; Meazza, C; Sironi, M; Gnocchi, P; Ghezzi, P

    1996-12-01

    The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.

  11. 3-MCPD 1-Palmitate Induced Tubular Cell Apoptosis In Vivo via JNK/p53 Pathways

    Science.gov (United States)

    Liu, Man; Huang, Guoren; Wang, Thomas T.Y.; Sun, Xiangjun; Yu, Liangli (Lucy)

    2016-01-01

    Fatty acid esters of 3-chloro-1, 2-propanediol (3-MCPD esters) are a group of processing induced food contaminants with nephrotoxicity but the molecular mechanism(s) remains unclear. This study investigated whether and how the JNK/p53 pathway may play a role in the nephrotoxic effect of 3-MCPD esters using 3-MCPD 1-palmitate (MPE) as a probe compound in Sprague Dawley rats. Microarray analysis of the kidney from the Sprague Dawley rats treated with MPE, using Gene Ontology categories and KEGG pathways, revealed that MPE altered mRNA expressions of the genes involved in the mitogen-activated protein kinase (JNK and ERK), p53, and apoptotic signal transduction pathways. The changes in the mRNA expressions were confirmed by qRT-PCR and Western blot analyses and were consistent with the induction of tubular cell apoptosis as determined by histopathological, TUNEL, and immunohistochemistry analyses in the kidneys of the Sprague Dawley rats. Additionally, p53 knockout attenuated the apoptosis, and the apoptosis-related protein bax expression and cleaved caspase-3 activation induced by MPE in the p53 knockout C57BL/6 mice, whereas JNK inhibitor SP600125 but not ERK inhibitor U0126 inhibited MPE-induced apoptosis, supporting the conclusion that JNK/p53 might play a critical role in the tubular cell apoptosis induced by MPE and other 3-MCPD fatty acid esters. PMID:27008853

  12. Sublethal Exposure to Diatomaceous Earth Increases Net Fecundity of Flour Beetles (Tribolium confusum) by Inhibiting Egg Cannibalism

    Science.gov (United States)

    Shostak, Allen W.

    2014-01-01

    Population regulation results from an interplay of numerous intrinsic and external factors, and for many insects cannibalism is such a factor. This study confirms a previously-reported observation that sublethal exposure to the fossilized remains of diatoms (i.e. diatomaceous earth) increases net fecundity (eggs produced minus eggs destroyed/day) of flour beetles, Tribolium confusum. The aim was to experimentally test two non-mutually-exclusive ecological mechanisms potentially responsible for the increased net fecundity: higher egg production and lower egg cannibalism. Adult T. confusum were maintained at low or high density in medium containing sublethal (0–4%) diatomaceous earth. Net fecundity increased up to 2.1× control values during diatomaceous earth exposure, and returned to control levels following removal from diatomaceous earth. Cannibalism assays on adults showed that diatomaceous earth reduced the number of eggs produced to 0.7× control values at low density and to 0.8× controls at high density, and also reduced egg cannibalism rates of adults to as little as 0.4× control values, but at high density only. Diatomaceous earth also reduced cannibalism by larvae on eggs to 0.3× control values. So, while the presence of diatomaceous earth reduced egg production, net fecundity increased as a result of strong suppression of the normal egg cannibalism by adults and larvae that occurs at high beetle density. Undisturbed cultures containing sublethal diatomaceous earth concentrations reached higher population densities than diatomaceous earth-free controls. Cohort studies on survival from egg to adult indicated that this population increase was due largely to decreased egg cannibalism by adult females. This is the first report of inhibition of egg cannibalism by diatomaceous earth on larval or adult insects. The ability of diatomaceous earth to alter cannibalism behavior without causing mortality makes it an ideal investigative tool for cannibalism

  13. Impaired terrestrial and arboreal locomotor performance in the western fence lizard (Sceloporus occidentalis) after exposure to an AChE-inhibiting pesticide

    International Nuclear Information System (INIS)

    DuRant, Sarah E.; Hopkins, William A.; Talent, Larry G.

    2007-01-01

    We examined the effects of a commonly used AChE-inhibiting pesticide on terrestrial and arboreal sprint performance, important traits for predator avoidance and prey capture, in the western fence lizard (Sceloporus occidentalis). Lizards were exposed to carbaryl (2.5, 25, and 250 μg/g) and were raced before and 4, 24, and 96 h after dosing. In the terrestrial setting, exposure to low concentrations of carbaryl had stimulatory effects on performance, but exposure to the highest concentration was inhibitory. No stimulatory effects of carbaryl were noted in the arboreal environment and performance in lizards was reduced after exposure to both the medium and highest dose of carbaryl. Our findings suggest that acute exposure to high concentrations of carbaryl can have important sublethal consequences on fitness-related traits in reptiles and that arboreal locomotor performance is a more sensitive indicator of AChE-inhibiting pesticide poisoning than terrestrial locomotor performance. - Exposure to an acetylcholinesterase-inhibiting pesticide alters locomotor performance in western fence lizards

  14. Impaired terrestrial and arboreal locomotor performance in the western fence lizard (Sceloporus occidentalis) after exposure to an AChE-inhibiting pesticide

    Energy Technology Data Exchange (ETDEWEB)

    DuRant, Sarah E. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States); University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States); Hopkins, William A. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States) and University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States)]. E-mail: hopkinsw@vt.edu; Talent, Larry G. [Department of Zoology, Oklahoma State University, Stillwater, OK 74078 (United States)

    2007-09-15

    We examined the effects of a commonly used AChE-inhibiting pesticide on terrestrial and arboreal sprint performance, important traits for predator avoidance and prey capture, in the western fence lizard (Sceloporus occidentalis). Lizards were exposed to carbaryl (2.5, 25, and 250 {mu}g/g) and were raced before and 4, 24, and 96 h after dosing. In the terrestrial setting, exposure to low concentrations of carbaryl had stimulatory effects on performance, but exposure to the highest concentration was inhibitory. No stimulatory effects of carbaryl were noted in the arboreal environment and performance in lizards was reduced after exposure to both the medium and highest dose of carbaryl. Our findings suggest that acute exposure to high concentrations of carbaryl can have important sublethal consequences on fitness-related traits in reptiles and that arboreal locomotor performance is a more sensitive indicator of AChE-inhibiting pesticide poisoning than terrestrial locomotor performance. - Exposure to an acetylcholinesterase-inhibiting pesticide alters locomotor performance in western fence lizards.

  15. Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult.

    Science.gov (United States)

    Qi, Zhangyang; Wu, Meihao; Fu, Yun; Huang, Tengfei; Wang, Tingting; Sun, Yanjie; Feng, Zhibo; Li, Changzheng

    2017-01-01

    The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer's disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ. P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). An MTT assay was used to assess Aβ cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aβ-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF) fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aβ, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aβ were determined via spectrophotometry. A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aβ-mediated ROS production and may inhibit the direct interaction between Aβ and the cellular membrane. Furthermore, P-curcumin could scavenge Aβ-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin's ability to attenuate direct interaction between Aβ and cell membranes, the binding affinity of Aβ to curcumin and P-curcumin was determined. The association

  16. Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult

    Directory of Open Access Journals (Sweden)

    Zhangyang Qi

    2017-11-01

    Full Text Available Background/Aims: The generation of reactive oxygen species (ROS caused by amyloid-β (Aβ is considered to be one of mechanisms underlying the development of Alzheimer’s disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ. Methods: P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR and high-resolution mass spectrometry (HRMS. An MTT assay was used to assess Aβ cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aβ-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aβ, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aβ were determined via spectrophotometry. Results: A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aβ-mediated ROS production and may inhibit the direct interaction between Aβ and the cellular membrane. Furthermore, P-curcumin could scavenge Aβ-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin’s ability to attenuate direct interaction between Aβ and cell membranes, the binding affinity of Aβ to curcumin

  17. Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells.

    Science.gov (United States)

    Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

    2018-04-01

    Exposure to specific electromagnetic field (EMF) patterns can affect a variety of biological systems. We have shown that exposure to Thomas-EMF, a low-intensity, frequency-modulated (25-6 Hz) EMF pattern, inhibited growth and altered cell signaling in malignant cells. Exposure to Thomas-EMF for 1 h/day inhibited the growth of malignant cells including B16-BL6 mouse melanoma cells, MDA-MB-231, MDA-MB-468, BT-20, and MCF-7 human breast cancer and HeLa cervical cancer cells but did not affect non-malignant cells. The Thomas-EMF-dependent changes in cell proliferation were mediated by adenosine 3',5'-cyclic monophosphate (cAMP) and extracellular-signal-regulated kinase (ERK) signaling pathways. Exposure of malignant cells to Thomas-EMF transiently changed the level of cellular cAMP and promoted ERK phosphorylation. Pharmacologic inhibitors (SQ22536) and activators (forskolin) of cAMP production both blocked the ability of Thomas-EMF to inhibit cell proliferation, and an inhibitor of the MAP kinase pathway (PD98059) was able to partially block Thomas-EMF-dependent inhibition of cell proliferation. Genetic modulation of protein kinase A (PKA) in B16-BL6 cells also altered the effect of Thomas-EMF on cell proliferation. Cells transfected with the constitutively active form of PKA (PKA-CA), which interfered with ERK phosphorylation, also interfered with the Thomas-EMF effect on cell proliferation. The non-malignant cells did not show any EMF-dependent changes in cAMP levels, ERK phosphorylation, or cell growth. These data indicate that exposure to the specific Thomas-EMF pattern can inhibit the growth of malignant cells in a manner dependent on contributions from the cAMP and MAP kinase pathways. Bioelectromagnetics. 39;217-230, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Beta-lactam antibiotic-induced platelet dysfunction: Evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin

    International Nuclear Information System (INIS)

    Burroughs, S.F.; Johnson, G.J.

    1990-01-01

    beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of [14C]-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; but no irreversible inhibition of alpha 2 adrenergic receptors, measured with [3H]-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist [3H]-U46619 and antagonist [3H]-SQ29548, occurred. However, low-affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ([Ca2+]i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in [Ca2+]i. The loss of low-affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane

  19. Molecular dynamics of palmitic acid and lead palmitate in cross-linked linseed oil films: Implications from deuterium magnetic resonance for lead soap formation in traditional oil paintings.

    Science.gov (United States)

    Catalano, Jaclyn; Murphy, Anna; Yao, Yao; Zumbulyadis, Nicholas; Centeno, Silvia A; Dybowski, Cecil

    2018-02-01

    Many oil paintings, dating from the 15th century to the present, are affected by the formation of heavy-metal carboxylates (soaps) that alter the structural integrity and appearance of the works. Through transport phenomena not yet understood, free fatty acids formed from oils used as binders migrate through the paint film and react with heavy-metal ions that are constituents of pigments and/or driers, forming metal carboxylates. The local molecular dynamics of fatty acids and metal carboxylates are factors influencing material transport in these systems. We report temperature-dependent 2 H NMR spectra of palmitic acid and lead palmitate as pure materials, in cross-linked linseed oil films, and in a lead white linseed oil paint film as part of our broader research into metal soap formation. Local dynamics at the α carbon, at the terminal methyl group, and at the middle of the fatty acid chain were observed in specifically deuterated materials. Changes in the dynamic behavior with temperature were observed by the appearance of two species, a solid-like material and a liquid-like material. The relative amounts of the two phases and their deuterium NMR parameters indicate that the amount of liquid-like material and the local dynamics at that site increase with temperature. At the three locations along the chain and at all temperatures, there is a larger percentage of acyl chains of both palmitic acid and lead palmitate that are "mobile" or liquid-like in linseed oil films than there are in the pure materials. However, the percentage of liquid-like species is decreased in a lead white paint film, as compared to a linseed oil matrix. In addition, these experiments indicate that there is a larger percentage of liquid-like acyl chains of palmitic acid than of lead palmitate under identical conditions in these model paint systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Biological and Nutritional Properties of Palm Oil and Palmitic Acid: Effects on Health.

    Science.gov (United States)

    Mancini, Annamaria; Imperlini, Esther; Nigro, Ersilia; Montagnese, Concetta; Daniele, Aurora; Orrù, Stefania; Buono, Pasqualina

    2015-09-18

    A growing body of evidence highlights the close association between nutrition and human health. Fat is an essential macronutrient, and vegetable oils, such as palm oil, are widely used in the food industry and highly represented in the human diet. Palmitic acid, a saturated fatty acid, is the principal constituent of refined palm oil. In the last few decades, controversial studies have reported potential unhealthy effects of palm oil due to the high palmitic acid content. In this review we provide a concise and comprehensive update on the functional role of palm oil and palmitic acid in the development of obesity, type 2 diabetes mellitus, cardiovascular diseases and cancer. The atherogenic potential of palmitic acid and its stereospecific position in triacylglycerols are also discussed.

  1. [Inhibition rate of gamma-aminolevulinic acid dehydratase activity in erythrocytes as a reliable index for individual workers of low lead exposure].

    Science.gov (United States)

    Hirano, H; Omichi, M; Ohishi, H; Ishikawa, K; Hirashima, N

    1983-09-01

    As the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes is decreased by lead exposure, we considered that a net reduction of ALAD activity by lead in blood should be the difference between the activity fully activated with zinc (Zn2+) and dithiothreitol (DTT) and that without activation. The optimal condition of activation of ALAD was found by addition of 0.25 mM of Zn2+ and 10 mM of DTT in the reaction mixture. Judging from our previous results that the amount of inhibition of ALAD activity can be represented as the rate of inhibition and is closely correlated with the dose of lead administered to rabbits, the inhibition rate of ALAD activity and lead content in blood (Pb-B) of lead workers were measured. The scatter diagram obtained from the inhibition rate and lead content in blood has two groups being divided at 50 micrograms/ml of Pb-B. In one group less than 50 micrograms/100 ml of Pb-B, the inhibition rate has been closely related to Pb-B., the regression equation being Y = 1.82 X + 11.7, and the correlation coefficient + 0.926. In another group more than 50 micrograms/100 ml of Pb-B the inhibition rate remained constant at the 90% level. Measurement of the inhibition rate suggests to have practical validity for monitoring lead exposure in workers, and by means of a nomograph lead content in blood can be estimated from the inhibition rate.

  2. Adiponectin protects palmitic acid induced endothelial inflammation and insulin resistance via regulating ROS/IKKβ pathways.

    Science.gov (United States)

    Zhao, Wenwen; Wu, Chuanhong; Li, Shaojing; Chen, Xiuping

    2016-12-01

    Endothelial inflammation and insulin resistance (IR) has been closely associated with endothelial dysfunction. Adiponectin (APN), an adipocyte-secreted hormone from adipose tissues, showed cardioprotective effects. Here, the protective effect of APN on palmitic acid (PA)-induced endothelial inflammation and IR was investigated. Cultured human umbilical vein endothelial cells (HUVECs) were treated with PA without or without APN pretreatment. The expression of inflammatory cytokines TNF-α, IL-6, adhesion molecule ICAM-1 were determined by western blotting, ELISA, and real-time PCR. The protein expression and protein-protein interaction were determined by western blotting and immunoprecipitation. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) production were monitored with fluorescence probes. PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1 at protein and mRNA levels, which was significantly inhibited by APN. PA treatment caused increase of ROS generation, NOX2, p-IKKβ, p-IκBα, p-p65 expression, and p-IκBα-IKKβ interaction, which were all partly reversed by APN. ROS scavenger N-acetylcysteine (NAC) and NF-κB inhibitor PDTC showed similar effect on PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1. Furthermore, APN and NAC pretreatment restored PA-induced increase of p-IRS-1(S307), decrease of p-IRS-1(Tyr). In addition, insulin-triggered expression of p-IRS-1(Tyr), p-PI3K, p-AKT, p-eNOS and NO generation were inhibited by PA, which were also restored by both APN and NAC. These results suggested that APN ameliorated endothelial inflammation and IR through ROS/IKKβ pathway. This study shed new insights into the mechanisms of APN's cardiovascular protective effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yunxia, E-mail: wwwdluyx@sina.com [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032 (China); Cheng, Jingjing [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Chen, Li [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Department of Medical Laboratory, Anhui Provincial Hospital, Hefei, Anhui 230001 (China); Li, Chaofei; Chen, Guanjun [Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032 (China); Gui, Li [The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032 (China); Shen, Bing [Department of Physiology, Anhui Medical University, Hefei, Anhui 230032 (China); Zhang, Qiu [Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022 (China)

    2015-02-27

    Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown. In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in primary mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We found that FF treatment improved serum lipid levels and pathological changes in thoracic aorta, accompanied with decreased ER stress and increased phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different concentrations of PA treatment. The dose- and time-dependent inhibition of cell proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and expression of ER stress related genes were all inverted by FA pretreatment in PA-treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic HFD feeding and acute stimulation of PA, this effect is related with decreased ER stress and increased phosphorylation of eNOS. - Highlights: • Fenofibrate treatment improved pathological changes in thoracic aorta by chronic high-fat-diet feeding. • Fenofibrate pretreatment improved endothelium-dependent vasodilation impaired by different concentrations of palmitic acid. • The inhibition of proliferation in endothelial cells by palmitic acid were inverted by fenofibric

  4. Manic Symptoms during a Switch from Paliperidone ER to Paliperidone Palmitate in a Patient with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Kadir Demirci

    2015-01-01

    Full Text Available Some antipsychotic drugs have treatment efficacy for mania and bipolar disorder. However, these drugs may rarely cause manic symptoms in some schizophrenic patients. We hereby report a 22-year-old female patient with schizophrenia who experienced a manic episode during a switch from paliperidone ER to paliperidone palmitate. This case is an important reminder that an abrupt switch from oral paliperidone to paliperidone palmitate may predispose certain patients to hypomanic or manic symptoms.

  5. Structure-activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure.

    Science.gov (United States)

    Mook, Robert A; Wang, Jiangbo; Ren, Xiu-Rong; Chen, Minyong; Spasojevic, Ivan; Barak, Larry S; Lyerly, H Kim; Chen, Wei

    2015-09-01

    The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. Niclosamide is a multi-functional drug that possesses important biological activity in addition to inhibition of Wnt/β-catenin signaling. Here, we studied the SAR of Wnt signaling inhibition in the anilide and salicylamide region of Niclosamide. We found that the 4'-nitro substituent can be effectively replaced by trifluoromethyl or chlorine and that the potency of inhibition was dependent on the substitution pattern in the anilide ring. Non-anilide, N-methyl amides and reverse amide derivatives lost significant potency, while acylated salicylamide derivatives inhibited signaling with potency similar to non-acyl derivatives. Niclosamide's low systemic exposure when dosed orally may hinder its use to treat systemic disease. To overcome this limitation we identified an acyl derivative of Niclosamide, DK-520 (compound 32), that significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. The studies herein provide a medicinal chemical foundation to improve the pharmacokinetic exposure of Niclosamide and Wnt-signaling inhibitors based on the Niclosamide chemotype. The identification of novel derivatives of Niclosamide that metabolize to Niclosamide and increase its drug exposure may provide important research tools for in vivo studies and provide drug candidates for treating cancers with dysregulated Wnt signaling including drug-resistant cancers. Moreover, since Niclosamide is a multi-functional drug, new research tools such as DK520 could directly result in novel treatments against bacterial and viral infection, lupus, and metabolic

  6. Structure–activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure

    Science.gov (United States)

    Mook, Robert A.; Wang, Jiangbo; Ren, Xiu-Rong; Chen, Minyong; Spasojevic, Ivan; Barak, Larry S.; Lyerly, H. Kim; Chen, Wei

    2015-01-01

    The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. Niclosamide is a multi-functional drug that possesses important biological activity in addition to inhibition of Wnt/β-catenin signaling. Here, we studied the SAR of Wnt signaling inhibition in the anilide and salicylamide region of Niclosamide. We found that the 4′-nitro substituent can be effectively replaced by trifluoromethyl or chlorine and that the potency of inhibition was dependent on the substitution pattern in the anilide ring. Non-anilide, N-methyl amides and reverse amide derivatives lost significant potency, while acylated salicylamide derivatives inhibited signaling with potency similar to non-acyl derivatives. Niclosamide's low systemic exposure when dosed orally may hinder its use to treat systemic disease. To overcome this limitation we identified an acyl derivative of Niclosamide, DK-520 (compound 32), that significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. The studies herein provide a medicinal chemical foundation to improve the pharmacokinetic exposure of Niclosamide and Wnt-signaling inhibitors based on the Niclosamide chemotype. The identification of novel derivatives of Niclosamide that metabolize to Niclosamide and increase its drug exposure may provide important research tools for in vivo studies and provide drug candidates for treating cancers with dysregulated Wnt signaling including drug-resistant cancers. Moreover, since Niclosamide is a multifunctional drug, new research tools such as DK520 could directly result in novel treatments against bacterial and viral infection, lupus, and metabolic

  7. Prenatal Alcohol Exposure Increases Histamine H3 Receptor-Mediated Inhibition of Glutamatergic Neurotransmission in Rat Dentate Gyrus.

    Science.gov (United States)

    Varaschin, Rafael K; Allen, Nyika A; Rosenberg, Martina J; Valenzuela, C Fernando; Savage, Daniel D

    2018-02-01

    We have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus, long-term potentiation (LTP), and memory are ameliorated by the histamine H 3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the dentate gyrus and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H 3 receptor number and function. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution 4 hours each day throughout gestation. This pattern of drinking, which produces a mean peak maternal serum ethanol concentration of 60.8 ± 5.8 mg/dl, did not affect maternal weight gain, litter size, or offspring birthweight. Radiohistochemical studies in adult offspring revealed that specific [ 3 H]-A349821 binding to histamine H 3 receptors was not different in PAE rats compared to controls. However, H 3 receptor-mediated G i /G o protein-effector coupling, as measured by methimepip-stimulated [ 35 S]-GTPγS binding, was significantly increased in cerebral cortex, cerebellum, and dentate gyrus of PAE rats compared to control. A LIGAND analysis of detailed methimepip concentration-response curves in dentate gyrus indicated that PAE significantly elevates receptor-effector coupling by a lower affinity H 3 receptor population without significantly altering the affinities of H 3 receptor subpopulations. In agreement with the [ 35 S]-GTPγS studies, a similar range of methimepip concentrations also inhibited electrically evoked field excitatory postsynaptic potential responses and increased paired-pulse ratio, a measure of decreased glutamate release, to a significantly greater extent in dentate gyrus slices from PAE rats than in controls. These results suggest that a PAE-induced elevation in H 3 receptor-mediated inhibition of glutamate release from

  8. Uncoupling effect of palmitate is exacerbated in skeletal muscle mitochondria of sea-acclimatized king penguins (Aptenodytes patagonicus).

    Science.gov (United States)

    Rey, Benjamin; Duchamp, Claude; Roussel, Damien

    2017-09-01

    In king penguin juveniles, the environmental transition from a terrestrial to a marine habitat, occurring at fledging, drastically stimulates lipid catabolism and the remodelling of muscle mitochondria to sustain extensive swimming activity and thermoregulation in the cold circumpolar oceans. However, the exact nature of these mechanisms remains only partially resolved. Here we investigated, in vitro, the uncoupling effect of increasing doses of fatty acids in pectoralis muscle intermyofibrillar mitochondria isolated, either from terrestrial never-immersed or experimentally cold water immersed pre-fledging king penguins or from sea-acclimatized fledged penguins. Mitochondria exhibited much greater palmitate-induced uncoupling respiration and higher maximal oxidative capacity after acclimatization to marine life. Such effects were not reproduced experimentally after repeated immersions in cold water, suggesting that the plasticity of mitochondrial characteristics may not be primarily driven by cold exposure per se but by other aspects of sea acclimatization. Copyright © 2017. Published by Elsevier Inc.

  9. Interaction of Palmitic Acid with Metoprolol Succinate at the Binding Sites of Bovine Serum Albumin

    Directory of Open Access Journals (Sweden)

    Mashiur Rahman

    2014-12-01

    Full Text Available Purpose: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. Methods: The binding of metoprolol succinate to bovine serum albumin (BSA was studied by equilibrium dialysis method (ED at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. Results: Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 105 M-1 with low capacity (n1 = 2 and low affinity association (k2 = 4.0×105 M-1 constant with high capacity (n2 = 8 at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10-5 M to 16×10-5 M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. Conclusion: This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.

  10. Activation versus inhibition of microsomal glutathione S-transferase activity by acrolein. Dependence on the concentration and time of acrolein exposure.

    Science.gov (United States)

    Sthijns, Mireille M J P E; den Hartog, Gertjan J M; Scasso, Caterina; Haenen, Jan P; Bast, Aalt; Haenen, Guido R M M

    2017-09-25

    The toxicity of acrolein, an α,β-unsaturated aldehyde, is due to its soft electrophilic nature and primarily involves the adduction of protein thiols. The thiol glutathione (GSH) forms the first line of defense against acrolein. The present study confirms that acrolein added to isolated rat liver microsomes can increase microsomal GSH transferase (MGST) activity 2-3 fold, which can be seen as a direct adaptive increase in the protection against acrolein. At a relatively high exposure level, acrolein appeared to inhibit MGST. The activation is due to adduction of thiol groups, and the inactivation probably involves adduction of amino groups in the enzyme by acrolein. The preference of acrolein to react with thiol groups over amino groups can explain why the enzyme is activated at a low exposure level and inhibited at a high exposure level of acrolein. These opposite forms of direct adaptation on the level of enzyme activity further narrow the thin line between survival and promotion of cell death, governed by the level of exposure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Comparison of palmitic acid kinetics during glucose or ketone body infusions

    Energy Technology Data Exchange (ETDEWEB)

    Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

    1986-03-05

    Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of (1-/sup 14/C) palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat.

  12. The Effects of plasticizers and palmitic acid toward the properties of the carrageenan Film

    Science.gov (United States)

    Heru Wibowo, Atmanto; Listiyawati, Oktaviana; Purnawan, Candra

    2016-02-01

    Varied plasticizers and palmitic acid additive have been added in the carrageenan film. The film was made by mixing of the carrageenan and plasticizers (glycerol, polyethylene glycol, polyvinyl alcohol) with composition of 92:3, 90:6, 87:9, 84:12, 81:15(%w/w) and in the presence of palmitic acid as additive with 1%, 2%, 3%, 4%, 5% of total weight. Casting method was used for the film molding and drying at 60oC with the oven for 12 hours. To investigate the effects of plasticizers and additive, some mechanical tests on film were performed. The test result concludes that plasticizers in the film decreased the tensile strength and increased the elongation break of the carrageenan film. The additive of palmitic acid decreased the tensile strength of the carrageenan film and also decreased the-the water absorbance of the film. The highest tensile strength of films made was with the formulation of carrageenan: PEG with composition of 92:3 (% w/w). The highest elongation break of the film was for carrageenan:PVA with the composition of 81: 15 (%w/w) and carrageenan:palmitic acid:PEG with the composition of 92: 3: 1 (%w/w). The lowest water absorption of the film was achieved for carrageenan:PVA:palmitic acid with the composition of 87: 3: 5 (%w/w).

  13. Comparison of palmitic acid kinetics during glucose or ketone body infusions

    International Nuclear Information System (INIS)

    Birkhahn, R.H.; Block, D.J.; Birkhahn, G.C.; Thomford, N.R.

    1986-01-01

    Ketone body interactions can be observed for extended ketosis by infusion by monoacetoacetin (the monoglyceride of acetoacetic acid). Palmitic acid kinetics were compared on the 5th day of glucose or ketone body-glucose infusions. 20 rats were fed complete diets intravenously at the rate of 50 ml/day. All diets contained vitamins, trace minerals, electrolytes, amino acids and 1 kcal/ml of non-protein energy. Rats were divided by energy source: Group A (n = 10) received energy from glucose and Group B (n = 10) from 72% monoacetoacetin plus 28% glucose. Diets were given at 1/2 and 3/4 rats on days 1 and 2, respectively and at full rate for days 3-5. Urinary nitrogen losses, body weight and dietary intake were measured daily. Palmitate kinetics was measured on day 5 using a continuous infusion of [1- 14 C] palmitate and measuring C-14 in breath and plasma and plasma palmitate by GC. The two groups had similar body weight changes and urinary nitrogen losses over the 3 days of full intake Group A had lower plasma palmitate (88 +/- 7 vs 105 +/- 6 micromol/l) but similar turnover (17.1 +/- 2.4 vs 15.0 +/- 1.9 mmol/hr) and oxidation 2.3 +/- 0.3 vs 2.2 +/- 0.05 mmol/hr) compared to Group B. These data show that feeding monoacetoacetin intravenously does not stimulate fatty acid metabolism in the well nourished rat

  14. Metabolic shift in lung alveolar cell mitochondria following acrolein exposure.

    Science.gov (United States)

    Agarwal, Amit R; Yin, Fei; Cadenas, Enrique

    2013-11-15

    Acrolein, an α,β unsaturated electrophile, is an environmental pollutant released in ambient air from diesel exhausts and cooking oils. This study examines the role of acrolein in altering mitochondrial function and metabolism in lung-specific cells. RLE-6TN, H441, and primary alveolar type II (pAT2) cells were exposed to acrolein for 4 h, and its effect on mitochondrial oxygen consumption rates was studied by XF Extracellular Flux analysis. Low-dose acrolein exposure decreased mitochondrial respiration in a dose-dependent manner because of alteration in the metabolism of glucose in all the three cell types. Acrolein inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, leading to decreased substrate availability for mitochondrial respiration in RLE-6TN, H441, and pAT2 cells; the reduced GAPDH activity was compensated in pAT2 cells by an increase in the activity of glucose-6-phosphate dehydrogenase, the regulatory control of the pentose phosphate pathway. The decrease in pyruvate from glucose metabolism resulted in utilization of alternative sources to support mitochondrial energy production: palmitate-BSA complex increased mitochondrial respiration in RLE-6TN and pAT2 cells. The presence of palmitate in alveolar cells for surfactant biosynthesis may prove to be the alternative fuel source for mitochondrial respiration. Accordingly, a decrease in phosphatidylcholine levels and an increase in phospholipase A2 activity were found in the alveolar cells after acrolein exposure. These findings have implications for understanding the decrease in surfactant levels frequently observed in pathophysiological situations with altered lung function following exposure to environmental toxicants.

  15. Double up! Examining the effects of adding inhibition training to food cue exposure in chocolate-loving female students.

    Science.gov (United States)

    Bongers, Peggy; Houben, Katrijn; Jansen, Anita

    2018-02-01

    In the present we study investigated whether addition of a Go/No Go training enhanced the effects of food cue exposure. We assessed desire to eat, salivation, CS-US expectancies, and eating in the absence of hunger (EAH) during and after cue exposure. Participants (N = 71) were chocolate-loving female students who tried to eat less chocolate in daily life. They received two sessions of either cue exposure with Go/No Go training (EXP + GNG), cue exposure with a sham training (EXP + shamGNG), or a control procedure with sham training (CON + shamGNG). Results showed that the exposure groups had higher desire to eat and higher levels of salivation during exposure compared to the control group during the control intervention, and that within session and between session habituation occurred in all conditions. In contrast to our hypotheses, lower levels of desire and salivation in the EXP + GNG compared to the EXP + shamGNG group at the end of exposure were not found. In addition, there was an overall decrease in CS-US expectancies with no group differences, and these beliefs were unrelated to EAH. Furthermore, groups did not differ on intake of either the exposed chocolate, non-exposed chocolate or other snack food items. It is concluded that a short Go/No Go training does not have an effect on two sessions of cue exposure treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Free fatty acid palmitate activates unfolded protein response pathway and promotes apoptosis in meniscus cells.

    Science.gov (United States)

    Haywood, J; Yammani, R R

    2016-05-01

    Obesity is the major risk factor for the development of osteoarthritis (OA); however, the mechanisms involved are not clearly understood. Obesity is associated with increased production of adipokine and elevated levels of circulating free fatty acids (FFA). A recent study has shown that saturated fatty acid palmitate induced pro-inflammatory and pro-apoptotic pathways in chondrocytes. Meniscus has been shown to be more susceptible than articular cartilage to catabolic stimuli. Thus, the aim of this study was to determine the effect of FFA (specifically, palmitate) on meniscus cells. Cultured primary porcine meniscus cells were stimulated with 500 μM FFA (palmitate and oleate) for 24 h to induce endoplasmic reticulum (ER) stress. After treatment, cell lysates were prepared and immunoblotted for C/EBP homologous protein (CHOP). To determine the activation of unfolded protein response (UPR) signaling, cell lysates were probed for cJun n-terminal kinase (JNK), cleaved caspase -3 and Xbp-1s, an alternative mRNA splicing product generated due to Ire1α activation. Treatment of isolated primary meniscus cells with palmitate but not oleate induced expression of CHOP and Xbp-1s. Palmitate treatment of meniscus cells also activated JNK and increased expression of caspase-3, thus promoting apoptosis in meniscus cells. Palmitate induces ER stress and promotes apoptotic pathways in meniscus cells. This is the first study to establish ER stress as a key metabolic mechanistic link between obesity and OA, in addition to (or operating with) biomechanical factors. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  17. PRESENTED AT NC SOCIETY OF TOXICOLOGY MEETING IN RESEARCH TRIANGLE PARK, NC ON 2/16/2006: PERIPUBERTAL PROCHLORAZ EXPOSURE STRONGLY INHIBITS TESTOSTERONE PRODUCTION, BUT HAS WEAK EFFECTS ON PUBERTY

    Science.gov (United States)

    Prochloraz (PCZ) is an imidazole fungicide that inhibits steroidogenesis and acts as an androgen receptor antagonist. We hypothesized that pubertal exposure to prochloraz would delay preputial separation and development of reproductive organs. Sprague Dawley rats were dosed wit...

  18. Sinonasal Epithelial Wound Resealing in an In Vitro Model: Inhibition of Wound Closure with IL-4 Exposure

    Science.gov (United States)

    Wise, Sarah K.; Den Beste, Kyle A.; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma

    2013-01-01

    Background Prolonged healing and persistent inflammation following surgery for rhinosinusitis impacts patient satisfaction and healthcare resources. Cytokines interleukin (IL)-4, 5, and 13 are important mediators in Th2 inflammatory rhinosinusitis. Decreased wound healing has been demonstrated with Th2 cytokine exposure, but this has not been extensively studied in sinonasal epithelium. We hypothesized that in vitro exposure of primary sinonasal epithelial cell cultures to Th2 inflammatory cytokine IL-4 and IL-13 would impair wound resealing and decrease expression of annexin A2 at the wound edge. Methods Following 24-hour exposure to IL-4, 5, or 13 versus controls, sterile linear mechanical wounds were created in primary sinonasal epithelial cultures (n = 12 wounds per condition). Wounds were followed for 36 hours or until complete closure and residual wound areas were calculated by image analysis. Group differences in annexin A2 were assessed by immunofluorescence labeling, confocal microscopy, and Western blots. Results Significant wound closure differences were identified across cytokine exposure groups (pprotein levels were decreased in IL-4 treated wounds when compared to control wounds (p<0.01). Conclusions Th2 cytokine IL-4 decreases sinonasal epithelial wound closure in vitro. Annexin A2 is also diminished with IL-4 exposure. This supports the hypothesis that IL-4 exposure impairs sinonasal epithelial wound healing and may contribute to prolonged healing in Th2 inflammatory rhinosinusitis. PMID:23468432

  19. Acetate transiently inhibits myocardial contraction by increasing mitochondrial calcium uptake.

    Science.gov (United States)

    Schooley, James F; Namboodiri, Aryan M A; Cox, Rachel T; Bünger, Rolf; Flagg, Thomas P

    2014-12-09

    There is a close relationship between cardiovascular disease and cardiac energy metabolism, and we have previously demonstrated that palmitate inhibits myocyte contraction by increasing Kv channel activity and decreasing the action potential duration. Glucose and long chain fatty acids are the major fuel sources supporting cardiac function; however, cardiac myocytes can utilize a variety of substrates for energy generation, and previous studies demonstrate the acetate is rapidly taken up and oxidized by the heart. In this study, we tested the effects of acetate on contractile function of isolated mouse ventricular myocytes. Acute exposure of myocytes to 10 mM sodium acetate caused a marked, but transient, decrease in systolic sarcomere shortening (1.49 ± 0.20% vs. 5.58 ± 0.49% in control), accompanied by a significant increase in diastolic sarcomere length (1.81 ± 0.01 μm vs. 1.77 ± 0.01 μm in control), with a near linear dose response in the 1-10 mM range. Unlike palmitate, acetate caused no change in action potential duration; however, acetate markedly increased mitochondrial Ca(2+) uptake. Moreover, pretreatment of cells with the mitochondrial Ca(2+) uptake blocker, Ru-360 (10 μM), markedly suppressed the effect of acetate on contraction. Lehninger and others have previously demonstrated that the anions of weak aliphatic acids such as acetate stimulate Ca(2+) uptake in isolated mitochondria. Here we show that this effect of acetate appears to extend to isolated cardiac myocytes where it transiently modulates cell contraction.

  20. Disruptions of working memory and inhibition mediate the association between exposure to institutionalization and symptoms of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Tibu, F; Sheridan, M A; McLaughlin, K A; Nelson, C A; Fox, N A; Zeanah, C H

    2016-02-01

    Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD. A sample of 136 children (aged 6-30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners' offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity. Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years. Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.

  1. Palmitate and stearate binding to human serum albumin. Determination of relative binding constants

    DEFF Research Database (Denmark)

    Vorum, H; Fisker, K; Honoré, B

    1997-01-01

    Multiple binding equilibria of two apparently insoluble ligands, palmitate and stearate, to defatted human serum albumin were studied in a 66 mM sodium phosphate buffer (pH 7.4) at 37 degrees C, by determination of dialytic exchange rates of ligands among identical equilibrium solutions. The expe...

  2. The effect of vitamin A palmitate eye gel on ocular surface recovery after LASIK

    Directory of Open Access Journals (Sweden)

    Yan Lu

    2013-04-01

    Full Text Available AIM: To study the effect of vitamin A palmitate eye gel on ocular surface reconstruction after laser in situ keratomileusis(LASIK, and to evaluate the efficacy and safety. METHODS: One hundred and twenty patients(240 eyesperforming LASIK were enrolled in this study. The right and left eyes were randomly divided into experimental group and control group. The experimental group were treated with vitamin A palmitate eye gel for 1 month, four times a day after LASIK, and the same as control group in other treatments. The SchirmerⅠ test, break-up time(BUTand corneal sensation were detect at preoperation and the postoperative 1st day, 1st month, 3rd month in two groups. RESULTS: There were significant difference in BUT and tear secretion quantity between the experimental group and the control group at the postoperative 1st month and 3rd month(P0.05, which revealed that vitamin A palmitate eye gel had no obvious effect on recovery of corneal sensation after LASIK. During the treatment, there was no adverse drug event occurred. CONCLUSION: Early use of vitamin A palmitate eye gel postoperatively is applicable for ocular surface reconstruction, but has no obvious effect on the regeneration of corneal sensation.

  3. Regional cerebral palmitate incorporation following transient bilateral carotid occlusion in awake gerbils

    Energy Technology Data Exchange (ETDEWEB)

    Tone, O.; Miller, J.C.; Bell, J.M.; Rapoport, S.I.

    1987-11-01

    (/sup 14/C)Palmitate was injected intravenously in awake gerbils at various times after 5 minutes of bilateral carotid artery occlusion or a sham operation. Regional rates of incorporation of plasma palmitate into the hippocampus and other regions of the anterior circulation were determined relative to the mean rate of incorporation into regions of the posterior circulation using quantitative autoradiography and a ratio method of analysis. One day after bilateral carotid occlusion, relative palmitate incorporation was elevated significantly by 16% in the CA4 pyramidal cell layer and by 20% in the dentate gyrus of the hippocampus compared with sham-operated gerbils. At 3 days, significant elevations of this magnitude were found in the CA3 and CA4 cell layers, whereas relative incorporation was reduced by 26% in the CA1 pyramidal cell layer. At 7 days, the only significant difference from control was a 15% elevated incorporation in the CA3 pyramidal cell layer. Histologic examination indicated substantial cell death in the CA1 pyramidal layer at 3 days, with extensive glial reaction and phagocytic invasion at 7 days. Our results suggest that the turnover of palmitate-containing lipids is reduced in the CA1 layer of the gerbil hippocampus but that lipid synthesis is stimulated in hippocampal regions (CA3, CA4, dentate gyrus) affected by but recovering from transient bilateral carotid occlusion.

  4. Regional cerebral palmitate incorporation following transient bilateral carotid occlusion in awake gerbils

    International Nuclear Information System (INIS)

    Tone, O.; Miller, J.C.; Bell, J.M.; Rapoport, S.I.

    1987-01-01

    [ 14 C]Palmitate was injected intravenously in awake gerbils at various times after 5 minutes of bilateral carotid artery occlusion or a sham operation. Regional rates of incorporation of plasma palmitate into the hippocampus and other regions of the anterior circulation were determined relative to the mean rate of incorporation into regions of the posterior circulation using quantitative autoradiography and a ratio method of analysis. One day after bilateral carotid occlusion, relative palmitate incorporation was elevated significantly by 16% in the CA4 pyramidal cell layer and by 20% in the dentate gyrus of the hippocampus compared with sham-operated gerbils. At 3 days, significant elevations of this magnitude were found in the CA3 and CA4 cell layers, whereas relative incorporation was reduced by 26% in the CA1 pyramidal cell layer. At 7 days, the only significant difference from control was a 15% elevated incorporation in the CA3 pyramidal cell layer. Histologic examination indicated substantial cell death in the CA1 pyramidal layer at 3 days, with extensive glial reaction and phagocytic invasion at 7 days. Our results suggest that the turnover of palmitate-containing lipids is reduced in the CA1 layer of the gerbil hippocampus but that lipid synthesis is stimulated in hippocampal regions (CA3, CA4, dentate gyrus) affected by but recovering from transient bilateral carotid occlusion

  5. Synthesis and characterization of arabinose-palmitic acid esters by enzymatic esterification

    NARCIS (Netherlands)

    Pappalardo, Valeria M.; Boeriu, Carmen G.; Zaccheria, Federica; Ravasio, Nicoletta

    2017-01-01

    The direct esterification of palmitic acid with L-(+)-arabinose has been carried out. The use of Candida antartica lipase B as the catalyst and the choice of suitable solvent and experimental conditions allowed carrying out the reaction successfully. In particular 10% dimethyl-sulfoxide in

  6. HDO of Methyl Palmitate over Silica-Supported Ni Phosphides: Insight into Ni/P Effect

    Directory of Open Access Journals (Sweden)

    Irina V. Deliy

    2017-10-01

    Full Text Available Two sets of silica-supported nickel phosphide catalysts with a nickel content of about 2.5 and 10 wt % and Ni/P molar ratio 2/1, 1/1 and 1/2 in each set, were prepared by way of a temperature-programmed reduction method using (Ni(CH3COO2 and ((NH42HPO4 as a precursor. The NixPy/SiO2 catalysts were characterized using chemical analysis N2 physisorption, XRD, TEM, 31P MAS NMR. Methyl palmitate hydrodeoxygenation (HDO was performed in a trickle-bed reactor at 3 MPa and 290 °C with LHSV ranging from 0.3 to 16 h−1. The Ni/P ratio was found to affect the nickel phosphide phase composition, POx groups content and catalytic properties in methyl palmitate HDO with the TOF increased along with a decline of Ni/P ratio and a growth of POx groups’ content. Taking into account the possible routes of methyl palmitate conversion (metal-catalyzed hydrogenolysis or acid-catalyzed hydrolysis, we proposed that the enhancement of acid POx groups’ content with the Ni/P ratio decrease provides an enhancement of the rate of methyl palmitate conversion through the acceleration of acid-catalyzed hydrolysis.

  7. Palmitate Antagonizes Wnt/Beta-catenin Signaling in 3T3-L1 Pre-adipocytes

    Science.gov (United States)

    Long chain saturated free fatty acids such as palmitate (PA) produce insulin resistance, endoplasmic reticulum stress, and apoptosis in mature adipocytes and pre-adipocytes. In pre-adipocytes, saturated free fatty acids also promote adipogenic induction in the presence of adipogenic hormones. Wnt/be...

  8. Impact of palmitic acid coating on the water uptake and loss of ammonium sulfate particles

    Directory of Open Access Journals (Sweden)

    R. M. Garland

    2005-01-01

    Full Text Available While water insoluble organics are prevalent in the atmosphere, it is not clear how the presence of such species alters the chemical and physical properties of atmospheric aerosols. Here we use a combination of FTIR spectroscopy, Transmission Electron Microscopy (TEM and Aerosol Mass Spectrometry (AMS to characterize ammonium sulfate particles coated with palmitic acid. Coated aerosols were generated by atomizing pure ammonium sulfate, mixing the particles with a heated flow of nitrogen with palmitic acid vapor, and then flowing the mixture through an in-line oven to create internally mixed particles. The mixing state of the particles was probed using the AMS data and images from the TEM. Both of these probes suggest that the particles were internally mixed. Water uptake by the mixed particles was then probed at 273 K. It was found that for ammonium sulfate containing ~20 wt% palmitic acid the deliquescence relative humidity (DRH was the same as for pure ammonium sulfate (80±3% RH. For particles with ~50 wt% palmitic acid however, the mixed particles began to take up water at relative humidities as low at 69% and continued to slowly take up water to 85% RH without fully deliquescing. In addition to studies of water uptake, water loss was also investigated. Here coatings of up to 50 wt% had no impact on the efflorescence relative humidity. These studies suggest that even if insoluble substances coat salt particles in the atmosphere, there may be relatively little effect on the resulting water uptake and loss.

  9. Improved hydroxypropyl methylcellulose (HPMC) films through incorporation of amylose-sodium palmitate inclusion complexes

    Science.gov (United States)

    Polymer film blends of hydroxypropyl methylcellulose (HPMC) and amylose-sodium palmitate inclusion complexes (Na-Palm) were produced with no plasticizer, and were observed to have improved physical and gas barrier properties as compared with pure HPMC. The crystalline amylose helices incorporating t...

  10. Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes.

    Science.gov (United States)

    Jung, Jong Gab; Choi, Sung-E; Hwang, Yoon-Jung; Lee, Sang-A; Kim, Eun Kyoung; Lee, Min-Seok; Han, Seung Jin; Kim, Hae Jin; Kim, Dae Jung; Kang, Yup; Lee, Kwan-Woo

    2011-10-15

    Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and α-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. These results suggest that pyruvate depletion plays a critical role in PIGR and PIIGU; thus, pyruvate supplementation may help prevent obesity-induced insulin resistance in muscle cells. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Kirsten Roomp

    Full Text Available Studies on the pathophysiology of type 2 diabetes mellitus (T2DM have linked the accumulation of lipid metabolites to the development of beta-cell dysfunction and impaired insulin secretion. In most in vitro models of T2DM, rodent islets or beta-cell lines are used and typically focus is on specific cellular pathways or organs. Our aim was to, firstly, develop a combined lipidomics and proteomics approach for lipotoxicity in isolated human islets and, secondly, investigate if the approach could delineate novel and/ or confirm reported mechanisms of lipotoxicity. To this end isolated human pancreatic islets, exposed to chronically elevated palmitate concentrations for 0, 2 and 7 days, were functionally characterized and their levels of multiple targeted lipid and untargeted protein species determined. Glucose-stimulated insulin secretion from the islets increased on day 2 and decreased on day 7. At day 7 islet insulin content decreased and the proinsulin to insulin content ratio doubled. Amounts of cholesterol, stearic acid, C16 dihydroceramide and C24:1 sphingomyelin, obtained from the lipidomic screen, increased time-dependently in the palmitate-exposed islets. The proteomic screen identified matching changes in proteins involved in lipid biosynthesis indicating up-regulated cholesterol and lipid biosynthesis in the islets. Furthermore, proteins associated with immature secretory granules were decreased when palmitate exposure time was increased despite their high affinity for cholesterol. Proteins associated with mature secretory granules remained unchanged. Pathway analysis based on the protein and lipid expression profiles implicated autocrine effects of insulin in lipotoxicity. Taken together the study demonstrates that combining different omics approaches has potential in mapping of multiple simultaneous cellular events. However, it also shows that challenges exist for effectively combining lipidomics and proteomics in primary cells. Our

  12. Paliperidone Palmitate for Schizoaffective Disorder: A Review of the Clinical Evidence.

    Science.gov (United States)

    Greenberg, William M; Citrome, Leslie

    2015-12-01

    Despite being frequently diagnosed, there has been very limited study of efficacious treatments for schizoaffective disorder. Paliperidone had been approved for the treatment of schizoaffective disorder, and a recently completed relapse prevention study of the use of a once-monthly injectable paliperidone formulation has also led to an indication for that preparation to treat schizoaffective disorder. To review the efficacy and tolerability of paliperidone for schizoaffective disorder, we conducted a systematic literature search of studies of paliperidone in the treatment of schizoaffective disorder, and briefly reviewed evidence regarding the somewhat controversial nature of that diagnostic entity. We located several studies of the use of paliperidone extended release in the treatment of schizoaffective disorder, but only one completed study of the use of paliperidone palmitate, which demonstrated efficacy in preventing relapse. Three other studies are currently recruiting participants. Efficacy and tolerability were similar to the profile of oral paliperidone in the treatment of individuals with schizophrenia. These results were similar for both individuals treated with paliperidone palmitate alone, and for those treated with paliperidone palmitate with adjunctive mood stabilizers and/or antidepressants. The use of paliperidone palmitate does not require initial co-administration of oral paliperidone, has relatively little risk of drug-drug interactions, and its pharmacokinetics are favorable for once-monthly administration, an important treatment option for individuals with psychotic disorders, who may often be non-adherent to effective medication regimens. Paliperidone palmitate is an approved treatment for schizoaffective disorder, and can be efficacious with or without commonly employed adjunctive treatments.

  13. The novel, peripherally restricted GABAB receptor agonist lesogaberan (AZD3355) inhibits acid reflux and reduces esophageal acid exposure as measured with 24-h pHmetry in dogs.

    Science.gov (United States)

    Brändén, Lena; Fredriksson, Anita; Harring, Emelie; Jensen, Jörgen; Lehmann, Anders

    2010-05-25

    While patients with symptoms of gastroesophageal reflux disease generally respond well to proton pump inhibitors, 20-30% continue to experience troublesome symptoms. In such cases, agents that target transient lower esophageal sphincter (LES) relaxation may be useful as add-on therapy to proton pump inhibitors. The GABAB receptor agonist baclofen inhibits transient LES relaxation but it is not an ideal agent due to central nervous system activity. Lesogaberan (AZD3355) is a peripherally restricted GABAB receptor agonist with limited central nervous system activity that inhibits transient LES relaxation in dogs. In the present study, the comparative effects of lesogaberan (7 micromol/kg) and baclofen (2.8 micromol/kg) on reflux were studied in dogs using 24-h pHmetry. Drugs (or vehicle control) were administered orally prior to the first meal of the day, and the number of reflux episodes (pH or = 5 s) and acid exposure time were computed for the 24-h monitoring period. The mean (S.E.M.) number of reflux episodes/24 h was 4.6 (0.4) and 6.4 (0.6) for lesogaberan and baclofen, respectively, versus 10.7 (0.5) for control (PAcid exposure time was 51.2 (4.5) min for control versus 23.6 (3.8) min for lesogaberan (Pacid reflux in dogs, with comparable efficacy to baclofen. Copyright 2010 Elsevier B.V. All rights reserved.

  14. The dissimilar time course of temporary threshold shifts and reduction of inhibition in the inferior colliculus following intense sound exposure

    NARCIS (Netherlands)

    Heeringa, A. N.; van Dijk, P.

    Excessive noise exposure is known to produce an auditory threshold shift, which can be permanent or transient in nature. Recent studies showed that noise-induced temporary threshold shifts are associated with loss of synaptic connections to the inner hair cells and with cochlear nerve degeneration,

  15. Efficient inhibition of heavy metal release from mine tailings against acid rain exposure by triethylenetetramine intercalated montmorillonite (TETA-Mt).

    Science.gov (United States)

    Gong, Beini; Wu, Pingxiao; Huang, Zhujian; Li, Yuanyuan; Yang, Shanshan; Dang, Zhi; Ruan, Bo; Kang, Chunxi

    2016-11-15

    The potential application of triethylenetetramine intercalated montmorillonite (TETA-Mt) in mine tailings treatment and AMD (acid mine drainage) remediation was investigated with batch experiments. The structural and morphological characteristics of TETA-Mt were analyzed with XRD, FTIR, DTG-TG and SEM. The inhibition efficiencies of TETA-Mt against heavy metal release from mine tailings when exposed to acid rain leaching was examined and compared with that of triethylenetetramine (TETA) and Mt. Results showed that the overall inhibition by TETA-Mt surpassed that by TETA or Mt for various heavy metal ions over an acid rain pH range of 3-5.6 and a temperature range of 25-40°C. When mine tailings were exposed to acid rain of pH 4.8 (the average rain pH of the mining site where the mine tailings were from), TETA-Mt achieved an inhibition efficiency of over 90% for Cu(2+), Zn(2+), Cd(2+) and Mn(2+) release, and 70% for Pb(2+) at 25°C. It was shown that TETA-Mt has a strong buffering capacity. Moreover, TETA-Mt was able to adsorb heavy metal ions and the adsorption process was fast, suggesting that coordination was mainly responsible. These results showed the potential of TETA-Mt in AMD mitigation, especially in acid rain affected mining area. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Evaluation of the role of damage to photosystem II in the inhibition of CO2 assimilation in pea leaves on exposure to UV-B radiation

    International Nuclear Information System (INIS)

    Nogues, S.; Baker, N.R.

    1995-01-01

    Mature pea (Pisum sativum L., cv. Meteor) leaves were exposed to two levels of UV-B radiation, with and without supplementary UV-C radiation, during 15 h photoperiods. Simultaneous measurements of CO 2 assimilation and modulated chlorophyll fluorescence parameters demonstrated that irradiation with UV-B resulted in decreases in CO 2 assimilation that are not accompanied by decreases in the maximum quantum efficiency of photosystem II (PSII) primary photochemistry. Increased exposure to UV-B resulted in a further loss of CO 2 assimilation and decreases in the maximum quantum efficiency of PSII primary photochemistry, which were accompanied by a loss of the capacity of thylakoids isolated from the leaves to bind atrazine, thus demonstrating that photodamage to PSII reaction centres had occurred. Addition of UV-C to the UV-B treatments increased markedly the rate of inhibition of photosynthesis, but the relationships between CO 2 assimilation and PSII characteristics remained the same, indicating that UV-B and UV-C inhibit leaf photosynthesis by a similar mechanism. It is concluded that PSII is not the primary target site involved in the onset of the inhibition of photosynthesis in pea leaves induced by irradiation with UV-B. (author)

  17. Exercise Training Mitigates Water Pipe Smoke Exposure-Induced Pulmonary Impairment via Inhibiting NF-κB and Activating Nrf2 Signalling Pathways

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2018-01-01

    Full Text Available Water pipe smoking is a tobacco smoking method commonly used in Eastern countries and is gaining popularity in Europe and North America, in particular among adolescents and young adults. Several clinical and experimental studies have reported that exposure to water pipe smoke (WPS induces lung inflammation and impairment of pulmonary function. However, the mechanisms of such effects are not understood, as are data on the possible palliative effect of exercise training. The present study evaluated the effects of regular aerobic exercise training (treadmill: 5 days/week, 40 min/day on subchronic exposure to WPS (30 minutes/day, 5 days/week for 2 months. C57BL/6 mice were exposed to air or WPS with or without exercise training. Airway resistance measured using forced oscillation technique was significantly and dose-dependently increased in the WPS-exposed group when compared with the air-exposed one. Exercise training significantly prevented the effect of WPS on airway resistance. Histologically, the lungs of WPS-exposed mice had focal moderate interstitial inflammatory cell infiltration consisting of neutrophil polymorphs, plasma cells, and lymphocytes. There was a mild increase in intra-alveolar macrophages and a focal damage to alveolar septae in some foci. Exercise training significantly alleviated these effects and also decreased the WPS-induced increase of tumor necrosis factor α and interleukin 6 concentrations and attenuated the increase of 8-isoprostane in lung homogenates. Likewise, the lung DNA damage induced by WPS was significantly inhibited by exercise training. Moreover, exercise training inhibited nuclear factor kappa-B (NF-κB expression induced by WPS and increased that of nuclear factor erythroid 2-related factor 2 (Nrf2. Our findings suggest that exercise training significantly mitigated WPS-induced increase in airway resistance, inflammation, oxidative stress, and DNA damage via mechanisms that include inhibiting NF-κB and

  18. Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Cho Hyunju

    2013-01-01

    Full Text Available Abstract Background Palmitic acid, the most common saturated free fatty acid, has been implicated in ER (endoplasmic reticulum stress-mediated apoptosis. This lipoapotosis is dependent, in part, on the upregulation of the activating transcription factor-4 (ATF4. To better understand the mechanisms by which palmitate upregulates the expression level of ATF4, we integrated literature information on palmitate-induced ER stress signaling into a discrete dynamic model. The model provides an in silico framework that enables simulations and predictions. The model predictions were confirmed through further experiments in human hepatocellular carcinoma (HepG2 cells and the results were used to update the model and our current understanding of the signaling induced by palmitate. Results The three key things from the in silico simulation and experimental results are: 1 palmitate induces different signaling pathways (PKR (double-stranded RNA-activated protein kinase, PERK (PKR-like ER kinase, PKA (cyclic AMP (cAMP-dependent protein kinase A in a time dependent-manner, 2 both ATF4 and CREB1 (cAMP-responsive element-binding protein 1 interact with the Atf4 promoter to contribute to a prolonged accumulation of ATF4, and 3 CREB1 is involved in ER-stress induced apoptosis upon palmitate treatment, by regulating ATF4 expression and possibly Ca2+ dependent-CaM (calmodulin signaling pathway. Conclusion The in silico model helped to delineate the essential signaling pathways in palmitate-mediated apoptosis.

  19. Inhibition of NAPDH Oxidase 2 (NOX2 Prevents Oxidative Stress and Mitochondrial Abnormalities Caused by Saturated Fat in Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Leroy C Joseph

    Full Text Available Obesity and high saturated fat intake increase the risk of heart failure and arrhythmias. The molecular mechanisms are poorly understood. We hypothesized that physiologic levels of saturated fat could increase mitochondrial reactive oxygen species (ROS in cardiomyocytes, leading to abnormalities of calcium homeostasis and mitochondrial function. We investigated the effect of saturated fat on mitochondrial function and calcium homeostasis in isolated ventricular myocytes. The saturated fatty acid palmitate causes a decrease in mitochondrial respiration in cardiomyocytes. Palmitate, but not the monounsaturated fatty acid oleate, causes an increase in both total cellular ROS and mitochondrial ROS. Palmitate depolarizes the mitochondrial inner membrane and causes mitochondrial calcium overload by increasing sarcoplasmic reticulum calcium leak. Inhibitors of PKC or NOX2 prevent mitochondrial dysfunction and the increase in ROS, demonstrating that PKC-NOX2 activation is also required for amplification of palmitate induced-ROS. Cardiomyocytes from mice with genetic deletion of NOX2 do not have palmitate-induced ROS or mitochondrial dysfunction. We conclude that palmitate induces mitochondrial ROS that is amplified by NOX2, causing greater mitochondrial ROS generation and partial depolarization of the mitochondrial inner membrane. The abnormal sarcoplasmic reticulum calcium leak caused by palmitate could promote arrhythmia and heart failure. NOX2 inhibition is a potential therapy for heart disease caused by diabetes or obesity.

  20. The effects of MEK1/2 inhibition on cigarette smoke exposure-induced ET receptor upregulation in rat cerebral arteries

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Lei [Division of Experimental Vascular Research, Institute of Clinical Sciences in Lund, Lund University (Sweden); Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an, Shaanxi (China); Ping, Na-Na; Cao, Yong-Xiao [Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an, Shaanxi (China); Li, Wei, E-mail: 13572512207@163.com [Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an, Shaanxi (China); Cai, Yan [Department of Pharmacology, School of Basic Medical Sciences, Xi' an Jiaotong University Health Science Center, Xi' an, Shaanxi (China); Warfvinge, Karin; Edvinsson, Lars [Division of Experimental Vascular Research, Institute of Clinical Sciences in Lund, Lund University (Sweden)

    2016-08-01

    Cigarette smoking, a major stroke risk factor, upregulates endothelin receptors in cerebral arteries. The present study examined the effects of MEK1/2 pathway inhibition on cigarette smoke exposure-induced ET receptor upregulation. Rats were exposed to the secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of MEK1/2 inhibitor, U0126 for another 4 weeks. The urine cotinine levels were assessed with high-performance liquid chromatography. Contractile responses of isolated cerebral arteries were recorded by a sensitive wire myograph. The mRNA and protein expression levels of receptor and MEK/ERK1/2 pathway molecules were examined by real-time PCR and Western blotting, respectively. Cerebral artery receptor localization was determined with immunohistochemistry. The results showed the urine cotinine levels from SHS exposure group were significantly higher than those from the fresh group. In addition, the MEK1/2 inhibitor, U0126 significantly reduced SHS exposure-increased ET{sub A} receptor mRNA and protein levels as well as contractile responses mediated by ET{sub A} receptors. The immunoreactivity of increased ET{sub A} receptor expression was primarily cytoplasmic in smooth muscle cells. In contrast, ET{sub B} receptor was noted in endothelial cells. However, the SHS-induced decrease in endothelium-dependent relaxation was unchanged after U0126 treatment. Furthermore, SHS increased the phosphorylation of MEK1/2 and ERK1/2 protein in cerebral arteries. By using U0126 could inhibit the phosphorylated ERK1/2 protein but not MEK1/2. Taken together, our data show that treatment with MEK1/2 pathway inhibitor offsets SHS exposure-induced ET{sub A} receptor upregulation in rat cerebral arteries. - Highlights: • Cigarette smoke exposure induces ET{sub A} receptor upregulation in rat cerebral arteries. • U0126 can alleviate the receptor upregulation. • The mechanism relies on MEK/ERK1/2 pathway activation. • We may provide a new target for the

  1. The effects of MEK1/2 inhibition on cigarette smoke exposure-induced ET receptor upregulation in rat cerebral arteries

    International Nuclear Information System (INIS)

    Cao, Lei; Ping, Na-Na; Cao, Yong-Xiao; Li, Wei; Cai, Yan; Warfvinge, Karin; Edvinsson, Lars

    2016-01-01

    Cigarette smoking, a major stroke risk factor, upregulates endothelin receptors in cerebral arteries. The present study examined the effects of MEK1/2 pathway inhibition on cigarette smoke exposure-induced ET receptor upregulation. Rats were exposed to the secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of MEK1/2 inhibitor, U0126 for another 4 weeks. The urine cotinine levels were assessed with high-performance liquid chromatography. Contractile responses of isolated cerebral arteries were recorded by a sensitive wire myograph. The mRNA and protein expression levels of receptor and MEK/ERK1/2 pathway molecules were examined by real-time PCR and Western blotting, respectively. Cerebral artery receptor localization was determined with immunohistochemistry. The results showed the urine cotinine levels from SHS exposure group were significantly higher than those from the fresh group. In addition, the MEK1/2 inhibitor, U0126 significantly reduced SHS exposure-increased ET A receptor mRNA and protein levels as well as contractile responses mediated by ET A receptors. The immunoreactivity of increased ET A receptor expression was primarily cytoplasmic in smooth muscle cells. In contrast, ET B receptor was noted in endothelial cells. However, the SHS-induced decrease in endothelium-dependent relaxation was unchanged after U0126 treatment. Furthermore, SHS increased the phosphorylation of MEK1/2 and ERK1/2 protein in cerebral arteries. By using U0126 could inhibit the phosphorylated ERK1/2 protein but not MEK1/2. Taken together, our data show that treatment with MEK1/2 pathway inhibitor offsets SHS exposure-induced ET A receptor upregulation in rat cerebral arteries. - Highlights: • Cigarette smoke exposure induces ET A receptor upregulation in rat cerebral arteries. • U0126 can alleviate the receptor upregulation. • The mechanism relies on MEK/ERK1/2 pathway activation. • We may provide a new target for the treatment of SHS

  2. Time-dependent inhibition of Na+/K+-ATPase induced by single and simultaneous exposure to lead and cadmium

    Science.gov (United States)

    Vasić, V.; Kojić, D.; Krinulović, K.; Čolović, M.; Vujačić, A.; Stojić, D.

    2007-09-01

    Time-dependent interactions of Na+/K+-ATPase, isolated from rat brain synaptic plasma membranes (SPMs), with Cd2+ and Pb2+ ions in a single exposure and in a mixture were investigated in vitro. The interference of the enzyme with these metal ions was studied as a function of different protein concentrations and exposure time. The aim of the work was to investigate the possibility of selective recognition of Cd2+ and Pb2+ ions in a mixture, on the basis of the different rates of their protein-ligand interactions. Decreasing protein concentration increased the sensitivity of Na+/K+-ATPase toward both metals. The selectivity in protein-ligand interactions was obtained by variation of preincubation time (incubation before starting the enzymatic reaction).

  3. Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways.

    Science.gov (United States)

    Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

    2017-06-27

    The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use.

  4. Effects of Agricultural Management Policies on the Exposure of Black-Winged Stilts (Himantopus himantopus Chicks to Cholinesterase-Inhibiting Pesticides in Rice Fields.

    Directory of Open Access Journals (Sweden)

    Gregorio M Toral

    Full Text Available Levels of exposure to pesticides in rice fields can be significant depending on the environmental policies practiced. The aim of European Union integrated management policy is to reduce pesticide use and impact on environment. Rice fields provide an alternative breeding habitat for many waterbirds that are exposed to the pesticides used and therefore can be valuable indicators of their risk for wildlife. To evaluate integrated management success we examined exposure of Black-winged Stilts (Himantopus himantopus to cholinesterase-inhibiting pesticides in rice fields under different types of management by measuring plasma cholinesterase activity. Cholinesterase activity was lower in birds sampled in (a 2008 after a period of intense pesticide application, than in (b 2005-2007 and 2011 in rice fields subject to integrated management in Doñana (SW Spain and (c in control natural wetlands in Spain and Morocco. During 2009 and 2010, cholinesterase activity was lower in rice fields in Doñana than in rice fields in Larache and Sidi Allal Tazi (NW Morocco. Our results suggest that integrated management successfully reduced the exposure of Black-winged Stilts to pesticides in most of the years. Care should be taken to implement mosquito and pest crop controls on time and with environmentally friendly products in order to reduce its impact on wildlife.

  5. Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Ji, Zhi-Hong; Xu, Zhong-Qi; Zhao, Hong; Yu, Xin-Yu

    2017-03-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory decline and cognitive impairment. Amyloid beta (Aβ) has been proposed as the causative role for the pathogenesis of AD. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. Daucosterol palmitate (DSP), a plant steroid with anti-glutamate excitotoxicity effect, was isolated from the anti-aging traditional Chinese medicinal herb Alpinia oxyphylla Miq. in our previous study. Based on the anti-glutamate excitotoxicity effect of DSP, in this study we investigated potential benefit and mechanism of DSP in ameliorating learning and memory impairment in AD model rats. Results from this study showed that DSP administration effectively ameliorated Aβ-induced learning and memory impairment in rats, markedly inhibited Aβ-induced hippocampal ROS production, effectively prevented Aβ-induced hippocampal neuronal damage and significantly restored hippocampal synaptophysin expression level. This study suggests that DSP may be a potential candidate for development as a therapeutic agent for AD cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Palmitate and insulin synergistically induce IL-6 expression in human monocytes

    Directory of Open Access Journals (Sweden)

    Lumpkin Charles K

    2010-11-01

    Full Text Available Abstract Background Insulin resistance is associated with a proinflammatory state that promotes the development of complications such as type 2 diabetes mellitus (T2DM and atherosclerosis. The metabolic stimuli that initiate and propagate proinflammatory cytokine production and the cellular origin of proinflammatory cytokines in insulin resistance have not been fully elucidated. Circulating proinflammatory monocytes show signs of enhanced inflammation in obese, insulin resistant subjects and are thus a potential source of proinflammatory cytokine production. The specific, circulating metabolic factors that might stimulate monocyte inflammation in insulin resistant subjects are poorly characterized. We have examined whether saturated nonesterified fatty acids (NEFA and insulin, which increase in concentration with developing insulin resistance, can trigger the production of interleukin (IL-6 and tumor necrosis factor (TNF-α in human monocytes. Methods Messenger RNA and protein levels of the proinflammatory cytokines IL-6 and TNF-α were measured by quantitative real-time PCR (qRT-PCR and Luminex bioassays. Student's t-test was used with a significance level of p Results Esterification of palmitate with coenzyme A (CoA was necessary, while β-oxidation and ceramide biosynthesis were not required, for the induction of IL-6 and TNF-α in THP-1 monocytes. Monocytes incubated with insulin and palmitate together produced more IL-6 mRNA and protein, and more TNF-α protein, compared to monocytes incubated with palmitate alone. Incubation of monocytes with insulin alone did not affect the production of IL-6 or TNF-α. Both PI3K-Akt and MEK/ERK signalling pathways are important for cytokine induction by palmitate. MEK/ERK signalling is necessary for synergistic induction of IL-6 by palmitate and insulin. Conclusions High levels of saturated NEFA, such as palmitate, when combined with hyperinsulinemia, may activate human monocytes to produce

  7. The dissimilar time course of temporary threshold shifts and reduction of inhibition in the inferior colliculus following intense sound exposure.

    Science.gov (United States)

    Heeringa, A N; van Dijk, P

    2014-06-01

    Excessive noise exposure is known to produce an auditory threshold shift, which can be permanent or transient in nature. Recent studies showed that noise-induced temporary threshold shifts are associated with loss of synaptic connections to the inner hair cells and with cochlear nerve degeneration, which is reflected in a decreased amplitude of wave I of the auditory brainstem response (ABR). This suggests that, despite normal auditory thresholds, central auditory processing may be abnormal. We recorded changes in central auditory processing following a sound-induced temporary threshold shift. Anesthetized guinea pigs were exposed for 1 h to a pure tone of 11 kHz (124 dB sound pressure level). Hearing thresholds, amplitudes of ABR waves I and IV, and spontaneous and tone-evoked firing rates in the inferior colliculus (IC) were assessed immediately, one week, two weeks, and four weeks post exposure. Hearing thresholds were elevated immediately following overexposure, but recovered within one week. The amplitude of the ABR wave I was decreased in all sound-exposed animals for all test periods. In contrast, the ABR wave IV amplitude was only decreased immediately after overexposure and recovered within a week. The proportion of IC units that show inhibitory responses to pure tones decreased substantially up to two weeks after overexposure, especially when stimulated with high frequencies. The proportion of excitatory responses to low frequencies was increased. Spontaneous activity was unaffected by the overexposure. Despite rapid normalization of auditory thresholds, our results suggest an increased central gain following sound exposure and an abnormal balance between excitatory and inhibitory responses in the midbrain up to two weeks after overexposure. These findings may be associated with hyperacusis after a sound-induced temporary threshold shift. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Inhibition of P-glycoprotein and multidrug resistance-associated protein 2 regulates the hepatobiliary excretion and plasma exposure of thienorphine and its glucuronide conjugate

    Directory of Open Access Journals (Sweden)

    Ling-Lei Kong

    2016-08-01

    Full Text Available Thienorphine (TNP is a novel partial opioid agonist that has completed phase II clinical evaluation as a promising drug candidate for the treatment of opioid dependence. Previous studies have shown that TNP and its glucuronide conjugate (TNP-G undergo significant bile excretion. The purpose of this study was to investigate the roles of efflux transporters in regulating biliary excretion and plasma exposure of TNP and TNP-G. An ATPase assay suggested that TNP and TNP-G were substrates of P-gp and MRP2, respectively. The in vitro data from rat hepatocytes showed that bile excretion of TNP and TNP-G was regulated by the P-gp and MRP2 modulators. The accumulation of TNP and TNP-G in HepG2 cells significantly increased by the treatment of mdr1a or MRP2 siRNA for P-gp or MRP2 modulation. In intact rats, the bile excretion and pharmacokinetic profiles of TNP and TNP-G were remarkably changed with tariquidar and probenecid pretreatment, respectively. Tariquidar increased the Cmax and AUC0-t and decreased MRT and T1/2 of TNP, whereas probenecid decreased the plasma exposure of TNP-G and increased its T1/2. Knockdown P-gp and MRP2 function using siRNA significantly increased the plasma exposure of TNP and TNP-G and reduced their mean retention time in mice. These results indicated the important roles of P-gp and MRP2 in hepatobiliary excretion and plasma exposure of TNP and TNP-G. Inhibition of the efflux transporters may affect the pharmacokinetics of TNP and result in a drug-drug interaction between TNP and the concomitant transporter inhibitor or inducer in clinic.

  9. Impairment of object recognition memory by maternal bisphenol A exposure is associated with inhibition of Akt and ERK/CREB/BDNF pathway in the male offspring hippocampus.

    Science.gov (United States)

    Wang, Chong; Li, Zhihui; Han, Haijun; Luo, Guangying; Zhou, Bingrui; Wang, Shaolin; Wang, Jundong

    2016-02-03

    Bisphenol A (BPA) is a commonly used endocrine-disrupting chemical used as a component of polycarbonates plastics that has potential adverse effects on human health. Exposure to BPA during development has been implicated in memory deficits, but the mechanism of action underlying the effect is not fully understood. In this study, we investigated the effect of maternal exposure to BPA on object recognition memory and the expressions of proteins important for memory, especially focusing on the ERK/CREB/BDNF pathway. Pregnant Sprague-Dawley female rats were orally treated with either vehicle or BPA (0.05, 0.5, 5 or 50 mg/kg BW/day) during days 9-20 of gestation. Male offspring were tested on postnatal day 21 with the object recognition task. Recognition memory was assessed using the object recognition index (index=the time spent exploring the novel object/(the time spent exploring the novel object+the time spent exploring the familiar object)). In the test session performed 90 min after the training session, BPA-exposed male offspring not only spent more time in exploring the familiar object at the highest dose than the control, but also displayed a significantly decreased the object recognition index at the doses of 0.5, 5 and 50 mg/kg BW/day. During the test session performed 24h after the training session, BPA-treated males did not change the time spent exploring the familiar object, but had a decreased object recognition index at 5 and 50 mg/kg BW/day, when compared to control group. These findings indicate that object recognition memory was susceptible to maternal BPA exposure. Western blot analysis of hippocampi from BPA-treated male offspring revealed a decrease in Akt, phospho-Akt, p44/42 MAPK and phospho-p44/42 MAPK protein levels, compared to controls. In addition, BPA significantly inhibited the levels of phosphorylation of CREB and BDNF in the hippocampus. Our results show that maternal BPA exposure may full impair object recognition memory, and that

  10. Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid-induced insulin resistance.

    Science.gov (United States)

    Shinjo, Satoko; Jiang, Shuying; Nameta, Masaaki; Suzuki, Tomohiro; Kanai, Mai; Nomura, Yuta; Goda, Nobuhito

    2017-10-01

    The mitochondria-associated ER membrane (MAM) is a specialized subdomain of ER that physically connects with mitochondria. Although disruption of inter-organellar crosstalk via the MAM impairs cellular homeostasis, its pathological significance in insulin resistance in type 2 diabetes mellitus remains unclear. Here, we reveal the importance of reduced MAM formation in the induction of fatty acid-evoked insulin resistance in hepatocytes. Palmitic acid (PA) repressed insulin-stimulated Akt phosphorylation in HepG2 cells within 12h. Treatment with an inhibitor of the ER stress response failed to restore PA-mediated suppression of Akt activation. Mitochondrial reactive oxygen species (ROS) production did not increase in PA-treated cells. Even short-term exposure (3h) to PA reduced the calcium flux from ER to mitochondria, followed by a significant decrease in MAM contact area, suggesting that PA suppressed the functional interaction between ER and mitochondria. Forced expression of mitofusin-2, a critical component of the MAM, partially restored MAM contact area and ameliorated the PA-elicited suppression of insulin sensitivity with Ser473 phosphorylation of Akt selectively improved. These results suggest that loss of proximity between ER and mitochondria, but not perturbation of homeostasis in the two organelles individually, plays crucial roles in PA-evoked Akt inactivation in hepatic insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Exposure to high glutamate concentration activates aerobic glycolysis but inhibits ATP-linked respiration in cultured cortical astrocytes.

    Science.gov (United States)

    Shen, Yao; Tian, Yueyang; Shi, Xiaojie; Yang, Jianbo; Ouyang, Li; Gao, Jieqiong; Lu, Jianxin

    2014-08-01

    Astrocytes play a key role in removing the synaptically released glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. However, high concentration of glutamate leads to toxicity in astrocytes, and the underlying mechanisms are unclear. The purpose of this study was to investigate whether energy metabolism disorder, especially impairment of mitochondrial respiration, is involved in the glutamate-induced gliotoxicity. Exposure to 10-mM glutamate for 48 h stimulated glycolysis and respiration in astrocytes. However, the increased oxygen consumption was used for proton leak and non-mitochondrial respiration, but not for oxidative phosphorylation and ATP generation. When the exposure time extended to 72 h, glycolysis was still activated for ATP generation, but the mitochondrial ATP-linked respiration of astrocytes was reduced. The glutamate-induced astrocyte damage can be mimicked by the non-metabolized substrate d-aspartate but reversed by the non-selective glutamate transporter inhibitor TBOA. In addition, the glutamate toxicity can be partially reversed by vitamin E. These findings demonstrate that changes of bioenergetic profile occur in cultured cortical astrocytes exposed to high concentration of glutamate and highlight the role of mitochondria respiration in glutamate-induced gliotoxicity in cortical astrocytes. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure

    International Nuclear Information System (INIS)

    Fujimura, Masatake; Usuki, Fusako; Kawamura, Miwako; Izumo, Shuji

    2011-01-01

    Methylmercury (MeHg) is an environmental neurotoxicant which induces neuropathological changes in both the central nervous and peripheral sensory nervous systems. Our recent study demonstrated that down-regulation of Ras-related C3 botulinum toxin substrate 1 (Rac1), which is known to promote neuritic extension, preceded MeHg-induced damage in cultured cortical neurons, suggesting that MeHg-mediated axonal degeneration is due to the disturbance of neuritic extension. Therefore we hypothesized that MeHg-induced axonal degeneration might be caused by neuritic extension/retraction incoordination. This idea brought our attention to the Ras homolog gene (Rho)/Rho-associated coiled coil-forming protein kinase (ROCK) pathway because it has been known to be associated with the development of axon and apoptotic neuronal cell death. Here we show that inhibition of the Rho/ROCK pathway prevents MeHg-intoxication both in vitro and in vivo. A Rho inhibitor, C3 toxin, and 2 ROCK inhibitors, Fasudil and Y-27632, significantly protected against MeHg-induced axonal degeneration and apoptotic neuronal cell death in cultured cortical neuronal cells exposed to 100 nM MeHg for 3 days. Furthermore, Fasudil partially prevented the loss of large pale neurons in dorsal root ganglia, axonal degeneration in dorsal spinal root nerves, and vacuolar degeneration in the dorsal columns of the spinal cord in MeHg-intoxicated model rats (20 ppm MeHg in drinking water for 28 days). Hind limb crossing sign, a characteristic MeHg-intoxicated sign, was significantly suppressed in this model. The results suggest that inhibition of the Rho/ROCK pathway rescues MeHg-mediated neuritic extension/retraction incoordination and is effective for the prevention of MeHg-induced axonal degeneration and apoptotic neuronal cell death.

  13. Efficient dermal delivery of retinyl palmitate: Progressive polarimetry and Raman spectroscopy to evaluate the structure and efficacy.

    Science.gov (United States)

    Lee, Jun Bae; Lee, Dong Ryeol; Choi, Nak Cho; Jang, Jihui; Park, Chun Ho; Yoon, Moung Seok; Lee, Miyoung; Won, Kyoungae; Hwang, Jae Sung; Kim, B Moon

    2015-10-12

    Over the past decades, there has been a growing interest in dermal drug delivery. Although various novel delivery devices and methods have been developed, dermal delivery is still challenging because of problems such as poor drug permeation, instability of vesicles and drug leakage from vesicles induced by fusion of vesicles. To solve the vesicle instability problems in current dermal delivery systems, we developed materials comprised of liquid crystals as a new delivery vehicle of retinyl palmitate and report the characterization of the liquid crystals using a Mueller matrix polarimetry. The stability of the liquid-crystal materials was evaluated using the polarimeter as a novel evaluation tool along with other conventional methods. The dermal delivery of retinyl palmitate was investigated through the use of confocal Raman spectroscopy. The results indicate that the permeation of retinyl palmitate was enhanced by up to 106% compared to that using an ordinary emulsion with retinyl palmitate. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium

    International Nuclear Information System (INIS)

    Schwaiger, M.; Schelbert, H.R.; Keen, R.; Vinten-Johansen, J.; Hansen, H.; Selin, C.; Barrio, J.; Huang, S.C.; Phelps, M.E.

    1985-01-01

    Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury

  15. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

    OpenAIRE

    Benoit, Stephen C.; Kemp, Christopher J.; Elias, Carol F.; Abplanalp, William; Herman, James P.; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G.; Holland, William L.; Clegg, Deborah J.

    2009-01-01

    Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of ...

  16. Cystic fibrosis bronchial epithelial cells are lipointoxicated by membrane palmitate accumulation.

    Directory of Open Access Journals (Sweden)

    Laurie-Anne Payet

    Full Text Available The F508del-CFTR mutation, responsible for Cystic Fibrosis (CF, leads to the retention of the protein in the endoplasmic reticulum (ER. The mistrafficking of this mutant form can be corrected by pharmacological chaperones, but these molecules showed limitations in clinical trials. We therefore hypothesized that important factors in CF patients may have not been considered in the in vitro assays. CF has also been associated with an altered lipid homeostasis, i. e. a decrease in polyunsaturated fatty acid levels in plasma and tissues. However, the precise fatty acyl content of membrane phospholipids from human CF bronchial epithelial cells had not been studied to date. Since the saturation level of phospholipids can modulate crucial membrane properties, with potential impacts on membrane protein folding/trafficking, we analyzed this parameter for freshly isolated bronchial epithelial cells from CF patients. Interestingly, we could show that Palmitate, a saturated fatty acid, accumulates within Phosphatidylcholine (PC in CF freshly isolated cells, in a process that could result from hypoxia. The observed PC pattern can be recapitulated in the CFBE41o(- cell line by incubation with 100 µM Palmitate. At this concentration, Palmitate induces an ER stress, impacts calcium homeostasis and leads to a decrease in the activity of the corrected F508del-CFTR. Overall, these data suggest that bronchial epithelial cells are lipointoxicated by hypoxia-related Palmitate accumulation in CF patients. We propose that this phenomenon could be an important bottleneck for F508del-CFTR trafficking correction by pharmacological agents in clinical trials.

  17. Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aβ40 Insult

    OpenAIRE

    Zhangyang Qi; Meihao Wu; Yun Fu; Tengfei Huang; Tingting Wang; Yanjie Sun; Zhibo Feng; Changzheng Li

    2017-01-01

    Background/Aims: The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer’s disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane...

  18. A Case of Ileus in a Patient with Schizophrenia Under Paliperidone Palmitate Treatment

    OpenAIRE

    Can, Serdar S?leyman; Kabaday?, Esra

    2016-01-01

    Constipation is a side effect of antipsychotic drugs that have high affinity for muscarinic cholinergic receptors. In addition, ileus is an important side effect of antipsychotic treatment, with potentially morbid and mortal consequences if early detection fails. In this report, a colonic ileus case is described in a patient with schizophrenia under the treatment of paliperidone palmitate. Consequently, complete physical examination and close screening of side effects are recommended when ant...

  19. Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression

    International Nuclear Information System (INIS)

    Myllymaeki, S.A.; Karjalainen, M.; Haavisto, T.E.; Toppari, J.; Paranko, J.

    2005-01-01

    Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg) subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening

  20. Cardiac development in zebrafish and human embryonic stem cells is inhibited by exposure to tobacco cigarettes and e-cigarettes.

    Directory of Open Access Journals (Sweden)

    Nathan J Palpant

    Full Text Available Maternal smoking is a risk factor for low birth weight and other adverse developmental outcomes.We sought to determine the impact of standard tobacco cigarettes and e-cigarettes on heart development in vitro and in vivo.Zebrafish (Danio rerio were used to assess developmental effects in vivo and cardiac differentiation of human embryonic stem cells (hESCs was used as a model for in vitro cardiac development.In zebrafish, exposure to both types of cigarettes results in broad, dose-dependent developmental defects coupled with severe heart malformation, pericardial edema and reduced heart function. Tobacco cigarettes are more toxic than e-cigarettes at comparable nicotine concentrations. During cardiac differentiation of hESCs, tobacco smoke exposure results in a delayed transition through mesoderm. Both types of cigarettes decrease expression of cardiac transcription factors in cardiac progenitor cells, suggesting a persistent delay in differentiation. In definitive human cardiomyocytes, both e-cigarette- and tobacco cigarette-treated samples showed reduced expression of sarcomeric genes such as MLC2v and MYL6. Furthermore, tobacco cigarette-treated samples had delayed onset of beating and showed low levels and aberrant localization of N-cadherin, reduced myofilament content with significantly reduced sarcomere length, and increased expression of the immature cardiac marker smooth muscle alpha-actin.These data indicate a negative effect of both tobacco cigarettes and e-cigarettes on heart development in vitro and in vivo. Tobacco cigarettes are more toxic than E-cigarettes and exhibit a broader spectrum of cardiac developmental defects.

  1. Synthesis and preliminary evaluation of {sup 18}F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation

    Energy Technology Data Exchange (ETDEWEB)

    DeGrado, Timothy R. E-mail: trd@petsparc.mc.duke.edu; Wang Shuyan; Holden, James E.; Nickles, R. Jerome; Taylor, Michael; Stone, Charles K

    2000-04-01

    Interest remains strong for the development of a noninvasive technique for assessment of regional fatty acid oxidation rate in the myocardium. {sup 18}F-labeled 4-thia palmitate (FTP, 16-[{sup 18}F]fluoro-4-thia-hexadecanoic acid) has been synthesized and preliminarily evaluated as a metabolically trapped probe of myocardial fatty acid oxidation for positron emission tomography (PET). The radiotracer is synthesized by Kryptofix 2.2.2/K{sub 2}CO{sub 3} assisted nucleophilic radiofluorination of an iodo-ester precursor, followed by alkaline hydrolysis and by purification by reverse phase high performance liquid chromatography. Biodistribution studies in rats showed high uptake and long retention of FTP in heart, liver, and kidneys consistent with relatively high fatty acid oxidation rates in these tissues. Inhibition of carnitine palmitoyl-transferase-I caused an 80% reduction in myocardial uptake, suggesting the dependence of trapping on the transport of tracer into the mitochondrion. Experiments with perfused rat hearts showed that the estimates of the fractional metabolic trapping rate (FR) of FTP tracked inhibition of oxidation rate of palmitate with hypoxia, whereas the FR of the 6-thia analog 17-[{sup 18}F]fluoro-6-thia-heptadecanoic acid was insensitive to hypoxia. In vivo defluorination of FTP in the rat was evidenced by bone uptake of radioactivity. A PET imaging study with FTP in normal swine showed excellent myocardial images, prolonged myocardial retention, and no bone uptake of radioactivity up to 3 h, the last finding suggesting a species dependence for defluorination of the omega-labeled fatty acid. The results support further investigation of FTP as a potential PET tracer for assessing regional fatty acid oxidation rate in the human myocardium.

  2. Synthesis and preliminary evaluation of 18F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation

    International Nuclear Information System (INIS)

    DeGrado, Timothy R.; Wang Shuyan; Holden, James E.; Nickles, R. Jerome; Taylor, Michael; Stone, Charles K.

    2000-01-01

    Interest remains strong for the development of a noninvasive technique for assessment of regional fatty acid oxidation rate in the myocardium. 18 F-labeled 4-thia palmitate (FTP, 16-[ 18 F]fluoro-4-thia-hexadecanoic acid) has been synthesized and preliminarily evaluated as a metabolically trapped probe of myocardial fatty acid oxidation for positron emission tomography (PET). The radiotracer is synthesized by Kryptofix 2.2.2/K 2 CO 3 assisted nucleophilic radiofluorination of an iodo-ester precursor, followed by alkaline hydrolysis and by purification by reverse phase high performance liquid chromatography. Biodistribution studies in rats showed high uptake and long retention of FTP in heart, liver, and kidneys consistent with relatively high fatty acid oxidation rates in these tissues. Inhibition of carnitine palmitoyl-transferase-I caused an 80% reduction in myocardial uptake, suggesting the dependence of trapping on the transport of tracer into the mitochondrion. Experiments with perfused rat hearts showed that the estimates of the fractional metabolic trapping rate (FR) of FTP tracked inhibition of oxidation rate of palmitate with hypoxia, whereas the FR of the 6-thia analog 17-[ 18 F]fluoro-6-thia-heptadecanoic acid was insensitive to hypoxia. In vivo defluorination of FTP in the rat was evidenced by bone uptake of radioactivity. A PET imaging study with FTP in normal swine showed excellent myocardial images, prolonged myocardial retention, and no bone uptake of radioactivity up to 3 h, the last finding suggesting a species dependence for defluorination of the omega-labeled fatty acid. The results support further investigation of FTP as a potential PET tracer for assessing regional fatty acid oxidation rate in the human myocardium

  3. 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.

  4. 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.

  5. Inhibiting TGFβ1 has a protective effect on mouse bone marrow suppression following ionizing radiation exposure in vitro

    International Nuclear Information System (INIS)

    Zhang Heng; Yan Hao; Wang Xinzhuo; Niu Jingxiu; Wang Hui; Wang Yingai; Meng Aimin; Li Jin

    2013-01-01

    Ionizing radiation (IR) causes not only acute tissue damage but also residual bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to the induction of reactive oxygen species (ROS) pressure in hematopoietic cells. In this study, we examined if SB431542, a transforming growth factor β1 (TGFβ1) inhibitor, can mitigate IR-induced BM suppression in vitro. Our results showed that treatment with SB431542 protected mice bone marrow mononuclear cells (BMMNCs), hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) from IR-induced suppression using cell viability assays, clonogenic assays and competitive repopulation assays. Moreover, expression of gene-related ROS production in hematopoietic cells was analyzed. The expression of NADPH oxidative 1 (NOX1), NOX2 and NOX4 was increased in irradiated BMMNCs, and that of NOX2 and NOX4 was reduced by SB431542 treatment. Therefore, the results from this study suggest that SB431542, a TGFβ1 inhibitor, alleviates IR-induced BM suppression at least in part via inhibiting IR-induced NOX2 and NOX4 expression. (author)

  6. Fast algal eco-toxicity assessment: Influence of light intensity and exposure time on Chlorella vulgaris inhibition by atrazine and DCMU.

    Science.gov (United States)

    Camuel, Alexandre; Guieysse, Benoit; Alcántara, Cynthia; Béchet, Quentin

    2017-06-01

    In order to develop a rapid assay suitable for algal eco-toxicity assessments under conditions representative of natural ecosystems, this study evaluated the short-term (Chlorella vulgaris was exposed to these herbicides under 'standard' low light intensity (as prescribed by OECD201 guideline), the 20min-EC 50 values recorded via oxygen productivity (atrazine: 1.32±0.07μM; DCMU: 0.31±0.005μM) were similar the 96-h EC 50 recorded via algal growth (atrazine: 0.56μM; DCMU: 0.41μM), and within the range of values reported in the literature. 20min-EC50 values increased by factors of 3.0 and 2.1 for atrazine and DCMU, respectively, when light intensity increased from 60 to 1400μmolm -2 s -1 of photosynthetically active radiation, or PAR. Further investigation showed that exposure time significantly also impacted the sensitivity of C. vulgaris under high light intensity (>840μmolm -2 s -1 as PAR) as the EC 50 for atrazine and DCMU decreased by up to 6.2 and 2.1 folds, respectively, after 50min of exposure at a light irradiance of 1400μmolm -2 s -1 as PAR. This decrease was particularly marked at high light intensities and low algae concentrations and is explained by the herbicide disruption of the electron transfer chain triggering photo-inhibition at high light intensities. Eco-toxicity assessments aiming to understand the potential impact of toxic compounds on natural ecosystems should therefore be performed over sufficient exposure times (>20min for C. vulgaris) and under light intensities relevant to these ecosystems. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effects of combined exposure to pyridostigmine bromide and shaker stress on acoustic startle response, pre-pulse inhibition and open field behavior in mice.

    Science.gov (United States)

    Dubovicky, M; Paton, S; Morris, M; Mach, M; Lucot, J B

    2007-01-01

    The present study investigated the effect of combined exposure of pyridostigmine bromide (PB) and chronic shaker stress on acoustic startle responses (ASR), pre-pulse inhibition (PPI) and open field behavior of adult C57BL/6J mice. PB (10 mg kg(-1) day(-1) for 7 days) or saline was administered subcutaneously using osmotic Alzet minipumps implanted under the skin on the back of the mice. At the same time, the mice were exposed to 7 days of intermittent shaker stress. They were tested for ASR (100 dB and 120 dB stimuli) and PPI (70 dB + 100 dB and 70 dB + 120 dB) in the acoustic startle monitor system. The mice were assessed during the shaker stress on days 2 and 7 and 7, 14, 21 and 28 days after discontinuation of treatment. Separate groups of mice were tested in the open field in 15 min sessions on days 1, 3 and 6 during shaker stress and PB treatment. Exposure of mice to PB resulted in an exaggerated ASR, reduced PPI and non-significant decrease in locomotor activity. These behavioral changes were apparent only during exposure to PB. Repeated shaker stress did not have any effect on sensorimotor functions or open field behavior of mice. There was no prolonged or delayed effect of PB and/or stress on individual behavioral variables. The study found C57BL/6J mice to be behaviorally sensitive to PB treatment. (c) 2007 John Wiley & Sons, Ltd.

  8. Modification of Turen Bentonite with AlCl3 for Esterification of Palmitic Acid

    Directory of Open Access Journals (Sweden)

    Abdulloh Abdulloh

    2014-03-01

    Full Text Available Natural Turen bentonite has been modified and applied as catalyst for palmitic acid esterification. Modification of natural Turen bentonite was conducted by cation exchange method using AlCl3 solution. Catalyst characterization was performed on X-ray Fluoroscence, X-ray Diffraction, nitrogen adsorption-desorption and infrared spectroscopy techniques. The catalytic activity test in the esterification reaction of palmitic acid with methanol was conducted by bath at 65 °C with a variation of reaction time of 1, 2, 3, 4 and 5 h. Catalytic activity has been observed qualitatively using GC-MS and quantitatively by changes in acid number. The analysis showed the formation of Al3+-bentonite. Observation on the elements has shown that the presence of calcium decreased from 10.2% to 4.17%, with an increase of aluminium content from 9.9% to 13%. Diffraction line at 2θ 5.7379º became 5.6489º, along with changes in d-spacing of 15.3895 Å to 15.6319 Å. The surface area increased from 83.78 m2/g to 91.26 m2/g, while Brönsted acid sites increased from 10.2 µmol/g to 67.5 µmol/g and Lewis acid sites increased from 94.9 µmol/g to 132 µmol/g. Furthermore, Al3+-bentonite has showed as active catalyst in the esterification reaction of palmitic acid with palmitic acid with conversion of 78.78% for 5 h. © 2014 BCREC UNDIP. All rights reservedReceived: 24th September 2013; Revised: 31st December 2013; Accepted: 26th January 2014[How to Cite: Abdulloh, A., Maryam, S., Aminah, N.S., Triyono, T., Trisunaryanti, W., Mudasir, M., Prasetyoko, D. (2014. Modification of Turen’s Bentonite with AlCl3 for Esterification of Palmitic Acid. Bulletin of Chemical Reaction Engineering & Catalysis, 9 (1: 66-73. (doi:10.9767/bcrec.9.1.5513.66-73][Permalink/DOI: http://dx.doi.org/10.9767/bcrec.9.1.5513.66-73

  9. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling.

    Science.gov (United States)

    Moon, Eunjung; Han, Jeong Eun; Jeon, Sejin; Ryu, Jong Hoon; Choi, Ji Woong; Chun, Jerold

    2015-01-01

    Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  10. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Eunjung Moon

    2015-01-01

    Full Text Available Initial and recurrent stroke produces central nervous system (CNS damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  11. Oleate ameliorates palmitate-induced reduction of NAMPT activity and NAD levels in primary human hepatocytes and hepatocarcinoma cells.

    Science.gov (United States)

    Penke, Melanie; Schuster, Susanne; Gorski, Theresa; Gebhardt, Rolf; Kiess, Wieland; Garten, Antje

    2017-10-03

    Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide adenine dinucleotide (NAD) levels are crucial for liver function. The saturated fatty acid palmitate and the unsaturated fatty acid oleate are the main free fatty acids in adipose tissue and human diet. We asked how these fatty acids affect cell survival, NAMPT and NAD levels in HepG2 cells and primary human hepatocytes. HepG2 cells were stimulated with palmitate (0.5mM), oleate (1mM) or a combination of both (0.5mM/1mM) as well as nicotinamide mononucleotide (NMN) (0.5 mM) or the specific NAMPT inhibitor FK866 (10nM). Cell survival was measured by WST-1 assay and Annexin V/propidium iodide staining. NAD levels were determined by NAD/NADH Assay or HPLC. Protein and mRNA levels were analysed by Western blot analyses and qPCR, respectively. NAMPT enzyme activity was measured using radiolabelled 14 C-nicotinamide. Lipids were stained by Oil red O staining. Palmitate significantly reduced cell survival and induced apoptosis at physiological doses. NAMPT activity and NAD levels significantly declined after 48h of palmitate. In addition, NAMPT mRNA expression was enhanced which was associated with increased NAMPT release into the supernatant, while intracellular NAMPT protein levels remained stable. Oleate alone did not influence cell viability and NAMPT activity but ameliorated the negative impact of palmitate on cell survival, NAMPT activity and NAD levels, as well as the increased NAMPT mRNA expression and secretion. NMN was able to normalize intracellular NAD levels but did not ameliorate cell viability after co-stimulation with palmitate. FK866, a specific NAMPT inhibitor did not influence lipid accumulation after oleate-treatment. Palmitate targets NAMPT activity with a consequent cellular depletion of NAD. Oleate protects from palmitate-induced apoptosis and variation of NAMPT and NAD levels. Palmitate-induced cell stress leads to an increase of NAMPT mRNA and accumulation in the supernatant. However

  12. Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

    International Nuclear Information System (INIS)

    Vito, Stephen T.; Austin, Adam T.; Banks, Christopher N.; Inceoglu, Bora; Bruun, Donald A.; Zolkowska, Dorota; Tancredi, Daniel J.; Rogawski, Michael A.; Hammock, Bruce D.; Lein, Pamela J.

    2014-01-01

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABA A R) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABA A R positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABA A R antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase inhibitor alters

  13. Nuclear factor-κB is a common upstream signal for growth differentiation factor-5 expression in brown adipocytes exposed to pro-inflammatory cytokines and palmitate

    Energy Technology Data Exchange (ETDEWEB)

    Hinoi, Eiichi; Iezaki, Takashi; Ozaki, Kakeru; Yoneda, Yukio, E-mail: yyoneda@p.kanazawa-u.ac.jp

    2014-10-03

    Highlights: • GDF5 expression is up-regulated by IL-1β, TNF-α and palmitate in brown pre-adipocytes. • NF-κB stimulates promoter activity and expression of GDF5 in brown pre-adipocytes. • Recruitment of NF-κB to the GDF5 promoter is facilitated in BAT from ob/ob mice. • An NF-κB inhibitor prevents upregulation of GDF5 expression in brown pre-adipocytes. - Abstract: We have previously demonstrated that genetic and acquired obesity similarly led to drastic upregulation in brown adipose tissue (BAT), rather than white adipose tissue, of expression of both mRNA and corresponding protein for the bone morphogenic protein/growth differentiation factor (GDF) member GDF5 capable of promoting brown adipogenesis. In this study, we evaluated expression profiles of GDF5 in cultured murine brown pre-adipocytes exposed to pro-inflammatory cytokines and free fatty acids (FFAs), which are all shown to play a role in the pathogenesis of obesity. Both interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were effective in up-regulating GDF5 expression in a concentration-dependent manner, while similar upregulation was seen in cells exposed to the saturated FFA palmitate, but not to the unsaturated FFA oleate. In silico analysis revealed existence of the putative nuclear factor-κB (NF-κB) binding site in the 5′-flanking region of mouse GDF5, whereas introduction of NF-κB subunits drastically facilitated both promoter activity and expression of GDF5 in brown pre-adipocytes. Chromatin immunoprecipitation analysis confirmed significant facilitation of the recruitment of NF-κB to the GDF5 promoter in lysed extracts of BAT from leptin-deficient ob/ob obese mice. Upregulation o GDF5 expression was invariably inhibited by an NF-κB inhibitor in cultured brown pre-adipocytes exposed to IL-1β, TNF-α and palmitate. These results suggest that obesity leads to upregulation of GDF5 expression responsible for the promotion of brown adipogenesis through a mechanism

  14. A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal sustained delivery of corticosteroid for treatment of macular edema.

    Science.gov (United States)

    Daull, Philippe; Paterson, Christopher A; Kuppermann, Baruch D; Garrigue, Jean-Sébastien

    2013-03-01

    Dexamethasone palmitate (DXP) is a lipophilic prodrug of dexamethasone (DXM), a potent corticosteroid used to treat a variety of ophthalmic diseases. The aim of the study was to characterize the sustained release capacity (in rabbit), efficacy (in rat and rabbit), and safety (in rabbit, cat, and minipig) of intravitreal (IVT) DXP emulsions in preclinical models. Oil-in-water emulsions of DXP were administered by IVT injections in rats, rabbits, cats, or minipigs. Efficacy was assessed in rabbits by the inhibition of VEGF-induced vascular leakage and in rats by inhibition of laser-induced choroidal neovascularization. Concentrations of DXP and DXM in aqueous humor, vitreous, retina, choroid, and blood were determined to characterize the ocular and systemic pharmacokinetic (PK) profile. Complete ophthalmic examinations (indirect ophthalmoscopy, slit-lamp biomacroscopy, electroretinography, tonometry) were performed to assess the ocular safety of IVT DXP doses up to 2,600 μg in minipig, followed by histopathologic examinations. A validated feline model of DXM-induced elevated intraocular pressure (IOP) was used to assess the ocular hypertensive impact (i.e., the safety) of an IVT injection of DXP emulsion. Rat and rabbit efficacy data demonstrated that IVT injections of DXP emulsions were effective. Rabbit PK data demonstrated that following a single 1,280 μg IVT injection resulted in sustained DXM levels in the retina and choroid (1,179.6 and 577.7 ng/g with a half-life of 189 and 103 days, respectively) sufficient to inhibit VEGF-induced vascular hyper-permeability for up to 9 months. No adverse ocular findings were observed in the rabbit at the 1,280 μg DXP dose. Plasma levels of DXP and DXM were close to the lower limit of quantification (0.5 ng/mL). In minipigs, no systemic effects were observed at a dose up to 2,600 μg DXP. In steroid responsive cats, IVT DXP emulsions increased IOP to a lesser extent than triamcinolone acetonide with a more rapid return to

  15. Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

    Science.gov (United States)

    Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

    2016-05-01

    Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

  16. Phase equilibrium measurements and thermodynamic modelling for the system (CO2 + ethyl palmitate + ethanol) at high pressures

    International Nuclear Information System (INIS)

    Gaschi, Priscilla S.; Mafra, Marcos R.; Ndiaye, Papa M.; Corazza, Marcos L.

    2013-01-01

    Graphical abstract: Ethyl palmitate and biodiesel comparison in a pressure–composition diagram for the systems (CO 2 + ethyl palmitate + biodiesel), at different temperatures. Highlights: ► We measured VLE, LLE, and VLLE for the system (CO 2 + ethyl palmitate + ethanol). ► The saturation pressures were obtained using a variable-volume view cell. ► Phase envelope of (CO 2 + ethyl palmitate) is different that (CO 2 + soybean oil biodiesel). ► The experimental data were modeled using PR-vdW2 and PR–WS equations of state. - Abstract: This work reports phase equilibrium measurements for the binary {CO 2 (1) + ethyl palmitate(2)} and ternary {CO 2 (1) + ethyl palmitate(2) + ethanol(3)} systems at high pressures. There is currently great interest in biodiesel production processes involving supercritical and/or pressurized solvents, such as non-catalytic supercritical biodiesel production and enzyme-catalysed biodiesel production. Also, supercritical CO 2 can offer an interesting alternative for glycerol separation in the biodiesel purification step in a water-free process. In this context, the main goal of this work was to investigate the phase behaviour of binary and ternary systems involving CO 2 , a pure constituent of biodiesel ethyl palmitate and ethanol. Experiments were carried out in a high-pressure variable-volume view cell with operating temperatures ranging from (303.15 to 353.15) K and pressures up to 21 MPa. The CO 2 mole fraction ranged from 0.5033 to 0.9913 for the binary {CO 2 (1) + ethyl palmitate(2)} system and from 0.4436 to 0.9712 for ternary system {CO 2 (1) + ethyl palmitate(2) + ethanol(3)} system with ethyl ester to ethanol molar ratios of (1:6), (1:3), and (1:1). For the systems investigated, vapour–liquid (VL), liquid–liquid (LL) and vapour–liquid–liquid (VLL) phase transitions were observed. The experimental data sets were successfully modeled using the Peng–Robinson equation of state with the classical van der Waals

  17. The role of zinc supplementation in the inhibition of tissue damage caused by exposure to electromagnetic field in rat lung and liver tissues.

    Science.gov (United States)

    Baltaci, A K; Mogulkoc, R; Salbacak, A; Celik, I; Sivrikaya, A

    2012-01-01

    The objective of the present study was to examine the effects of zinc supplementation on the oxidant damage in lung and liver tissues in rats exposed to a 50-Hz frequency magnetic field for 5 minutes every other day over a period of 6 months. The study included 24 adult male Sprague-Dawley rats, which were divided into the three groups in equal numbers: Group 1, the control group (G1); Group 2, the group exposed to an electromagnetic field (G2); and Group 3, the group, which was exposed to an EMF and supplemented with zinc (G3). At the end of the 6-month procedures, the animals were decapitated to collect lung and liver tissue samples, in which MDA was analyzed using the "TBARS method (nmol/g/protein)", GSH by the "biuret method (mg/g/protein)" and zinc levels by atomic emission (µg/dl). MDA levels in lung and liver tissues in G2 were higher than those in G1 and G3, and the levels in G3 were higher than those in G1 (pelectromagnetic field caused cellular damage in lung and liver tissues and zinc supplementation inhibited the inflicted cellular damage. Another important result of this study that needs emphasis was that exposure to an electromagnetic field led to a significant decrease in zinc levels in lung and liver tissues (Tab. 3, Ref. 23).

  18. Rats and rabbits as pharmacokinetic screening tools for long acting intramuscular depots: case study with paliperidone palmitate suspension.

    Science.gov (United States)

    Patel, Harilal; Patel, Prakash; Modi, Nirav; Patel, Pinakin; Wagh, Yogesh; George, Alex; Desai, Nirmal; Srinivas, Nuggehally R

    2018-05-08

    Development of prodrug of 9-hydroxyrisperidone (paliperidone) long-acting intramuscular injection has enabled delivery over four-week time period with improved compliance. The key aim of this work was to establish a reliable preclinical model which may potentially serve as a screening tool for judging the pharmacokinetics of paliperidone formulation(s) prior to human clinical work. Sparse sampling composite study was used in rats, (Wistar/Sprague-Dawley (SD; n = 10)) and a serial blood sampling study design was used in rabbits (n = 4). Animals received intramuscular injection of paliperidone palmitate in the thigh muscle at dose of 16 (rats) and 4.5 mg/kg (rabbits). Samples were drawn in rats (retro-orbital sinus) and rabbits (central ear artery) and were analysed for paliperidone using liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) assay. The plasma data was subjected to pharmacokinetic analysis. Following intramuscular injection of depot formulation in Wistar/SD rats and rabbits, absorption of paliperidone was slow and gradual with median value of time to reach maximum concentration (T max ) occurring on day 7. The exposures (i.e. area under the curve (AUC; 0-28) days) were 18,597, 21,865 and 18,120 ng.h/mL, in Wistar, SD and rabbits, respectively. The clearance was slow and supported long half-life (8-10 days). Either one of the two models can serve as a research tool for establishing pharmacokinetics of paliperidone formulation(s).

  19. Mmu-miR-615-3p regulates lipoapoptosis by inhibiting C/EBP homologous protein.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Miyamoto

    Full Text Available Lipoapoptosis occurring due to an excess of saturated free fatty acids such as palmitate is a key pathogenic event in the initiation of nonalcoholic fatty liver disease. Palmitate loading of cells activates the endoplasmic reticulum stress response, including induction of the proapoptotic transcription factor C/EBP homologous protein (CHOP. Furthermore, the loss of microRNAs is implicated in regulating apoptosis under conditions of endoplasmic reticulum (ER stress. The aim of this study was to identify specific microRNAs regulating CHOP expression during palmitate-induced ER stress. Five microRNAs were repressed under palmitate-induced endoplasmic reticulum stress conditions in hepatocyte cell lines (miR-92b-3p, miR-328-3p, miR-484, miR-574-5p, and miR-615-3p. We identified miR-615-3p as a candidate microRNA which was repressed by palmitate treatment and regulated CHOP protein expression, by RNA sequencing and in silico analyses, respectively. There is a single miR-615-3p binding site in the 3'untranslated region (UTR of the Chop transcript. We characterized this as a functional binding site using a reporter gene-based assay. Augmentation of miR-615-3p levels, using a precursor molecule, repressed CHOP expression; and under these conditions palmitate- or tunicamycin-induced cell death were significantly reduced. Our results suggest that palmitate-induced apoptosis requires maximal expression of CHOP which is achieved via the downregulation of its repressive microRNA, miR-615-3p. We speculate that enhancement of miR-615-3p levels may be of therapeutic benefit by inhibiting palmitate-induced hepatocyte lipoapoptosis.

  20. Synthesis of Renewable Diesel Range Alkanes by Hydrodeoxygenation of Palmitic Acid over 5% Ni/CNTs under Mild Conditions

    Directory of Open Access Journals (Sweden)

    Yanan Duan

    2017-03-01

    Full Text Available Recently, the catalytic upgrading of bio-oil to renewable diesel has been attracting more and more attention. In the current paper, carbon nanotube (CNT-supported nickel catalysts, namely, 5% Ni/CNTs, were prepared for liquid hydrocarbon production through the deoxygenation of palmitic acid, the model compound of bio-oil under a mild condition of 240 °C reaction temperature and 2 MPa H2 pressure. The experimental results revealed that the main reaction product was pentadecane (yield of 89.64% at an optimum palmitic acid conversion of 97.25% via the hydrodecarbonylation (HDC process. The deoxygenation mechanism for palmitic acid conversion was also investigated. This study provides technical parameters and a theoretical basis for further industrialization in the bio-oil upgrading process.

  1. Beta Palmitate Improves Bone Length and Quality during Catch-Up Growth in Young Rats

    Directory of Open Access Journals (Sweden)

    Meytal Bar-Maisels

    2017-07-01

    Full Text Available Palmitic acid (PA is the most abundant saturated fatty acid in human milk, where it is heavily concentrated in the sn-2-position (termed beta palmitate, BPA and as such is conserved in all women, regardless of their diet or ethnicity, indicating its physiological and metabolic importance. We hypothesized that BPA improves the efficiency of nutrition-induced catch up growth as compared to sn-1,3 PA, which is present in vegetable oil. Pre-pubertal male rats were subjected to a 17 days food restriction followed by re-feeding for nine days with 1,3 PA or BPA-containing diets. We measured bone length, epiphyseal growth plate height (EGP, histology, bone quality (micro-CT and 3-point bending assay, and gene expression (Affymetrix. The BPA-containing diet improved most growth parameters: humeri length and EGP height were greater in the BPA-fed animals. Further analysis of the EGP revealed that the hypertrophic zone was significantly higher in the BPA group. In addition, Affymetrix analysis revealed that the diet affected the expression of several genes in the liver and EGP. Despite the very subtle difference between the diets and the short re-feeding period, we found a small but significant improvement in most growth parameters in the BPA-fed rats. This pre-clinical study may have important implications, especially for children with growth disorders and children with special nutritional needs.

  2. Paliperidone Palmitate Improves and Maintains Functioning in Asia-Pacific Patients with Schizophrenia.

    Science.gov (United States)

    Zhang, Hongyan; Turkoz, Ibrahim; Zhuo, Jianmin; Mathews, Maju; Tan, Wilson; Feng, Yu

    2017-11-01

    Post hoc analyses (two single-arm studies) were conducted to determine the impact of once-monthly injection of paliperidone palmitate on functioning in adult patients with schizophrenia in the Asia-Pacific region. Study 1 enrolled hospitalized patients with acute exacerbation of schizophrenia, and study 2 enrolled patients with recently diagnosed schizophrenia unsatisfactorily treated with oral antipsychotics. Patients received paliperidone palmitate, 150 mg eq. on day 1, 100 mg eq. on day 8, then once monthly (50-150 mg eq.) (study 1, days 36 and 64; study 2, 18 months). Functional status was evaluated by Personal and Social Performance score in both studies and employment only in study 2. In study 1, 54 of 184 patients (29.4%) with an unfavorable level of functioning at the baseline improved to a favorable level (Personal and Social Performance score greater than 70) at day 92. This improvement was significantly greater among patients with recently diagnosed schizophrenia (5 years or less) compared with patients with chronic schizophrenia (more than 5 years): 40% versus 22% (p schizophrenia. Janssen-Cilag Asia-Pacific Medical Affairs.

  3. Lauric and palmitic acids eutectic mixture as latent heat storage material for low temperature heating applications

    International Nuclear Information System (INIS)

    Tuncbilek, Kadir; Sari, Ahmet; Tarhan, Sefa; Erguenes, Gazanfer; Kaygusuz, Kamil

    2005-01-01

    Palmitic acid (PA, 59.8 deg. C) and lauric acid (LA, 42.6 deg. C) are phase change materials (PCM) having quite high melting temperatures which can limit their use in low temperature solar applications such as solar space heating and greenhouse heating. However, their melting temperatures can be tailored to appropriate value by preparing a eutectic mixture of the lauric and the palmitic acids. In the present study, the thermal analysis based on differential scanning calorimetry (DSC) technique shows that the mixture of 69.0 wt% LA and 31 wt% PA forms a eutectic mixture having melting temperature of 35.2 deg. C and the latent heat of fusion of 166.3 J g -1 . This study also considers the experimental determination of the thermal characteristics of the eutectic mixture during the heat charging and discharging processes. Radial and axial temperature distribution, heat transfer coefficient between the heat transfer fluid (HTF) pipe and the PCM, heat recovery rate and heat charging and discharging fractions were experimentally established employing a vertical concentric pipe-in-pipe energy storage system. The changes of these characteristics were evaluated with respect to the effect of inlet HTF temperature and mass flow rate. The DSC thermal analysis and the experimental results indicate that the LA-PA eutectic mixture can be a potential material for low temperature thermal energy storage applications in terms of its thermo-physical and thermal characteristics

  4. Palmitic acid/polypyrrole composites as form-stable phase change materials for thermal energy storage

    International Nuclear Information System (INIS)

    Silakhori, Mahyar; Metselaar, Hendrik Simon Cornelis; Mahlia, Teuku Meurah Indra; Fauzi, Hadi; Baradaran, Saeid; Naghavi, Mohammad Sajad

    2014-01-01

    Highlights: • A novel phase change composite of palmitic acid–polypyrrole(PA–PPy) was fabricated. • Thermal properties of PA–PPy are characterized in different mass ratios of PA–PPy. • Thermal cycling test showed that form stable PCM had a favorable thermal reliability. - Abstract: In this study a novel palmitic acid (PA)/polypyrrole (PPy) form-stable PCMs were readily prepared by in situ polymerization method. PA was used as thermal energy storage material and PPy was operated as supporting material. Form-stable PCMs were investigated by SEM (scanning electron microscopy) and FTIR (Fourier transform infrared spectrometer) analysis that illustrated PA Particles were wrapped by PPy particles. XRD (X-ray diffractometer) was used for crystalline phase of PA/PPy composites. Thermogravimetry analysis (TGA) and differential scanning calorimetry (DSC) were used for investigating Thermal stability and thermal energy storage properties of prepared form-stable PCMs. According to the obtained results the form stable PCMs exhibited favorable thermal stability in terms of their phase change temperature. The form-stable PCMs (79.9 wt% loading of PA) were considered as the highest loading PCM with desirable latent heat storage of 166.3 J/g and good thermal stability. Accelerated thermal cycling tests also showed that form stable PCM had an acceptable thermal reliability. As a consequence of acceptable thermal properties, thermal stability and chemical stability, we can consider the new kind of form stable PCMs for low temperature solar thermal energy storage applications

  5. Preparation and Characterization of a Solid Acid Catalyst from Macro Fungi Residue for Methyl Palmitate Production

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    Min Wang

    2015-07-01

    Full Text Available During the process of fungal polysaccharide extraction for health care products and food factories, a large quantity of macro-fungi residues are produced, but most of the residues are abandoned and become environmental pollutants. A solid acid catalyst, prepared by sulfonating carbonized Phellinus igniarius residue, was shown to be an efficient and environmentally benign catalyst for the esterification of palmitate acid (PA and methanol. As a comparison, two types of common biomass catalysts, wheat straws and wood chips, were prepared. In this study, characterizations, including scanning electron microscopy, thermo-gravimetric analysis, Fourier transform infrared spectrometry, Brunauer-Emmett-Teller assays and elemental analysis, and reaction conditions for the synthesis of methyl palmitate (MP using solid acid catalysts were investigated. Experiments showed that the solid acid catalyst prepared from P. igniarius residue had a higher catalytic activity than the other two catalysts, and the highest yield of MP catalyzed by P. igniarius residue solid acid catalyst was 91.5% under the following optimum conditions: molar ratio of methanol/PA of 10:1, reaction temperature of 60 °C, mass ratio of catalyst/substrate of 2%, and a reaction time of 1.5 h. Thus, the use of this catalyst offers a method for producing MP.

  6. Metabolic reserve in normal myocardium assessed by positron emission tomography with C-11 palmitate

    International Nuclear Information System (INIS)

    Tamaki, Nagara; Kawamoto, Masahide; Takahashi, Norio; Yonekura, Yoshiharu; Magata, Yasuhiro; Nohara, Ryuji; Kambara, Hirofumi; Kawai, Chuichi; Konishi, Junji

    1991-01-01

    Positron emission tomography (PET) with C-11 palmitate has been used in estimating the myocardial utilization of free fatty acid. To assess the metabolic reserve in normal subjects, a PET study was performed at control and during dobutamine infusion at 2 hour intervals in 5 normal subjects. Following monoexponential curve fitting of the time activity curve of the myocardium, the clearance half time (min) and residual fraction (%) were calculated as indices of β-oxydation of free fatty acid. A significant increase in the heart rate and systolic blood pressure were observed during dobutamine infusion (65±5 vs 100±29 bpm, p<0.05 and 119±12 vs 144±16 mmHg, p<0.01, respectively). The clearance half-time and the residual fraction were significantly decreased (23.4±2.6 vs 15.8±2.3 min and 67.0±2.5 vs 58.6±4.0%, p<0.05, each). When the left ventricular myocardium was divided into 4 segments, these indices were similar at control and uniformly decreased without regional differences during dobutamine infusion. These data suggest that β-oxydation of free fatty acid may be uniformly increased in the left ventricular myocardium in relation to the increase in cardiac work in normal subjects. PET with C-11 palmitate at control and during dobutamine infusion is considered to be promising in assessing metabolic reserve in the myocardium. (author)

  7. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

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    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  8. D-isoascorbyl palmitate: lipase-catalyzed synthesis, structural characterization and process optimization using response surface methodology.

    Science.gov (United States)

    Sun, Wen-Jing; Zhao, Hong-Xia; Cui, Feng-Jie; Li, Yun-Hong; Yu, Si-Lian; Zhou, Qiang; Qian, Jing-Ya; Dong, Ying

    2013-07-08

    Isoascorbic acid is a stereoisomer of L-ascorbic acid, and widely used as a food antioxidant. However, its highly hydrophilic behavior prevents its application in cosmetics or fats and oils-based foods. To overcome this problem, D-isoascorbyl palmitate was synthesized in the present study for improving the isoascorbic acid's oil solubility with an immobilized lipase in organic media. The structural information of synthesized product was clarified using LC-ESI-MS, FT-IR, 1H and 13C NMR analysis, and process parameters for high yield of D-isoascorbyl palmitate were optimized by using One-factor-at-a-time experiments and response surface methodology (RSM). The synthesized product had the purity of 95% and its structural characteristics were confirmed as isoascorbyl palmitate by LC-ESI-MS, FT-IR, 1H, and 13C NMR analysis. Results from "one-factor-at-a-time" experiments indicated that the enzyme load, reaction temperature and D-isoascorbic-to-palmitic acid molar ratio had a significant effect on the D-isoascorbyl palmitate conversion rate. 95.32% of conversion rate was obtained by using response surface methodology (RSM) under the the optimized condition: enzyme load of 20% (w/w), reaction temperature of 53°C and D- isoascorbic-to-palmitic acid molar ratio of 1:4 when the reaction parameters were set as: acetone 20 mL, 40 g/L of molecular sieves content, 200 rpm speed for 24-h reaction time. The findings of this study can become a reference for developing industrial processes for the preparation of isoascorbic acid ester, which might be used in food additives, cosmetic formulations and for the synthesis of other isoascorbic acid derivatives.

  9. Palmitate diet-induced loss of cardiac caveolin-3: a novel mechanism for lipid-induced contractile dysfunction.

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    Catherine J Knowles

    Full Text Available Obesity is associated with an increased risk of cardiomyopathy, and mechanisms linking the underlying risk and dietary factors are not well understood. We tested the hypothesis that dietary intake of saturated fat increases the levels of sphingolipids, namely ceramide and sphingomyelin in cardiac cell membranes that disrupt caveolae, specialized membrane micro-domains and important for cellular signaling. C57BL/6 mice were fed two high-fat diets: palmitate diet (21% total fat, 47% is palmitate, and MCT diet (21% medium-chain triglycerides, no palmitate. We established that high-palmitate feeding for 12 weeks leads to 40% and 50% increases in ceramide and sphingomyelin, respectively, in cellular membranes. Concomitant with sphingolipid accumulation, we observed a 40% reduction in systolic contractile performance. To explore the relationship of increased sphingolipids with caveolins, we analyzed caveolin protein levels and intracellular localization in isolated cardiomyocytes. In normal cardiomyocytes, caveolin-1 and caveolin-3 co-localize at the plasma membrane and the T-tubule system. However, mice maintained on palmitate lost 80% of caveolin-3, mainly from the T-tubule system. Mice maintained on MCT diet had a 90% reduction in caveolin-1. These data show that caveolin isoforms are sensitive to the lipid environment. These data are further supported by similar findings in human cardiac tissue samples from non-obese, obese, non-obese cardiomyopathic, and obese cardiomyopathic patients. To further elucidate the contractile dysfunction associated with the loss of caveolin-3, we determined the localization of the ryanodine receptor and found lower expression and loss of the striated appearance of this protein. We suggest that palmitate-induced loss of caveolin-3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release.

  10. Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Vito, Stephen T., E-mail: stvito@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Austin, Adam T., E-mail: aaustin@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Banks, Christopher N., E-mail: Christopher.Banks@oehha.ca.gov [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Inceoglu, Bora, E-mail: abinceoglu@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Bruun, Donald A., E-mail: dabruun@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Zolkowska, Dorota, E-mail: dzolkowska@gmail.com [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Tancredi, Daniel J., E-mail: djtancredi@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Rogawski, Michael A., E-mail: rogawski@ucdavis.edu [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States)

    2014-12-01

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABA{sub A}R) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABA{sub A}R positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABA{sub A}R antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase

  11. Ultrasound-assisted lipase-catalyzed synthesis of D-isoascorbyl palmitate: process optimization and Kinetic evaluation.

    Science.gov (United States)

    Cui, Feng-Jie; Zhao, Hong-Xia; Sun, Wen-Jing; Wei, Zhuan; Yu, Si-Lian; Zhou, Qiang; Dong, Ying

    2013-12-09

    D-isoascorbic acid is a food antioxidant additive and used in accordance with Good Manufacturing Practice (GMP). High solubility in water (about 150 g/L at 25°C) reduces its effectiveness in stabilizing fats and oils. Our research group had successfully synthesized D-isoascorbyl palmitate using immobilized lipase Novozym 435 as a biocatalyst. Low production efficiency of D-isoascorbyl palmitate is still a problem for industrial production due to the long reaction time of over 24 h. In the present work, ultrasonic treatment was applied for accelerating the reaction process. The operation parameters were optimized to obtain the maximum D-isoascorbyl palmitate conversion rate by using a 5-level-4-factor Central Composite Design (CCD) and Response Surface Methdology (RSM). The reaction apparent kinetic parameters under the ultrasound treatment and mechanical shaking conditions were also determined and compared. Results showed that ultrasound treatment decreased the reaction time by over 50%. D-isoascorbyl palmitate yielded to 94.32 ± 0.17% and the productivity reached to 8.67 g L-1 h-1 under the optimized conditions as: 9% of enzyme load (w/w), 61°C of reaction temperature, 1:5 of D- isoascorbic-to-palmitic acid molar ratio, and 137 W of the ultrasound power. The immobilized lipase Novozym 435 could be reused for 7 times with 65% of the remained D-isoascorbyl palmitate conversion rate. The reaction kinetics showed that the maximum apparent reaction rate (vmax) of the ultrasound-assisted reaction was 2.85 times higher than that of the mechanical shaking, which proved that ultrasound treatment significantly enhanced the reaction efficiency. A systematic study on ultrasound-assisted enzymatic esterification for D-isoascorbyl palmitate production is reported. The results show a promising perspective of the ultrasound technique to reduce the reaction time and improve the production efficiency. The commercial D-isoascorbyl palmitate synthesis will be potentially

  12. Bactericidal activity of self-assembled palmitic and stearic fatty acid crystals on highly ordered pyrolytic graphite.

    Science.gov (United States)

    Ivanova, Elena P; Nguyen, Song Ha; Guo, Yachong; Baulin, Vladimir A; Webb, Hayden K; Truong, Vi Khanh; Wandiyanto, Jason V; Garvey, Christopher J; Mahon, Peter J; Mainwaring, David E; Crawford, Russell J

    2017-09-01

    The wings of insects such as cicadas and dragonflies have been found to possess nanostructure arrays that are assembled from fatty acids. These arrays can physically interact with the bacterial cell membranes, leading to the death of the cell. Such mechanobactericidal surfaces are of significant interest, as they can kill bacteria without the need for antibacterial chemicals. Here, we report on the bactericidal effect of two of the main lipid components of the insect wing epicuticle, palmitic (C16) and stearic (C18) fatty acids. Films of these fatty acids were re-crystallised on the surface of highly ordered pyrolytic graphite. It appeared that the presence of two additional CH 2 groups in the alkyl chain resulted in the formation of different surface structures. Scanning electron microscopy and atomic force microscopy showed that the palmitic acid microcrystallites were more asymmetric than those of the stearic acid, where the palmitic acid microcrystallites were observed to be an angular abutment in the scanning electron micrographs. The principal differences between the two types of long-chain saturated fatty acid crystallites were the larger density of peaks in the upper contact plane of the palmitic acid crystallites, as well as their greater proportion of asymmetrical shapes, in comparison to that of the stearic acid film. These two parameters might contribute to higher bactericidal activity on surfaces derived from palmitic acid. Both the palmitic and stearic acid crystallite surfaces displayed activity against Gram-negative, rod-shaped Pseudomonas aeruginosa and Gram-positive, spherical Staphylococcus aureus cells. These microcrystallite interfaces might be a useful tool in the fabrication of effective bactericidal nanocoatings. Nanostructured cicada and dragonfly wing surfaces have been discovered to be able physically kill bacterial cells. Here, we report on the successful fabrication of bactericidal three-dimensional structures of two main lipid

  13. Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite.

    Directory of Open Access Journals (Sweden)

    Zhuang-Gui Chen

    Full Text Available Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP, an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1 were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

  14. Exposure to apoptotic activated CD4+ T cells induces maturation and APOBEC3G-mediated inhibition of HIV-1 infection in dendritic cells.

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    Venkatramanan Mohanram

    Full Text Available Dendritic cells (DCs are activated by signaling via pathogen-specific receptors or exposure to inflammatory mediators. Here we show that co-culturing DCs with apoptotic HIV-infected activated CD4(+ T cells (ApoInf or apoptotic uninfected activated CD4(+ T cells (ApoAct induced expression of co-stimulatory molecules and cytokine release. In addition, we measured a reduced HIV infection rate in DCs after co-culture with ApoAct. A prerequisite for reduced HIV infection in DCs was activation of CD4(+ T cells before apoptosis induction. DCs exposed to ApoAct or ApoInf secreted MIP-1α, MIP-1β, MCP-1, and TNF-α; this effect was retained in the presence of exogenous HIV. The ApoAct-mediated induction of co-stimulatory CD86 molecules and reduction of HIV infection in DCs were partially abrogated after blocking TNF-α using monoclonal antibodies. APOBEC3G expression in DCs was increased in co-cultures of DCs and ApoAct but not by apoptotic resting CD4(+ T cells (ApoRest. Silencing of APOBEC3G in DC abrogated the HIV inhibitory effect mediated by ApoAct. Sequence analyses of an env region revealed significant induction of G-to-A hypermutations in the context of GG or GA dinucleotides in DNA isolated from DCs exposed to HIV and ApoAct. Thus, ApoAct-mediated DC maturation resulted in induction of APOBEC3G that was important for inhibition of HIV-infection in DCs. These findings underscore the complexity of differential DC responses evoked upon interaction with resting as compared with activated dying cells during HIV infection.

  15. Optimization of α-tocopherol and ascorbyl palmitate addition for the stabilization of sardine oil

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    Morales-Medina, R.

    2015-06-01

    Full Text Available The purpose of the present work was to optimize the addition of natural antioxidants (α- tocopherol and ascorbyl palmitate for the stabilization of sardine oil rich in omega-3 PUFA. The optimal values for peroxide value (PV, which minimizes primary oxidation products, were obtained at low concentrations of α-tocopherol (50–207 ppm, high content of ascorbyl palmitate (450 ppm and 50 ppm citric acid. On the other hand, optimal values for p-anisidine value (AV, which minimizes secondary oxidation products, were found at medium concentrations of α-tocopherol (478–493 ppm, high contents of ascorbyl palmitate (390–450 ppm and 50 ppm citric acid. The conflicting effect of α-tocopherol on the individual optimization of PV and AV motivated the generation of a Pareto front (set of non inferior solutions employing the weighted-sum multi-objective optimization technique.El objetivo de este trabajo fue optimizar la adición de antioxidantes naturales (α-tocoferol y palmitato de ascorbilo para la estabilización de aceite de sardina rico en omega-3 PUFA. Bajas concentraciones de α-tocoferol (50–207 ppm combinadas con la adicción de antioxidantes secundarios como palmitato de ascorbilo (450 ppm y ácido cítrico (50 ppm, minimizaron la formación de hidroperóxidos en el aceite de sardina estudiado. Sin embargo, los productos secundarios de oxidación se redujeron para concentraciones medias de α-tocoferol (478–493 ppm, altas de palmitato de ascorbilo (390–450 ppm y 50 ppm de ácido cítrico. El efecto contradictorio de la concentración de α-tocoferol en la optimización individual del índice de peróxidos e índice de p-anisidina motivó la realización de una optimización simultánea que permite satisfacer la optimización de cada una de las variables individuales en el grado deseado.

  16. Selection and Characterization of Palmitic Acid Responsive Patients with an OXPHOS Complex I Defect

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    Tom E. J. Theunissen

    2017-10-01

    Full Text Available Mitochondrial disorders are genetically and clinically heterogeneous, mainly affecting high energy-demanding organs due to impaired oxidative phosphorylation (OXPHOS. Currently, effective treatments for OXPHOS defects, with complex I deficiency being the most prevalent, are not available. Yet, clinical practice has shown that some complex I deficient patients benefit from a high-fat or ketogenic diet, but it is unclear how these therapeutic diets influence mitochondrial function and more importantly, which complex I patients could benefit from such treatment. Dietary studies in a complex I deficient patient with exercise intolerance showed increased muscle endurance on a high-fat diet compared to a high-carbohydrate diet. We performed whole-exome sequencing to characterize the genetic defect. A pathogenic homozygous p.G212V missense mutation was identified in the TMEM126B gene, encoding an early assembly factor of complex I. A complementation study in fibroblasts confirmed that the p.G212V mutation caused the complex I deficiency. The mechanism turned out to be an incomplete assembly of the peripheral arm of complex I, leading to a decrease in the amount of mature complex I. The patient clinically improved on a high-fat diet, which was supported by the 25% increase in maximal OXPHOS capacity in TMEM126B defective fibroblast by the saturated fatty acid palmitic acid, whereas oleic acid did not have any effect in those fibroblasts. Fibroblasts of other patients with a characterized complex I gene defect were tested in the same way. Patient fibroblasts with complex I defects in NDUFS7 and NDUFAF5 responded to palmitic acid, whereas ACAD9, NDUFA12, and NDUFV2 defects were non-responding. Although the data are too limited to draw a definite conclusion on the mechanism, there is a tendency that protein defects involved in early assembly complexes, improve with palmitic acid, whereas proteins defects involved in late assembly, do not. Our data show at

  17. Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo

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    Zhang Y

    2017-01-01

    Full Text Available Youwen Zhang, Deyin Tong, Daobiao Che, Bing Pei, Xiaodong Xia, Gaofeng Yuan, Xin Jin Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People’s Republic of China Abstract: The roles of ginsenoside compound K (CK in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 µg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects. Keywords: ginsenoside CK, ascorbyl palmitate, TPGS, mixed micelles, anti-tumor therapy

  18. Clinical effect of vitamin A palmitate eye gel on early ocular surface reconstruction after thermal or chemical injuries

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    Fen-Dui Zhang

    2015-11-01

    Full Text Available AIM: To evaluate the clinical effect of vitamin A palmitate eye gel on early ocular surface reconstruction after thermal or chemical injuries. METHODS: Seventy-eight cases with thermal or chemical injuries to eyes were selected and divided into two groups by randomized, double-blind, positive drug parallel controlled method: group A(40 cases were treated with vitamin A palmitate eye geland group B \\〖38 cases were treated with basic fibroblast growth factor(bFGF\\〗. The bFGF and vitamin A palmitate eye gel were used 4 times a day. The treatment course was 14d. Restoration of epithelial defect, Schirmer's test values, tear break-up time(BUT, and subjective assessment of symptoms and signs were observed on D1, D3, D5, D7, D10 and D14.RESULTS: In group A, 31 cases were cured, 5 cases were effective, with the cure rate of 76% and efficiency 90%. In group B, 32 cases were cured, 3 cases were effective, with the cure rate of 84% and efficiency 92%. There were no significant differences between the two groups(P>0.05. However, there were significant differences on the results of Schirmer's test and BUT(PPCONCLUSION: Vitamin A palmitate eye gel is valuable and safe on early ocular surface reconstruction of the eyes suffered from thermal or chemical injuries.

  19. Recovery outcomes of schizophrenia patients treated with paliperidone palmitate in a community setting: patient and provider perspectives on recovery.

    Science.gov (United States)

    Williams, Wesley; McKinney, Christopher; Martinez, Larry; Benson, Carmela

    2016-01-01

    This study evaluated the effect of paliperidone palmitate long-acting injectable (LAI) antipsychotic on recovery-oriented mental health outcomes from the perspective of healthcare providers and patients during the treatment of patients with schizophrenia or schizoaffective disorders. Archival data for patients with a primary diagnosis of schizophrenia or schizoaffective disorder receiving ≥6 months of paliperidone palmitate LAI were retrieved from the electronic medical records system at the Mental Health Center of Denver. Mental health recovery was assessed from both a provider's (Recovery Markers Inventory [RMI]) and patient's (Consumer Recovery Measure [CRM]) perspective. A three-level hierarchical linear model (HLM) was utilized to determine changes in CRM and RMI scores by including independent variables in the models: intercept, months from treatment (slope), treatment time period (pretreatment and treatment), age, gender, primary diagnosis, substance abuse diagnosis, concurrent medications, and adherence to paliperidone palmitate LAI. A total of 219 patients were identified and included in the study. Results of the final three-level HLMs indicated an overall increase in CRM scores (p a retrospective, non-comparative design, and did not adjust for multiplicity Conclusions: The current study demonstrates that changes in recovery-oriented mental health outcomes can be detected following the administration of a specific antipsychotic treatment in persons with schizophrenia or schizoaffective disorders. Furthermore, patients receiving paliperidone palmitate LAI can effectively improve recovery-oriented outcomes, thereby supporting the drug's use as schizophrenia treatment from a recovery-oriented perspective.

  20. Quantitative analysis of retinol and retinol palmitate in vitamin tablets using {sup 1}H-nuclear magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young Hae; Kim, Hye Kyong; Wilson, Erica G.; Erkelens, Cornelis; Trijzelaar, Ben; Verpoorte, Robert

    2004-06-04

    {sup 1}H-NMR spectrometry was applied to the quantitative analysis of Vitamin A in four different types of vitamin tablets without any chromatographic purification or saponification. The experiment was performed analysing the H-15 resonance, which appears at {delta} 4.32 for retinol and {delta} 4.69 for retinol palmitate, well separated from other resonances in the {sup 1}H-NMR spectrum. Compounds were quantified using the relative ratio of the integral of the H-15 signal to that of a known amount of internal standard (200 {mu}g/ml), anthracene. In order to evaluate the feasibility of avoiding the saponification of retinol palmitate in the preparation of samples, several solvents such as dimethylsulfoxide, n-hexane, methanol, water, and 0.1 M of HCl were tested as possible extraction solvents. Among these, dimethylsulfoxide showed the best yield of retinol palmitate. This method, using dimethylsulfoxide extraction and {sup 1}H-NMR, allows rapid and simple quantitation of retinol palmitate in tablets avoiding tedious saponification.

  1. Quantitative analysis of retinol and retinol palmitate in vitamin tablets using 1H-nuclear magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Choi, Young Hae; Kim, Hye Kyong; Wilson, Erica G.; Erkelens, Cornelis; Trijzelaar, Ben; Verpoorte, Robert

    2004-01-01

    1 H-NMR spectrometry was applied to the quantitative analysis of Vitamin A in four different types of vitamin tablets without any chromatographic purification or saponification. The experiment was performed analysing the H-15 resonance, which appears at δ 4.32 for retinol and δ 4.69 for retinol palmitate, well separated from other resonances in the 1 H-NMR spectrum. Compounds were quantified using the relative ratio of the integral of the H-15 signal to that of a known amount of internal standard (200 μg/ml), anthracene. In order to evaluate the feasibility of avoiding the saponification of retinol palmitate in the preparation of samples, several solvents such as dimethylsulfoxide, n-hexane, methanol, water, and 0.1 M of HCl were tested as possible extraction solvents. Among these, dimethylsulfoxide showed the best yield of retinol palmitate. This method, using dimethylsulfoxide extraction and 1 H-NMR, allows rapid and simple quantitation of retinol palmitate in tablets avoiding tedious saponification

  2. Synergy analysis reveals association between insulin signaling and desmoplakin expression in palmitate treated HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Xuewei Wang

    Full Text Available The regulation of complex cellular activities in palmitate treated HepG2 cells, and the ensuing cytotoxic phenotype, involves cooperative interactions between genes. While previous approaches have largely focused on identifying individual target genes, elucidating interacting genes has thus far remained elusive. We applied the concept of information synergy to reconstruct a "gene-cooperativity" network for palmititate-induced cytotoxicity in liver cells. Our approach integrated gene expression data with metabolic profiles to select a subset of genes for network reconstruction. Subsequent analysis of the network revealed insulin signaling as the most significantly enriched pathway, and desmoplakin (DSP as its top neighbor. We determined that palmitate significantly reduces DSP expression, and treatment with insulin restores the lost expression of DSP. Insulin resistance is a common pathological feature of fatty liver and related ailments, whereas loss of DSP has been noted in liver carcinoma. Reduced DSP expression can lead to loss of cell-cell adhesion via desmosomes, and disrupt the keratin intermediate filament network. Our findings suggest that DSP expression may be perturbed by palmitate and, along with insulin resistance, may play a role in palmitate induced cytotoxicity, and serve as potential targets for further studies on non-alcoholic fatty liver disease (NAFLD.

  3. Ascorbyl palmitate, gamma-tocopherol, and EDTA affect lipid oxidation in fish oil enriched salad dressing differently

    DEFF Research Database (Denmark)

    Let, M.B.; Jacobsen, Charlotte; Meyer, Anne S.

    2007-01-01

    The aim of the study was to investigate the ability of γ-tocopherol, ethylenediaminetetraacetate (EDTA), and ascorbyl palmitate to protect fish oil enriched salad dressing against oxidation during a 6 week storage period at room temperature. The lipid-soluble γ-tocopherol (220 and 880 µg g-1...

  4. Palmitate activates autophagy in INS-1E β-cells and in isolated rat and human pancreatic islets.

    Directory of Open Access Journals (Sweden)

    Luisa Martino

    Full Text Available We have investigated the in vitro effects of increased levels of glucose and free fatty acids on autophagy activation in pancreatic beta cells. INS-1E cells and isolated rat and human pancreatic islets were incubated for various times (from 2 to 24 h at different concentrations of glucose and/or palmitic acid. Then, cell survival was evaluated and autophagy activation was explored by using various biochemical and morphological techniques. In INS-1E cells as well as in rat and human islets, 0.5 and 1.0 mM palmitate markedly increased autophagic vacuole formation, whereas high glucose was ineffective alone and caused little additional change when combined with palmitate. Furthermore, LC3-II immunofluorescence co-localized with that of cathepsin D, a lysosomal marker, showing that the autophagic flux was not hampered in PA-treated cells. These effects were maintained up to 18-24 h incubation and were associated with a significant decline of cell survival correlated with both palmitate concentration and incubation time. Ultrastructural analysis showed that autophagy activation, as evidenced by the occurrence of many autophagic vacuoles in the cytoplasm of beta cells, was associated with a diffuse and remarkable swelling of the endoplasmic reticulum. Our results indicate that among the metabolic alterations typically associated with type 2 diabetes, high free fatty acids levels could play a role in the activation of autophagy in beta cells, through a mechanism that might involve the induction of endoplasmic reticulum stress.

  5. Determination of Fatty Acid Metabolism with Dynamic [11C]Palmitate Positron Emission Tomography of Mouse Heart In Vivo

    Directory of Open Access Journals (Sweden)

    Yinlin Li

    2015-09-01

    Full Text Available The goal of this study was to establish a quantitative method for measuring fatty acid (FA metabolism with partial volume (PV and spill-over (SP corrections using dynamic [11C]palmitate positron emission tomographic (PET images of mouse heart in vivo. Twenty-minute dynamic [11C]palmitate PET scans of four 18- to 20-week-old male C57BL/6 mice under isoflurane anesthesia were performed using a Focus F-120 PET scanner. A model-corrected blood input function, by which the input function with SP and PV corrections and the metabolic rate constants (k1–k5 are simultaneously estimated from the dynamic [11C]palmitate PET images of mouse hearts in a four-compartment tracer kinetic model, was used to determine rates of myocardial fatty acid oxidation (MFAO, myocardial FA esterification, myocardial FA use, and myocardial FA uptake. The MFAO thus measured in C57BL/6 mice was 375.03 ± 43.83 nmol/min/g. This compares well to the MFAO measured in perfused working C57BL/6 mouse hearts ex vivo of about 350 nmol/g/min and 400 nmol/min/g. FA metabolism was measured for the first time in mouse heart in vivo using dynamic [11C]palmitate PET in a four-compartment tracer kinetic model. MFAO obtained with this model was validated by results previously obtained with mouse hearts ex vivo.

  6. Mixed monolayers of dipalmitoyl phosphatidylcholine and ethyl palmitate at the air/water interface

    Energy Technology Data Exchange (ETDEWEB)

    Gzyl, Barbara [Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Cracow (Poland)]. E-mail: gzyl@chemia.uj.edu.pl; Paluch, Maria [Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Cracow (Poland)

    2005-06-30

    The behaviour of monolayers containing dipalmitoyl phosphatidylcholine and ethyl palmitate and their mixtures at different molar fraction, using surface pressure-molecular area results, was investigated. The negative deviation from additivity of the mean molecular areas as a function of the mixture composition indicates the miscibility. The miscibility was confirmed by applying the two-dimensional phase rule, since the collapse pressure values vary with the composition of the mixtures. Also the free energy of mixing {delta}G{sub mix} and the excess free energy of mixing {delta}G{sub mix}{sup E} were determined. The negative values of {delta}G{sub mix} and {delta}G{sub mix}{sup E} indicate that the mixed monolayers are thermodynamically more stable compared to the pure ones and that the compounds in the two dimensional state experience mainly attractive interactions.

  7. Thermal properties of silica-filled high density polyethylene composites compatibilized with glut palmitate

    Science.gov (United States)

    Samsudin, Dalina; Ismail, Hanafi; Othman, Nadras; Hamid, Zuratul Ain Abdul

    2017-07-01

    A study of thermal properties resulting from the utilization of Glut Palmitate (GP) on the silica filled high density polyethylene (HDPE) composites was carried out. The composites with the incorporation of GP at 0.5, 1.0, 2.0 and 3.0 phr were prepared by using an internal mixer at the temperature 180 °C and the rotor speed of 50 rpm. The thermal behaviours of the composites were then investigated using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). It was found that the crystallinity and the thermal stability of the composites increased with the incorporation of GP. The highest crystallinity contents and decomposition temperatures were observed at the 1 phr GP loading.

  8. Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate

    DEFF Research Database (Denmark)

    Green, C J; Bunprajun, T; Pedersen, B K

    2013-01-01

    in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance......  The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture...... and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism...

  9. Structure-Based Design and Synthesis of a Small Molecule that Exhibits Anti-inflammatory Activity by Inhibition of MyD88-mediated Signaling to Bacterial Toxin Exposure.

    Science.gov (United States)

    Alam, Shahabuddin; Javor, Sacha; Degardin, Melissa; Ajami, Dariush; Rebek, Mitra; Kissner, Teri L; Waag, David M; Rebek, Julius; Saikh, Kamal U

    2015-08-01

    Both Gram-positive and Gram-negative pathogens or pathogen-derived components, such as staphylococcal enterotoxins (SEs) and endotoxin (LPS) exposure, activate MyD88-mediated pro-inflammatory cellular immunity for host defense. However, dysregulated MyD88-mediated signaling triggers exaggerated immune response that often leads to toxic shock and death. Previously, we reported a small molecule compound 1 mimicking BB-loop structure of MyD88 was capable of inhibiting pro-inflammatory response to SEB exposure in mice. In this study, we designed a dimeric structure compound 4210 covalently linked with compound 1 by a non-polar cyclohexane linker which strongly inhibited the production of pro-inflammatory cytokines in human primary cells to SEB (IC50 1-50 μm) or LPS extracted from Francisella tularensis, Escherichia coli, or Burkholderia mallei (IC50 10-200 μm). Consistent with cytokine inhibition, in a ligand-induced cell-based reporter assay, compound 4210 inhibited Burkholderia mallei or LPS-induced MyD88-mediated NF-kB-dependent expression of reporter activity (IC50 10-30 μm). Furthermore, results from a newly expressed MyD88 revealed that 4210 inhibited MyD88 dimer formation which is critical for pro-inflammatory signaling. Importantly, a single administration of compound 4210 in mice showed complete protection from lethal toxin challenge. Collectively, these results demonstrated that compound 4210 inhibits toxin-induced inflated pro-inflammatory immune signaling, thus displays a potential bacterial toxin therapeutic. © 2014 John Wiley & Sons A/S.

  10. Metabolic fate of radiolabeled palmitate in ischemic canine myocardium: implications for positron emission tomography

    International Nuclear Information System (INIS)

    Rosamond, T.L.; Abendschein, D.R.; Sobel, B.E.; Bergmann, S.R.; Fox, K.A.

    1987-01-01

    Interpretation of dynamic and integrated myocardial tomograms requires elucidation of the biochemical fate of the tracer and characterization of its tissue distribution and rate of efflux. The fate of [1- 11 C] and [1- 14 C]palmitate was studied in 13 open-chest dogs during control or ischemic extracorporeal perfusion of the left circumflex coronary artery. Residue detection of myocardial radioactivity, and radio-biochemical analyses of sequential transmural biopsies and arterial and coronary venous effluent were performed for 30 min after intracoronary bolus administration of tracer. In control hearts, 10.3% of initially extracted tracer was retained in tissue (2.9% in triglyceride, 3.5% in phospholipid, and 3.9% in other lipid and aqueous fractions), 73.7% was oxidized, and 16.1% back-diffused unaltered. With ischemia (pump flow 10% of normal), 28.1% was retained (18% in triglyceride, 6.0% in phospholipid, and 4.1% in other lipid and aqueous fractions), 27.2% was oxidized, and 44.4% back diffused (p less than 0.05 compared to control). Throughout the 30-min study interval, triglyceride, diglyceride, and nonesterified fatty acid comprised a significantly greater fraction of initially extracted radioactivity in ischemic than in control hearts. Thus, during ischemia externally detected clearance rates cannot be used as a direct measure of fatty acid metabolism because of marked influences on efflux of nonmetabolized radiolabeled palmitate and the distribution of tracer retained in tissue. Quantitative measurements of specific metabolic processes by tomography will require development and validation of tracers confined to individual metabolic pathways or pools

  11. KINETIC STUDY OF PALMITIC ACID ESTERIFICATION CATALYZED BY Rhizopus oryzae RESTING CELLS

    Directory of Open Access Journals (Sweden)

    JONH J MÉNDEZ

    2009-01-01

    Full Text Available ABSTRACT In the present study, a kinetic model for the biocatalytic synthesis of esters using Rhizopus oryzae resting cells is proposed. The kinetic study has been made in a range of 30-50 °C and atmospheric pressure. The Influence of operating variables, water content, pH, amount of mycelium was studied. Different values of temperature, initial mycelium concentration and acid/alcohol molar ratio were tested. Initial rates were estimated from the slope of the concentration of palmitic acid, or their corresponding ester at conversions of less than 10%, versus time and reported as mmol l-1 min -1. The values of kinetic constants were computed using the freeware program SIMFIT (http:\\\\www.simfit.man.ac.uk. Key words: bound lipase, esterification, fungal resting cells, Rhizopus oryzae, palmitic acid, propanol. RESUMEN En el presente estudio, un modelo cinético para la síntesis de esteres usando Rhizopus oryzae resting cells es propuesto. El estudio cinético fue realizado en un rango de temperatura de 30-50 ºC a presión atmosférica reducida. La influencia de las variables de operación tales como temperatura, pH y contenido de agua fueron estudiadas. Diferentes valores de concentración de micelio y relación molar de ácido/alcohol son ensayadas, Las velocidades iníciales se estimaron de la curva de concentración de acido palmítico, y su correspondiente conversión a ester en menos del 10%, frente a tiempo y reportadas en mmol I-1 min -1. Los valores de las constantes cinéticas fueron calculados usando el programa freeware SIMFIT (http:\\\\www.simfit.man.ac.uk. Palabras clave: Lipasas, esterificación, resting cells, Rhizopus oryzae, acido palmítico, propanol.

  12. PALMITIC AND OLEIC ACIDS AND THEIR ROLE IN PATHOGENESIS OF ATHEROSCLEROSIS

    Directory of Open Access Journals (Sweden)

    V. N. Titov

    2014-01-01

    Full Text Available On the basis of phylogenetic theory of general pathology, the cause of a noninfectious disease whose occurrence in a population is more than 5–7% is an impaired biological function or reaction to the environment. From the general biology viewpoint, high mortality rate related to cardio-vascular diseases and atherosclerosis (intercellular deficiency of polyenic fatty acids (PFA is just extinction of the Homo sapiens population upon adaptation to new environmental factors. The biological function of throphology (feeding and biological reaction of exotrophy (external feeding are impaired in several aspects, the major of which is nonphysiologically high dietary content of saturated fatty acids, primarily, of palmitic fatty acid (FA. The lipoprotein system formed at early stages of phylogenesis cannot transport and provide physiological deposition of great amounts of palmitic FA, which leads to the development of an adaption (compensatory and accumulation disease. This results in hypermipidemia, impaired bioavailability of PFA to cells, compesatory production of humoral mediators from ω-9 eicosatrienoic mead FA, disorders in physiological parameters of cell plasma membrane and integral proteins, nonphysiological conformation of apoВ-100 in lipoproteins, formation of ligandless lipoproteins (biological litter and impairments in the biological function of endoecology, utilization of ligandless lipoproteins in arterial intima by phylogenetically early macrophages that do not hydrolyze polyenic cholesterol esters, increase in the intensity of the biological reaction of inflammation, and destructive and inflammatory lesions in arterial intima of an atheromatosis or atherothrombosis type. Atheromatous masses are catabolites of PFA which were not internalized by phylogenetically late cells via receptor-mediated pathway.

  13. Localization of viable, ischemic myocardium by positron-emission tomography with 11C-palmitate

    International Nuclear Information System (INIS)

    Lerch, R.A.; Ambos, H.D.; Bergmann, S.R.; Welch, M.J.; Ter-Pogossian, M.M.; Sobel, B.E.

    1981-01-01

    A study was performed to determine whether viable, but ischemic, tissue could be detected and localized in vivo based on external detection of impaired fatty acid metabolism. Accordingly, regional clearance of 11 C-palmitate was assessed by sequential PET in 15 anesthetized dogs. Clearance was consistently monoexponential from 5-15 minutes after administration of the tracer. In the absence of coronary stenosis (n = 7), clearance was homogeneous throughout the heart, with an average rate constant (k) of -0.060 +/- 0.005 min -1 (+/- SEM) and a coefficient of variation (CV) of 11.1 +/- 2.1% in each heart. Homogeneity persisted when the heart rate was increased from 84.4 +/- 6.0 to 202.7 +/- 11.5 beats/min with atropine (CV 13.2 +/- 3.5%). With left circumflex coronary stenosis (less than or equal to70% reduction in vessel diameter), homogeneity of 11 C-clearance under control conditions and with tachycardia did not differ from clearance in hearts without coronary stenosis. However, with stenosis >70% sufficient to induce ischemia without gross infarction, regional clearance of 11 C became markedly heterogeneous under control conditions (CV 28.1 +/- 5.5%, p 11 C in regions supplied by the stenotic vessel (k = -0.044 +/- 0.011 min -1 ) compared with clearance in well perfused regions (k = -0.064 +/- 0.011 min -1 , p 11 C-palmitate delineates zones of viable, ischemic myocardium that characteristically exhibit impaired oxidation of extracted fatty acid

  14. Palmitic acid-labeled lipids selectively incorporated into platelet cytoskeleton during aggregation

    International Nuclear Information System (INIS)

    Packham, M.A.; Guccione, M.A.; Bryant, N.L.; Livne, A.

    1990-01-01

    Previous experiments showed that during the early stages (20-30 seconds) of aggregation induced by adenosine diphosphate (ADP, 2 microM) or thrombin (0.1 U/mL) of rabbit or human platelets prelabeled with [3H]palmitic acid, labeled lipid became associated with the cytoskeleton isolated after lysis with 1% Triton X-100, 5 mM EGTA [ethylene glycol-bis-(beta-aminoethyl ether)]-N,N,N',N'-tetra-acetic acid. The association appeared to be related to the number of sites of contact and was independent of the release of granule contents. We have now investigated the nature of the labeled lipids by thin-layer and column chromatography and found differences between the distribution of the label in intact platelets (both stimulated and unstimulated) and the isolated cytoskeletons. In both species, and with either ADP or thrombin as aggregating agent, 70-85% of the label in both intact platelets and in the cytoskeletons was in phospholipids. The distribution of label among the phospholipids in the cytoskeletons was similar to that in intact platelets except that the percentage of label in phosphatidylcholine was significantly higher in the cytoskeletons of human platelets than in the intact platelets, and the percentage of label in phosphatidylserine/phosphatidylinositol was significantly lower in the cytoskeletons of rabbit platelets and thrombin-aggregated human platelets than in intact platelets. The cytoskeletons contained a lower percentage of label in triacylglycerol, diacylglycerol, and cholesterol ester than the intact platelets. Contrary to a report in the literature, we found no evidence for the incorporation of diacylglycerol and palmitic acid into the cytoskeleton

  15. ClC-3 deficiency protects preadipocytes against apoptosis induced by palmitate in vitro and in type 2 diabetes mice.

    Science.gov (United States)

    Huang, Yun-Ying; Huang, Xiong-Qin; Zhao, Li-Yan; Sun, Fang-Yun; Chen, Wen-Liang; Du, Jie-Yi; Yuan, Feng; Li, Jie; Huang, Xue-Lian; Liu, Jie; Lv, Xiao-Fei; Guan, Yong-Yuan; Chen, Jian-Wen; Wang, Guan-Lei

    2014-11-01

    Palmitate, a common saturated free fatty acid (FFA), has been demonstrated to induce preadipocyte apoptosis in the absence of adipogenic stimuli, suggesting that preadipocytes may be prone to apoptosis under adipogenic insufficient conditions, like type 2 diabetes mellitus (T2DM). ClC-3, encoding Cl(-) channel or Cl(-)/H(+) antiporter, is critical for cell fate choices of proliferation versus apoptosis under diseased conditions. However, it is unknown whether ClC-3 is related with preadipocyte apoptosis induced by palmitate or T2DM. Palmitate, but not oleate, induced apoptosis and increase in ClC-3 protein expression and endoplasmic reticulum (ER) stress in 3T3-L1 preadipocyte. ClC-3 specific siRNA attenuated palmitate-induced apoptosis and increased protein levels of Grp78, ATF4, CHOP and phosphorylation of JNK1/2, whereas had no effects on increased phospho-PERK and phospho-eIF2α protein expression. Moreover, the enhanced apoptosis was shown in preadipocytes from high-sucrose/fat, low-dose STZ induced T2DM mouse model with hyperglycemia, hyperlipidemia (elevated serum TG and FFA levels) and insulin resistance. ClC-3 knockout significantly attenuated preadipocyte apoptosis and the above metabolic disorders in T2DM mice. These data demonstrated that ClC-3 deficiency prevent preadipocytes against palmitate-induced apoptosis via suppressing ER stress, and also suggested that ClC-3 may play a role in regulating cellular apoptosis and disorders of glucose and lipid metabolism during T2DM.

  16. Antioxidant effect of mogrosides against oxidative stress induced by palmitic acid in mouse insulinoma NIT-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Q.; Chen, S.Y.; Deng, L.D.; Feng, L.P.; Huang, L.Z.; Yu, R.R. [Department of Pharmacy, Guilin Medical University, Guilin (China)

    2013-11-18

    Excessive oxidative stress in pancreatic β cells, caused by glucose and fatty acids, is associated with the pathogenesis of type 2 diabetes. Mogrosides have shown antioxidant and antidiabetic activities in animal models of diabetes, but the underlying mechanisms remain unclear. This study evaluated the antioxidant effect of mogrosides on insulinoma cells under oxidative stress caused by palmitic acid, and investigated the underlying molecular mechanisms. Mouse insulinoma NIT-1 cells were cultured in medium containing 0.75 mM palmitic acid, mimicking oxidative stress. The effects of 1 mM mogrosides were determined with the dichlorodihydrofluorescein diacetate assay for intracellular reactive oxygen species (ROS) and FITC-Annexin V/PI assay for cell apoptosis. Expression of glucose transporter-2 (GLUT2) and pyruvate kinase was determined by semi-quantitative reverse-transcription polymerase chain reaction. Palmitic acid significantly increased intracellular ROS concentration 2-fold (P<0.05), and decreased expression of GLUT2 (by 60%, P<0.05) and pyruvate kinase (by 80%, P<0.05) mRNAs in NIT-1 cells. Compared with palmitic acid, co-treatment with 1 mM mogrosides for 48 h significantly reduced intracellular ROS concentration and restored mRNA expression levels of GLUT2 and pyruvate kinase. However, mogrosides did not reverse palmitic acid-induced apoptosis in NIT-1 cells. Our results indicate that mogrosides might exert their antioxidant effect by reducing intracellular ROS and regulating expression of genes involved in glucose metabolism. Further research is needed to achieve a better understanding of the signaling pathway involved in the antioxidant effect of mogrosides.

  17. Perturbation of N-linked oligosaccharide structure results in an altered incorporation of [3H]palmitate into specific proteins in Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Wellner, R.B.; Ghosh, P.C.; Roecklein, B.; Wu, H.C.

    1987-01-01

    Increased [ 3 H]palmitate incorporation into specific cellular proteins has been reported to occur in Chinese hamster ovary and yeast mutant cells. In this paper we report studies concerning the relationship between N-linked oligosaccharide structure and [ 3 H]palmitate incorporation into proteins of Chinese hamster ovary (CHO) cells. We have compared the incorporation of [ 3 H]palmitate into proteins of wild-type and four different mutant CHO cell lines defective in various steps of N-linked protein glycosylation. Sodium dodecyl sulfate-gel electrophoretic analysis showed that three of the mutants exhibited increased [ 3 H]palmitate incorporation into several CHO cellular proteins (approximately 30,000-38,000 molecular weight) as compared to the wild-type cells. One of the affected mutants which accumulates the Man5Gn2Asn intermediate structure was examined in detail. In agreement with earlier reports, virtually all of the [ 3 H] palmitate-labeled proteins of both wild-type and mutant cell lines are membrane-bound. Pretreatment of the mutant cell line with tunicamycin blocked the increased [ 3 H]palmitate incorporation into the two specific proteins (both of approximately 30,000 molecular weight) observed in untreated cells; the decreased incorporation of [ 3 H]palmitate into the 30,000 molecular weight species was accompanied by a concomitant increase in the incorporation of [ 3 H]palmitate into two proteins of approximately 20,000 molecular weight. Pretreatment of wild-type cells with tunicamycin also caused increased [ 3 H]palmitate incorporation into the 20,000 molecular weight species

  18. Synthesis, Structural Studies and Biological Evaluation of Connections of Thiosemicarbazide, 1,2,4-Triazole and 1,3,4-Thiadiazole with Palmitic Acid

    Directory of Open Access Journals (Sweden)

    Michał Jóźwiak

    2018-04-01

    Full Text Available Thirty new derivatives of palmitic acid were efficiently synthesized. All obtained compounds can be divided into three groups of derivatives: Thiosemicarbazides (compounds 1–10, 1,2,4-triazoles (compounds 1a–10a and 1,3,4-thiadiazoles (compounds 1b–10b moieties. 1H-NMR, 13C-NMR and MS methods were used to confirm the structure of derivatives. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans. Compounds 4, 5, 6, 8 showed significant inhibition against C. albicans. The range of MIC values was 50–1.56 μg/mL. The halogen atom, especially at the 3rd position of the phenyl group was significantly important for antifungal activity. The biological activity against Candida albicans and selected molecular descriptors were used as a basis for QSAR models, that have been determined by means of multiple linear regression. The models have been validated by means of the Leave-One-Out Cross Validation. The obtained QSAR models were characterized by high determination coefficients and good prediction power.

  19. Synthesis, Structural Studies and Biological Evaluation of Connections of Thiosemicarbazide, 1,2,4-Triazole and 1,3,4-Thiadiazole with Palmitic Acid.

    Science.gov (United States)

    Jóźwiak, Michał; Stępień, Karolina; Wrzosek, Małgorzata; Olejarz, Wioletta; Kubiak-Tomaszewska, Grażyna; Filipowska, Anna; Filipowski, Wojciech; Struga, Marta

    2018-04-03

    Thirty new derivatives of palmitic acid were efficiently synthesized. All obtained compounds can be divided into three groups of derivatives: Thiosemicarbazides (compounds 1 - 10 ), 1,2,4-triazoles (compounds 1a - 10a ) and 1,3,4-thiadiazoles (compounds 1b - 10b ) moieties. ¹H-NMR, 13 C-NMR and MS methods were used to confirm the structure of derivatives. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans . Compounds 4 , 5 , 6 , 8 showed significant inhibition against C. albicans . The range of MIC values was 50-1.56 μg/mL. The halogen atom, especially at the 3rd position of the phenyl group was significantly important for antifungal activity. The biological activity against Candida albicans and selected molecular descriptors were used as a basis for QSAR models, that have been determined by means of multiple linear regression. The models have been validated by means of the Leave-One-Out Cross Validation. The obtained QSAR models were characterized by high determination coefficients and good prediction power.

  20. Egr2 enhances insulin resistance via JAK2/STAT3/SOCS-1 pathway in HepG2 cells treated with palmitate.

    Science.gov (United States)

    Lu, Lin; Ye, Xinhua; Yao, Qing; Lu, Aijiao; Zhao, Zhen; Ding, Yang; Meng, Chuchen; Yu, Wenlong; Du, Yunfeng; Cheng, JinLuo

    2018-05-01

    Insulin resistance is generally responsible for the pathogenesis of type 2 diabetes mellitus (T2DM). Early growth response proteins-2 (Egr2) has been reported to be able to increase the expression of the suppressors of cytokine signaling-1 (SOCS-1), and impair insulin signaling pathway through suppression of insulin receptor substrates (IRS), including IRS-1 and IRS-2. However, whether Egr2 is directly involved in the development of insulin resistance, and how its potential contributions to insulin resistance still remain unknown. Here, our present investigation found that the expression levels of Egr2 were up-regulated when insulin resistance occurs, and knockdown of Egr2 abolished the effect of insulin resistance in HepG2 cells induced with palmitate (PA). Importantly, inhibition of Egr2 decreased the expression of SOCS-1 as well as reduced phosphorylation of JAK2 and STAT3. And, our data indicated that silencing of Egr2 accelerated hepatic glucose uptake and reversed the impaired lipid metabolism upon insulin resistance. In summary, the present study confirms that Egr2 could deteriorate insulin resistance via the pathway of JAK2/STAT3/SOCS-1 and may shed light on resolving insulin resistance and further the pathogenesis of T2DM. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Cytoprotective effect of kaempferol against palmitic acid-induced pancreatic β-cell death through modulation of autophagy via AMPK/mTOR signaling pathway.

    Science.gov (United States)

    Varshney, Ritu; Gupta, Sumeet; Roy, Partha

    2017-06-15

    Lipotoxicity of pancreatic β-cells is the pathological manifestation of obesity-linked type II diabetes. We intended to determine the cytoprotective effect of kaempferol on pancreatic β-cells undergoing apoptosis in palmitic acid (PA)-stressed condition. The data showed that kaempferol treatment increased cell viability and anti-apoptotic activity in PA-stressed RIN-5F cells and murine pancreatic islets. Furthermore, kaempferol's ability to instigate autophagy was illustrated by MDC-LysoTracker red staining and TEM analysis which corroborated well with the observed increase in LC3 puncta and LC3-II protein expressions along with the concomitant decline in p62 expression. Apart from this, the data showed that kaempferol up/down-regulates AMPK/mTOR phosphorylation respectively. Subsequently, upon inhibition of AMPK phosphorylation by AMPK inhibitors, kaempferol-mediated autophagy was abolished which further led to the decline in β-cell survival. Such observations collectively lead to the conclusion that, kaempferol exerts its cytoprotective role against lipotoxicity by activation of autophagy via AMPK/mTOR pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Structure–activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure

    OpenAIRE

    Mook, Robert A.; Wang, Jiangbo; Ren, Xiu-Rong; Chen, Minyong; Spasojevic, Ivan; Barak, Larry S.; Lyerly, H. Kim; Chen, Wei

    2015-01-01

    The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. Niclosamide is a multi-functional drug that possesses important biological activity in addition to inhibition of W...

  3. Mechanism of inhibition of the tumor suppressor Patched by Sonic Hedgehog.

    Science.gov (United States)

    Tukachinsky, Hanna; Petrov, Kostadin; Watanabe, Miyako; Salic, Adrian

    2016-10-04

    The Hedgehog cell-cell signaling pathway is crucial for animal development, and its misregulation is implicated in numerous birth defects and cancers. In unstimulated cells, pathway activity is inhibited by the tumor suppressor membrane protein, Patched. Hedgehog signaling is triggered by the secreted Hedgehog ligand, which binds and inhibits Patched, thus setting in motion the downstream events in signal transduction. Despite its critical importance, the mechanism by which Hedgehog antagonizes Patched has remained unknown. Here, we show that vertebrate Patched1 inhibition is caused by direct, palmitate-dependent interaction with the Sonic Hedgehog ligand. We find that a short palmitoylated N-terminal fragment of Sonic Hedgehog binds Patched1 and, strikingly, is sufficient to inhibit it and to activate signaling. The rest of Sonic Hedgehog confers high-affinity Patched1 binding and internalization through a distinct binding site, but, surprisingly, it is not absolutely required for signaling. The palmitate-dependent interaction with Patched1 is specifically impaired in a Sonic Hedgehog mutant causing human holoprosencephaly, the most frequent congenital brain malformation, explaining its drastically reduced potency. The palmitate-dependent interaction is also abolished in constitutively inhibited Patched1 point mutants causing the Gorlin cancer syndrome, suggesting that they might adopt a conformation distinct from the wild type. Our data demonstrate that Sonic Hedgehog signals via the palmitate-dependent arm of a two-pronged contact with Patched1. Furthermore, our results suggest that, during Hedgehog signaling, ligand binding inhibits Patched by trapping it in an inactive conformation, a mechanism that explains the dramatically reduced activity of oncogenic Patched1 mutants.

  4. Involvement of CD36 in Modulating the Decrease of NPY and AgRP Induced by Acute Palmitic Acid Stimulation in N1E-115 Cells

    Directory of Open Access Journals (Sweden)

    Yan Ma

    2017-06-01

    Full Text Available Central nervous system (CNS fatty acid sensing plays an important role in the regulation of food intake, and palmitic acid (PA is the most important long chain fatty acid (LCFA in the mammalian diet. To explore the effect of PA on central neuropeptide expression and the role of the cluster of the differentiation of 36 (CD36 in the process, N1E-115 cells were cultured with PA in the presence or absence of sulfosuccinimidyl-oleate (SSO, a CD36 inhibitor. Results showed that 10 μmol/L PA significantly reduced NPY and AgRP mRNA expression after 20 min of exposure, while the expression of CD36 was upregulated. The presence of SSO significantly attenuated the decrease of NPY and AgRP expression that was induced by PA alone, although no notable effect on PA- induced CD36 gene expression was observed. In conclusion, our study suggests the involvement of CD36 in the PA-induced decrease of NPY and AgRP in N1E-115 cells.

  5. Data on cell growth inhibition induced by anti-VEGF siRNA delivered by Stealth liposomes incorporating G2 PAMAM-cholesterol versus Metafectene® as a function of exposure time and siRNA concentration

    Directory of Open Access Journals (Sweden)

    Nasim Golkar

    2016-09-01

    Full Text Available In this data article, carboxyfluorescein-loaded liposomes were prepared and purified from free carboxyfluorescein using gel filtration chromatography in the first part. In the next part, following preparation of anti-VEGF siRNA loaded liposomes incorporating hydrophobically modified G2 PAMAM dendrimer (G2-Chol40% (Golkar et al., 2016 [1], the cell growth inhibition induced by the formulations (siRNA/Metafectene complexes and siRNA loaded liposomes incorporating hydrophobic G2 was evaluated at two exposure times through MTT assay in a breast cancer cell (SKBR-3 and compared by two-way ANOVA. Keywords: Anti-VEGF siRNA, Cell growth inhibition, Polyamidoaminedendrimer, Liposome

  6. Metabolism of U14C palmitic and 1-14C caproic acids by lettuce seeds during early germination

    International Nuclear Information System (INIS)

    Salon, C.; Raymond, P.; Pradet, A.

    1986-01-01

    Germinating lettuce embryos (before radicule emergence) were fed with either U 14 C palmitic acid or 1 14 C caproic acid until a metabolic steady state was reached. The bulk of labelled caproate was evolved as respiratory CO 2 (52%) and incorporated into organic and amino acids (38%) and only a small part incorporated into lipids whereas most of labelled palmitic acid was found into lipids (92%) and only 8% evolved as CO 2 and incorporated into organic and amino acids. The label distribution at steady state in intermediates linked to the T.C.A. cycle was interpreted using a metabolic model. They found that the two fatty acids were degraded by β-oxidation and incorporated into the T.C.A. cycle as acetylCoA suggesting that β-oxidation is located in the mitochondria. The results also indicate that lipids contribute for at least 90% to the carbon supply to respiration

  7. Enhancement in electrical conductivity of pastes containing submicron Ag-coated Cu filler with palmitic acid surface modification

    Science.gov (United States)

    Choi, Eun Byeol; Lee, Jong-Hyun

    2017-09-01

    The fabrication and applied use of submicron Ag-coated Cu (Cu@Ag) particles as a filler material for epoxy-based conductive pastes having the advantages of a lower material cost and antioxidation behavior were studied. Submicron Cu@Ag particles were successfully prepared and surface-modified using palmitic acid. Diffuse reflectance infrared Fourier transform spectroscopy and thermogravimetric differential scanning calorimetry results indicated the formation of an organic layer by the chemical interaction between the Cu@Ag surface and palmitic acid and the survival of the organic layer after treatment at 160 °C for 3 h in air. The printed pastes containing both commercial micron Cu@Ag flakes and the fabricated submicron Cu@Ag particles showed a greatly reduced electrical resistivity (4.68 × 10-4 Ω cm) after surface modification compared to an initial value of 1.85 × 10-3 Ω cm when cured.

  8. Palmitate-induced ER stress increases trastuzumab sensitivity in HER2/neu-positive breast cancer cells

    International Nuclear Information System (INIS)

    Baumann, Jan; Wong, Jason; Sun, Yan; Conklin, Douglas S.

    2016-01-01

    HER2/neu-positive breast cancer cells have recently been shown to use a unique Warburg-like metabolism for survival and aggressive behavior. These cells exhibit increased fatty acid synthesis and storage compared to normal breast cells or other tumor cells. Disruption of this synthetic process results in apoptosis. Since the addition of physiological doses of exogenous palmitate induces cell death in HER2/neu-positive breast cancer cells, the pathway is likely operating at its limits in these cells. We have studied the response of HER2/neu-positive breast cancer cells to physiological concentrations of exogenous palmitate to identify lipotoxicity-associated consequences of this physiology. Since epidemiological data show that a diet rich in saturated fatty acids is negatively associated with the development of HER2/neu-positive cancer, this cellular physiology may be relevant to the etiology and treatment of the disease. We sought to identify signaling pathways that are regulated by physiological concentrations of exogenous palmitate specifically in HER2/neu-positive breast cancer cells and gain insights into the molecular mechanism and its relevance to disease prevention and treatment. Transcriptional profiling was performed to assess programs that are regulated in HER2-normal MCF7 and HER2/neu-positive SKBR3 breast cancer cells in response to exogenous palmitate. Computational analyses were used to define and predict functional relationships and identify networks that are differentially regulated in the two cell lines. These predictions were tested using reporter assays, fluorescence-based high content microscopy, flow cytometry and immunoblotting. Physiological effects were confirmed in HER2/neu-positive BT474 and HCC1569 breast cancer cell lines. Exogenous palmitate induces functionally distinct transcriptional programs in HER2/neu-positive breast cancer cells. In the lipogenic HER2/neu-positive SKBR3 cell line, palmitate induces a G2 phase cell cycle delay and

  9. Gas chromatography-mass spectrometry of ethyl palmitate calibration and resolution with ethyl oleate as biomarker ethanol sub acute in urine application study

    Science.gov (United States)

    Suaniti, Ni Made; Manurung, Manuntun

    2016-03-01

    Gas Chromatography-Mass Spectrometry is used to separate two and more compounds and identify fragment ion specific of biomarker ethanol such as palmitic acid ethyl ester (PAEE), as one of the fatty acid ethyl esters as early detection through conyugated reaction. This study aims to calibrate ethyl palmitate and develop analysis with oleate acid. This methode can be used analysis ethanol and its chemistry biomarker in ethanol sub-acute consumption as analytical forensic toxicology. The result show that ethanol level in urine rats Wistar were 9.21 and decreased 6.59 ppm after 48 hours consumption. Calibration curve of ethyl palmitate was y = 0.2035 x + 1.0465 and R2 = 0.9886. Resolution between ethyl palmitate and oleate were >1.5 as good separation with fragment ion specific was 88 and the retention time was 18 minutes.

  10. Palmitic Acid Induces Osteoblastic Differentiation in Vascular Smooth Muscle Cells through ACSL3 and NF-κB, Novel Targets of Eicosapentaenoic Acid

    Science.gov (United States)

    Kageyama, Aiko; Matsui, Hiroki; Ohta, Masahiko; Sambuichi, Keisuke; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Yokoyama, Tomoyuki; Kurabayashi, Masahiko

    2013-01-01

    Free fatty acids (FFAs), elevated in metabolic syndrome and diabetes, play a crucial role in the development of atherosclerotic cardiovascular disease, and eicosapentaenoic acid (EPA) counteracts many aspects of FFA-induced vascular pathology. Although vascular calcification is invariably associated with atherosclerosis, the mechanisms involved are not completely elucidated. In this study, we tested the hypothesis that EPA prevents the osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC) induced by palmitic acid (PA), the most abundant long-chain saturated fatty acid in plasma. PA increased and EPA abolished the expression of the genes for bone-related proteins, including bone morphogenetic protein (BMP)-2, Msx2 and osteopontin in human aortic smooth muscle cells (HASMC). Among the long-chain acyl-CoA synthetase (ACSL) subfamily, ACSL3 expression was predominant in HASMC, and PA robustly increased and EPA efficiently inhibited ACSL3 expression. Importantly, PA-induced osteoblastic differentiation was mediated, at least in part, by ACSL3 activation because acyl-CoA synthetase (ACS) inhibitor or siRNA targeted to ACSL3 completely prevented the PA induction of both BMP-2 and Msx2. Conversely, adenovirus-mediated ACSL3 overexpression enhanced PA-induced BMP-2 and Msx2 expression. In addition, EPA, ACSL3 siRNA and ACS inhibitor attenuated calcium deposition and caspase activation induced by PA. Notably, PA induced activation of NF-κB, and NF-κB inhibitor prevented PA-induction of osteoblastic gene expression and calcium deposition. Immunohistochemistry revealed the prominent expression of ACSL3 in VSMC and macrophages in human non-calcifying and calcifying atherosclerotic plaques from the carotid arteries. These results identify ACSL3 and NF-κB as mediators of PA-induced osteoblastic differentiation and calcium deposition in VSMC and suggest that EPA prevents vascular calcification by inhibiting such a new molecular pathway elicited

  11. An 11-bp insertion in Zea mays fatb reduces the palmitic acid content of fatty acids in maize grain.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available The ratio of saturated to unsaturated fatty acids in maize kernels strongly impacts human and livestock health, but is a complex trait that is difficult to select based on phenotype. Map-based cloning of quantitative trait loci (QTL is a powerful but time-consuming method for the dissection of complex traits. Here, we combine linkage and association analyses to fine map QTL-Pal9, a QTL influencing levels of palmitic acid, an important class of saturated fatty acid. QTL-Pal9 was mapped to a 90-kb region, in which we identified a candidate gene, Zea mays fatb (Zmfatb, which encodes acyl-ACP thioesterase. An 11-bp insertion in the last exon of Zmfatb decreases palmitic acid content and concentration, leading to an optimization of the ratio of saturated to unsaturated fatty acids while having no effect on total oil content. We used three-dimensional structure analysis to explain the functional mechanism of the ZmFATB protein and confirmed the proposed model in vitro and in vivo. We measured the genetic effect of the functional site in 15 different genetic backgrounds and found a maximum change of 4.57 mg/g palmitic acid content, which accounts for ∼20-60% of the variation in the ratio of saturated to unsaturated fatty acids. A PCR-based marker for QTL-Pal9 was developed for marker-assisted selection of nutritionally healthier maize lines. The method presented here provides a new, efficient way to clone QTL, and the cloned palmitic acid QTL sheds lights on the genetic mechanism of oil biosynthesis and targeted maize molecular breeding.

  12. Effect of artichoke extract (Cynara scolymus L.) on palmitic-1-14C acid oxidation in rats.

    Science.gov (United States)

    Juzyszyn, Zygmunt; Czerny, Boguslaw; Pawlik, Andrzej; Drozdzik, Marek

    2008-05-01

    Studies on the effect of the artichoke extract (AE) on oxidation of palmitic-1-14C acid administered intravenously to rats at a dose 25 and 50 mg/kg bw demonstrated marked enhancement of both 14CO2 expiration rate and 14CO2 recovery in the expired air. The extract suppressed accumulation of palmitic-1-14C acid in serum lipids and epididymal fat pad tissue as well. The effects of the extract on 14CO2 expiration rate, 14CO2 recovery, as well as accumulation of palmitic-1-14C acid were dose dependent. Total14CO2 recovery in expired air during 60 min was elevated by 17.3% (p < 0.05) and 52.1% (p < 0.001) in rats administered the extract at a dose of 25 and 50 mg/kg, respectively. The rats supplemented with the AE at a dose of 25 and 50 mg/kg bw were characterized by 10.0% (not significant) and 19% (p < 0.05) decrease in( 14)C radioactivity of serum lipids as well as reduction of epididymal fat tissue 14C radioactivity by 8.7 and 17.5% (p < 0.05), respectively, in comparison with the control rats. Thus, the results demonstrate that the AE possess stimulatory properties with respect to oxidation of palmitic acid administered to rats, and provide new information on the mechanism of antilipemic activity of the extract associated with activation of lipid oxidation in the organism.

  13. An 11-bp Insertion in Zea mays fatb Reduces the Palmitic Acid Content of Fatty Acids in Maize Grain

    Science.gov (United States)

    Li, Qing; Yang, Xiaohong; Zheng, Debo; Warburton, Marilyn; Chai, Yuchao; Zhang, Pan; Guo, Yuqiu; Yan, Jianbing; Li, Jiansheng

    2011-01-01

    The ratio of saturated to unsaturated fatty acids in maize kernels strongly impacts human and livestock health, but is a complex trait that is difficult to select based on phenotype. Map-based cloning of quantitative trait loci (QTL) is a powerful but time-consuming method for the dissection of complex traits. Here, we combine linkage and association analyses to fine map QTL-Pal9, a QTL influencing levels of palmitic acid, an important class of saturated fatty acid. QTL-Pal9 was mapped to a 90-kb region, in which we identified a candidate gene, Zea mays fatb (Zmfatb), which encodes acyl-ACP thioesterase. An 11-bp insertion in the last exon of Zmfatb decreases palmitic acid content and concentration, leading to an optimization of the ratio of saturated to unsaturated fatty acids while having no effect on total oil content. We used three-dimensional structure analysis to explain the functional mechanism of the ZmFATB protein and confirmed the proposed model in vitro and in vivo. We measured the genetic effect of the functional site in 15 different genetic backgrounds and found a maximum change of 4.57 mg/g palmitic acid content, which accounts for ∼20–60% of the variation in the ratio of saturated to unsaturated fatty acids. A PCR-based marker for QTL-Pal9 was developed for marker-assisted selection of nutritionally healthier maize lines. The method presented here provides a new, efficient way to clone QTL, and the cloned palmitic acid QTL sheds lights on the genetic mechanism of oil biosynthesis and targeted maize molecular breeding. PMID:21931818

  14. Palmitic Acid on Salt Subphases and in Mixed Monolayers of Cerebrosides: Application to Atmospheric Aerosol Chemistry

    Directory of Open Access Journals (Sweden)

    Ellen M. Adams

    2013-10-01

    Full Text Available Palmitic acid (PA has been found to be a major constituent in marine aerosols, and is commonly used to investigate organic containing atmospheric aerosols, and is therefore used here as a proxy system. Surface pressure-area isotherms (π-A, Brewster angle microscopy (BAM, and vibrational sum frequency generation (VSFG were used to observe a PA monolayer during film compression on subphases of ultrapure water, CaCl2 and MgCl2 aqueous solutions, and artificial seawater (ASW. π-A isotherms indicate that salt subphases alter the phase behavior of PA, and BAM further reveals that a condensation of the monolayer occurs when compared to pure water. VSFG spectra and BAM images show that Mg2+ and Ca2+ induce ordering of the PA acyl chains, and it was determined that the interaction of Mg2+ with the monolayer is weaker than Ca2+. π-A isotherms and BAM were also used to monitor mixed monolayers of PA and cerebroside, a simple glycolipid. Results reveal that PA also has a condensing effect on the cerebroside monolayer. Thermodynamic analysis indicates that attractive interactions between the two components exist; this may be due to hydrogen bonding of the galactose and carbonyl headgroups. BAM images of the collapse structures show that mixed monolayers of PA and cerebroside are miscible at all surface pressures. These results suggest that the surface morphology of organic-coated aerosols is influenced by the chemical composition of the aqueous core and the organic film itself.

  15. Nanocarrier with self-antioxidative property for stabilizing and delivering ascorbyl palmitate into skin.

    Science.gov (United States)

    Janesirisakule, Sirinapa; Sinthusake, Tarit; Wanichwecharungruang, Supason

    2013-08-01

    The concept of a nanocarrier with a self-antioxidative property to deliver and stabilize a labile drug while at the same time providing a free radical scavenging activity is demonstrated. Curcumin was grafted onto a poly(vinyl alcohol) [PV(OH)] chain, and the nanocarriers fabricated from the obtained curcumin-grafted PV(OH) polymer [CUR-PV(OH)] showed a good free radical scavenging activity. Ascorbyl palmitate (AP) could be effectively loaded into the CUR-PV(OH) at 29% by weight. The CUR-PV(OH)-encapsulated AP was 77% more stable than the free (unencapsulated) AP, and 47% more stable than AP encapsulated in the control nanocarrier with no antioxidative property [cinnamoyl-grafted PV(OH); CIN-PV(OH)]. Although coencapsulation of curcumin and AP into CIN-PV(OH) showed some improvement on the AP stability, AP was more stable when encapsulated in CUR-PV(OH). Compared with the free AP, encapsulated AP within the CUR-PV(OH) nanocarriers showed not only a better penetration into pig skin dermis via hair follicle pathway followed by the release and diffusion of the AP, but also a greater AP stability after skin application. Although a proof of principle is shown for CUR-PV(OH) and AP, it is likely that other carriers of the same principal could be designed and applied to different oxidation-sensitive drugs. Copyright © 2013 Wiley Periodicals, Inc.

  16. Calculation procedure for formulating lauric and palmitic fat blends based on the grouping of triacylglycerol melting points

    Directory of Open Access Journals (Sweden)

    B. P. Nusantoro

    2018-01-01

    Full Text Available A calculation procedure for formulating lauric and palmitic fat blends has been developed based on grouping TAG melting points. This procedure offered more flexibility in choosing the initial fats and oils and eventually gave deeper insight into the existing chemical compositions and better prediction on the physicochemical properties and microstructure of the fat blends. The amount of high, medium and low melting TAGs could be adjusted using the given calculation procedure to obtain the desired functional properties in the fat blends. Solid fat contents and melting behavior of formulated fat blends showed particular patterns with respect to ratio adjustments of the melting TAG groups. These outcomes also suggested that both TAG species and their quantity had a significant influence on the crystallization behavior of the fat blends. Palmitic fat blends, in general, were found to exhibit higher SFC values than those of Lauric fat blends. Instead of the similarity in crystal microstructure, lauric fat blends were stabilized at β polymorph while palmitic fat blends were stabilized at β’ polymorph.

  17. Optimization of 2-ethylhexyl palmitate production using lipozyme RM IM as catalyst in a solvent-free system.

    Science.gov (United States)

    Richetti, Aline; Leite, Selma G F; Antunes, Octávio A C; de Souza, Andrea L F; Lerin, Lindomar A; Dallago, Rogério M; Paroul, Natalia; Di Luccio, Marco; Oliveira, J Vladimir; Treichel, Helen; de Oliveira, Débora

    2010-04-01

    This work reports the application of a lipase in the 2-ethylhexyl palmitate esterification in a solvent-free system with an immobilized lipase (Lipozyme RM IM). A sequential strategy was used applying two experimental designs to optimize the 2-ethylhexyl palmitate production. An empirical model was then built so as to assess the effects of process variables on the reaction conversion. Afterwards, the operating conditions that optimized 2-ethylhexyl palmitate production were established as being acid/alcohol molar ratio 1:3, temperature of 70 degrees C, stirring rate of 150 rpm, 10 wt.% of enzyme, leading to a reaction conversion as high as 95%. From this point, a kinetic study was carried out evaluating the effect of acid:alcohol molar ratio, the enzyme concentration and the temperature on product conversion. The results obtained in this step permit to verify that an excess of alcohol (acid to alcohol molar ratio of 1:6), relatively low enzyme concentration (10 wt.%) and temperature of 70 degrees C, led to conversions next to 100%.

  18. Preparation and characterization Al3+-bentonite Turen Malang for esterification fatty acid (palmitic acid, oleic acid and linoleic acid)

    Science.gov (United States)

    Abdulloh, Abdulloh; Aminah, Nanik Siti; Triyono, Mudasir, Trisunaryanti, Wega

    2016-03-01

    Catalyst preparation and characterization of Al3+-bentonite for esterification of palmitic acid, oleic acid and linoleic acid has been done. Al3+-bentonite catalyst was prepared from natural bentonite of Turen Malang through cation exchange reaction using AlCl3 solution. The catalysts obtained were characterized by XRD, XRF, pyridine-FTIR and surface area analyser using the BET method. Catalyst activity test of Al3+-bentonite for esterification reaction was done at 65°C using molar ratio of metanol-fatty acid of 30:1 and 0.25 g of Al3+-bentonite catalyst for the period of ½, 1, 2, 3, 4 and 5 hours. Based on the characterization results, the Al3+-bentonite Turen Malang catalyst has a d-spacing of 15.63 Ǻ, acid sites of Brönsted and Lewis respectively of 230.79 µmol/g and 99.39 µmol/g, surface area of 507.3 m2/g and the average of radius pore of 20.09 Å. GC-MS analysis results of the oil phase after esterification reaction showed the formation of biodiesel (FAME: Fatty acid methyl ester), namely methyl palmitate, methyl oleate and methyl linoleate. The number of conversions resulted in esterification reaction using Al3+-bentonite Turen Malang catalyst was 74.61%, 37.75%, and 20, 93% for the esterification of palmitic acid, oleic acid and linoleic acid respectively.

  19. Calculation procedure for formulating lauric and palmitic fat blends based on the grouping of triacylglycerol melting points

    International Nuclear Information System (INIS)

    Nusantoro, B.P.; Yanty, N.A.M.; Van de Walle, D.; Hidayat, C.; Danthine, S.; Dewettinck, K.

    2017-01-01

    A calculation procedure for formulating lauric and palmitic fat blends has been developed based on grouping TAG melting points. This procedure offered more flexibility in choosing the initial fats and oils and eventually gave deeper insight into the existing chemical compositions and better prediction on the physicochemical properties and microstructure of the fat blends. The amount of high, medium and low melting TAGs could be adjusted using the given calculation procedure to obtain the desired functional properties in the fat blends. Solid fat contents and melting behavior of formulated fat blends showed particular patterns with respect to ratio adjustments of the melting TAG groups. These outcomes also suggested that both TAG species and their quantity had a significant influence on the crystallization behavior of the fat blends. Palmitic fat blends, in general, were found to exhibit higher SFC values than those of Lauric fat blends. Instead of the similarity in crystal microstructure, lauric fat blends were stabilized at β polymorph while palmitic fat blends were stabilized at β’ polymorph. [es

  20. Synthesis and characterization of microencapsulated myristic acid–palmitic acid eutectic mixture as phase change material for thermal energy storage

    International Nuclear Information System (INIS)

    Alva, Guruprasad; Huang, Xiang; Liu, Lingkun; Fang, Guiyin

    2017-01-01

    Highlights: •Myristic acid–palmitic acid eutectic was microencapsulated with silica shell. •Structure, morphology of microencapsulated phase change material were investigated. •Thermal capacity, stability of microencapsulated phase change material were analyzed. •Silica shell improved thermal stability of microencapsulated phase change material. -- Abstract: In this work microencapsulation of myristic acid–palmitic acid (MA–PA) eutectic mixture with silica shell using sol−gel method has been attempted. The core phase change material (PCM) for thermal energy storage was myristic acid−palmitic acid eutectic mixture and the shell material to prevent the PCM core from leakage was silica prepared from methyl triethoxysilane (MTES). Thermal properties of the microcapsules were measured by differential scanning calorimeter (DSC). The morphology and particle size of the microcapsules were examined by scanning electronic microscope (SEM). Fourier transformation infrared spectrophotometer (FT–IR) and X–ray diffractometer (XRD) were used to investigate the chemical structure and crystalloid phase of the microcapsules respectively. The DSC results indicated that microencapsulated phase change material (MPCM) melts at 46.08 °C with a latent heat of 169.69 kJ kg −1 and solidifies at 44.35 °C with a latent heat of 159.59 kJ kg −1 . The thermal stability of the microcapsules was analyzed by a thermogravimeter (TGA). The results indicated that the MPCM has good thermal stability and is suitable for thermal energy storage application.

  1. Number needed to treat and number needed to harm with paliperidone palmitate relative to long-acting haloperidol, bromperidol, and fluphenazine decanoate for treatment of patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Srihari Gopal

    2011-03-01

    Full Text Available Srihari Gopal1, Joris Berwaerts1, Isaac Nuamah1, Kasem Akhras2, Danielle Coppola1, Ella Daly1, David Hough1, Joseph Palumbo11Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, NJ, USA; 2Johnson & Johnson Pharmaceutical Services, LLC, Raritan, NJ, USABackground: We analyzed data retrieved through a PubMed search of randomized, placebo-controlled trials of first-generation antipsychotic long-acting injectables (haloperidol decanoate, bromperidol decanoate, and fluphenazine decanoate, and a company database of paliperidone palmitate, to compare the benefit-risk ratio in patients with schizophrenia.Methods: From the eight studies that met our selection criteria, two efficacy and six safety parameters were selected for calculation of number needed to treat (NNT, number needed to harm (NNH, and the likelihood of being helped or harmed (LHH using comparisons of active drug relative to placebo. NNTs for prevention of relapse ranged from 2 to 5 for paliperidone palmitate, haloperidol decanoate, and fluphenazine decanoate, indicating a moderate to large effect size.Results: Among the selected maintenance studies, NNH varied considerably, but indicated a lower likelihood of encountering extrapyramidal side effects, such as akathisia, tremor, and tardive dyskinesia, with paliperidone palmitate versus placebo than with first-generation antipsychotic depot agents versus placebo. This was further supported by an overall higher NNH for paliperidone palmitate versus placebo with respect to anticholinergic use and Abnormal Involuntary Movement Scale positive score. LHH for preventing relapse versus use of anticholinergics was 15 for paliperidone palmitate and 3 for fluphenazine decanoate, favoring paliperidone palmitate.Conclusion: Overall, paliperidone palmitate had a similar NNT and a more favorable NNH compared with the first-generation long-acting injectables assessed.Keywords: long-acting injectables, first-generation antipsychotics

  2. Effect of α-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes

    Directory of Open Access Journals (Sweden)

    Dong Lei

    2011-07-01

    Full Text Available Abstract Background Hepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease (NAFLD. In this study, we investigated the effects of saturated and unsaturated fatty acids (FA on apoptosis in primary rat hepatocytes. Methods The primary rat hepatocytes were treated with palmitic acid and/or α-linolenic acid in vitro. The expression of proteins associated with endoplasmic reticulum (ER stress, apoptosis, caspase-3 levels were detected after the treatment. Results The treatment with palmitic acid produced a significant increase in cell death. The unfolded protein response (UPR-associated genes CHOP, GRP78, and GRP94 were induced to higher expression levels by palmitic acid. Co-treatment with α-linolenic acid reversed the apoptotic effect and levels of all three indicators of ER stress exerted by palmitic acid. Tunicamycin, which induces ER stress produced similar effects to those obtained using palmitic acid; its effects were also reversed by α-linolenic acid. Conclusions α-Linolenic acid may provide a useful strategy to avoid the lipotoxicity of dietary palmitic acid and nutrient overload accompanied with obesity and NAFLD.

  3. Evidence for ceramide synthase inhibition in humans exposed to fumonisins in maize-based foods and living in low or high exposure communities in Guatemala

    Science.gov (United States)

    Fumonisins (FB) are mycotoxins commonly found in corn and in foods made from corn. Fumonisin B1 (FB1), the most common FB, causes diseases in farm animals and causes liver and kidney toxicity and cancer in rodents. The key event in its mechanism of toxicity in animals is inhibition of the enzyme c...

  4. Fumonisin exposure in women linked to inhibition of an enzyme that is a key event in farm and laboratory animal diseases.

    Science.gov (United States)

    Fumonisin B1 (FB1) is a toxic chemical produced by molds. The molds that produce fumonisin are common in corn. Consumption of contaminated corn by farm animals has been shown to be the cause of animal disease. The proximate cause (key event) in the induction of diseases in animals is inhibition of t...

  5. Cholinesterase Inhibition and Depression of the Photic After Discharge of Flash Evoked Potentials Following Acute or Repeated Exposures to a Mixture of Carbaryl and Propoxur

    Science.gov (United States)

    While information exists regarding inhibition of cholinesterase (ChE) activity, little is known about neurophysiological changes produced by a mixture of N-methyl carbamate pesticides. Previously, we reported that acute treatment with propoxur or carbaryl decreased the duration o...

  6. Hospitalizations and economic analysis in psychotic patients with paliperidone palmitate long-acting injection.

    Science.gov (United States)

    Mesones-Peral, Jesús E; Gurillo-Muñoz, Pedro; Sánchez-Sicilia, Mari Paz; Miller, Adam; Griñant-Fernández, Alejandra

    Prevent hospitalizations in psychotic disorders is an important aim, so long-acting antipsychotic is a good option that can control better the correct adherence. Moreover, in the current economic context pharmacoeconomic studies are necessary. We estimate the effect in prevention of paliperidone palmitate long-acting injection (PP-LAI) and calculate the economic cost in the 12 months preceding the start of treatment with PP-LAI and 12 months later. Mirror image study of 71 outpatients diagnosed with psychotic disorders and treated with PP-LAI. In a first analysis, we measured along one year: number of hospitalizations/year, number of hospitalization in days, number of emergency assists/year and if there is antipsychotics associated to long-acting treatment. After this phase, we applied Fees Act of Valencia for economic analysis and estimate of the cost per hospitalization (€ 5,640.41) and hospital emergency (€ 187.61). After one year of treatment with PP-LAI (mean dose=130.65mg/month), we obtained greater numbers in assistance variables: total hospitalizations decrease, 78.8% (P=.009); shortening in hospitalization days, 89.4% (P=.009); abridgement of number of emergency assists, 79.1% (P=.002); decrease of rate of antipsychotics associated to long-acting treatment, 21% (P<.0001); increase in monotherapy, 53.8% (P<.0001). Therefore, after 12 months of treatment with PP-LAI we obtained a reduction in inpatient spending (savings of € 175,766.54) and increased spending on antipsychotics 32% (equivalent to € 151,126.92). PP-LAI can be an effective therapy for the treatment of patients with severe psychotic disorders: improves symptomatic stability and can prevent hospitalizations with cost-effective symptom control. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-09

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  8. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    International Nuclear Information System (INIS)

    Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  9. Androgenic effect of honeybee drone milk in castrated rats: roles of methyl palmitate and methyl oleate.

    Science.gov (United States)

    Seres, A B; Ducza, E; Báthori, M; Hunyadi, A; Béni, Z; Dékány, M; Hajagos-Tóth, J; Verli, J; Gáspár, Róbert

    2014-04-28

    Numerous honeybee (Apis mellifera) products have been used in traditional medicine to treat infertility and to increase vitality in both men and women. Drone milk (DM) is a relatively little-known honeybee product with a putative sexual hormone effect. The oestrogenic effect of a fraction of DM has recently been reported in rats. However, no information is available on the androgenic effects of DM. The purpose of the present study was to determine the androgen-like effect of DM in male rats and to identify effective compounds. A modified Hershberger assay was used to investigate the androgenic effect of crude DM, and the plasma level of testosterone was measured. The prostatic mRNA and protein expression of Spot14-like androgen-inducible protein (SLAP) were also examined with real-time PCR and Western blot techniques. GC-MS and NMR spectroscopic investigations were performed to identify the active components gained by bioactivity-guided fractionation. The crude DM increased the relative weights of the androgen-dependent organs and the plasma testosterone level in castrated rats and these actions were flutamide-sensitive. DM increased the tissue mRNA and protein level of SLAP, providing further evidence of its androgen-like character. After bioactivity-guided fractionation, two fatty acid esters, methyl palmitate (MP) and methyl oleate (MO), were identified as active compounds. MP alone showed an androgenic effect, whereas MO increased the weight of androgen-sensitive tissues and the plasma testosterone level only in combination. The experimental data of DM and its active compounds (MO and MP) show androgenic activity confirming the traditional usage of DM. DM or MP or/and MO treatments may project a natural mode for the therapy of male infertility. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Determination of physicochemical properties and degradation kinetics of triamcinolone acetonide palmitate in vitro.

    Science.gov (United States)

    Peng, Cuilian; Liu, Cong; Tang, Xing

    2010-12-01

    Triamcinolone acetonide palmitate (TAP) is a lipophilic prodrug of triamcinolone acetonide (TAA) to improve the insoluble TAA physicochemical properties for the preparation of emulsions. This investigation has focused on the preformulation study of TAP, including its physicochemical properties and hydrolysis kinetics in vitro. The solubility of TAP in medium-chain triglyceride is about twice greater than that in soybean oil (long-chain triglyceride) (19.17 versus 9.55 mg/g) at 25°C, and in all investigated cases, lecithin (80, 160, and 240 mg/g) as solubilizer provided increased solubility of drugs in medium-chain triglyceride and long-chain triglyceride, whereas the maximum water solubility of TAP was 0.10 μg/mL. The partition coefficient (log P) of TAP was 5.79 irrespective of the pH conditions. The hydrolysis of TAP followed pseudo-first-order kinetics in aqueous solutions, and the stable pH range was from pH 5.0 to 9.0. The in vitro enzymolysis kinetics of TAP in rat plasma and liver homogenate was evaluated by measuring the decrease of TAP as well as the increase of TAA at 37°C for 96 hours. The results demonstrated that the TAP may be hydrolyzed mainly by rat plasma esterase and, to a minor extent, by liver esterase, and the hydrolysis half-life of TAP in 100% rat plasma was 17.53 ± 6.85 hours at pH 7.4. All these results indicated that TAP had successfully obtained higher lipid-soluble property for the preparation of intravenous emulsion and may be an effective prodrug for sustained release of TAA in vivo.

  11. Intravenous IgA complexed with antigen reduces primary antibody response to the antigen and anaphylaxis upon antigen re-exposure by inhibiting Th1 and Th2 activation in mice.

    Science.gov (United States)

    Yamaki, Kouya; Miyatake, Kenji; Nakashima, Takayuki; Morioka, Ayumi; Yamamoto, Midori; Ishibashi, Yuki; Ito, Ayaka; Kuranishi, Ayu; Yoshino, Shin

    2014-10-01

    Serum IgG, IgE and IgM have been shown to enhance the primary antibody responses upon exposure to the soluble antigens recognized by those antibodies. However, how IgA affects these responses remains unknown. We investigated the effects of intravenously administered monoclonal IgA on the immune responses in mice. DBA/1J mice were immunized with ovalbumin in the presence or absence of anti-ovalbumin monoclonal IgA. The Th1 and Th2 immune responses to ovalbumin and the anaphylaxis induced by re-exposure to ovalbumin were measured. IgA complexed with antigen attenuated the primary antibody responses to the antigen in mice, in contrast to IgG2b and IgE. The primary antibody responses, i.e. the de novo synthesis of anti-ovalbumin IgG2a, IgG1 and IgE in the serum, and the subsequent anaphylaxis induced with re-exposure to ovalbumin were reduced by the co-injection of anti-ovalbumin monoclonal IgA at ovalbumin immunization. The Th1, Th2 and Tr1 cytokines interferon-γ, interleukin-4 and interleukin-10, respectively, released from ovalbumin-restimulated cultured splenocytes collected from allergic mice were also reduced by the treatment. The induction of interferon-γ and interleukin-4 secretion by splenocytes from ovalbumin-immunized mice stimulated in vitro with ovalbumin was also significantly reduced by the antigen complexed with anti-ovalbumin IgA. These data suggest that the direct inhibition of Th1 and Th2 activation by anti-ovalbumin monoclonal IgA participates in the inhibition of the primary antibody responses. IgA plays important immunosuppressive roles under physiological and pathological conditions and is a promising candidate drug for the treatment of immune disorders.

  12. Sex-specific differences in corticosterone secretion, behavioral phenotypes and expression of TrkB.T1 and TrkB.FL receptor isoforms: Impact of systemic TrkB inhibition and combinatory stress exposure in adolescence.

    Science.gov (United States)

    Azogu, Idu; Liang, Jacky; Plamondon, Helene

    2018-05-09

    Stress exposure has been implicated in the development of mood disorders, although little is known about the lasting effects of repeated stress during the adolescent period on sex-specific differences in endocrine and plasticity-signaling responses in adulthood. Using a 10-day combinatory stress paradigm (postnatal day (PND) 26 to 35), we examined sex-specific impact of adolescent stress and inhibition of tyrosine-related kinase B (TrkB) receptor (ANA-12; 0.5 mg/kg, i.p.) on 1) adolescent blood corticosterone levels, 2) adult locomotion and anxiety-like behavior, and 3) region-specific differences in endogenous TrkB full-length (TrkB.FL) and truncated (TrkB.T1) receptor isoforms. Blood collected on days 1, 5 and 10 revealed elevated basal and stress-induced CORT secretion in females compared to males, while ANA-12 attenuated CORT elevations post stress in both sexes. As adults, all females exhibited higher locomotor and exploratory activity than males in the open field test and elevated plus maze, and differences were comparable in the forced swim within stress-naïve and stress groups. Biochemically, vehicle-treated males showed elevated TrkB.T1 and TrkB.FL compared to vehicle-treated females in the PFC, hippocampus and NAc, and levels were consistently attenuated by ANA-12 treatment in non-stress males. With regards to stress exposure, expression of both isoforms was strongly down-regulated in the NAc of males only and was associated with increased TrkB.T1 in the PFC. ANA-12 enhanced expression in females, independent of stress exposure, compared to vehicle-treated counterparts, expression being increased for TrkB.T1 versus TrkB.FL and magnitude of the changes being region-specific. In contrast, ANA-12 effects in stressed males were restricted to inhibition of both isoforms in the hippocampus. Together, our findings support that TrkB activation, contingent on stress exposure, differentially affects TrkB isoform regulation during adulthood. Sex

  13. [11C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia

    International Nuclear Information System (INIS)

    Guiducci, Letizia; Jaervisalo, Mikko; Kiss, Jan; Nagren, Kjell; Viljanen, Antti; Naum, Alexandru G.; Gastaldelli, Amalia; Savunen, Timo; Knuuti, Juhani; Salvadori, Piero A.; Ferrannini, Ele; Nuutila, Pirjo; Iozzo, Patricia

    2006-01-01

    Purpose: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [ 11 C]palmitate injection during fasting and insulin stimulation. Methods: Plasma [ 11 C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. Results: At 10 min, plasma levels of unchanged [ 11 C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P≤.03), suggesting faster clearance. Levels of unmetabolized [ 11 C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [ 11 C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92±1% and 82±6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. Conclusion: The study indicates that the redistribution of [ 11 C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG constitute an additional

  14. [{sup 11}C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia

    Energy Technology Data Exchange (ETDEWEB)

    Guiducci, Letizia [SSSUP Medical Sciences Branch, Pisa 56100 (Italy); Turku PET Centre, University of Turku, Turku 20520 (Finland); PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Jaervisalo, Mikko [Turku PET Centre, University of Turku, Turku 20520 (Finland); Kiss, Jan [Turku PET Centre, University of Turku, Turku 20520 (Finland); Department of Surgery, University of Turku, Turku 20520 (Finland); Nagren, Kjell [Turku PET Centre, University of Turku, Turku 20520 (Finland); Viljanen, Antti [Turku PET Centre, University of Turku, Turku 20520 (Finland); Naum, Alexandru G. [Turku PET Centre, University of Turku, Turku 20520 (Finland); Gastaldelli, Amalia [PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Savunen, Timo [Department of Surgery, University of Turku, Turku 20520 (Finland); Knuuti, Juhani [Turku PET Centre, University of Turku, Turku 20520 (Finland); Salvadori, Piero A. [PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Ferrannini, Ele [PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy); Department of Internal Medicine, University of Pisa School of Medicine, Pisa 56100 (Italy); Nuutila, Pirjo [Turku PET Centre, University of Turku, Turku 20520 (Finland); Department of Medicine, University of Turku, Turku 20520 (Finland); Iozzo, Patricia [Turku PET Centre, University of Turku, Turku 20520 (Finland) and PET Centre, Institute of Clinical Physiology, CNR National Research Council, 56100 Pisa (Italy)]. E-mail: patricia.iozzo@ifc.cnr.it

    2006-05-15

    Purpose: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [{sup 11}C]palmitate injection during fasting and insulin stimulation. Methods: Plasma [{sup 11}C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. Results: At 10 min, plasma levels of unchanged [{sup 11}C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P{<=}.03), suggesting faster clearance. Levels of unmetabolized [{sup 11}C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [{sup 11}C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92{+-}1% and 82{+-}6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. Conclusion: The study indicates that the redistribution of [{sup 11}C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG

  15. In Vivo Reactivation by Oximes of Inhibited Blood, Brain and Peripheral Tissue Cholinesterase Activity Following Exposure to Nerve Agents in Guinea Pigs

    Science.gov (United States)

    2010-01-01

    nerve agent intoxication ( salivation , rhinorrhea, tremors,muscle asciculations, convulsions) at 60min following the 1.0× LD50 dose f GB, GF, VR or VX...reactivation of GF-, soman-, or VR-inhibited enzyme byHI-6 andHLö7. However, these in vitro experiments [24,25] were conducted with a pH of 8.0 at 25 ◦C...data. Even the study of Worek et al. [23] that was performed at a pH of 7.4 at 37 ◦C, whose in vitro kinetic data obtained from guinea pig RBC ghosts

  16. Preparation and properties of highly conductive palmitic acid/graphene oxide composites as thermal energy storage materials

    International Nuclear Information System (INIS)

    Mehrali, Mohammad; Latibari, Sara Tahan; Mehrali, Mehdi; Indra Mahlia, Teuku Meurah; Cornelis Metselaar, Hendrik Simon

    2013-01-01

    PA/GO (palmitic acid/graphene oxide) as PCMs (phase change materials) prepared by vacuum impregnation method, have high thermal conductivity. The GO (graphene oxide) composite was used as supporting material to improve thermal conductivity and shape stabilization of composite PCM (phase change material). SEM (Scanning electronic microscope), FT-IR (Fourier transformation infrared spectroscope) and XRD (X-ray diffractometer) were applied to determine microstructure, chemical structure and crystalloid phase of palmitic acid/GO composites, respectively. DSC (Differential scanning calorimeter) test was done to investigate thermal properties which include melting and solidifying temperatures and latent heat. FT-IR analysis represented that the composite instruction of porous palmitic acid and GO were physical. The temperatures of melting, freezing and latent heats of the composite measured through DSC analysis were 60.45, 60.05 °C, 101.23 and 101.49 kJ/kg, respectively. Thermal cycling test showed that the form-stable composite PCM has good thermal reliability and chemical stability. Thermal conductivity of the composite PCM was improved by more than three times from 0.21 to 1.02. As a result, due to their acceptable thermal properties, good thermal reliability, chemical stability and great thermal conductivities, we can consider the prepared form-stable composites as highly conductive PCMs for thermal energy storage applications. - Highlights: • Novel composite PCM with high thermal conductivity and latent heat storage. • New thermal cycling test for thermal reliability of composite PCMs. • Increasing thermal conductivity of composite PCM with graphene oxide. • Increasing thermal stability of phase change material by adding graphene oxide

  17. PHYSICAL AND CHEMICAL STABILITY ANALYSIS OF COSMETIC MULTI- PLE EMULSIONS LOADED WITH ASCORBYL PALMITATE AND SODIUM ASCORBYL PHOSPHATE SALTS.

    Science.gov (United States)

    Khan, Hira; Akhtar, Naveed; Ali, Atif; Khan, Haji M Shoaib; Sohail, Muhammad; Naeem, Muhammad; Nawaz, Zarqa

    2016-09-01

    Stability of hydrophilic and lipophilic vitamin C derivatives for quenching synergistic antioxidant activities and to treat oxidative related diseases is a major issue. This study was aimed to encapsulate hydrophilic and lipophilic vitamin C derivatives (ascorbyl palmitate and sodium ascorbyl phosphate) as functional ingredients in a newly formulated multiple emulsion of the W//W type to attain the synergistic antioxidant effects and the resultant system's long term physical and chemical stability. Several multiple emulsions using the same concentration of emulsifiers but different concentrations of ascorbyl palmitate and sodium ascorbyl phosphate were developed. Three finally selected multiple emulsions (ME₁, ME₂ and ME₃) were evaluated for physical stability in terms of rheology, microscopy, conductivity, pH, and organoleptic characteristics under different storage conditions for 3 months. Chemical stability was determined by HPLC on Sykam GmbH HPLC system (Germany), equipped with a variable UV detector. Results showed that at accelerated storage conditions all the three multiple emulsions had shear thinning behavior of varying shear stress with no influence of location of functional ingredients in a carrier system. Conductivity values increased and pH values remained within the skin pH range for 3 months. Microscopic analysis showed an increase in globule size with the passage of time, especially at higher temperatures while decreased at low temperatures. Centrifugation test did not cause phase separation till the 45th day, but little effects after 2 months. Chemical stability analysis by HPLC at the end of 3 months showed that ascorbyl palmitate and sodium ascorbyl phosphate were almost stable in all multiple emulsions with no influence of their location in a carrier system. Multiple emulsions were found a stable carrier for hydrophilic and lipophilic vitamin C derivatives to enhance their desired effects. Considering that many topical formulations

  18. Effect of C2 ceramide on the inositol phospholipid metabolism (uptake of 32P, 3H-serine and 3H-palmitic acid) and apoptosis-related morphological changes in Tetrahymena

    International Nuclear Information System (INIS)

    Kovacs, P.; Hegyesi, H.; Koehidai, L.; Nemes, P.; Csaba, G.

    1999-01-01

    Sphingomyelin metabolites have significant role in the regulation of many life processes of mammalian cells. In the present experiments the influence of phospholipid turnover and apoptosis related morphologic signs by one of this metabolite, C 2 ceramide was studied, and compared to the control, untreated cells, in the unicellular Tetrahymena. The incorporation of phospholipid head group components (serine, phosphorus) show a clear time-dependence; while the incorporation of fatty acid component (palmitic acid) is very fast: no significant alterations were found between 5- and 60-min incubations. C 2 ceramide treatment didn't alter 3 H-palmitic acid incorporation into phospholipids, however 3 H-serine incorporation was mainly inhibited. The amount of total incorporated 32 P was also decreased, on the other hand the lover concentration C 2 ceramide (10 μM) elevated the synthesis of inositol phospholipids. The higher concentration of C 2 ceramide (50 μM) had inhibitory effect on the synthesis of each phospholipids examined. This means that in the presence of the C 2 ceramide the synthesis, recovery and turnover of phospholipids, participating in signal transduction, are altered. However these observations were based the uptake of labeled phospholipid precursors, which gives information on the dynamics of the process, without using lipid mass measurements. C 2 ceramide also caused the rounding off the cells, DNA degradation and nuclear condensation. These latter observations point to morphological signs of apoptosis. The results call attention to the role of sphingomyelin metabolites on signalization of unicellulars, to the cross-talk between the inositol phospholipids and sphingomyelin metabolites, and the role of these molecules in the apoptotic processes at a low evolutionary level. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  19. Differences in partitioning of meal fatty acids into blood lipid fractions: a comparison of linoleate, oleate, and palmitate

    OpenAIRE

    Hodson, Leanne; McQuaid, Siobh?n E.; Karpe, Fredrik; Frayn, Keith N.; Fielding, Barbara A.

    2008-01-01

    There has been much interest in the health effects of dietary fat, but few studies have comprehensively compared the acute metabolic fate of specific fatty acids in vivo. We hypothesized that different classes of fatty acids would be variably partitioned in metabolic pathways and that this would become evident over 24 h. We traced the fate of fatty acids using equal amounts of [U-13C]linoleate, [U-13C]oleate, and [U-13C]palmitate given in a test breakfast meal in 12 healthy subjects. There wa...

  20. Behavioral effects of D3 receptor inhibition and 5-HT4 receptor activation on animals undergoing chronic cannabinoid exposure during adolescence.

    Science.gov (United States)

    Abboussi, Oualid; Said, Nadia; Fifel, Karim; Lakehayli, Sara; Tazi, Abdelouahhab; El Ganouni, Soumaya

    2016-04-01

    Chronic exposure to cannabinoids during adolescence results in long-lasting behavioral deficits that match some symptomatologic aspects of schizophrenia. The aim of this study was to investigate the reversibility of the emotional and the cognitive effects of chronic exposure to cannabinoids during adolescence, via subsequent modulation of the serotoninergic 5-HT4 and dopaminergic D3 receptors. RS67333 as a 5-HT4 agonist and U-99194A as a D3 antagonist were administered separately at 1 mg/kg and 20 mg/kg, and in combination at 0.5 mg/kg and 10 mg/kg to adult animals undergoing chronic treatment with the synthetic cannabinoid receptor agonist WIN55,212-2 (1 mg/kg) during adolescence. Animals were tested for anxiety-like behavior and episodic-like memory in the open field and novel object recognition tests respectively 30 minutes after the last drug administration. Chronic WIN55,212-2 treated animals exhibited a lasting disruption of episodic memory and increased anxiety levels. The effect on episodic-like memory were partially restored by acute administration of RS67333 and U-99194A and completely by administration of both drugs in combination at lower doses. However, only RS67333 (20 mg/kg) improved the anxiogenic-like effect of WIN55,212-2. These findings give further support that chronic exposure to cannabinoids during adolescence may be used as an animal model for schizophrenia, and highlight D3 and 5-HT4 receptors as potential targets for an enhanced treatment of the cognitive aspect of this disease.

  1. Acute exposure to UV-B sensitizes cucumber, tomato, and Arabidopsis plants to photooxidative stress by inhibiting thermal energy dissipation and antioxidant defense

    International Nuclear Information System (INIS)

    Moon, Yu-Ran; Lee, Min-Hee; Chung, Byung-Yeoup; Kim, Jin-Hong; Tovuu, Altanzaya; Lee, Choon-Hwan; Park, Youn-Il

    2011-01-01

    The purpose of this study was to characterize a change in Non-photochemical quenching (NPQ) upon exposure to ultraviolet-B (UV-B), the xanthophyll cycle-dependent and -independent NPQs were compared in Cucumis sativus, Lycopersicum esculentum, and Arabidopsis thaliana leaves. The xanthophyll cycle-dependent NPQ was dramatically but reversibly suppressed by UV-B radiation. This suppression was correlated more strongly with a marked decrease in photosynthetic electron transport rather than changes in xanthophyll cycle enzymes such as violaxanthin de-epoxidase and zeaxanthin epoxidase. Accordingly, the UV-B-induced suppression of NPQ cannot be attributed to changes in expressions of violaxanthin de-epoxidase (VDE) and zeaxanthin epoxidase (ZEP). However, suppression of the xanthophyll cycle-dependent NPQ could only account for the 77 K fluorescence emission spectra of thylakoid membranes and the increased level of 1 O 2 production, but not for the decreased levels of hydroxyl radical O 2 - production and H 2 O 2 scavenging. These results suggest that a gradual reduction of H 2 O 2 scavenging activity as well as a transient and reversible suppression of thermal energy dissipation may contribute differentially to increased photooxidative damages in cucumber, tomato, and Arabidopsis plants after acute exposure to UV-B radiation. (author)

  2. Hypothalamic PGC-1α Protects Against High-Fat Diet Exposure by Regulating ERα

    Directory of Open Access Journals (Sweden)

    Eugenia Morselli

    2014-10-01

    Full Text Available High-fat diets (HFDs lead to obesity and inflammation in the central nervous system (CNS. Estrogens and estrogen receptor α (ERα protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

  3. Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα.

    Science.gov (United States)

    Morselli, Eugenia; Fuente-Martin, Esther; Finan, Brian; Kim, Min; Frank, Aaron; Garcia-Caceres, Cristina; Navas, Carlos Rodriguez; Gordillo, Ruth; Neinast, Michael; Kalainayakan, Sarada P; Li, Dan L; Gao, Yuanqing; Yi, Chun-Xia; Hahner, Lisa; Palmer, Biff F; Tschöp, Matthias H; Clegg, Deborah J

    2014-10-23

    High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor α (ERα) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA) and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

  4. Inhibition of galectin-3 ameliorates the consequences of cardiac lipotoxicity in a rat model of diet-induced obesity

    Directory of Open Access Journals (Sweden)

    Gema Marín-Royo

    2018-02-01

    Full Text Available Obesity is accompanied by metabolic alterations characterized by insulin resistance and cardiac lipotoxicity. Galectin-3 (Gal-3 induces cardiac inflammation and fibrosis in the context of obesity; however, its role in the metabolic consequences of obesity is not totally established. We have investigated the potential role of Gal-3 in the cardiac metabolic disturbances associated with obesity. In addition, we have explored whether this participation is, at least partially, acting on mitochondrial damage. Gal-3 inhibition in rats that were fed a high-fat diet (HFD for 6 weeks with modified citrus pectin (MCP; 100 mg/kg/day attenuated the increase in cardiac levels of total triglyceride (TG. MCP treatment also prevented the increase in cardiac protein levels of carnitine palmitoyl transferase IA, mitofusin 1, and mitochondrial complexes I and II, reactive oxygen species accumulation and decrease in those of complex V but did not affect the reduction in 18F-fluorodeoxyglucose uptake observed in HFD rats. The exposure of cardiac myoblasts (H9c2 to palmitic acid increased the rate of respiration, mainly due to an increase in the proton leak, glycolysis, oxidative stress, β-oxidation and reduced mitochondrial membrane potential. Inhibition of Gal-3 activity was unable to affect these changes. Our findings indicate that Gal-3 inhibition attenuates some of the consequences of cardiac lipotoxicity induced by a HFD since it reduced TG and lysophosphatidyl choline (LPC levels. These reductions were accompanied by amelioration of the mitochondrial damage observed in HFD rats, although no improvement was observed regarding insulin resistance. These findings increase the interest for Gal-3 as a potential new target for therapeutic intervention to prevent obesity-associated cardiac lipotoxicity and subsequent mitochondrial dysfunction.

  5. Ethanolic extract of Passiflora edulis Sims leaves inhibits protein glycation and restores the oxidative burst in diabetic rat macrophages after Candida albicans exposure

    Directory of Open Access Journals (Sweden)

    Carolina Fernandes Ribas Martins

    2015-12-01

    Full Text Available abstract This study was conducted to evaluate the effects of the ethanolic extract of Passiflora edulis leaves on blood glucose, protein glycation, NADPH oxidase activity and macrophage phagocytic capacity after Candida albicans exposure in diabetic rats. The Passiflora edulis Sims leaves were dried to 40°C, powdered, extracted by maceration in 70% ethanol, evaporated under reduced pressure and lyophilised. The biochemical tests performed were total phenolic content (TP as determined by the Folin-Ciocalteu assay, trapping potential DPPH assay and total iron-reducing potential. Diabetes was induced by alloxan injection. Protein glycation was determined by AGE and fructosamine serum concentrations. Extract-treated diabetic animals demonstrated lower fructosamine concentrations compared with the diabetic group. Our results suggest that ethanolic Passiflora edulis Sims leaf extraction may have beneficial effects on diabetes and may improve glycaemic control in diabetic rats.

  6. Low-fat yogurt consumption reduces biomarkers of chronic inflammation and inhibits markers of endotoxin exposure in healthy premenopausal women: a randomised controlled trial.

    Science.gov (United States)

    Pei, Ruisong; DiMarco, Diana M; Putt, Kelley K; Martin, Derek A; Gu, Qinlei; Chitchumroonchokchai, Chureeporn; White, Heather M; Scarlett, Cameron O; Bruno, Richard S; Bolling, Bradley W

    2017-12-01

    The anti-inflammatory mechanisms of low-fat dairy product consumption are largely unknown. The objective of this study was to determine whether low-fat yogurt reduces biomarkers of chronic inflammation and endotoxin exposure in women. Premenopausal women (BMI 18·5-27 and 30-40 kg/m2) were randomised to consume 339 g of low-fat yogurt (yogurt non-obese (YN); yogurt obese (YO)) or 324 g of soya pudding (control non-obese; control obese (CO)) daily for 9 weeks (n 30/group). Fasting blood samples were analysed for IL-6, TNF-α/soluble TNF II (sTNF-RII), high-sensitivity C-reactive protein, 2-arachidonoyl glycerol, anandamide, monocyte gene expression, soluble CD14 (sCD14), lipopolysaccharide (LPS), LPS binding protein (LBP), IgM endotoxin-core antibody (IgM EndoCAb), and zonulin. BMI, waist circumference and blood pressure were also determined. After 9-week yogurt consumption, YO and YN had decreased TNF-α/sTNFR-RII. Yogurt consumption increased plasma IgM EndoCAb regardless of obesity status. sCD14 was not affected by diet, but LBP/sCD14 was lowered by yogurt consumption in both YN and YO. Yogurt intervention increased plasma 2-arachidonoylglycerol in YO but not YN. YO peripheral blood mononuclear cells expression of NF-κB inhibitor α and transforming growth factor β1 increased relative to CO at 9 weeks. Other biomarkers were unchanged by diet. CO and YO gained approximately 0·9 kg in body weight. YO had 3·6 % lower diastolic blood pressure at week 3. Low-fat yogurt for 9 weeks reduced biomarkers of chronic inflammation and endotoxin exposure in premenopausal women compared with a non-dairy control food. This trial was registered as NCT01686204.

  7. Incorporation of [14C]-palmitate into lipids of Brassica cells during the induction of freezing tolerance

    International Nuclear Information System (INIS)

    Lynch, D.V.; Joseph, R.A.

    1989-01-01

    Changes in plasma membrane lipid composition have been causally related to increased freezing tolerance. Studies of lipid metabolism during ABA induction of freezing tolerance in Brassica napus suspension cultures were undertaken. Cells were labeled with [ 14 C]-palmitate four days after transfer to fresh medium (control) or medium containing ABA (which increases freezing tolerance). At times between one and 20 hrs after labeling, ABA-treated cells incorporated almost twice the amount of label as controls cells. Approximately 80% of the radioactivity was associated with neutral lipids in ABA-treated cells and controls. Incorporation of label into total cellular polar lipids was 4.9 x 10 5 dpm/mg protein for control cells and 1 x 10 6 dpm/mg protein for cells transferred to medium containing ABA. Analysis of lipids following alkaline hydrolysis indicated that incorporation of [ 14 C]-palmitate into glucosylceramide of ABA-treated cells was less than 60% of control values when expressed relative to that of the total polar lipids. Incorporation into ceramides was also depressed in ABA-treated cells

  8. Deoxygenation of Palmitic and Lauric Acids over Pt/ZIF-67 Membrane/Zeolite 5A Bead Catalysts.

    Science.gov (United States)

    Yang, Liqiu; Carreon, Moises A

    2017-09-20

    The deoxygenation of palmitic and lauric acids over 0.5 wt % Pt/ZIF-67 membrane/zeolite 5A bead catalysts is demonstrated. Almost complete conversion (% deoxygenation of ≥95%) of these two fatty acids was observed over both fresh and recycled catalyst after a 2 h reaction time. The catalysts displayed high selectivity to pentadecane and undecane via decarboxylation reaction pathway even at low 0.5 wt % Pt loading. Selectivity to pentadecane and undecane as high as ∼92% and ∼94% was observed under CO 2 atmosphere when palmitic and lauric acids were used respectively as reactants. Depending on the reaction gas atmosphere, two distinctive reaction pathways were observed: decarboxylation and hydrodeoxygenation. Specifically, it was found that decarboxylation reaction pathway was more favorable in the presence of helium and CO 2 , while hydrodeoxygenation pathway strongly competed against the decarboxylation pathway when hydrogen was employed during the deoxygenation reactions. Esters were identified as the key reaction intermediates leading to decarboxylation and hydrodeoxygenation pathways.

  9. Intestinal absorption and distribution of 14C-palmitic acid in an young Indian freshwater major carp, Labeo rohita (Hamilton)

    International Nuclear Information System (INIS)

    Sinha, G.M.; Chakrabarti, P.

    1983-01-01

    The mechanism of absorption and distribution of radioactive lipids in the various regions of the intestine and hepatopancreas of young Labeo rohita (Ham.) was investigated after feeding with small-sized earthworms (Pheretima posthuma), preinjected with 14 C-Palmitic acid. Dietary free fatty acids were mainly absorbed in the various regions (anterior, middle and posterior) of the intestine-the absorption capacity, however, varying greatly from region to region. The absorption of free fatty acids through the luminal brush border of the various regions of the intestine started at 24 hr of post-feeding (h.p.f.) with labelled diet and recorded its peak during 32 +- 2 h.p.f. However, middle intestine was found to be more active for such absorption than the other two regions (anterior and posterior). Incorporation of labelled Palmitic acid in the columnar epithelial cells and its subsequent transportation in the hepatic tissues, via lymphatic systems took place with in a short interval after absorption. However, absorption was completed within 40 h.p.f. when deposition of radioactive lipids was found to be maximum in the columnar epithelial cells of the various regions of the intestine and hepatic tissues. (author)

  10. Optimization of methanol crystallization for highly efficient separation of palmitic acid from palm fatty acid mixture using response surface methodology

    Directory of Open Access Journals (Sweden)

    A. A.W. Japir

    2018-01-01

    Full Text Available The objective of the current study was to develop parameters for the separation of palmitic acid (PA from a crude palm oil saturated fatty acid (SFAs mixture by using the methanol crystallization method. The conditions of methanol crystallization were optimized by the response surface methodology (RSM with the D-optimal design. The procedure of developing the solvent crystallization method was based on various different parameters. The fatty acid composition was carried out using a gas chromatography flame ionization detector (GC-FID as fatty acid methyl esters. The highest percentage of SFAs was more than 96% with the percentage yield of 87.5% under the optimal conditions of fatty acids-to-methanol ratio of 1: 20 (w/v, the crystallization temperature of -15 °C, and the crystallization time of 24 hours, respectively. The composition of separated SFAs in the solid fraction contains 96.7% of palmitic acid (C16:0 as a dominant component and 3.3% of stearic acid (C18:0. The results showed that utilizing methanol as a crystallization solvent is recommended because of its high efficiency, low cost, stability, availability, comparative ease of recovery and its ability to form needle-like crystals which have good filtering and washing characteristics.

  11. Optimization of methanol crystallization for highly efficient separation of palmitic acid from palm fatty acid mixture using response surface methodology

    International Nuclear Information System (INIS)

    Japir, A.A.W.; Salimon, J.; Derawi, D.; Yahaya, B.H.; Jamil, M.S.M.; Yusop, M.R.

    2017-01-01

    The objective of the current study was to develop parameters for the separation of palmitic acid (PA) from a crude palm oil saturated fatty acid (SFAs) mixture by using the methanol crystallization method. The conditions of methanol crystallization were optimized by the response surface methodology (RSM) with the D-optimal design. The procedure of developing the solvent crystallization method was based on various different parameters. The fatty acid composition was carried out using a gas chromatography flame ionization detector (GC-FID) as fatty acid methyl esters. The highest percentage of SFAs was more than 96% with the percentage yield of 87.5% under the optimal conditions of fatty acids-to-methanol ratio of 1: 20 (w/v), the crystallization temperature of -15 °C, and the crystallization time of 24 hours, respectively. The composition of separated SFAs in the solid fraction contains 96.7% of palmitic acid (C16:0) as a dominant component and 3.3% of stearic acid (C18:0). The results showed that utilizing methanol as a crystallization solvent is recommended because of its high efficiency, low cost, stability, availability, comparative ease of recovery and its ability to form needle-like crystals which have good filtering and washing characteristics. [es

  12. Improving the physical and moisture barrier properties of Lepidium perfoliatum seed gum biodegradable film with stearic and palmitic acids.

    Science.gov (United States)

    Seyedi, Samira; Koocheki, Arash; Mohebbi, Mohebbat; Zahedi, Younes

    2015-01-01

    Stearic and palmitic fatty acids (10%, 20% and 30%, W/W gum) were used to improve the barrier properties of Lepidium perfoliatum seed gum (LPSG) film. The impact of the incorporation of fatty acids into the film matrix was studied by investigating the physical, mechanical, and barrier properties of the films. Addition of stearic and palmitic fatty acids to LPSG films reduced their water vapor permeability (WVP), moisture content, water solubility and water adsorption. Increasing fatty acid concentration from 10% to 30%, reduced the elongation at break (EB). Lower values of tensile strength (TS) and elastic modulus (EM) were obtained in the presence of higher fatty acids concentrations. Incorporation of fatty acids led to production of opaque films and the opacity increased as function of fatty acids concentration. Results showed that moisture content, water solubility and WVP decreased as the chain length of fatty acid increased. Therefore, LPSG-fatty acids composite film could be used for packaging in which a low affinity toward water is needed. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Whole-body biodistribution, dosimetry and metabolite correction of [11C]palmitate: A PET tracer for imaging of fatty acid metabolism

    DEFF Research Database (Denmark)

    Christensen, Nana Louise; Jakobsen, Steen; Schacht, Anna Christina

    2017-01-01

    INTRODUCTION: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were...... performed in 2 pigs and 2 healthy volunteers by whole-body [11C]palmitate PET scans. Metabolite studies were performed in 40 participants (healthy and with type 2 diabetes) under basal and hyperinsulinemic conditions. Metabolites were estimated using 2 approaches and subsequently compared: Indirect [11C]CO2...

  14. Whole-body biodistribution, dosimetry and metabolite correction of [11C]palmitate: A PET tracer for imaging of fatty acid metabolism

    DEFF Research Database (Denmark)

    Christensen, Nana Louise; Jakobsen, Steen; Schacht, Anna Christina

    2017-01-01

    release and parent [11C]palmitate measured by a solid-phase extraction (SPE) method. Finally, myocardial fatty acid uptake was calculated in a patient cohort using input functions derived from individual metabolite correction compared with population-based metabolite correction. RESULTS: In humans, mean......INTRODUCTION: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were...

  15. Toxic Shock Syndrome Toxin-1-Mediated Toxicity Inhibited by Neutralizing Antibodies Late in the Course of Continual in Vivo and in Vitro Exposure

    Directory of Open Access Journals (Sweden)

    Norbert Stich

    2014-05-01

    Full Text Available Toxic shock syndrome (TSS results from the host’s overwhelming inflammatory response and cytokine storm mainly due to superantigens (SAgs. There is no effective specific therapy. Application of immunoglobulins has been shown to improve the outcome of the disease and to neutralize SAgs both in vivo and in vitro. However, in most experiments that have been performed, antiserum was either pre-incubated with SAg, or both were applied simultaneously. To mirror more closely the clinical situation, we applied a multiple dose (over five days lethal challenge in a rabbit model. Treatment with toxic shock syndrome toxin 1 (TSST-1 neutralizing antibody was fully protective, even when administered late in the course of the challenge. Kinetic studies on the effect of superantigen toxins are scarce. We performed in vitro kinetic studies by neutralizing the toxin with antibodies at well-defined time points. T-cell activation was determined by assessing T-cell proliferation (3H-thymidine incorporation, determination of IL-2 release in the cell supernatant (ELISA, and IL-2 gene activation (real-time PCR (RT-PCR. Here we show that T-cell activation occurs continuously. The application of TSST-1 neutralizing antiserum reduced IL-2 and TNFα release into the cell supernatant, even if added at later time points. Interference with the prolonged stimulation of proinflammatory cytokines is likely to be in vivo relevant, as postexposure treatment protected rabbits against the multiple dose lethal SAg challenge. Our results shed new light on the treatment of TSS by specific antibodies even at late stages of exposure.

  16. Study on the metabolism of 15 p-131iodine phenyl pentadecanoic acid [p-iodine phenyl pentadecanoic acid] as a tracer of free fatty acids in comparison to 1-14C-palmitic acid (C-palmitic acid)

    International Nuclear Information System (INIS)

    Sauer, J.W.

    1986-01-01

    In an animal experiment under identical metabolic influences the metabolism of a new radiopharmaceutical, 15 p- 131 iodine phenyl pentadecanoic acid (IPPA), was compared to the marked physiological fatty acid, 1- 14 C-palmitic acid (PA). The pharmacological kinetics of both tracers in tissues with widely varied turnover rates of fatty acids (heart, lung, liver, kidney, spleen, small intestine, skeletal muscle) was studied. By alkali extraction of the tissue lipids and then a chromatographic separation of the lipid fractions quantitatively comparable statements about the metabolism of PA and IPPA were made possible. The analyses of autoradiographs of the chromatographically separated lipids show a qualitatively congruous assimilation of both markers in the major lipid fractions. The quantitative evaluation shows minor differences as a result of a preferred assimilation of IPPA in triglycerides and of PA in phospholipids. The fractionated separation of tissue lipids which had been marked with PA and IPPA in vivo agrees very well with values which have been determined by other authors using 14 C- or 3 H-marked fatty acids. The close correlation of the tissue-specific metabolism kinetics of both markers makes it clear that both fatty acids are metabolized by similar, respectively, primarily identical metabolic pathyways. In conclusion, this study makes clear the extensive congruence of the metabolism kinetics of IPPA and the kinetics of the physiological palmitic acid. As a result of the presented results of the γ-radiating radiopharmaceutical IPPA as a free fatty acid analog new possibilities for the non-invasive external comprehension of lipid metabolism are opened up, whose use especially in the diagnostic of heart diseases promises success. (orig./MG) [de

  17. Serotonin- and Dopamine-Related Gene Expression in db/db Mice Islets and in MIN6 β-Cells Treated with Palmitate and Oleate

    Directory of Open Access Journals (Sweden)

    L. R. Cataldo

    2016-01-01

    Full Text Available High circulating nonesterified fatty acids (NEFAs concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent β-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated β-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 β-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 β-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (−25%; p<0.0001 and oleate (−43%; p<0.0001 were detected in MIN6 β-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 β-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content.

  18. The combination of ascorbic acid 6-palmitate and [Fe III 3(µ3-O)]7+ as a catalyst for the oxidation of unsaturated lipids

    NARCIS (Netherlands)

    Micciche, F.; Long, G.J.; Shahin, A.M.; Grandjean, F.; Ming, W.; Haveren, van J.; Linde, van der R.

    2007-01-01

    Recently, iron 2-ethylhexanoate (Fe-eh, 1) in combination with ascorbic acid 6-palmitate (AsA6p) has been reported as a good catalytic system for the oxidation of ethyl linoleate (EL), an unsaturated lipid. In response to the fascinating chemistry of this bio-inspired iron-based catalyst the

  19. Synergetic Effect of Ni2P/SiO2 and γ-Al2O3 Physical Mixture in Hydrodeoxygenation of Methyl Palmitate

    Directory of Open Access Journals (Sweden)

    Ivan V. Shamanaev

    2017-11-01

    Full Text Available The Ni2P/SiO2 catalyst, which was prepared by in situ temperature-programmed reduction and in the mixture with the inert (SiC, SiO2 or acidic (γ-Al2O3 material was studied in methyl palmitate hydrodeoxygenation (HDO. Methyl palmitate HDO was carried out at temperatures of 270–330 °C, H2/feed volume ratio of 600 Nm3/m3, and H2 pressure of 3.0 MPa. Ni2P/SiO2 catalyst, diluted with γ-Al2O3 showed a higher activity than Ni2P/SiO2 catalyst diluted with SiC or SiO2. The conversion of methyl palmitate increased significantly in the presence of γ-Al2O3 most probably due to the acceleration of the acid-catalyzed reaction of ester hydrolysis. The synergism of Ni2P/SiO2 and γ-Al2O3 in methyl palmitate HDO can be explained by the cooperation of the metal sites of Ni2P/SiO2 and the acid sites of γ-Al2O3 in consecutive metal-catalyzed and acid-catalyzed reactions of HDO. The obtained results let us conclude that the balancing of metal and acid sites plays an important role in the development of the efficient catalyst for the HDO of fatty acid esters over supported phosphide catalysts.

  20. Saturated fatty acid palmitate induces extracellular release of histone H3: A possible mechanistic basis for high-fat diet-induced inflammation and thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Shrestha, Chandan [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Ito, Takashi [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Kawahara, Ko-ichi [Department of Biomedical Engineering, Osaka Institute of Technology, Osaka (Japan); Shrestha, Binita; Yamakuchi, Munekazu; Hashiguchi, Teruto [Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Maruyama, Ikuro, E-mail: rinken@m3.kufm.kagoshima-u.ac.jp [Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan)

    2013-08-09

    Highlights: •High-fat diet feeding and palmitate induces the release of nuclear protein histone H3. •ROS production and JNK signaling mediates the release of histone H3. •Extracellular histones induces proinflammatory and procoagulant response. -- Abstract: Chronic low-grade inflammation is a key contributor to high-fat diet (HFD)-related diseases, such as type 2 diabetes, non-alcoholic steatohepatitis, and atherosclerosis. The inflammation is characterized by infiltration of inflammatory cells, particularly macrophages, into obese adipose tissue. However, the molecular mechanisms by which a HFD induces low-grade inflammation are poorly understood. Here, we show that histone H3, a major protein component of chromatin, is released into the extracellular space when mice are fed a HFD or macrophages are stimulated with the saturated fatty acid palmitate. In a murine macrophage cell line, RAW 264.7, palmitate activated reactive oxygen species (ROS) production and JNK signaling. Inhibitors of these pathways dampened palmitate-induced histone H3 release, suggesting that the extracellular release of histone H3 was mediated, in part, through ROS and JNK signaling. Extracellular histone activated endothelial cells toexpress the adhesion molecules ICAM-1 and VCAM-1 and the procoagulant molecule tissue factor, which are known to contribute to inflammatory cell recruitment and thrombosis. These results suggest the possible contribution of extracellular histone to the pathogenesis of HFD-induced inflammation and thrombosis.

  1. Saturated fatty acid palmitate induces extracellular release of histone H3: A possible mechanistic basis for high-fat diet-induced inflammation and thrombosis

    International Nuclear Information System (INIS)

    Shrestha, Chandan; Ito, Takashi; Kawahara, Ko-ichi; Shrestha, Binita; Yamakuchi, Munekazu; Hashiguchi, Teruto; Maruyama, Ikuro

    2013-01-01

    Highlights: •High-fat diet feeding and palmitate induces the release of nuclear protein histone H3. •ROS production and JNK signaling mediates the release of histone H3. •Extracellular histones induces proinflammatory and procoagulant response. -- Abstract: Chronic low-grade inflammation is a key contributor to high-fat diet (HFD)-related diseases, such as type 2 diabetes, non-alcoholic steatohepatitis, and atherosclerosis. The inflammation is characterized by infiltration of inflammatory cells, particularly macrophages, into obese adipose tissue. However, the molecular mechanisms by which a HFD induces low-grade inflammation are poorly understood. Here, we show that histone H3, a major protein component of chromatin, is released into the extracellular space when mice are fed a HFD or macrophages are stimulated with the saturated fatty acid palmitate. In a murine macrophage cell line, RAW 264.7, palmitate activated reactive oxygen species (ROS) production and JNK signaling. Inhibitors of these pathways dampened palmitate-induced histone H3 release, suggesting that the extracellular release of histone H3 was mediated, in part, through ROS and JNK signaling. Extracellular histone activated endothelial cells toexpress the adhesion molecules ICAM-1 and VCAM-1 and the procoagulant molecule tissue factor, which are known to contribute to inflammatory cell recruitment and thrombosis. These results suggest the possible contribution of extracellular histone to the pathogenesis of HFD-induced inflammation and thrombosis

  2. Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of dry eye: a Japanese Phase II clinical trial.

    Science.gov (United States)

    Toshida, Hiroshi; Funaki, Toshinari; Ono, Koichi; Tabuchi, Nobuhito; Watanabe, Sota; Seki, Tamotsu; Otake, Hiroshi; Kato, Takuji; Ebihara, Nobuyuki; Murakami, Akira

    2017-01-01

    The purpose of this study was to investigate the efficacy and safety of the administration of retinol palmitate (VApal) ophthalmic solution (500 IU/mL) for the treatment of patients with dry eye. This study included 66 patients with dry eye. After a 2-week washout period, patients were randomized (1:1) into either a VApal ophthalmic solution or a placebo group, and a single drop of either solution was administered six times daily for 4 weeks. Efficacy measures were 12 subjective symptoms, rose bengal (RB) and fluorescein staining scores, tear film breakup time, and tear secretion. Safety measures included clinical blood and urine analyses and adverse event recordings. In comparisons of the two groups, the mean change in RB staining score from baseline was significantly lower in the VApal group at 2 and 4 weeks ( P ophthalmic solution (500 IU/mL) is safe and effective for the treatment of patients with dry eye.

  3. Incorporation of [14C]-L-leucine in splenic and hepatic tissue of rats 'chemically splenectomized' by ethyl palmitate

    International Nuclear Information System (INIS)

    Sebestik, V.; Kselikova, M.; Freiova, M.; Potmesilova, I.

    1978-01-01

    In experiments with 'chemically splenectomized' rats by an i.v. application of ethyl palmitate (EP) emulsion and using [ 14 C]-L-leucine, the protein synthesis in spleen and liver was followed. Two hours following EP application protein synthesis in the spleen was significantly decreased; after 24 hrs and 4 days the incorporation increased moderately above normal values, and in the subsequent intervals protein synthesis was again lowered. In the liver a significant increase of protein synthesis 24 hrs and 4 days after EP injection was observed. Changes of proteins synthesis in the spleen are evidently related to damage of the tissue and its subsequent regeneration. Changes in the liver are manifestations rather of an increased metabolic load during EP degradation. (author)

  4. Polarized Raman and Infrared Spectroscopy and ab Initio Calculation of Palmitic and Stearic Acids in the Bm and C Forms.

    Science.gov (United States)

    L da Silva, L F; Andrade-Filho, T; Freire, P T C; Filho, J Mendes; da Silva Filho, J G; Saraiva, G D; Moreira, S G C; de Sousa, F F

    2017-06-29

    A complete experimental study on the vibrational properties of palmitic and stearic acids crystallized in the B m and C forms, both belonging to the monoclinic system with the P2 1 /a (C 2h 5 ) space group, through polarized Raman and infrared spectroscopy, is reported in this paper. Density functional theory calculations were also performed to assign the normal modes and to help in the interpretation of the experimental data. The different polarizations were compared and their influence on the spectral profiles, in both the lattice and the internal mode regions, was discussed. In general, the Raman and infrared spectra exhibit accentuated differences among the polymorphic forms, which are associated with the different molecular modifications, defined as gauche and all-trans conformations. Insights about interaction among different groups are also furnished.

  5. Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [11C]-labeled fatty acids

    International Nuclear Information System (INIS)

    Angsten, Gertrud; Valind, Sven; Takalo, Reijo; Neu, Henrik; Meurling, Staffan; Langstroem, Bengt

    2005-01-01

    Methods: Anesthetized pigs were studied with [ 11 C]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [ 11 C]-FAs from blood was measured together with the relative distribution of [ 11 C]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. Results: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. Conclusions: [ 11 C]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [ 11 C]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs

  6. Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [{sup 11}C]-labeled fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Angsten, Gertrud [Department of Pediatric Surgery, University Children' s Hospital, S-751 85 Uppsala (Sweden)]. E-mail: gertrud.angsten@surgsci.uu.se; Valind, Sven [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Clinical Physiology, University Hospital, S-751 85 Uppsala (Sweden); Takalo, Reijo [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Clinical Physiology, University Hospital, S-751 85 Uppsala (Sweden); Neu, Henrik [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Organic Chemistry, Uppsala University, S-751 24 Uppsala (Sweden); Meurling, Staffan [Department of Pediatric Surgery, University Children' s Hospital, S-751 85 Uppsala (Sweden); Langstroem, Bengt [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Organic Chemistry, Uppsala University, S-751 24 Uppsala (Sweden)

    2005-07-01

    Methods: Anesthetized pigs were studied with [{sup 11}C]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [{sup 11}C]-FAs from blood was measured together with the relative distribution of [{sup 11}C]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. Results: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. Conclusions: [{sup 11}C]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [{sup 11}C]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs.

  7. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases human hepatic stellate cell activation

    International Nuclear Information System (INIS)

    Harvey, Wendy A.; Jurgensen, Kimberly; Pu, Xinzhu; Lamb, Cheri L.; Cornell, Kenneth A.; Clark, Reilly J.; Klocke, Carolyn; Mitchell, Kristen A.

    2016-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a halogenated aromatic hydrocarbon that elicits toxicity through the aryl hydrocarbon receptor (AhR). In the liver, gross markers of TCDD toxicity are attributed to AhR activation in parenchymal hepatocytes. However, less is known regarding the consequences of TCDD treatment on non-parenchymal cells in the liver. Hepatic stellate cells (HSCs) are non-parenchymal cells that store vitamin A when quiescent. Upon liver injury, activated HSCs lose this storage ability and instead function in the development and maintenance of inflammation and fibrosis through the production of pro-inflammatory mediators and collagen type I. Reports that TCDD exposure disrupts hepatic retinoid homeostasis and dysregulates extracellular matrix remodeling in the liver led us to speculate that TCDD treatment may disrupt HSC activity. The human HSC line LX-2 was used to test the hypothesis that TCDD treatment directly activates HSCs. Results indicate that exposure to 10 nM TCDD almost Completely inhibited lipid droplet storage in LX-2 cells cultured with retinol and palmitic acid. TCDD treatment also increased LX-2 cell proliferation, expression of α-smooth muscle actin, and production of monocyte chemoattractant protein-1 (MCP-1), all of which are characteristics of activated HSCs. However, TCDD treatment had no effect on Col1a1 mRNA levels in LX-2 cells stimulated with the potent profibrogenic mediator, transforming growth factor-β. The TCDD-mediated increase in LX-2 cell proliferation, but not MCP-1 production, was abolished when phosphoinositide 3-kinase was inhibited. These results indicate that HSCs are susceptible to direct modulation by TCDD and that TCDD likely increases HSC activation through a multi-faceted mechanism.

  8. Preparation and thermal properties of form-stable palmitic acid/active aluminum oxide composites as phase change materials for latent heat storage

    International Nuclear Information System (INIS)

    Fang, Guiyin; Li, Hui; Cao, Lei; Shan, Feng

    2012-01-01

    Form-stable palmitic acid (PA)/active aluminum oxide composites as phase change materials were prepared by adsorbing liquid palmitic acid into active aluminum oxide. In the composites, the palmitic acid was used as latent heat storage materials, and the active aluminum oxide was used as supporting material. Fourier transformation infrared spectroscope (FT-IR), X-ray diffractometer (XRD) and scanning electronic microscope (SEM) were used to determine the chemical structure, crystalloid phase and microstructure of the composites, respectively. The thermal properties and thermal stability were investigated by a differential scanning calorimeter (DSC) and a thermogravimetry analyzer (TGA). The FT-IR analyses results indicated that there is no chemical interaction between the palmitic acid and active aluminum oxide. The SEM results showed that the palmitic acid was well adsorbed into porous network of the active aluminum oxide. The DSC results indicated that the composites melt at 60.25 °C with a latent heat of 84.48 kJ kg −1 and solidify at 56.86 °C with a latent heat of 78.79 kJ kg −1 when the mass ratio of the PA to active aluminum oxide is 0.9:1. Compared with that of the PA, the melting and solidifying time of the composites CPCM5 was reduced by 20.6% and 21.4% because of the increased heat transfer rate through EG addition. The TGA results showed that the active aluminum oxide can improve the thermal stability of the composites. -- Highlights: ► Form-stable PA/active aluminum oxide composites as PCMs were prepared. ► Chemical structure, crystalloid phase and microstructure of composites were determined. ► Thermal properties and thermal stability of the composites were investigated. ► Expanded graphite can improve thermal conductivity of the composites.

  9. Thermal properties and heat storage analysis of palmitic acid-TiO_2 composite as nano-enhanced organic phase change material (NEOPCM)

    International Nuclear Information System (INIS)

    Sharma, R.K.; Ganesan, P.; Tyagi, V.V.; Metselaar, H.S.C.; Sandaran, S.C.

    2016-01-01

    Highlights: • Novel composite of palmitic acid and TiO_2 nanoparticles with enhanced thermal energy storage capabilities • The composite is thermally reliable and chemically stable. • Thermal conductivity of the composite increases significantly with the loading. - Graphical Abstract: - Abstract: In the present study, the phase change behavior of prepared novel composites of palmitic acid and solid nanoparticles of titanium dioxide (TiO_2) for thermal energy storage has been investigated. The nanoparticles are dispersed into the base fluid in various mass fractions (0.5, 1, 3, and 5%), and their effects on the thermo-physical properties have been investigated. Structural analysis has been carried out by using FESEM, and crystallography was checked by XRD technique. The chemical/functional groups of the base fluid and composite PCMs have been analyzed by using FT-IR spectrum. The observations showed that the TiO_2 nanoparticles do not affect the chemical structure of palmitic acid; however they improve the chemical stability. The phase transition temperature and latent heat of fusion has shown the significant stability with the increase in nanoparticle weight fractions. The accelerated thermal cycle test of the composite shows good thermal reliability for 1500 melt/freeze cycles. Thermal conductivity of palmitic acid increased gradually by 12.7, 20.6, 46.6, and 80% for the nanoparticle weight fractions of 0.5, 1, 3, and 5% respectively. Based on the results, it can be mentioned that the prepared palmitic acid based nano-enhanced organic phase change composite materials can be very well used as potential solar thermal energy storage materials.

  10. Inhibition of Long Chain Fatty Acyl-CoA Synthetase (ACSL) and Ischemia Reperfusion Injury

    Science.gov (United States)

    Prior, Allan M.; Zhang, Man; Blakeman, Nina; Datta, Palika; Pham, Hung; Young, Lindon H.; Weis, Margaret T.; Hua, Duy H.

    2014-01-01

    Various triacsin C analogs, containing different alkenyl chains and carboxylic acid bioisoteres including 4-aminobenzoic acid, isothiazolidine dioxide, hydroxylamine, hydroxytriazene, and oxadiazolidine dione, were synthesized and their inhibitions of long chain fatty acyl-CoA synthetase (ACSL) were examined. Two methods, a cell-based assay of ACSL activity and an in situ [14C]-palmitate incorporation into extractable lipids were used to study the inhibition. Using an in vivo leukocyte recruitment inhibition protocol, the translocation of one or more cell adhesion molecules from the cytoplasm to the plasma membrane on either the endothelium or leukocyte or both was inhibited by inhibitors 1, 9, and triacsin C. The results suggest that inhibition of ACSL may attenuate the vascular inflammatory component associated with ischemia reperfusion injury and lead to a decrease of infarct expansion. PMID:24480468

  11. TRAF1 knockdown alleviates palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wanlu [Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Tang, Zhuqi; Zhu, Xiaohui [Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province (China); Xia, Nana; Zhao, Yun; Wang, Suxin [Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Cui, Shiwei, E-mail: neifenmicui@163.com [Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province (China); Wang, Cuifang, E-mail: binghuodinghuo@163.com [Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province (China)

    2015-11-20

    High-fat diet (HFD) and inflammation are key contributors to insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). With HFD, plasma free fatty acids (FFAs) can activate the nuclear factor-κB (NF-κB) in target tissues, then initiate negative crosstalk between FFAs and insulin signaling. However, the molecular link between IR and inflammation remains to be identified. We here reported that tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, was involved in the onset of IR in hepatocytes. TRAF1 was significantly up-regulated in insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In addition, we showed that depletion of TRAF1 led to inhibition of the activity of NF-κB. Given the fact that the activation of NF-κB played a facilitating role in IR, the phosphorylation of Akt and GSK3β was also analyzed. We found that depletion of TRAF1 markedly reversed PA-induced attenuation of the phosphorylation of Akt and GSK3β in the cells. The accumulation of lipid droplets in hepatocyte and expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also determined and found to display a similar tendency with the phosphorylation of Akt and GSK3β. Glucose uptake assay indicated that knocking down TRAF1 blocked the effect of PA on the suppression of glucose uptake. These data implicated that TRAF1 knockdown might alleviate PA-induced IR in HepG2 cells through NF-κB pathway. - Highlights: • TRAF1 accelerated PA-induced IR in HepG2 cells mediated through NF-κB signaling. • Knockdown of TRAF1 alleviated PA-induced IR in HepG2 cells. • Knockdown of TRAF1 alleviated PA-induced lipid accumulation in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced suppression of glucose uptake in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced gluconeogenesis in HepG2 cells.

  12. TRAF1 knockdown alleviates palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway

    International Nuclear Information System (INIS)

    Zhang, Wanlu; Tang, Zhuqi; Zhu, Xiaohui; Xia, Nana; Zhao, Yun; Wang, Suxin; Cui, Shiwei; Wang, Cuifang

    2015-01-01

    High-fat diet (HFD) and inflammation are key contributors to insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). With HFD, plasma free fatty acids (FFAs) can activate the nuclear factor-κB (NF-κB) in target tissues, then initiate negative crosstalk between FFAs and insulin signaling. However, the molecular link between IR and inflammation remains to be identified. We here reported that tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, was involved in the onset of IR in hepatocytes. TRAF1 was significantly up-regulated in insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In addition, we showed that depletion of TRAF1 led to inhibition of the activity of NF-κB. Given the fact that the activation of NF-κB played a facilitating role in IR, the phosphorylation of Akt and GSK3β was also analyzed. We found that depletion of TRAF1 markedly reversed PA-induced attenuation of the phosphorylation of Akt and GSK3β in the cells. The accumulation of lipid droplets in hepatocyte and expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also determined and found to display a similar tendency with the phosphorylation of Akt and GSK3β. Glucose uptake assay indicated that knocking down TRAF1 blocked the effect of PA on the suppression of glucose uptake. These data implicated that TRAF1 knockdown might alleviate PA-induced IR in HepG2 cells through NF-κB pathway. - Highlights: • TRAF1 accelerated PA-induced IR in HepG2 cells mediated through NF-κB signaling. • Knockdown of TRAF1 alleviated PA-induced IR in HepG2 cells. • Knockdown of TRAF1 alleviated PA-induced lipid accumulation in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced suppression of glucose uptake in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced gluconeogenesis in HepG2 cells.

  13. A Technique: Exposure Therapy

    Directory of Open Access Journals (Sweden)

    Serkan AKKOYUNLU

    2013-07-01

    Full Text Available Introduction: Exposure with response prevention is an effective treatment for all anxiety disorders. According to the behavioral learning theories, fears which are conditioned via classical conditioning are reinforced by respondent conditioning. Avoidance and safety seeking behaviors prevent disconfirmation of anxious beliefs. In exposure client faces stimulates or cues that elicit fear or distress, by this avoidance is inhibited. Clients are also encouraged to resists performing safety seeking behaviors or rituals that they utilize to reduce fear or distress. Accomplishing these habituation or extinction is achieved. In addition to this clients learn that feared consequences does not realize or not harmful as they believed by experiencing. Emotional processing is believed to be the mechanism of change in exposure.Objective: The aim of this review is to provide a definition of exposure and its effectiveness briefly, and describe how to implement exposure, its steps and remarkable aspects using. Exposure therapies and treatments that involve exposure are proved to be effective in all anxiety disorders. Exposure therapy can be divided in three parts: Assessment and providing a treatment rationale, creating an exposure hierarchy and response prevention plan, implementing exposure sessions. Clients must also continue to perform exposure between sessions. Therapy transcripts are also provided to exemplify these parts. Conclusion: Exposure with response prevention is a basic and effective technique. Every cognitive behavior therapist must be able to implement this technique and be cognizant of pearls of this procedure.

  14. Anxiety and retrieval inhibition: support for an enhanced inhibition account.

    Science.gov (United States)

    Nuñez, Mia; Gregory, Josh; Zinbarg, Richard E

    2017-02-01

    Retrieval inhibition of negative associations is important for exposure therapy for anxiety, but the relationship between memory inhibition and anxiety is not well understood-anxiety could either be associated with enhanced or deficient inhibition. The present study tested these two competing hypotheses by measuring retrieval inhibition of negative stimuli by related neutral stimuli. Non-clinically anxious undergraduates completed measures of trait and state anxiety and completed a retrieval induced forgetting task. Adaptive forgetting varied with state anxiety. Low levels of state anxiety were associated with no evidence for retrieval inhibition for either threatening or non-threatening categories. Participants in the middle tertile of state anxiety scores exhibited retrieval inhibition for non-threatening categories but not for threatening categories. Participants in the highest tertile of state anxiety, however, exhibited retrieval inhibition for both threatening and non-threatening categories with the magnitude of retrieval inhibition being greater for threatening than non-threatening categories. The data are in line with the avoidance aspect of the vigilance-avoidance theory of anxiety and inhibition. Implications for cognitive behavioural therapy practices are discussed.

  15. Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Fu Dong-Jing

    2011-05-01

    Full Text Available Abstract Background Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal. These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability. Methods In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively or placebo (NCT#00590577. Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE rates and relative risks (RR with 95% confidence intervals (CI versus placebo were determined. Results Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS mean PANSS total score at Day 8 (p = 0.037. After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ≤ 0.007 vs. placebo and Day 36 (p Conclusions Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1 compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose

  16. Corrosion inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, A O

    1965-12-29

    An acid corrosion-inhibiting composition consists essentially of a sugar, and an alkali metal salt selected from the group consisting of iodides and bromides. The weight ratio of the sugar to the alkali metal salt is between 2:1 and about 20,000:1. Also, a corrosion- inhibited phosphoric acid composition comprising at least about 20 wt% of phosphoric acid and between about 0.1 wt% and about 10 wt% of molasses, and between about 0.0005 wt% and about 1 wt% of potassium iodide. The weight ratio of molasses to iodide is greater than about 2:1. (11 claims)

  17. Additions of caffeic acid, ascorbyl palmitate or gamma-tocopherol to fish oil-enriched energy bars affect lipid oxidation differently

    DEFF Research Database (Denmark)

    Horn, Anna Frisenfeldt; Nielsen, Nina Skall; Jacobsen, Charlotte

    2009-01-01

    The objectives of the study were to investigate the effects of caffeic acid, ascorbyl palmitate and gamma-tocopherol on protection of fish oil-enriched energy bars against lipid oxidation during storage for 10 weeks at room temperature. The lipophilic gamma-tocopherol reduced lipid oxidation during...... storage when added at a concentration above 440 mu g/g fish oil. However, the best antioxidative effect was observed when it was added at a concentration of 660 mu g/g fish oil. In contrast, prooxidative effects were observed when using either gamma-tocopherol at concentrations below 220 mu g/g fish oil......, or the hydrophilic caffeic acid, or the amphiphilic ascorbyl palmitate at concentrations of 75, 150 and 300 mu g/g fish oil. Prooxidative effects were observed as an increase in the formation of lipid hydroperoxides and volatile secondary oxidation products, as well as the development of rancid off...

  18. Methodological challenges in indirect treatment comparisons: spotlight on a recent comparison of long-acting injectable aripiprazole versus paliperidone palmitate in the treatment of schizophrenia.

    Science.gov (United States)

    Singh, Arun; Gopal, Srihari; Kim, Edward; Mathews, Maju; Kern-Sliwa, Jennifer; Turkoz, Ibrahim; Wooller, Annette; Berlin, Jesse

    2018-03-01

    In a recent study, an indirect treatment comparison was performed to examine the relative efficacy and tolerability of aripiprazole once monthly and paliperidone palmitate once monthly. The authors concluded that the results may suggest relative advantages for aripiprazole once monthly over paliperidone palmitate once monthly in the short-term treatment of schizophrenia. However, the validity of the study is compromised as an indirect treatment comparison using extant data may violate important assumptions. Other methodological issues identified further highlight the challenges of performing indirect treatment comparisons.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

  19. Effects of exogenous fatty acids and inhibition of de novo fatty acid synthesis on disaturated phosphatidylcholine production by fetal lung cells and adult type II cells.

    Science.gov (United States)

    Maniscalco, W M; Finkelstein, J N; Parkhurst, A B

    1989-05-01

    De novo fatty acid synthesis may be an important source of saturated fatty acids for fetal lung disaturated phosphatidylcholine (DSPC) production. To investigate the roles of de novo fatty acid synthesis and exogenous fatty acids, we incubated dispersed fetal lung cells and freshly isolated adult type II cells with exogenous palmitate and oleate and measured DSPC synthesis. Unlike adult type II cells, fetal lung cells did not increase DSPC synthesis when exogenous palmitate was available; adult type II cells increased DSPC synthesis by 70% in the presence of palmitate. Exogenous oleate decreased DSPC synthesis by 48% in fetal cells but not in adult type II cells. Incubation of fetal lung cells with TOFA [2-furancarboxylate, 5-(tetradecyloxy)-sodium], a metabolic inhibitor of fatty acid synthesis, decreased fatty acid synthesis by 65%. There was a simultaneous 56% inhibition of DSPC production, but no effect on protein, DNA, or glyceride-glycerol production, measured by precursor incorporation. The inhibition of DSPC synthesis associated with TOFA was partially prevented by exogenous palmitate but not oleate. Fetal cells prepared from explants that had been cultured in dexamethasone also had TOFA-associated inhibition of DSPC synthesis that was similar to non-dexamethasone-exposed cells. These studies suggest that under baseline conditions of low fatty acid availability, such as in the fetus, de novo fatty acid synthesis in fetal cells, but not in adult type II cells, provides sufficient saturated fatty acids to support maximal DSPC production. Inhibition of de novo fatty acid synthesis resulting in decreased DSPC production in fetal lung cells in conditions of low fatty acid availability suggests that fatty acid synthesis may be central to maintain DSPC synthesis in the fetus.

  20. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to beta-palmitate and increased calcium absorption pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following an application from IDACE, submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to beta...... (middle or beta) position of the glycerol backbone. Beta-palmitate is considered to be sufficiently characterised. The claimed effect is “beta palmitate enrichment contributes to increase calcium absorption”. The target population proposed by the applicant is infants from birth to 12 months of age......, the Panel took into account the biological plausibility of the mechanism by which beta-palmitate could exert the claimed effect and that three small human intervention studies in preterm and term infants provided some evidence that a higher degree of palmitic acid in the sn-2 position of formula...

  1. Effects of substrate availability on myocardial C-11 palmitate kinetics by positron emission tomography in normal subjects and patients with ventricular dysfunction

    International Nuclear Information System (INIS)

    Schelbert, H.R.; Henze, E.; Sochor, H.; Grossman, R.G.; Huang, S.C.; Barrio, J.R.; Schwaiger, M.; Phelps, M.E.

    1986-01-01

    The possibility of demonstrating noninvasively with C-11 palmitate and positron emission tomography (PET) changes in myocardial substrate metabolism in normal and diseased human myocardium in response to altered substrate availability in blood and disease-related abnormalities was examined in five normal volunteers and 16 patients with ventricular dysfunction. C-11 palmitate injection and serial PET imaging were performed after an overnight fast (control period) and again 2 hours later after oral glucose (50 gm). Myocardial C-11 time-activity curves from serial PET images revealed a biexponential clearance pattern. An early rapid phase, defined by relative size and clearance half-time, reflects C-11 palmitate oxidation and the late slow phase tracer deposition in the endogenous lipid pool. During the control period, the tracer fraction entering the early rapid phase averaged 47 +/- 13% (SD) in normal subjects and 45 +/- 12% in patients. Corresponding clearance half-times were 19 +/- 7 and 20 +/- 5 minutes, respectively. Heart rate and blood pressure remained unchanged after glucose, but plasma glucose levels rose by 72.5% in normal subjects and by 98.9% in patients, while free fatty acid levels fell by 72% and 42% respectively. In normal subjects, the tracer fraction in the early rapid phase fell by 43% (p less than 0.005) and the clearance half-time increased by 46%. In patients, the response of C-11 palmitate tissue kinetics to glucose was variable. In nine patients, it was similar to normal subjects while in the other seven patients, the tracer fraction entering the rapid clearance phase increased after glucose by 30% (p less than 0.05) associated with a 36% (p less than 0.05) decline in clearance half-times. This was unrelated to disease etiology or plasma substrate levels but occurred mostly in left ventricles with more severely depressed function

  2. A simple and robust quantitative analysis of retinol and retinyl palmitate using a liquid chromatographic isocratic method

    Directory of Open Access Journals (Sweden)

    Satoshi Yokota

    2018-04-01

    Full Text Available Vitamin A is a vital nutritional substances that regulates biological activities including development, but is also associated with disease onset. The extent of vitamin A intake influences the retinoid content in the liver, the most important organ for the storage of vitamin A. Measurement of endogenous retinoid in biological samples is important to understand retinoid homeostasis. Here we present a reliable, highly sensitive, and robust method for the quantification of retinol and retinyl palmitate using a reverse-phase HPLC/UV isocratic method. We determined the impact of chronic dietary vitamin A on retinoid levels in livers of mice fed an AIN-93G semi-purified diet (4 IU/g compared with an excess vitamin A diet (1000 IU/g over a period from birth to 10 weeks of age. Coefficients of variation for intra-assays for both retinoids were less than 5%, suggesting a higher reproducibility than any other HPLC/UV gradient method. Limits of detection and quantification for retinol were 0.08 pmol, and 0.27 pmol, respectively, which are remarkably higher than previous results. Supplementation with higher doses of vitamin A over the study period significantly increased liver retinol and retinyl palmitate concentrations in adult mice. The assays described here provide a sensitive and rigorous quantification of endogenous retinol and retinyl palmitate, which can be used to help determine retinoid homeostasis in disease states, such as toxic hepatitis and liver cancer. Keywords: Vitamin A excess, Retinol, Retinyl palmitate, Liver

  3. Red palm oil-supplemented and biofortified cassava gari increase the carotenoid and retinyl palmitate concentrations of triacylglycerol-rich plasma in women.

    Science.gov (United States)

    Zhu, Chenghao; Cai, Yimeng; Gertz, Erik R; La Frano, Michael R; Burnett, Dustin J; Burri, Betty J

    2015-11-01

    Boiled biofortified cassava containing β-carotene can increase retinyl palmitate in triacylglycerol-rich plasma. Thus, it might alleviate vitamin A deficiency. Cassava requires extensive preparation to decrease its level of cyanogenic glucosides, which can be fatal. Garification is a popular method of preparing cassava that removes cyanogen glucosides. Our objective was to compare the effectiveness of biofortified gari to gari prepared with red palm oil. The study was a randomized crossover trial in 8 American women. Three gari preparations separated by 2-week washout periods were consumed. Treatments (containing 200-225.9 g gari) were as follows: biofortified gari (containing 1 mg β-carotene), red palm oil-fortified gari (1 mg β-carotene), and unfortified gari with a 0.3-mg retinyl palmitate reference dose. Blood was collected 6 times from -0.5 to 9.5 hours after ingestion. Triacylglycerol-rich plasma was separated by ultracentrifugation and analyzed by high-performance liquid chromatography (HPLC) with diode array detection. Area under the curve for β-carotene, α-carotene, and retinyl palmitate increased after the fortified meals were fed (P palm oil treatment was greater than that induced by the biofortified treatment (P palm oil and biofortified gari, respectively. These results show that both treatments increased β-carotene, α-carotene, and retinyl palmitate in triacylglycerol-rich plasma concentrations in healthy well-nourished adult women, supporting our hypothesis that both interventions could support efforts to alleviate vitamin A deficiency. Published by Elsevier Inc.

  4. Estimated medical cost reductions for paliperidone palmitate vs placebo in a randomized, double-blind relapse-prevention trial of patients with schizoaffective disorder.

    Science.gov (United States)

    Joshi, K; Lin, J; Lingohr-Smith, M; Fu, D J

    2015-01-01

    The objective of this economic model was to estimate the difference in medical costs among patients treated with paliperidone palmitate once-monthly injectable antipsychotic (PP1M) vs placebo, based on clinical event rates reported in the 15-month randomized, double-blind, placebo-controlled, parallel-group study of paliperidone palmitate evaluating time to relapse in subjects with schizoaffective disorder. Rates of psychotic, depressive, and/or manic relapses and serious and non-serious treatment-emergent adverse events (TEAEs) were obtained from the long-term paliperidone palmitate vs placebo relapse prevention study. The total annual medical cost for a relapse from a US payer perspective was obtained from published literature and the costs for serious and non-serious TEAEs were based on Common Procedure Terminology codes. Total annual medical cost differences for patients treated with PP1M vs placebo were then estimated. Additionally, one-way and Monte Carlo sensitivity analyses were conducted. Lower rates of relapse (-18.3%) and serious TEAEs (-3.9%) were associated with use of PP1M vs placebo as reported in the long-term paliperidone palmitate vs placebo relapse prevention study. As a result of the reduction in these clinical event rates, the total annual medical cost was reduced by $7140 per patient treated with PP1M vs placebo. One-way sensitivity analysis showed that variations in relapse rates had the greatest impact on the estimated medical cost differences (range: -$9786, -$4670). Of the 10,000 random cycles of Monte Carlo simulations, 100% showed a medical cost difference schizoaffective disorder was associated with a significantly lower rate of relapse and a reduction in medical costs compared to placebo. Further evaluation in the real-world setting is warranted.

  5. Effect of Retinol Palmitate on Corneal and Conjunctival Mucin Gene Expression in a Rat Dry Eye Model After Injury.

    Science.gov (United States)

    Tabuchi, Nobuhito; Toshida, Hiroshi; Koike, Daisuke; Odaka, Akito; Suto, Chikako; Ohta, Toshihiko; Murakami, Akira

    We examined the wound-healing effect of retinol palmitate (VApal) on mucin gene and protein expressions in a rat dry eye model based on lacrimal gland (LG) resection after injury. The rat dry eye model was prepared by surgical resection of the main LG in male Long-Evans rats. After alkaline injury of the central part of the lower palpebral conjunctiva bilaterally, VApal eye drops at 1,500 IU/mL in one eye and a vehicle in the fellow eye were both administered 6 times a day for 7 days. The expression of mucin gene and protein was analyzed by real-time polymerase chain reaction or enzyme-linked immunosorbent assay in the cornea and conjunctiva of MUC1, MUC4, MUC16, and MUC5AC after 1, 3, (5), and 7 days of treatment with VApal. Significant decreases in fluorescein-stained areas and rose bengal scores were observed in VApal-treated dry eyes compared with vehicle-treated dry eyes at both 3 (P dry eye model after injury. VApal also promoted conjunctival MUC16 expression. These results indicate that VApal has efficacy in improving keratoconjunctival epithelial damage associated with decreased tear production.

  6. Topical Application of Retinyl Palmitate-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

    Directory of Open Access Journals (Sweden)

    Marcela B. Oliveira

    2014-01-01

    Full Text Available The objective of this study was to perform a structural characterization and evaluate the in vitro safety profile and in vitro antioxidant activity of liquid crystalline systems (LCS with and without retinyl palmitate (RP. LCS containing polyether functional siloxane (PFS as a surfactant, silicon glycol copolymer (SGC as oil phase, and water in the ratios 30 : 25 : 45 and 40 : 50 : 10 with (OLSv = RP-loaded opaque liquid system and TLSv = RP-loaded transparent liquid system, respectively and without (OLS and TLS, respectively RP were studied. Samples were characterized using polarized light microscopy (PLM and rheology analysis. In vitro safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. In vitro antioxidant activity was performed by the DPPH method. PLM analysis showed the presence of lamellar LCS just to TLS. Regardless of the presence of RP, the rheological studies showed the pseudoplastic behavior of the formulations. The results showed that the incorporation of RP in LCS improved the safety profile of the drug. In vitro antioxidant activity suggests that LCS presented a higher capacity to maintain the antioxidant activity of RP. PFS-based systems may be a promising platform for RP topical application for the treatment of skin aging.

  7. Multivariate optimization of a synergistic blend of oleoresin sage (Salvia officinalis L.) and ascorbyl palmitate to stabilize sunflower oil.

    Science.gov (United States)

    Upadhyay, Rohit; Mishra, Hari Niwas

    2016-04-01

    The simultaneous optimization of a synergistic blend of oleoresin sage (SAG) and ascorbyl palmitate (AP) in sunflower oil (SO) was performed using central composite and rotatable design coupled with principal component analysis (PCA) and response surface methodology (RSM). The physicochemical parameters viz., peroxide value, anisidine value, free fatty acids, induction period, total polar matter, antioxidant capacity and conjugated diene value were considered as response variables. PCA reduced the original set of correlated responses to few uncorrelated principal components (PC). The PC1 (eigen value, 5.78; data variance explained, 82.53 %) was selected for optimization using RSM. The quadratic model adequately described the data (R (2) = 0. 91, p  0.05). The contour plot of PC 1 score indicated the optimal synergistic combination of 1289.19 and 218.06 ppm for SAG and AP, respectively. This combination of SAG and AP resulted in shelf life of 320 days at 25 °C estimated using linear shelf life prediction model. In conclusion, the versatility of PCA-RSM approach has resulted in an easy interpretation in multiple response optimizations. This approach can be considered as a useful guide to develop new oil blends stabilized with food additives from natural sources.

  8. Effect of vitamin A palmitate ophthalmic gel adjunctive therapy on tear film stability and inflammatory cytokines in patients with dry eye

    Directory of Open Access Journals (Sweden)

    Ya-Yuan Lu

    2018-06-01

    Full Text Available AIM:To investigate the effect of sodium hyaluronate eye drops combined with vitamin A palmitate ophthalmic gel on levels of tear film stability and inflammatory cytokines in patients with dry eye. METHODS: A total of 100 patients with dry eye treated in our hospital from January 2015 to February 2017 were randomly divided into control group and observation group, 50 cases in each group. Patients in the control group were treated with sodium hyaluronate eye drops. Patients in the observation group were given vitamin A palmitate ophthalmic gel on the basis of the control group, and then the clinical efficacy, tear film stability and the level of inflammatory cytokines were detected in the two groups. RESULTS: After treatment, the levels of BUT and SⅠt in both groups increased significantly compared with that before treatment, and FL was significantly lower than that before treatment. The levels of BUT and SⅠt in the observation group after treatment were 11.24±0.22s and 11.4±0.17mm/5min respectively, which was high than that of control groups(PPPPCONCLUSION: Sodium hyaluronate eye drops combined with vitamin A palmitate ophthalmic gel can relieve the symptoms of patients with dry eye effectively, increase the stability of tear film, and reduce the levels of inflammatory factors in tears, which is reliable in clinical application.

  9. Effect of temperature on thermal oxidation of palmitic acid studied by combination of EPR spin trapping technique and SPME-GC-MS/MS.

    Science.gov (United States)

    Chen, Hongjian; Wang, Yong; Cao, Peirang; Liu, Yuanfa

    2017-11-01

    Effect of temperatures on thermal oxidation of palmitic acid was studied by the combination of EPR and GC-MS/MS. DMPO was used as the spin trap. The experimental spectrum was simulated with alkyl and alkoxyl spin adducts. Total amount of spins, a parameter to indicate radical concentrations, detected at 180°C was nearly 10 times higher than that at 175°C. Besides, total amounts of spins detected at 180°C decreased rapidly because of the reaction between radical adducts and newly formed radicals. Signal intensities of alkyl radical adducts increased rapidly from 0.405 to 4.785 from 175°C to 180°C. Besides, more palmitic acid degraded to oxidized compounds from 175°C to 180°C than that of other temperature ranges. The C-C linkages between carbons 2 to 6 were easier to be oxidized at 180°C. The results all implied that oxidation rates of palmitic acid samples increased rapidly from 175°C to 180°C. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Incorporation of radioactive labelled cholin and palmitate into lung lecithin of rabbits treated with high doses of bromcarbamides, barbiturates and diazepam

    International Nuclear Information System (INIS)

    Wichert, P. von; Schmidt, C.; Pomraenke, K.; Wiegers, U.

    1977-01-01

    Severe intoxications with bromcarbamides often show respiratory complications. To answer the question if there is a direct effect of the drug on lung tissue the incorporation of radioactive labelled choline and palmitate into lung lecithin was investigated. The phospholipid metabolism is in close relation to the surfactant system of the lung. Secondly the influence of bromcarbamides was compared with other hypnotic drugs. There was a reduction of palmitate incorporation into lung lecithin down to 40%, whereas the incorporation of choline increases in bromcarbamide intoxication. The relation between palmitate and choline incorporation was 6.77 in the controls and it decreases to 2-3 in the bromcarbamide group. The total phospholipid content in the lung/g wet weight remained unchanged in all experiments. From this data it is concluded, that these drugs cause a reduction of fatty acid exchange of the lecithin molecules of the lung. This might lead to the production of non surface active lecithin. The clinical and the morphological aspects of severe bromcarbamide intoxication are consistent with a perturbation of the surfactant function. (orig./MG) [de

  11. Oxidative stability of a heme iron-fortified bakery product: Effectiveness of ascorbyl palmitate and co-spray-drying of heme iron with calcium caseinate.

    Science.gov (United States)

    Alemán, Mercedes; Bou, Ricard; Tres, Alba; Polo, Javier; Codony, Rafael; Guardiola, Francesc

    2016-04-01

    Fortification of food products with iron is a common strategy to prevent or overcome iron deficiency. However, any form of iron is a pro-oxidant and its addition will cause off-flavours and reduce a product's shelf life. A highly bioavailable heme iron ingredient was selected to fortify a chocolate cream used to fill sandwich-type cookies. Two different strategies were assessed for avoiding the heme iron catalytic effect on lipid oxidation: ascorbyl palmitate addition and co-spray-drying of heme iron with calcium caseinate. Oxidation development and sensory acceptability were monitored in the cookies over one-year of storage at room temperature in the dark. The addition of ascorbyl palmitate provided protection against oxidation and loss of tocopherols and tocotrienols during the preparation of cookies. In general, ascorbyl palmitate, either alone or in combination with the co-spray-dried heme iron, prevented primary oxidation and hexanal formation during storage. The combination of both strategies resulted in cookies that were acceptable from a sensory point of view after 1year of storage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Simultaneous determination of triamcinolone acetonide palmitate and triamcinolone acetonide in beagle dog plasma by UPLC-MS/MS and its application to a long-term pharmacokinetic study of triamcinolone acetonide palmitate lipid emulsion injection.

    Science.gov (United States)

    Liu, Hui; Yang, Mingjing; Wu, Panpan; Guan, Jiao; Men, Lei; Lin, Hongli; Tang, Xing; Zhao, Yunli; Yu, Zhiguo

    2015-02-01

    In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid-liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C18 column (50 mm × 2.1mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5→397.3, 435.3→415.3 and 393.3→355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1-1,000 ng/ml for TAP and 0.5-500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of -8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7-104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. STIR: Assessing and Training Response Inhibition Abilities

    Science.gov (United States)

    2014-07-30

    Learning to stop responding to alcohol cues reduces alcohol intake via reduced affective associations rather than increased response inhibition. Addiction ...requires an abstract application of the core learning principle1,2, and viable examples are often hard to find and/or assess. If exposure to non...inhibition training that expands upon previous successful “near transfer” response inhibition training efforts—such as treating alcohol addictions by

  14. Thermodynamic versus non-equilibrium stability of palmitic acid monolayers in calcium-enriched sea spray aerosol proxy systems.

    Science.gov (United States)

    Wellen Rudd, Bethany A; Vidalis, Andrew S; Allen, Heather C

    2018-04-16

    Of the major cations in seawater (Na+, Mg2+, Ca2+, K+), Ca2+ is found to be the most enriched in fine sea spray aerosols (SSA). In this work, we investigate the binding of Ca2+ to the carboxylic acid headgroup of palmitic acid (PA), a marine-abundant fatty acid, and the impact such binding has on the stability of PA monolayers in both equilibrium and non-equilibrium systems. A range of Ca2+ conditions from 10 μM to 300 mM was utilized to represent the relative concentration of Ca2+ in high and low relative humidity aerosol environments. The CO2- stretching modes of PA detected by surface-sensitive infrared reflection-absorption spectroscopy (IRRAS) reveal ionic binding motifs of the Ca2+ ion to the carboxylate group with varying degrees of hydration. Surface tensiometry was used to determine the thermodynamic equilibrium spreading pressure (ESP) of PA on the various aqueous CaCl2 subphases. Up to concentrations of 1 mM Ca2+, each system reached equilibrium, and Ca2+:PA surface complexation gave rise to a lower energy state revealed by elevated surface pressures relative to water. We show that PA films are not thermodynamically stable at marine aerosol-relevant Ca2+ concentrations ([Ca2+] ≥ 10 mM). IRRAS and vibrational sum frequency generation (VSFG) spectroscopy were used to investigate the surface presence of PA on high concentration Ca2+ aqueous subphases. Non-equilibrium relaxation (NER) experiments were also conducted and monitored by Brewster angle microscopy (BAM) to determine the effect of the Ca2+ ions on PA stability. At high surface pressures, the relaxation mechanisms of PA varied among the systems and were dependent on Ca2+ concentration.

  15. Stereochemistry of Endogenous Palmitic Acid Ester of 9-Hydroxystearic Acid and Relevance of Absolute Configuration to Regulation.

    Science.gov (United States)

    Nelson, Andrew T; Kolar, Matthew J; Chu, Qian; Syed, Ismail; Kahn, Barbara B; Saghatelian, Alan; Siegel, Dionicio

    2017-04-05

    Lipids have fundamental roles in the structure, energetics, and signaling of cells and organisms. The recent discovery of fatty acid esters of hydroxy fatty acids (FAHFAs), lipids with potent antidiabetic and anti-inflammatory activities, indicates that our understanding of the composition of lipidome and the function of lipids is incomplete. The ability to synthesize and test FAHFAs was critical in elucidating the roles of these lipids, but these studies were performed with racemic mixtures, and the role of stereochemistry remains unexplored. Here, we synthesized the R- and S- palmitic acid ester of 9-hydroxystearic acid (R-9-PAHSA, S-9-PAHSA). Access to highly enantioenriched PAHSAs enabled the development of a liquid chromatography-mass spectrometry (LC-MS) method to separate and quantify R- and S-9-PAHSA, and this approach identified R-9-PAHSA as the predominant stereoisomer that accumulates in adipose tissues from transgenic mice where FAHFAs were first discovered. Furthermore, biochemical analysis of 9-PAHSA biosynthesis and degradation indicate that the enzymes and pathways for PAHSA production are stereospecific, with cell lines favoring the production of R-9-PAHSA and carboxyl ester lipase (CEL), a PAHSA degradative enzyme, selectively hydrolyzing S-9-PAHSA. These studies highlight the role of stereochemistry in the production and degradation of PAHSAs and define the endogenous stereochemistry of 9-PAHSA in adipose tissue. This information will be useful in the identification and characterization of the pathway responsible for PAHSA biosynthesis, and access to enantiopure PAHSAs will elucidate the role of stereochemistry in PAHSA activity and metabolism in vivo.

  16. Intramuscular administration of paliperidone palmitate extended-release injectable microsuspension induces a subclinical inflammatory reaction modulating the pharmacokinetics in rats.

    Science.gov (United States)

    Darville, Nicolas; van Heerden, Marjolein; Vynckier, An; De Meulder, Marc; Sterkens, Patrick; Annaert, Pieter; Van den Mooter, Guy

    2014-07-01

    The present study aims at elucidating the intricate nature of the drug release and absorption following intramuscular (i.m.) injection of sustained-release prodrug nanocrystals/microcrystals. A paliperidone palmitate (PPP) long-acting suspension was characterized with regard to particle size (Dv,50 = 1.09 μm) and morphology prior to i.m. injection in rats. The local disposition was rigorously investigated by means of (immuno)histochemistry and transmission electron microscopy while the concurrent multiphasic pharmacokinetics was linked to the microanatomy. A transient (24 h) trauma-induced inflammation promptly evolved into a subclinical but chronic granulomatous inflammatory reaction initiated by the presence of solid material. The dense inflammatory envelope (CD68(+) macrophages) led to particle agglomeration with subsequent drop in dissolution rate beyond 24 h postinjection. This was associated with a decrease in apparent paliperidone (PP) absorption (near-zero order) until 96 h and a delayed time of occurrence of observed maximum drug plasma concentration (168 h). The infiltrating macrophages phagocytosed large fractions of the depot, thereby influencing the (pro)drug release. Radial angiogenesis (CD31(+)) was observed throughout the inflammatory rim from 72 h onwards and presumably contributed to the sustained systemic PP concentrations by maintaining a sufficient absorptive capacity. No solid-state transitions of the retrieved formulation were recorded with X-ray diffraction analysis. In summary, the initial formulation-driven prodrug (PPP) dissolution and drug (PP) absorption were followed by a complex phase determined by the relative contribution of formulation factors and dynamic physiological variables. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers.

    Science.gov (United States)

    Brezinova, Marie; Kuda, Ondrej; Hansikova, Jana; Rombaldova, Martina; Balas, Laurence; Bardova, Kristina; Durand, Thierry; Rossmeisl, Martin; Cerna, Marcela; Stranak, Zbynek; Kopecky, Jan

    2018-02-01

    To achieve optimal development of a newborn, breastfeeding is extensively recommended, but little is known about the role of non-nutritive bioactive milk components. We aimed to characterize the fatty acid esters of hydroxy fatty acids (FAHFAs), namely palmitic acid hydroxystearic acids (PAHSAs)-endogenous lipids with anti-inflammatory and anti-diabetic properties, in human breast milk. Breast milk samples from 30 lean (BMI=19-23) and 23 obese (BMI>30) women were collected 72h postpartum. Adipose tissue and milk samples were harvested from C57BL/6J mice. FAHFA lipid profiles were measured using reverse phase and chiral liquid chromatography-mass spectrometry method. PAHSA regioisomers as well as other FAHFAs were present in both human and murine milk. Unexpectedly, the levels of 5-PAHSA were higher relative to other regioisomers. The separation of both regioisomers and enantiomers of PAHSAs revealed that both R- and S-enantiomers were present in the biological samples, and that the majority of the 5-PAHSA signal is of R configuration. Total PAHSA levels were positively associated with weight gain during pregnancy, and 5-PAHSA as well as total PAHSA levels were significantly lower in the milk of the obese compared to the lean mothers. Our results document for the first time the presence of lipid mediators from the FAHFA family in breast milk, while giving an insight into the stereochemistry of PAHSAs. They also indicate the negative effect of obesity on 5-PAHSA levels. Future studies will be needed to explore the role and mechanism of action of FAHFAs in breast milk. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The role and mechanism of KCa3.1 channels in human monocyte migration induced by palmitic acid.

    Science.gov (United States)

    Ma, Xiao-Zhen; Pang, Zheng-Da; Wang, Jun-Hong; Song, Zheng; Zhao, Li-Mei; Du, Xiao-Jun; Deng, Xiu-Ling

    2018-05-21

    Monocyte migration into diseased tissues contributes to the pathogenesis of diseases. Intermediate-conductance Ca 2+ -activated K + (K Ca 3.1) channels play an important role in cell migration. However, the role of K Ca 3.1 channels in mediating monocyte migration induced by palmitic acid (PA) is still unclear. Using cultured THP-1 cells and peripheral blood mononuclear cells from healthy subjects, we investigated the role and signaling mechanisms of K Ca 3.1 channels in mediating the migration induced by PA. Using methods of Western blotting analysis, RNA interference, cell migration assay and ELISA, we found that PA-treated monocytes exhibited increment of the protein levels of K Ca 3.1 channel and monocyte chemoattractant protein-1 (MCP-1), and the effects were reversed by co-incubation of PA with anti-TLR2/4 antibodies or by specific inhibitors of p38-MAPK, or NF-κB. In addition, PA increased monocyte migration, which was abolished by a specific K Ca 3.1 channel blocker, TRAM-34, or K Ca 3.1 small interfering RNA (siRNA). The expression and secretion of MCP-1 induced by PA was also similarly prevented by TRAM-34 and K Ca 3.1 siRNA. These results demonstrate for the first time that PA upregulates K Ca 3.1 channels through TLR2/4, p38-MAPK and NF-κB pathway to promote the expression of MCP-1, and then induce the trans-endothelial migration of monocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Exposure Forecaster

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Exposure Forecaster Database (ExpoCastDB) is EPA's database for aggregating chemical exposure information and can be used to help with chemical exposure...

  20. Homo economicus belief inhibits trust.

    Directory of Open Access Journals (Sweden)

    Ziqiang Xin

    Full Text Available As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  1. Homo Economicus Belief Inhibits Trust

    Science.gov (United States)

    Xin, Ziqiang; Liu, Guofang

    2013-01-01

    As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners’ benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals’ homo economicus belief and inhibit their trust. It seems that people’s increasing homo economicus belief may serve as one cause of the worldwide decline of trust. PMID:24146907

  2. Inhibition of central de novo ceramide synthesis restores insulin signaling in hypothalamus and enhances β-cell function of obese Zucker rats

    Directory of Open Access Journals (Sweden)

    Mélanie Campana

    2018-02-01

    Full Text Available Objectives: Hypothalamic lipotoxicity has been shown to induce central insulin resistance and dysregulation of glucose homeostasis; nevertheless, elucidation of the regulatory mechanisms remains incomplete. Here, we aimed to determine the role of de novo ceramide synthesis in hypothalamus on the onset of central insulin resistance and the dysregulation of glucose homeostasis induced by obesity. Methods: Hypothalamic GT1-7 neuronal cells were treated with palmitate. De novo ceramide synthesis was inhibited either by pharmacological (myriocin or molecular (si-Serine Palmitoyl Transferase 2, siSPT2 approaches. Obese Zucker rats (OZR were intracerebroventricularly infused with myriocin to inhibit de novo ceramide synthesis. Insulin resistance was determined by quantification of Akt phosphorylation. Ceramide levels were quantified either by a radioactive kinase assay or by mass spectrometry analysis. Glucose homeostasis were evaluated in myriocin-treated OZR. Basal and glucose-stimulated parasympathetic tonus was recorded in OZR. Insulin secretion from islets and β-cell mass was also determined. Results: We show that palmitate impaired insulin signaling and increased ceramide levels in hypothalamic neuronal GT1-7 cells. In addition, the use of deuterated palmitic acid demonstrated that palmitate activated several enzymes of the de novo ceramide synthesis pathway in hypothalamic cells. Importantly, myriocin and siSPT2 treatment restored insulin signaling in palmitate-treated GT1-7 cells. Protein kinase C (PKC inhibitor or a dominant-negative PKCζ also counteracted palmitate-induced insulin resistance. Interestingly, attenuating the increase in levels of hypothalamic ceramides with intracerebroventricular infusion of myriocin in OZR improved their hypothalamic insulin-sensitivity. Importantly, central myriocin treatment partially restored glucose tolerance in OZR. This latter effect is related to the restoration of glucose-stimulated insulin

  3. , , , , , and Gene Expression in Single- and Co-cultured Bovine Satellite Cells and Intramuscular Preadipocytes Treated with Palmitic, Stearic, Oleic, and Linoleic Acid

    Directory of Open Access Journals (Sweden)

    S. H. Choi

    2015-03-01

    Full Text Available We previously demonstrated that bovine subcutaneous preadipocytes promote adipogenic gene expression in muscle satellite cells in a co-culture system. Herein we hypothesize that saturated fatty acids would promote adipogenic/lipogenic gene expression, whereas mono- and polyunsaturated fatty acids would have the opposite effect. Bovine semimembranosus satellite cells (BSC and intramuscular preadipocytes (IPA were isolated from crossbred steers and cultured with 10% fetal bovine serum (FBS/Dulbecco’s Modified Eagle Medium (DMEM and 1% antibiotics during the 3-d proliferation period. After proliferation, cells were treated for 3 d with 3% horse serum/DMEM (BSC or 5% FBS/DMEM (IPA with antibiotics. Media also contained 10 μg/mL insulin and 10 μg/mL pioglitazone. Subsequently, differentiating BSC and IPA were cultured in their respective media with 40 μM palmitic, stearic, oleic, or linoleic acid for 4 d. Finally, BSC and IPA were single- or co-cultured for an additional 2 h. All fatty acid treatments increased (p = 0.001 carnitine palmitoyltransferase-1 beta (CPT1β gene expression, but the increase in CPT1β gene expression was especially pronounced in IPA incubated with palmitic and stearic acid (6- to 17- fold increases. Oleic and linoleic acid decreased (p = 0.001 stearoyl-CoA desaturase (SCD gene expression over 80% in both BSC and IPA. Conversely, palmitic and stearic acid increased SCD gene expression three fold in co-cultured in IPA, and stearic acid increased AMPKα gene expression in single- and co-cultured BSC and IPA. Consistent with our hypothesis, saturated fatty acids, especially stearic acid, promoted adipogenic and lipogenic gene expression, whereas unsaturated fatty acids decreased expression of those genes associated with fatty acid metabolism.

  4. Inhibition of apparent photosynthesis by nitrogen oxides

    Energy Technology Data Exchange (ETDEWEB)

    Hill, A C; Bennett, J H

    1970-01-01

    The nitrogen oxides (NO/sub 2/ and NO) inhibited apparent photosynthesis of oats and alfalfa at concentrations below those required to cause visible injury. There appeared to be a threshold concentration of about 0.6 ppm for each pollutant. An additive effect in depressing apparent photosynthesis occurred when the plants were exposed to a mixture of NO and NO/sub 2/. Although NO produced a more rapid effect on the plants, lower concentrations of NO/sub 2/ were required to cause a given inhibition after 2 hour of exposure. Inhibition by nitric oxide was more closely related to its partial pressure than was inhibition by NO/sub 2/.

  5. Effect of hypoxia on the incorporation of [2-3H] glycerol and [1-14C[-palmitate into lipids of various brain regions

    International Nuclear Information System (INIS)

    Alberghina, M.; Giuffrida, A.M.

    1981-01-01

    The lipid metabolism in guinea pig brain after intermittent hypoxia, prolonged for 80 hrs, was markedly impaired. The in vivo incorporation of [2-3H] glycerol and [1-14C] palmitate into lipids of microsomes, mitochondria, myelin, and synaptosomes, purified form cerebral hemispheres, was significantly lower in the hypoxic animals than in the controls. The same effect was observed on the incorporation of labeled precursors into lipids of mitochondria purified from cerebellum and brainstem. In particular, the labeling of th major phospholipids present - ie, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) - in the mitochondria of the three brain regions examined decreased after hypoxic treatment

  6. Optimization of Palmitic Acid Composition in Crude Oleic Acid to Provide Specifications of Titer and Cloud Point of Distillate Oleic Acid using a Flash Distiller

    OpenAIRE

    Muhammad Yusuf Ritonga

    2010-01-01

    Titer and cloud point Distilled Oleic Acid’s higher than standard on feed composition palmitic acid (C15H31COOH) or C16 11.2 %. Feed composition C16, top temperature precut and bottom main distiller column were optimized to produce DOA. A factorial design 3 independent variables 3 X 2 X 3, twice repeating’s applied to observe effects of feed composition C16 to quality parameters. On the optimum C16 feed composition at 5.20 % was produced DOA with titer 6.8 oC, cloud point 5.0 oC (inside it...

  7. Optimization of Palmitic Acid Composition in Crude Oleic Acid to Provide Specifications of Titer and Cloud Point of Distillate Oleic Acid using a Flash Distiller

    Directory of Open Access Journals (Sweden)

    Muhammad Yusuf Ritonga

    2010-11-01

    Full Text Available Titer and cloud point of Distilled Oleic Acid is higher than is the standard on feed composition palmitic acid (C15H31COOH or C16 11.2 %. Feed composition C16, top temperature precut and bottom main distiller column were optimized to produce DOA. A factorial design with 3 independent variables, 3 X 2 X 3, repeated twice as much, is applied to observe effects of feed composition C16 to quality parameters. In the optimum C16, feed composition at 5.20 % produced DOA with titer 6.8 oC, cloud point 5.0 oC (inside its specification.

  8. Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of dry eye: a Japanese Phase II clinical trial

    Directory of Open Access Journals (Sweden)

    Toshida H

    2017-06-01

    Full Text Available Hiroshi Toshida,1 Toshinari Funaki,2 Koichi Ono,3 Nobuhito Tabuchi,4 Sota Watanabe,4 Tamotsu Seki,5 Hiroshi Otake,6 Takuji Kato,7 Nobuyuki Ebihara,8 Akira Murakami2 1Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka, 2Department of Ophthalmology, Juntendo University Graduate School of Medicine, 3Department of Ophthalmology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, 4Pharmaceutical Research Laboratories, Lion Corporation, Kanagawa, 5Tamagawa Eye Clinic, Tokyo, 6Otake Eye Clinic, Kanagawa, 7Kato Eye Clinic, Tokyo, 8Department of Ophthalmology, Juntendo University Urayasu Hospital, Chiba, Japan Purpose: The purpose of this study was to investigate the efficacy and safety of the administration of retinol palmitate (VApal ophthalmic solution (500 IU/mL for the treatment of patients with dry eye. Patients and methods: This study included 66 patients with dry eye. After a 2-week washout period, patients were randomized (1:1 into either a VApal ophthalmic solution or a placebo group, and a single drop of either solution was administered six times daily for 4 weeks. Efficacy measures were 12 subjective symptoms, rose bengal (RB and fluorescein staining scores, tear film breakup time, and tear secretion. Safety measures included clinical blood and urine analyses and adverse event recordings. Results: In comparisons of the two groups, the mean change in RB staining score from baseline was significantly lower in the VApal group at 2 and 4 weeks (P<0.05 and P<0.01, respectively. Furthermore, the fluorescein clearance rate (fluorescein staining score was significantly higher in the VApal group at 4 weeks (P<0.05. The VApal group showed a significant improvement in blurred vision at 1 and 2 weeks (P<0.01 and P<0.05, respectively, and the mean change in the total score for subjective symptoms from baseline was significantly lower in the VApal group at 1 week (P<0.05. In before- and after-intervention comparisons, the

  9. Comparison of Medicaid spending in schizoaffective patients treated with once monthly paliperidone palmitate or oral atypical antipsychotics.

    Science.gov (United States)

    Xiao, Yongling; Muser, Erik; Fu, Dong-Jing; Lafeuille, Marie-Hélène; Pilon, Dominic; Emond, Bruno; Wu, Allen; Duh, Mei Sheng; Lefebvre, Patrick

    2016-01-01

    Compared to oral atypical antipsychotics (OAAs), long-acting injectable antipsychotics require less frequent administration, and thus may improve adherence and reduce risk of relapse in schizoaffective disorder (SAD) patients. To evaluate the impact of once monthly paliperidone palmitate (PP) versus OAAs on healthcare resource utilization, Medicaid spending, and hospital readmission among SAD patients. Using FL, IA, KS, MS, MO, and NJ Medicaid data (January 2009-December 2013), adults with ≥2 SAD diagnoses initiated on PP or OAA (index date) were identified. Baseline characteristics and outcomes were assessed during the 12month pre- and post-index periods, respectively. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to reduce confounding and compare the estimated treatment effect for PP versus OAA. A total of 10,778 OAA-treated patients and 876 PP-treated patients were selected. Compared to OAAs, PP was associated with significantly lower medical costs (PSM: mean monthly cost difference [MMCD] = -$383, p < 0.001; IPTW: MMCD = -$403, p = 0.016), which offset the higher pharmacy costs associated with PP (PSM: MMCD = $270, p < 0.001; IPTW: MMCD = $350, p < 0.001) and resulted in similar total healthcare cost (PSM: MMCD = -$113, p = 0.414; IPTW: MMCD = -$53, p = 0.697) for PP versus OAA. Reduced risk of hospitalization (PSM: incidence rate ratio [IRR] = 0.85, p = 0.128; IPTW: IRR = 0.96, p = 0.004) and fewer hospitalization days (PSM: IRR = 0.74, p = 0.008; IPTW: IRR = 0.85, p < 0.001) were observed in PP versus OAA patients. Among hospitalized patients, PP was associated with a lower risk of 30 day hospital readmission compared to OAA (IPTW: odds ratio = 0.89, p = 0.041). Limitations The Medicaid data may not be representative of the nation or other states, and includes pre-rebate pharmacy costs (potentially over-estimated). Also

  10. Activation of PPAR{delta} up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Jun; Jiang, Li; Lue, Qingguo; Ke, Linqiu [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China); Li, Xiaoyu [State Key Laboratory of Oral Diseases, Sichuan University, No. 14, 3rd Section, Renmin South Road, Chengdu, Sichuan 610041 (China); Tong, Nanwei, E-mail: buddyjun@hotmail.com [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China)

    2010-01-15

    Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor {delta} (PPAR{delta}) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic {beta}-cells. After HIT-T15 cells (a {beta}-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPAR{delta}), we found that administration of GW increased the expression of PPAR{delta} mRNA. GW-induced activation of PPAR{delta} up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPAR{delta} plays an important role in protecting pancreatic {beta}-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

  11. Acidolysis of terebinth fruit oil with palmitic and caprylic acids in a recirculating packed bed reactor: optimization using response surface methodology

    Energy Technology Data Exchange (ETDEWEB)

    Koçak, D.; Keskin, H.; Fadiloglu, S.; Gögüs, F.

    2016-07-01

    The acidolysis reaction of terebinth fruit oil with caprylic and palmitic acid has been investigated. The reaction was catalyzed by lipase (Lipozyme IM from Rhizomucormiehei) and carried out in recirculating packed bed reactor. The effects of reaction parameters have been analyzed using response surface methodology. Reaction time (3.5–6.5 h), enzyme load (10–20%), substrate flow rate (4–8 mL·min−1 ) and substrate mole ratios (Terebinth oil : Palmitic acid : Caprylic acid, 1:1.83:1.22–1:3.07:2.05) were evaluated. The optimum reaction conditions were 5.9 h reaction time, 10% enzyme load, 4 mL·min−1 substrate flow rate and 1:3.10:2.07 substrate mole ratio. The structured lipid obtained at these optimum conditions had 52.23% desired triacylglycerols and a lower caloric value than that of terebinth fruit oil. The melting characteristics and microstructure of the structured lipid were similar to those of commercial margarine fat extracts. The results showed that the structured lipid had the highest oxidative stability among the studied fats. (Author)

  12. Comparative evaluation of labelling patterns and turnover of lipids, tagged by 15 (p-123I-phenyl-)pentadecanoic and 1-14C-palmitic acid

    International Nuclear Information System (INIS)

    Reske, S.N.; Sauer, W.; Reichmann, K.; Winkler, C.; Machulla, H.J.; Knust, E.J.

    1984-01-01

    Uptake and turnover of chloroform/methanol extractable tissue lipids labelled in vivo simultaneously with 15(p- 123 I-phenyl-)pentadecanoic and 1- 14 C-palmitic acid were compared. Lipid turnover studies were performed in fasted pentobarbital-anaesthetized Wistar rats in tissues with highly varying free fatty acid turnover rates. In all tissues investigated, i.e. heart, lung, liver, spleen and kidney, both tracers labelled nearly identical lipid fractions. The main tracer uptake was found in free fatty acids, phospholipids, diglycerides and triglycerides. A highly significant correlation of uptake and turnover in main tissue lipid fractions indicated an essentially identical metabolic pathway of both tracers in intermediary tissue lipid metabolism. Concordant tracer uptake and turnover patterns in tissue of lipids with highly varying fatty acid metabolic rates suggested that intrinsic metabolic activity of the tissue and respective lipid fraction was the major determinant of metabolic handling of both iodophenyl fatty- and palmitic acid. Thus, the feasibility of iodophenylpentadecanoic acid as free fatty acid tracer for studying tissue lipid metabolism is demonstrated. (author)

  13. Comparative evaluation of labelling patterns and turnover of lipids, tagged by 15 (p-/sup 123/I-phenyl-)pentadecanoic and 1-/sup 14/C-palmitic acid

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Sauer, W.; Reichmann, K.; Winkler, C. (Bonn Univ. (Germany, F.R.). Inst. fuer Klinische und Experimentelle Nuklearmedizin); Machulla, H.J.; Knust, E.J. (Essen Univ. (Germany, F.R.). Inst. fuer Medizinische Strahlenphysik und Strahlenbiologie)

    1984-06-15

    Uptake and turnover of chloroform/methanol extractable tissue lipids labelled in vivo simultaneously with 15(p-/sup 123/I-phenyl-)pentadecanoic and 1-/sup 14/C-palmitic acid were compared. Lipid turnover studies were performed in fasted pentobarbital-anaesthetized Wistar rats in tissues with highly varying free fatty acid turnover rates. In all tissues investigated, i.e. heart, lung, liver, spleen and kidney, both tracers labelled nearly identical lipid fractions. The main tracer uptake was found in free fatty acids, phospholipids, diglycerides and triglycerides. A highly significant correlation of uptake and turnover in main tissue lipid fractions indicated an essentially identical metabolic pathway of both tracers in intermediary tissue lipid metabolism. Concordant tracer uptake and turnover patterns in tissue of lipids with highly varying fatty acid metabolic rates suggested that intrinsic metabolic activity of the tissue and respective lipid fraction was the major determinant of metabolic handling of both iodophenyl fatty- and palmitic acid. Thus, the feasibility of iodophenylpentadecanoic acid as free fatty acid tracer for studying tissue lipid metabolism is demonstrated. 21 refs.

  14. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

    Science.gov (United States)

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

  15. BRAIN CHOLINESTERASE INHIBITION AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE (PHAD) OF FLASH EVOKED POTENTIALS (FEPS) IN LONG EVANS RATS FOLLOWING ACUTE OR REPEATED EXPOSURES TO A MIXTURE OF CARBARYL AND PROPOXUR.

    Science.gov (United States)

    Carbaryl and propoxur are N-methyl carbamate pesticides (NMCs) which are part of the EPA’s cumulative risk assessments for NMCs. These NMCs inhibit cholinesterase (ChE) activity and may lead to cholinergic disruption of CNS function. We used decreases in the PhAD of FEPs to indic...

  16. Inhibition of Acetylcholinesterase and Fatty Acid Composition in Theobroma grandiflorum Seeds

    Directory of Open Access Journals (Sweden)

    Casandra Valentina Itriago

    2017-07-01

    Full Text Available Theobroma grandiflorum is an important fruit tree from Sterculiaceae family, native to the Brazilian Amazon, known in the region as cupuaçu. The seeds have a high fat content (24% with characteristics that resemble those of cocoa (Theobroma cacao butter with potential applications in the cosmetic, pharmaceutical and food industries. The main objective of this work was to explore the seed fats from T. grandiflorum that were analyzed for fatty acid composition by Gas Chromatography with Flame Ionization Detector (GC-FID and to analyze their activity for acetylcholinesterase inhibition. Chromatographic analysis provided detection of nine fatty acids. The major fatty acids found in the species were oleic (40.0%, stearic (32.7%, arachidic (10.4% and palmitic (8.0%. The acetylcholinesterase inhibition by fats from seeds was over 40.48%. DOI: http://dx.doi.org/10.17807/orbital.v0i0.894 

  17. Preparation and properties of palmitic-stearic acid eutectic mixture/expanded graphite composite as phase change material for energy storage

    International Nuclear Information System (INIS)

    Zhang, Nan; Yuan, Yanping; Du, Yanxia; Cao, Xiaoling; Yuan, Yaguang

    2014-01-01

    A novel composite PCM (phase change material) with PA-SA (palmitic-stearic acid) eutectic mixture as PCM and EG (expanded graphite) as supporting material was prepared. The optimum absorption ratio of PA-SA/EG (Palmitic-stearic acid/expanded graphite) composite PCM was determined as PA-SA:EG = 13:1 (by mass). Scanning electron microscope and Fourier transformation infrared spectroscopy results show that PA-SA was uniformly distributed in the porous network structure of EG due to the physical action. Thermal property and thermal stability of the PA-SA/EG composite PCM were characterized by DSC (differential scanning calorimetry) and TGA (thermogravimetric analysis). DSC results indicated that the melting and freezing temperatures and latent heats of PA-SA/EG were measured as 53.89 °C and 54.37 °C, and 166.27 J/g and 166.13 J/g. TGA test results revealed that PA-SA/EG had a good thermal stability in working temperature range. Thermal cycling test results showed PA-SA/EG had a good thermal reliability after 720 thermal cycles. Thermal conductivity of the composite PCM was measured as 2.51 W/m K, much higher than that of PA-SA. The thermal energy storage and release rates of PA-SA/EG were also increased due to the high thermal conductivity of EG. In conclusion, the prepared PA-SA/EG composite PCM can be acted as a potential material for thermal energy storage due to the acceptable thermal properties, good thermal reliability and stability, high thermal conductivity. - Highlights: • PA-SA/EG (Palmitic-stearic acid/expanded graphite) composite PCM was prepared. • Optimum absorption ratio of PA-SA in EG was obtained as 13:1 (by mass). • Thermal conductivity and performance of PA-SA/EG have been significate improved. • PA-SA/EG has a good thermal reliability and thermal stability

  18. N-nitrosamines in processed meat products – analysis, occurrence, formation, mitigation and exposure

    DEFF Research Database (Denmark)

    Herrmann, Susan Strange

    and NVNA in meat. Secondly data on the occurrence of VNA and NVNA in processed meat products on the Danish market were to be generated and used for an evaluation of the exposure level resulting from consumption of processed meat products. A method allowing for the simultaneous determination of both VNA......, NPIP, NTCA and NMTCA were inversely related to the amount of erythorbic acid (396-1104 mg kg-1). The levels of the individual NA were reduced with up to 20 to 75%. No additional protection against NA formation was obtained by also adding ascorbyl palmitate, a fat soluble antioxidant. Sodium chloride...

  19. Early growth response protein 1 (EGR1) regulates pro-inflammatory gene expression in response to palmitate and TNF alpha in human placenta cells and is induced in obese placenta

    Science.gov (United States)

    Maternal obesity has been hypothesized to induce a pro-inflammatory response in the placenta. However, the specific factors contributing to this pro-infalmmatory response are yet to be determined. Our objective was to examine the effects of palmitic acid (PA), tumor necrosis factor alpha (TNF alph...

  20. Digestibility of Fatty Acids in the Gastrointestinal Tract of Dairy Cows Fed with Tallow or Saturated Fats Rich in Stearic Acid or Palmitic Acid

    DEFF Research Database (Denmark)

    Weisbjerg, Martin Riis; Hvelplund, Torben; Børsting, Christian Friis

    1992-01-01

    Fatty acid digestibility was studied with five lactating cows fed three different fat sources in a 5 × 5 latin square experiment. The treatments were 500 g of tallow, 500 or 1000 g of saturated fat rich in stearic acid (C18:0) (SARF) or 500 or 1000 g of saturated fat rich in palmitic acid (C16......:0) (PARF) per day. The total daily fatty acid intake was about 1100 g in rations with the highest fat inclusion. The fatty acid digestibilities were 76% for tallow, 74 and 64% for 500 and 1000 g SARF, respectively, and 87 and 81% for 500 and 1000 g of PARF, respectively. When compared to fatty acid...... digestibility for tallow predicted from a model based on literature values, PARF had a higher fatty acid digestibility at both fat intakes, and SARF had a lower fatty acid digestibility, especially at high fat intake....

  1. Prenatal immune challenge in rats: altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to poly IC.

    Science.gov (United States)

    Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

    2012-08-01

    Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic acid (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero maze, open-field activity, object burying, light-dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route-based learning when visible cues were unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)-amphetamine and an attenuated hyperactivity in response to MK-801. This model did not exhibit the cognitive, or latent inhibition deficits reported in Poly IC-treated rats but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction). Copyright © 2012 Wiley Periodicals, Inc.

  2. Antioxidants Inhibit Formation of 3-Monochloropropane-1,2-diol Esters in Model Reactions.

    Science.gov (United States)

    Li, Chang; Jia, Hanbing; Shen, Mingyue; Wang, Yuting; Nie, Shaoping; Chen, Yi; Zhou, Yongqiang; Wang, Yuanxing; Xie, Mingyong

    2015-11-11

    The capacities of six antioxidants to inhibit the formation of 3-monochloropropane-1,2 diol (3-MCPD) esters were examined in this study. Inhibitory capacities of the antioxidants were investigated both in chemical models containing the precursors (tripalmitoyl glycerol, 1,2-dipalmitoyl-sn-glycerol, monopalmitoyl glycerol, and sodium chloride) of 3-MCPD esters and in oil models (rapeseed oil and sodium chloride). Six antioxidants, butylated hydroxytoluene (BHT), butylated hydroxy anisole (BHA), tert-butyl hydroquinone (TBHQ), propyl gallate (PG), L-ascorbyl palmitate (AP), and α-tocopherol (VE), were found to exhibit inhibiting capacities on 3-MCPD ester formation both in chemical models and in oil models. TBHQ provided the highest inhibitory capacity both in chemical models and in oil models; 44% of 3-MCPD ester formation was inhibited in the presence of TBHQ (66 mg/kg of oil) after heating of rapeseed oil at 230 °C for 30 min, followed by PG and AP. BHT, BHA, and VE appeared to have weaker inhibitory abilities in both models. VE exhibited the lowest inhibition rate; 22% of 3-MCPD esters were inhibited in the presence of VE (172 mg/kg of oil) after heating of rapeseed oil at 230 °C for 30 min. In addition, the inhibition rates of PG and VE decreased dramatically with an increase in temperature or heating time. The results suggested that some antioxidants, such as TBHQ, PG, and AP, could be the potential inhibitors of 3-MCPD esters in practice.

  3. Phase change and heat transfer characteristics of a eutectic mixture of palmitic and stearic acids as PCM in a latent heat storage system

    International Nuclear Information System (INIS)

    Baran, Guelseren; Sari, Ahmet

    2003-01-01

    The phase change and heat transfer characteristics of a eutectic mixture of palmitic and stearic acids as phase change material (PCM) during the melting and solidification processes were determined experimentally in a vertical two concentric pipes energy storage system. This study deals with three important subjects. First is determination of the eutectic composition ratio of the palmitic acid (PA) and stearic acid (SA) binary system and measurement of its thermophysical properties by differential scanning calorimetry (DSC). Second is establishment of the phase transition characteristics of the mixture, such as the total melting and solidification temperatures and times, the heat transfer modes in the melted and solidified PCM and the effect of Reynolds and Stefan numbers as initial heat transfer fluid (HTF) conditions on the phase transition behaviors. Third is calculation of the heat transfer coefficients between the outside wall of the HTF pipe and the PCM, the heat recovery rates and heat fractions during the phase change processes of the mixture and also discussion of the effect of the inlet HTF parameters on these characteristics. The DSC results showed that the PA-SA binary system in the mixture ratio of 64.2:35.8 wt% forms a eutectic, which melts at 52.3 deg. C and has a latent heat of 181.7 J g -1 , and thus, these properties make it a suitable PCM for passive solar space heating and domestic water heating applications with respect to climate conditions. The experimental results also indicated that the eutectic mixture of PA-SA encapsulated in the annulus of concentric double pipes has good phase change and heat transfer characteristics during the melting and solidification processes, and it is an attractive candidate as a potential PCM for heat storage in latent heat thermal energy storage systems

  4. Impact of time of initiation of once-monthly paliperidone palmitate in hospitalized Asian patients with acute exacerbation of schizophrenia: a post hoc analysis from the PREVAIL study.

    Science.gov (United States)

    Li, Huafang; Li, Yan; Feng, Yu; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson

    2018-01-01

    To evaluate the differences in efficacy and safety outcomes in acute exacerbating schizophrenia patients between 2 subgroups (≤1 week and >1 week), differing in time interval from hospitalization to time of initiation of once-monthly paliperidone palmitate. PREVAIL was a multicenter, single-arm, open-label, prospective Phase IV study in hospitalized Asian patients (either sex, aged 18-65 years) diagnosed with schizophrenia ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition). Change from baseline to week 13 in primary (Positive and Negative Syndrome Scale [PANSS] total score), secondary endpoints (PANSS responder rate, PANSS subscale, PANSS Marder factor, Clinical Global Impression-Severity, and Personal and Social Performance scale scores, readiness for hospital discharge questionnaire) and safety were assessed in this post hoc analysis. Significant mean reduction from baseline to week 13 in the PANSS total score, 30% PANSS responder rates ( P ≤0.01), PANSS subscales (positive and general psychopathology; all P ≤0.01), PANSS Marder factor (positive symptoms, uncontrolled hostility, and excitement and anxiety/depression; all P ≤0.01), Personal and Social Performance scale scores ( P ≤0.05) and Clinical Global Impression-Severity categorical summary ( P ≤0.05) were significantly greater in the ≤1 week subgroup versus >1 week subgroup ( P ≤0.05). The readiness for hospital discharge questionnaire improved over time for the overall study population, but remained similar between subgroups at all-time points. Treatment-emergent adverse events were similar between the subgroups. Early initiation of once-monthly paliperidone palmitate in hospitalized patients with acute exacerbation of schizophrenia led to greater improvements in psychotic symptoms with comparable safety than treatment initiation following 1 week of hospitalization.

  5. Caffeine Promotes Conversion of Palmitic Acid to Palmitoleic Acid by Inducing Expression of fat-5 in Caenorhabditis elegans and scd1 in Mice.

    Science.gov (United States)

    Du, Xiaocui; Huang, Qin; Guan, Yun; Lv, Ming; He, Xiaofang; Fang, Chongye; Wang, Xuanjun; Sheng, Jun

    2018-01-01

    The synthesis and metabolism of fatty acids in an organism is related to many biological processes and is involved in several diseases. The effects of caffeine on fatty acid synthesis and fat storage in Caenorhabditis elegans and mice were studied. After 6 h of food deprivation, adult C. elegans were treated with 0.1 mg/mL caffeine for 24 h. Quantitative reverse-transcription polymerase chain reaction showed that, among all the genes involved in fat accumulation, the mRNA expression of fat-5 in caffeine-treated C. elegans was significantly higher than that of controls, whereas fat-6 and fat-7 displayed no significant difference. Gas chromatography-mass spectrometry was used to verify the fatty acid composition of C. elegans . Results showed that the ratio of palmitoleic acid (16:1) to that of palmitic acid (16:0) was higher in the caffeine-treated group. Several mutant strains, including those involved in the insulin-like growth factor-1, dopamine, and serotonin pathways, and nuclear hormone receptors ( nhrs ), were used to assess their necessity to the effects of caffeine. We found that mdt-15 was essential for the effects of caffeine, which was independent of nhr-49 and nhr -80. Caffeine may increase fat-5 expression by acting on mdt-15 . In high fat diet (HFD), but not in normal diet (ND) mice, caffeine induced expression of scd1 in both subcutaneous and epididymal white adipose tissue, which was consistent with the palmitoleic/palmitic ratio results by gas chromatograph analysis. In mature adipocytes, caffeine treatment induced both mRNA and protein expression of scd1 and pgc-1 α. Overall, our results provided a possible mechanism on how caffeine modulates metabolism homeostasis in vivo .

  6. The Deoxygenation Pathways of Palmitic Acid into Hydrocarbons on Silica-Supported Ni12P5 and Ni2P Catalysts

    Directory of Open Access Journals (Sweden)

    Wenjun Zhou

    2018-04-01

    Full Text Available Pure Ni12P5/SiO2 and pure Ni2P/SiO2 catalysts were obtained by adjusting the Ni and P molar ratios, while Ni/SiO2 catalyst was prepared as a reference against which the deoxygenation pathways of palmitic acid were investigated. The catalysts were characterized by N2 adsorption, X-ray diffraction (XRD, X-ray photoelectron spectroscopy (XPS, transmission election microscopy (TEM, infrared spectroscopy of pyridine adsorption (Py-IR, H2-adsorption and temperature-programmed desorption of hydrogen (H2-TPD. The crystallographic planes of Ni(111, Ni12P5(400, Ni2P(111 were found mainly exposed on the above three catalysts, respectively. It was found that the deoxygenation pathway of palmitic acid mainly proceeded via direct decarboxylation (DCO2 to form C15 on Ni/SiO2. In contrast, on the Ni12P5/SiO2 catalyst, there were two main competitive pathways producing C15 and C16, one of which mainly proceeded via the decarbonylation (DCO to form C15 accompanying water formation, and the other pathway produced C16 via the dehydration of hexadecanol intermediate, and the yield of C15 was approximately twofold that of C16. Over the Ni2P/SiO2 catalyst, two main deoxygenation pathways formed C15, one of which was mainly the DCO pathway and the other was dehydration accompanying the hexadecanal intermediate and then direct decarbonylation without water formation. The turn over frequency (TOF followed the order: Ni12P5/SiO2 > Ni/SiO2 > Ni2P/SiO2.

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

    Science.gov (United States)

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

    2017-08-01

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

  8. Mapping the low palmitate fap1 mutation and validation of its effects in soybean oil and agronomic traits in three soybean populations.

    Science.gov (United States)

    Cardinal, Andrea J; Whetten, Rebecca; Wang, Sanbao; Auclair, Jérôme; Hyten, David; Cregan, Perry; Bachlava, Eleni; Gillman, Jason; Ramirez, Martha; Dewey, Ralph; Upchurch, Greg; Miranda, Lilian; Burton, Joseph W

    2014-01-01

    fap 1 mutation is caused by a G174A change in GmKASIIIA that disrupts a donor splice site recognition and creates a GATCTG motif that enhanced its expression. Soybean oil with reduced palmitic acid content is desirable to reduce the health risks associated with consumption of this fatty acid. The objectives of this study were: to identify the genomic location of the reduced palmitate fap1 mutation, determine its molecular basis, estimate the amount of phenotypic variation in fatty acid composition explained by this locus, determine if there are epistatic interactions between the fap1 and fap nc loci and, determine if the fap1 mutation has pleiotropic effects on seed yield, oil and protein content in three soybean populations. This study detected two major QTL for 16:0 content located in chromosome 5 (GmFATB1a, fap nc) and chromosome 9 near BARCSOYSSR_09_1707 that explained, with their interaction, 66-94 % of the variation in 16:0 content in the three populations. Sequencing results of a putative candidate gene, GmKASIIIA, revealed a single unique polymorphism in the germplasm line C1726, which was predicted to disrupt the donor splice site recognition between exon one and intron one and produce a truncated KASIIIA protein. This G to A change also created the GATCTG motif that enhanced gene expression of the mutated GmKASIIIA gene. Lines homozygous for the GmKASIIIA mutation (fap1) had a significant reduction in 16:0, 18:0, and oil content; and an increase in unsaturated fatty acids content. There were significant epistatic interactions between GmKASIIIA (fap1) and fap nc for 16:0 and oil contents, and seed yield in two populations. In conclusion, the fap1 phenotype is caused by a single unique SNP in the GmKASIIIA gene.

  9. Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway.

    Science.gov (United States)

    Wei, Shengnan; Zhang, Ming; Yu, Yang; Lan, Xiaoxin; Yao, Fan; Yan, Xin; Chen, Li; Hatch, Grant M

    2016-01-01

    Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122

  10. Effects of chronic fly ash exposure on golden hamsters: changes in lung phospholipids and their fatty acid composition as a result of inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, I; Negishi, T; Kamihira, M

    1986-01-01

    Changes in lung phospholipids of golden hamsters exposed to 2 mg/mT coal fly ash for 180 days, 7 days/week, 20 hours/day were examined. In the exposed group the amount of phospholipids in lavaged lung organ increased significantly compared with the control group, but in pulmonary surfactant did not. As regards lipid composition of phospholipids in lavaged lung organ, phosphatidylcholine was slightly increased but sphingomyelin was decreased by exposure. Some significant changes in fatty acid composition of phospholipids were observed between exposed and control group. In pulmonary surfactant, palmitic acid showed no change but myristic acid and oleic acid decreased. On the other hand, in lavaged lung organ, palmitic acid increased but stearic acid and decosatetraenoic acid decreased. Arachidonic acid composition increased in both parts of lung. An increase in the proportion of polyunsaturated fatty acid in whole fatty acid of phospholipids was found in pulmonary surfactant of exposed hamsters. 24 refs., 2 figs., 3 tabs.

  11. CSN1S2 protein of goat milk inhibits the decrease of viability and increases the proliferation of MC3T3E1 pre-osteoblast cell in methyl glyoxal exposure

    Directory of Open Access Journals (Sweden)

    Choirunil Chotimah

    2015-03-01

    Full Text Available Objective: To investigate whether the CNS1S2 protein of goat milk is able to inhibit the toxicity of methyl glyoxal (MG towards MC3T3E1 pre-osteoblast cells. Methods: At confluency, pre-osteoblast cells were divided into five groups which included control (untreated, pre-osteoblast cells exposed to 5 µmol/L MG, pre-osteoblast cells exposed to MG in the presence of CSN1S2 protein at doses of 0.025, 0.050, and 0.100 mg/L, respectively. Analysis of reactive oxygen species was done with 2,7-dichlorodihydrofluorescein diacetate fluorochrome. The proliferation and viability of MC3T3E1 cells were measured by trypan blue staining. Malondialdehyde analysis was done colorimetrically. Results: Cell's viabilities were significantly lower in MG+0.050 mg/L CSN1S2 protein of goat milk compared to MG group (P<0.05. MG+0.100 mg/L CSN1S2 protein of goat milk significantly increased the cells viability compared to MG group (P<0.05. The levels of proliferation were significantly higher in MG+0.100 mg/L CSN1S2 protein of goat milk compared to control group and all treatment groups, respectively (P<0.05. Conclusions: High dose of CSN1S2 protein of goat milk (0.100 mg/L in high MG environment inhibits the decrease of viability due to the increases of the proliferation of MC3T3E1 preosteoblast cell.

  12. Exposure of a distinct PDCA-1+ (CD317 B cell population to agonistic anti-4-1BB (CD137 inhibits T and B cell responses both in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Dass S Vinay

    Full Text Available 4-1BB (CD137 is an important T cell activating molecule. Here we report that it also promotes development of a distinct B cell subpopulation co-expressing PDCA-1. 4-1BB is expressed constitutively, and its expression is increased when PDCA-1(+ B cells are activated. We found that despite a high level of surface expression of 4-1BB on PDCA-1(+ B cells, treatment of these cells with agonistic anti-4-1BB mAb stimulated the expression of only a few activation markers (B7-2, MHC II, PD-L2, cytokines (IL-12p40/p70, and chemokines (MCP-1, RANTES, as well as sTNFR1, and the immunosuppressive enzyme, IDO. Although the PDCA-1(+ B cells stimulated by anti-4-1BB expressed MHC II at high levels and took up antigens efficiently, Ig class switching was inhibited when they were pulsed with T-independent (TI or T-dependent (TD Ags and adoptively transferred into syngeneic recipients. Furthermore, when anti-4-1BB-treated PDCA-1(+ B cells were pulsed with OVA peptide and combined with Vα2(+CD4(+ T cells, Ag-specific cell division was inhibited both in vitro and in vivo. Our findings suggest that the 4-1BB signal transforms PDCA-1(+ B cells into propagators of negative immune regulation, and establish an important role for 4-1BB in PDCA-1(+ B cell development and function.

  13. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qiang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); The First Affiliated Hospital of Xiamen University, Xiamen (China); Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); Yu, Chundong, E-mail: cdyu@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China)

    2011-06-17

    Highlights: {yields} Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. {yields} FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. {yields} FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. {yields} FGFR4-ECD reduced tetracycline-induced fatty liver in mice. {yields} FGFR4-ECD partially restored tetracycline-repressed PPAR{alpha} expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  14. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Chen, Qiang; Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang; Yu, Chundong

    2011-01-01

    Highlights: → Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. → FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. → FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. → FGFR4-ECD reduced tetracycline-induced fatty liver in mice. → FGFR4-ECD partially restored tetracycline-repressed PPARα expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor α (PPARα), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  15. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    International Nuclear Information System (INIS)

    Mahalingam, Sharada; Gao, Liying; Gonnering, Marni; Helferich, William; Flaws, Jodi A.

    2016-01-01

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. - Highlights: • Equol exposure inhibits antral follicle growth. • Equol exposure increases follicle atresia. • Equol exposure inhibits sex steroid hormone levels. • Equol exposure inhibits mRNA levels of certain steroidogenic enzymes.

  16. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Mahalingam, Sharada, E-mail: mahalin2@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Gao, Liying, E-mail: lgao@uiuc.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Gonnering, Marni, E-mail: mgonne2@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Helferich, William, E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

    2016-03-15

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. - Highlights: • Equol exposure inhibits antral follicle growth. • Equol exposure increases follicle atresia. • Equol exposure inhibits sex steroid hormone levels. • Equol exposure inhibits mRNA levels of certain steroidogenic enzymes.

  17. INHIBITION IN SPEAKING PERFORMANCE

    OpenAIRE

    Humaera, Isna

    2015-01-01

    The most common problem encountered by the learner in the languageacquisition process is learner inhibition. Inhibition refers to a temperamentaltendency to display wariness, fearfulness, or restrain in response tounfamiliar people, objects, and situations. There are some factors that causeinhibition, such as lack of motivation, shyness, self-confidence, self-esteem,and language ego. There are also levels of inhibition, it refers to kinds ofinhibition and caused of inhibition itself. Teacher ...

  18. Impact of time of initiation of once-monthly paliperidone palmitate in hospitalized Asian patients with acute exacerbation of schizophrenia: a post hoc analysis from the PREVAIL study

    Directory of Open Access Journals (Sweden)

    Li H

    2018-04-01

    Full Text Available Huafang Li,1,2 Yan Li,1,2 Yu Feng,3 Jianmin Zhuo,4 Ibrahim Turkoz,5 Maju Mathews,5 Wilson Tan3 1Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China; 3Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 4Janssen China Research and Development, Shanghai, China; 5Janssen Research & Development LLC, Titusville, NJ, USA Purpose: To evaluate the differences in efficacy and safety outcomes in acute exacerbating schizophrenia patients between 2 subgroups (≤1 week and >1 week, differing in time interval from hospitalization to time of initiation of once-monthly paliperidone palmitate. Patients and methods: PREVAIL was a multicenter, single-arm, open-label, prospective Phase IV study in hospitalized Asian patients (either sex, aged 18–65 years diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Change from baseline to week 13 in primary (Positive and Negative Syndrome Scale [PANSS] total score, secondary endpoints (PANSS responder rate, PANSS subscale, PANSS Marder factor, Clinical Global Impression-Severity, and Personal and Social Performance scale scores, readiness for hospital discharge questionnaire and safety were assessed in this post hoc analysis. Results: Significant mean reduction from baseline to week 13 in the PANSS total score, 30% PANSS responder rates (P≤0.01, PANSS subscales (positive and general psychopathology; all P≤0.01, PANSS Marder factor (positive symptoms, uncontrolled hostility, and excitement and anxiety/depression; all P≤0.01, Personal and Social Performance scale scores (P≤0.05 and Clinical Global Impression-Severity categorical summary (P≤0.05 were significantly greater in the ≤1 week subgroup versus >1 week subgroup (P≤0.05. The readiness for hospital discharge questionnaire improved over time for the overall study population, but

  19. Nutrient digestibility and milk production responses to increasing levels of palmitic acid supplementation vary in cows receiving diets with or without whole cottonseed.

    Science.gov (United States)

    Rico, J E; de Souza, J; Allen, M S; Lock, A L

    2017-01-01

    Our study evaluated the dose-dependent effects of a palmitic acid-enriched supplement in basal diets with or without the inclusion of whole cottonseed on nutrient digestibility and production responses of dairy cows. Sixteen Holstein cows (149 ± 56 days in milk) were used in a split plot Latin square design experiment. Cows were blocked by 3.5% fat-corrected milk (FCM) and allocated to a main plot receiving either a basal diet with soyhulls (SH, = 8) or a basal diet with whole cottonseed (CS, = 8) that was fed throughout the experiment. A palmitic acid-enriched supplement (PA 88.5% C16:0) was fed at 0, 0.75, 1.50, or 2.25% of ration DM in a replicated 4 × 4 Latin Square design within each basal diet group. Periods were 14 d with the final 4 d used for data collection. PA dose increased milk fat content linearly, and cubically affected yields of milk fat and 3.5% FCM. The PA dose did not affect milk protein and lactose contents, BW, and BCS, but tended to increase yields of milk, milk protein, and milk lactose. Also, PA dose reduced DMI and 16-carbon fatty acid digestibility quadratically, and increased 18-carbon fatty acid digestibility quadratically. There were no effects of basal diet on the yield of milk or milk components, but DMI tended to decrease in CS compared with SH, increasing feed efficiency (3.5% FCM/DMI). Compared with SH, CS diets increased yield of preformed milk fatty acids and 16-carbon fatty acid digestibility, and tended to decrease 18-carbon fatty acid digestibility. We observed basal diet × PA dose interactions for yields of milk and milk protein and for 16-carbon and total fatty acid digestibility, as well as tendency for yields of milk fat and 3.5% FCM. Also, there was a tendency for an interaction between basal diet and PA dose for NDF digestibility, which increased more for CS with increasing PA than for SH. PA dose linearly decreased digestibility of total fatty acids in SH diets but did not affect it in CS diets Results demonstrate

  20. Influence of alcohol containing and alcohol free cosmetics on FAEE concentrations in hair. A performance evaluation of ethyl palmitate as sole marker, versus the sum of four FAEEs.

    Science.gov (United States)

    Dumitrascu, C; Paul, R; Kingston, R; Williams, Rachel

    2018-02-01

    Fatty acid ethyl esters (FAEE) are direct metabolites of ethanol and have been shown to be suitable markers for the evaluation of alcohol consumption. Previous research has suggested that the regular use of alcohol containing cosmetic products can influence the concentration of FAEE detected in hair. In this study we investigated the influence of alcohol containing and alcohol free hair cosmetics (hairspray and waxes) on the FAEE concentrations in hair. The effect of cosmetic treatment was measured against the impact on ethyl palmitate in isolation as compared to the sum of four esters. 10 volunteers treated part of their scalp with cosmetic products every day during a 2 month period (alcohol free hairspray n=2, hairspray containing alcohol (42% by volume) n=3, alcohol free wax n=2, wax containing alcohol (11% by volume) n=3). After the 2 month period of cosmetic application hair samples from volunteers were collected from both sides of the scalp. Hair samples were washed with n-heptane, and then cut finely into small pieces. All samples were subjected to clean-up by HS-SPME and then GC PCI-MS/MS for analysis of FAEEs. Comparison of FAEE concentrations between treated and untreated hair showed in some instances that application of hair spray or wax products caused an increase in FAEE levels. Products containing alcohol caused a more substantial increase in alcohol metabolite concentrations in hair when compared to alcohol free products. Three volunteers using an alcohol based hairspray in the study experienced a significant increase in FAEE levels (+27.4%, +205.5%, and +1287.5%), with one of the volunteers showing levels below the cut off for 'abstinence' in the untreated scalp portion, and levels above the cut off for 'chronic excessive consumption' in the treated scalp portion. Performance evaluation of ethyl palmitate as sole marker, compared to the sum of four esters approach suggested that the two quantification approaches react in a very similar manner to the

  1. (Vapor + liquid) equilibrium for the binary systems {l_brace}water + glycerol{r_brace} and {l_brace}ethanol + glycerol, ethyl stearate, and ethyl palmitate{r_brace} at low pressures

    Energy Technology Data Exchange (ETDEWEB)

    Coelho, Renata; Santos, Priscilla G. dos; Mafra, Marcos R. [Department of Chemical Engineering, Federal University of Parana, CEP 81531-990, Curitiba, PR (Brazil); Cardozo-Filho, Lucio [Department of Chemical Engineering, Maringa State University (UEM), Av. Colombo 5790, 87020-900 Maringa, PR (Brazil); Corazza, Marcos L., E-mail: corazza@ufpr.br [Department of Chemical Engineering, Federal University of Parana, CEP 81531-990, Curitiba, PR (Brazil)

    2011-12-15

    Highlights: > We measured VLE for the binary system {l_brace}ethyl stearate and palmitate + ethanol{r_brace}. > The boiling temperatures were obtained using Othmer-type ebuliometer. > The experimental data were modeled using NRTL, UNIQUAC, and UNIFAC models. - Abstract: This work reports the experimental measurements {l_brace}(vapor + liquid) equilibrium{r_brace} for the systems {l_brace}water(1) + glycerol(2){r_brace}, {l_brace}ethanol(1) + glycerol(2){r_brace}, {l_brace}ethanol(1) + ethyl stearate(2){r_brace}, and {l_brace}ethanol(1) + ethyl palmitate(2){r_brace}. Boiling temperatures were measured using an Othmer-type ebulliometer over a pressure range of 14 kPa to 96 kPa. The experimental data were well correlated using the NRTL and UNIQUAC models. The performance of the UNIFAC-Dortmund model in relation to predicting the phase equilibrium of the systems was also studied.

  2. The inhibition of the mitochondrial F1FO-ATPase activity when activated by Ca2+ opens new regulatory roles for NAD.

    Science.gov (United States)

    Nesci, Salvatore; Trombetti, Fabiana; Ventrella, Vittoria; Pirini, Maurizio; Pagliarani, Alessandra

    2018-01-26

    The mitochondrial F1FO-ATPase is uncompetitively inhibited by NAD+ only when the natural cofactor Mg2+ is replaced by Ca2+, a mode putatively involved in cell death. The Ca2+-dependent F1FO-ATPase is also inhibited when NAD+ concentration in mitochondria is raised by acetoacetate. The enzyme inhibition by NAD+ cannot be ascribed to any de-ac(et)ylation or ADP-ribosylation by sirtuines, as it is not reversed by nicotinamide. Moreover, the addition of acetyl-CoA or palmitate, which would favor the enzyme ac(et)ylation, does not affect the F1FO-ATPase activity. Consistently, NAD+ may play a new role, not associated with redox and non-redox enzymatic reactions, in the Ca2+-dependent regulation of the F1FO-ATPase activity.

  3. mTOR signaling promotes foam cell formation and inhibits foam cell egress through suppressing the SIRT1 signaling pathway.

    Science.gov (United States)

    Zheng, Haixiang; Fu, Yucai; Huang, Yusheng; Zheng, Xinde; Yu, Wei; Wang, Wei

    2017-09-01

    Atherosclerosis (AS) is a chronic immuno‑inflammatory disease accompanied by dyslipidemia. The authors previously demonstrated that sirtuin 1 (SIRT1) may prevent atherogenesis through influencing the liver X receptor/C‑C chemokine receptor type 7/nuclear factor‑κB (LXR‑CCR7/NF‑κB) signaling pathway. Previous studies have suggested a role for mammalian target of rapamycin (mTOR) signaling in the pathogenesis of cardiovascular diseases. The present study investigated the potential association between mTOR signaling and SIRT1‑LXR‑CCR7/NF‑κB signaling (SIRT1 signaling) in AS pathogenesis. To induce foam cell formation, U937 cells were differentiated into macrophages by exposure to phorbol 12‑myristate 13‑acetate (PMA) for 24 h, followed by treatment with palmitate and oxidized low density lipoprotein for a further 24 h. Oil red O staining revealed a large accumulation of lipid droplets present in foam cells. Western blot analysis demonstrated increased protein levels of phosphorylated (p)‑mTOR and its downstream factor p‑ribosomal protein S6 kinase (p70S6K). Reverse transcription‑quantitative polymerase chain reaction and western blot analyses additionally revealed decreased expression of SIRT1, LXRα and CCR7 and increased expression of NF‑κB and its downstream factor tumor necrosis factor‑α (TNF‑α) in an atherogenetic condition induced by lysophosphatidic acid (LPA). In addition, abundant lipid droplets accumulated in U937‑LPA‑treated foam cells. Rapamycin, an mTOR inhibitor, suppressed the expression and activity of mTOR and p70S6K, however enhanced expression of SIRT1, LXRα, and CCR7. Conversely, rapamycin deceased TNF‑α and NF‑κB activity, the latter of which was further confirmed by immunofluorescence analysis demonstrating increased levels of NF‑κB present in the cytoplasm compared with the nucleus. The findings of the present study suggest that mTOR signaling promotes foam cell formation and inhibits foam

  4. Palmitic acid follows a different metabolic pathway than oleic acid in human skeletal muscle cells; lower lipolysis rate despite an increased level of adipose triglyceride lipase.

    Science.gov (United States)

    Bakke, Siril S; Moro, Cedric; Nikolić, Nataša; Hessvik, Nina P; Badin, Pierre-Marie; Lauvhaug, Line; Fredriksson, Katarina; Hesselink, Matthijs K C; Boekschoten, Mark V; Kersten, Sander; Gaster, Michael; Thoresen, G Hege; Rustan, Arild C

    2012-10-01

    Development of insulin resistance is positively associated with dietary saturated fatty acids and negatively associated with monounsaturated fatty acids. To clarify aspects of this difference we have compared the metabolism of oleic (OA, monounsaturated) and palmitic acids (PA, saturated) in human myotubes. Human myotubes were treated with 100μM OA or PA and the metabolism of [(14)C]-labeled fatty acid was studied. We observed that PA had a lower lipolysis rate than OA, despite a more than two-fold higher protein level of adipose triglyceride lipase after 24h incubation with PA. PA was less incorporated into triacylglycerol and more incorporated into phospholipids after 24h. Supporting this, incubation with compounds modifying lipolysis and reesterification pathways suggested a less influenced PA than OA metabolism. In addition, PA showed a lower accumulation than OA, though PA was oxidized to a relatively higher extent than OA. Gene set enrichment analysis revealed that 24h of PA treatment upregulated lipogenesis and fatty acid β-oxidation and downregulated oxidative phosphorylation compared to OA. The differences in lipid accumulation and lipolysis between OA and PA were eliminated in combination with eicosapentaenoic acid (polyunsaturated fatty acid). In conclusion, this study reveals that the two most abundant fatty acids in our diet are partitioned toward different metabolic pathways in muscle cells, and this may be relevant to understand the link between dietary fat and skeletal muscle insulin resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Characterisation of Fecal Soap Fatty Acids, Calcium Contents, Bacterial Community and Short-Chain Fatty Acids in Sprague Dawley Rats Fed with Different sn-2 Palmitic Triacylglycerols Diets.

    Science.gov (United States)

    Wan, Jianchun; Hu, Songyou; Ni, Kefeng; Chang, Guifang; Sun, Xiangjun; Yu, Liangli

    2016-01-01

    The structure of dietary triacylglycerols is thought to influence fatty acid and calcium absorption, as well as intestinal microbiota population of the host. In the present study, we investigated the impact of palmitic acid (PA) esterified at the sn-2 position on absorption of fatty acid and calcium and composition of intestinal microorganisms in rats fed high-fat diets containing either low sn-2 PA (12.1%), medium sn-2 PA (40.4%) or high sn-2 PA (56.3%), respectively. Fecal fatty acid profiles in the soaps were measured by gas chromatography (GC), while fecal calcium concentration was detected by ICP-MS. The fecal microbial composition was assessed using a 16S rRNA high-throughput sequencing technology and fecal short-chain fatty acids were detected by ion chromatograph. Dietary supplementation with a high sn-2 PA fat significantly reduced total fecal contents of fatty acids soap and calcium compared with the medium or low sn-2 PA fat groups. Diet supplementation with sn-2 PA fat did not change the entire profile of the gut microbiota community at phylum level and the difference at genera level also were minimal in the three treatment groups. However, high sn-2 PA fat diet could potentially improve total short-chain fatty acids content in the feces, suggesting that high dietary sn-2 PA fat might have a beneficial effect on host intestinal health.

  6. Film fabrication of Fe or Fe3O4 nanoparticles mixed with palmitic acid for vertically aligned carbon nanotube growth using Langmuir-Blodgett technique

    Science.gov (United States)

    Nakamura, Kentaro; Kuriyama, Naoki; Takagiwa, Shota; Sato, Taiga; Kushida, Masahito

    2016-03-01

    Vertically aligned carbon nanotubes (VA-CNTs) were studied as a new catalyst support for polymer electrolyte fuel cells (PEFCs). Controlling the number density and the diameter of VA-CNTs may be necessary to optimize PEFC performance. As the catalyst for CNT growth, we fabricated Fe or Fe3O4 nanoparticle (NP) films by the Langmuir-Blodgett (LB) technique. The catalyst Fe or Fe3O4 NPs were widely separated by mixing with filler molecules [palmitic acid (C16)]. The number density of VA-CNTs was controlled by varying the ratio of catalyst NPs to C16 filler molecules. The VA-CNTs were synthesized from the catalyst NP-C16 LB films by thermal chemical vapor deposition (CVD) using acetylene gas as the carbon source. The developing solvents used in the LB technique and the hydrogen reduction conditions of CVD were optimized to improve the VA-CNT growth rate. We demonstrate that the proposed method can independently control both the density and the diameter of VA-CNTs.

  7. AICAR Protects against High Palmitate/High Insulin-Induced Intramyocellular Lipid Accumulation and Insulin Resistance in HL-1 Cardiac Cells by Inducing PPAR-Target Gene Expression

    Directory of Open Access Journals (Sweden)

    Ricardo Rodríguez-Calvo

    2015-01-01

    Full Text Available Here we studied the impact of 5-aminoimidazole-4-carboxamide riboside (AICAR, a well-known AMPK activator, on cardiac metabolic adaptation. AMPK activation by AICAR was confirmed by increased phospho-Thr172-AMPK and phospho-Ser79-ACC protein levels in HL-1 cardiomyocytes. Then, cells were exposed to AICAR stimulation for 24 h in the presence or absence of the AMPK inhibitor Compound C, and the mRNA levels of the three PPARs were analyzed by real-time RT-PCR. Treatment with AICAR induced gene expression of all three PPARs, but only the Ppara and Pparg regulation were dependent on AMPK. Next, we exposed HL-1 cells to high palmitate/high insulin (HP/HI conditions either in presence or in absence of AICAR, and we evaluated the expression of selected PPAR-targets genes. HP/HI induced insulin resistance and lipid storage was accompanied by increased Cd36, Acot1, and Ucp3 mRNA levels. AICAR treatment induced the expression of Acadvl and Glut4, which correlated to prevention of the HP/HI-induced intramyocellular lipid build-up, and attenuation of the HP/HI-induced impairment of glucose uptake. These data support the hypothesis that AICAR contributes to cardiac metabolic adaptation via regulation of transcriptional mechanisms.

  8. Vapour liquid equilibria of monocaprylin plus palmitic acid or methyl stearate at P = (1.20 and 2.50) kPa by using DSC technique

    International Nuclear Information System (INIS)

    Cunico, Larissa P.; Damaceno, Daniela S.; Matricarde Falleiro, Rafael M.; Sarup, Bent; Abildskov, Jens; Ceriani, Roberta; Gani, Rafiqul

    2015-01-01

    Highlights: • Novel VLE data for binary mixtures involving a partial acylglycerol (monocaprylin). • Use of a promising technique for measuring VLE/vapour pressure data (DSC technique). • The consistency of experimental data is analysed by a proposed methodology. • Regressed parameters are given for excess Gibbs thermodynamic models. • New regressed parameters are presented for UNIFAC to account for nonidealities. - Abstract: The Differential Scanning Calorimetry (DSC) technique is used for measuring isobaric (vapour + liquid) equilibria for two binary mixtures: {monocaprylin + palmitic acid (system 1) or methyl stearate (system 2)} at two different pressures P = (1.20 and 2.50) kPa. The obtained PTx data are correlated by Wilson, NRTL and UNIQUAC models. The original UNIFAC group contribution method is also considered and new binary interaction parameters for the main groups CH 2 , CCOO, OH and COOH are regressed, to account for the non-idealities found in these lipid systems. Established thermodynamic consistency tests are applied and attest the quality of the measured data. In terms of relevance of the selected components, system 1 can be found in the purification and deodorization steps during the production of edible oils, while, system 2 can be found in the purification steps of biodiesel. It should be noted that no such data could be found in the open literature, not only for the specific components selected but also for the combination of the classes of components considered; that is, acylglycerol plus fatty acid or fatty ester.

  9. Once-monthly injection of paliperidone palmitate in patients with recently diagnosed and chronic schizophrenia: a post-hoc comparison of efficacy and safety.

    Science.gov (United States)

    Si, Tianmei; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson; Feng, Yu

    2017-12-01

    The use of long-acting injectable antipsychotics in recently diagnosed schizophrenia remains less explored. We evaluated the efficacy and safety of paliperidone palmitate once-monthly (PP1M) treatment in adult patients with recently diagnosed vs. chronic schizophrenia. These post-hoc analyses included two multicenter studies. Study 1 (NCT01527305) enrolled recently diagnosed (≤5 years) and chronic (>5 years) patients; Study 2 (NCT01051531) enrolled recently diagnosed patients only. Recently diagnosed patients were further sub-grouped into ≤2 years or 2-5 years. The primary efficacy endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. In Study 1, 41.5% patients had recent diagnosis (≤2 years: 56.8%; 2-5 years: 43.2%); 58.5% had chronic schizophrenia. In Study 2, 52.8% and 47.2% patients were grouped into ≤2 years and 2-5 years, respectively. PANSS total score showed significantly greater improvement in patients with recently diagnosed vs. chronic schizophrenia. Similar results were obtained for PANSS responder rate, improvements in PANSS, and CGI-S scores. PP1M was efficacious in both recently diagnosed and chronic schizophrenia, with the benefits being more pronounced in patients with recently diagnosed schizophrenia. This adds to growing evidence recommending long-acting antipsychotic interventions at early stages of schizophrenia.

  10. CPT1α over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

    International Nuclear Information System (INIS)

    Jambor de Sousa, Ulrike L.; Koss, Michael D.; Fillies, Marion; Gahl, Anja; Scheeder, Martin R.L.; Cardoso, M. Cristina; Leonhardt, Heinrich; Geary, Nori; Langhans, Wolfgang; Leonhardt, Monika

    2005-01-01

    To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1α (CPT1α). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1α transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1α over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1α over-expressing cells in a concentration-dependent manner. Both, PA and CPT1α over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1α, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo

  11. Synthesis, characterization, and application of novel biodegradable self-assembled 2-(N-phthalimido) ethyl-palmitate nanoparticles for cancer therapy

    Science.gov (United States)

    Kasoju, Naresh; Bora, Debajeet K.; Bhonde, Ramesh R.; Bora, Utpal

    2010-03-01

    We report the synthesis of novel biodegradable nanoparticles (NPs) which can kill the cancer cells without any additional drug loading. The NP was a self-assembled form of a phthalimide based conjugate, in which the phthalimide moiety was responsible for the anticancer activity. We describe the synthesis of a novel 2-(N-phthalimido) ethyl palmitate (PHEP-Pal) conjugate and subsequent preparation of NPs by a simple self assembly process. The successful synthesis of conjugate was confirmed by various characterization studies including nuclear magnetic resonance spectroscope, Fourier transform infrared spectroscope, TOF-liquid chromatography mass spectroscope, differential scanning calorimetry, and X-ray diffraction unit. The synthesis, shape, size, and size distribution of PHEP-Pal NPs were determined by transmission electron microscope, atomic force microscope, and dynamic light scattering technique. Finally, cell culture studies using A549 and HeLa cells were done to evaluate the anticancer effect of PHEP-Pal NPs, which demonstrated the potency of these NPs for use in cancer chemotherapy.

  12. Topical Application of Trisodium Ascorbyl 6-Palmitate 2-Phosphate Actively Supplies Ascorbate to Skin Cells in an Ascorbate Transporter-Independent Manner

    Directory of Open Access Journals (Sweden)

    Shuichi Shibuya

    2017-06-01

    Full Text Available Ascorbic acid (AA possesses multiple beneficial functions, such as regulating collagen biosynthesis and redox balance in the skin. AA derivatives have been developed to overcome this compound’s high fragility and to assist with AA supplementation to the skin. However, how AA derivatives are transferred into cells and converted to AA in the skin remains unclear. In the present study, we showed that AA treatment failed to increase the cellular AA level in the presence of AA transporter inhibitors, indicating an AA transporter-dependent action. In contrast, torisodium ascorbyl 6-palmitate 2-phosphate (APPS treatment significantly enhanced the cellular AA level in skin cells despite the presence of inhibitors. In ex vivo experiments, APPS treatment also increased the AA content in a human epidermis model. Interestingly, APPS was readily metabolized and converted to AA in keratinocyte lysates via an intrinsic mechanism. Furthermore, APPS markedly repressed the intracellular superoxide generation and promoted viability associated with an enhanced AA level in Sod1-deficient skin cells. These findings indicate that APPS effectively restores the AA level and normalizes the redox balance in skin cells in an AA transporter-independent manner. Topical treatment of APPS is a beneficial strategy for supplying AA and improving the physiology of damaged skin.

  13. Estradiol Uses Different Mechanisms in Astrocytes from the Hippocampus of Male and Female Rats to Protect against Damage Induced by Palmitic Acid

    Directory of Open Access Journals (Sweden)

    Laura M. Frago

    2017-10-01

    Full Text Available An excess of saturated fatty acids can be toxic for tissues, including the brain, and this has been associated with the progression of neurodegenerative diseases. Since palmitic acid (PA is a free fatty acid that is abundant in the diet and circulation and can be harmful, we have investigated the effects of this fatty acid on lipotoxicity in hippocampal astrocytes and the mechanism involved. Moreover, as males and females have different susceptibilities to some neurodegenerative diseases, we accessed the responses of astrocytes from both sexes, as well as the possible involvement of estrogens in the protection against fatty acid toxicity. PA increased endoplasmic reticulum stress leading to cell death in astrocytes from both males and females. Estradiol (E2 increased the levels of protective factors, such as Hsp70 and the anti-inflammatory cytokine interleukin-10, in astrocytes from both sexes. In male astrocytes, E2 decreased pJNK, TNFα, and caspase-3 activation. In contrast, in female astrocytes E2 did not affect the activation of JNK or TNFα levels, but decreased apoptotic cell death. Hence, although E2 exerted protective effects against the detrimental effects of PA, the mechanisms involved appear to be different between male and female astrocytes. This sexually dimorphic difference in the protective mechanisms induced by E2 could be involved in the different susceptibilities of males and females to some neurodegenerative processes.

  14. Influence of palmitic acid and hexadecanol on the phase transition temperature and molecular packing of dipalmitoylphosphatidyl-choline monolayers at the air-water interface

    Science.gov (United States)

    Lee, Ka Yee C.; Gopal, Ajaykumar; von Nahmen, Anja; Zasadzinski, Joseph A.; Majewski, Jaroslaw; Smith, Gregory S.; Howes, Paul B.; Kjaer, Kristian

    2002-01-01

    Palmitic acid (PA) and 1-hexadecanol (HD) strongly affect the phase transition temperature and molecular packing of dipalmitoylphosphatidylcholine (DPPC) monolayers at the air-water interface. The phase behavior and morphology of mixed DPPC/PA as well as DPPC/HD monolayers were determined by pressure-area-isotherms and fluorescence microscopy. The molecular organization was probed by synchrotron grazing incidence x-ray diffraction using a liquid surface diffractometer. Addition of PA or HD to DPPC monolayers increases the temperature of the liquid-expanded to condensed phase transition. X-ray diffraction shows that DPPC forms mixed crystals both with PA and HD over a wide range of mixing ratios. At a surface pressure (π) of 40 mN/m, increasing the amount of the single chain surfactant leads to a reduction in tilt angle of the aliphatic chains from nearly 30° for pure DPPC to almost 0° in a 1:1 molar ratio of DPPC and PA or HD. At this composition we also find closest packing of the aliphatic chains. Further increase of the amount of PA or HD does not change the lattice or the tilt.

  15. Targeted metabolomic analysis reveals the association between the postprandial change in palmitic acid, branched-chain amino acids and insulin resistance in young obese subjects.

    Science.gov (United States)

    Liu, Liyan; Feng, Rennan; Guo, Fuchuan; Li, Ying; Jiao, Jundong; Sun, Changhao

    2015-04-01

    Obesity is the result of a positive energy balance and often leads to difficulties in maintaining normal postprandial metabolism. The changes in postprandial metabolites after an oral glucose tolerance test (OGTT) in young obese Chinese men are unclear. In this work, the aim is to investigate the complex metabolic alterations in obesity provoked by an OGTT using targeted metabolomics. We used gas chromatography-mass spectrometry and ultra high performance liquid chromatography-triple quadrupole mass spectrometry to analyze serum fatty acids, amino acids and biogenic amines profiles from 15 control and 15 obese subjects at 0, 30, 60, 90 and 120 min during an OGTT. Metabolite profiles from 30 obese subjects as independent samples were detected in order to validate the change of metabolites. There were the decreased levels of fatty acid, amino acids and biogenic amines after OGTT in obesity. At 120 min, percent change of 20 metabolites in obesity has statistical significance when comparing with the controls. The obese parameters was positively associated with changes in arginine and histidine (Pchange in palmitic acid (PA), branched-chain amino acids (BCAAs) and phenylalanine between 1 and 120 min were positively associated with fasting insulin and HOMA-IR (all Presistance in obesity. Our findings offer new insights in the complex physiological regulation of the metabolism during an OGTT in obesity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Paliperidone palmitate once-monthly reduces risk of relapse of psychotic, depressive, and manic symptoms and maintains functioning in a double-blind, randomized study of schizoaffective disorder.

    Science.gov (United States)

    Fu, Dong-Jing; Turkoz, Ibrahim; Simonson, R Bruce; Walling, David P; Schooler, Nina R; Lindenmayer, Jean-Pierre; Canuso, Carla M; Alphs, Larry

    2015-03-01

    Schizoaffective disorder is a complex illness for which optimal treatment is not well established. Results of the first controlled, relapse-prevention study of paliperidone palmitate once-monthly injectable (paliperidone monthly) in schizoaffective disorder are presented. The study was conducted between September 20, 2010, and October 22, 2013. Patients with schizoaffective disorder (confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders) experiencing acute exacerbation of psychotic and depressive/manic symptoms were stabilized with paliperidone monthly as monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and randomly assigned (1:1) to paliperidone monthly or placebo in a 15-month, double-blind, relapse-prevention phase. Randomization was stratified by administration as monotherapy or adjunctive therapy and by study center. The primary endpoint was time to relapse. 334 patients were evaluated. Paliperidone monthly significantly delayed time to relapse for psychotic, depressive, and manic symptoms compared with placebo (P schizoaffective disorder (5.9%, 3.0%), headache (3.5%, 5.5%), and nasopharyngitis (3.5%, 5.5%). Incidence of any extrapyramidal-related adverse event was 7.1% for placebo and 8.5% for paliperidone monthly. Paliperidone monthly as monotherapy or adjunctive therapy significantly delayed psychotic, depressive, and/or manic relapses; reduced their risk; and better maintained functioning in patients with schizoaffective disorder. Results support the value of maintenance treatment with paliperidone monthly in schizoaffective disorder. ClinicalTrials.gov identifier: NCT01193153. © Copyright 2015 Physicians Postgraduate Press, Inc.

  17. Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate.

    Science.gov (United States)

    Girardi, Paolo; Del Casale, Antonio; Rapinesi, Chiara; Kotzalidis, Georgios D; Splendori, Francesca; Verzura, Claudio; Trovini, Giada; Sorice, Serena; Carrus, Dario; Mancinelli, Iginia; Comparelli, Anna; De Filippis, Sergio; Francomano, Antonio; Ballerini, Andrea; Marcellusi, Andrea; Mennini, Francesco S; Ducci, Giuseppe; Sani, Gabriele; Pompili, Maurizio; Brugnoli, Roberto

    2018-05-01

    Long-acting injectable (LAI) antipsychotics can improve medication adherence and reduce hospitalisation rates compared with oral treatments. Paliperidone palmitate (PAL) and aripiprazole monohydrate (ARI) LAI treatments were associated with improvements in global functioning in patients with schizophrenia. The objective of this study was to assess the predictive factors of better overall functioning in patients with chronic schizophrenia and schizoaffective disorder treated with PAL and ARI. Enrolled were 143 (97 males, 46 females, mean age 38.24 years, SD = 12.65) patients with a diagnosis of schizophrenia or schizoaffective disorder, whom we allocated in two groups (PAL and ARI treatments). We assessed global functioning, amount of oral medications, adherence to oral treatment, and number of hospitalisations before LAI introduction and at assessment time point. Longer treatment time with LAIs (p schizoaffective disorder. Better improvement in functioning could be achieved with ARI in young individuals with recent illness onset and PAL in patients at risk for recurrent hospitalisations. Copyright © 2018 John Wiley & Sons, Ltd.

  18. Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats.

    Science.gov (United States)

    Yilmaz, Okkeş; Ozkan, Yusuf; Yildirim, Mehmet; Oztürk, A Ihsan; Erşan, Yasemin

    2002-01-01

    In this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)-induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P cholesterol level was high in diabetes and D + ALA groups (P acid raised in diabetes group (P acid in D + FO, D + ALA, and diabetes groups was lower than control (P acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P and D + ALA groups (P acid (LA) elevated in ALA + D, D + AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO groups was lower than control (P acid (AA) decreased in D + ALA, D+ AA6P, and diabetes groups (P acid (DHA) increased in D + AA6P and D + COM (P acid level raised in diabetes group, its level reduced in D + ALA and D + FO groups (P acid level in D + ALA and D + FO groups was higher than control (P acid degree was raised by the effects of ALA and FO. Copyright 2002 Wiley-Liss, Inc.

  19. Neutron exposure

    International Nuclear Information System (INIS)

    Prillinger, G.; Konynenburg, R.A. van

    1998-01-01

    As a result of the popularity of the Agencies report 'Neutron Irradiation Embrittlement of Reactor Pressure Vessel Steels' of 1975, it was decided that another report on this broad subject would be of use. In this report, background and contemporary views on specially identified areas of the subject are considered as self-contained chapters, written by experts. In chapter 6, LWR-PV neutron transport calculations and dosimetry methods and how they are combined to evaluate the neutron exposure of the steel of pressure vessels are discussed. An effort to correlate neutron exposure parameters with damage is made

  20. Impaired face recognition is associated with social inhibition.

    Science.gov (United States)

    Avery, Suzanne N; VanDerKlok, Ross M; Heckers, Stephan; Blackford, Jennifer U

    2016-02-28

    Face recognition is fundamental to successful social interaction. Individuals with deficits in face recognition are likely to have social functioning impairments that may lead to heightened risk for social anxiety. A critical component of social interaction is how quickly a face is learned during initial exposure to a new individual. Here, we used a novel Repeated Faces task to assess how quickly memory for faces is established. Face recognition was measured over multiple exposures in 52 young adults ranging from low to high in social inhibition, a core dimension of social anxiety. High social inhibition was associated with a smaller slope of change in recognition memory over repeated face exposure, indicating participants with higher social inhibition showed smaller improvements in recognition memory after seeing faces multiple times. We propose that impaired face learning is an important mechanism underlying social inhibition and may contribute to, or maintain, social anxiety. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Prolonged Treatment with Free Fatty Acids has Post Receptor Effect in Hepatic Insulin Resistance: Evidence that Fatty Acids, Oleate and Palmitate have Insignificant Effect on the Insulin Receptor Beta In Vivo and Ex Vivo Primary Hepatocytes

    Directory of Open Access Journals (Sweden)

    Rafik Ragheb

    2009-01-01

    Full Text Available In the current study, we used immunoprecipitation and immunoblotting to examine the levels and phosphorylation status of the insulin receptor-beta subunit (IR-β, as well as the down stream target in PI3K pathway, total PKB/Akt as well as their phosphorylated forms. The assessment of FFAs treatment showed no direct and significant effect on the PI3K stimulation, specifically the IR-β in primary hepatic control cells treated with insulin. Cells treated with either oleate or palmitate (360 µM showed no statistically significant values following insulin stimulation (P > 0.05. To further investigate the effect of both FFAs and high insulin (1 µg, we examined the effects of oleate and palmitate at 360 µM concentration on IR-β as well as PKB. There was no significant difference in the total protein levels and their phosphorylated forms in cells treated with or without oleate or plamitate. Interestingly, IR-β tyrosine phosphorylation showed a similar insignificant effect in vivo and ex vivo hepatic cells treated with oleate or palmitate in comparison to their controls in the fructose fed hamsters.

  2. Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

    International Nuclear Information System (INIS)

    Fazely, F.; Ledinko, N.; Smith, D.J.

    1986-01-01

    The biological activity of retinoids was assayed in an in vitro quantitative assay of human tumor cell invasion using human amnion basement membrane (BM). The effects measured were the inhibition of tumor cell migration through the BM and tumor cell degradative enzyme activity on 14 C-proline labeled collagenous and noncollagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested, the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.009 μg/mL, and of TC-106 cells at 0.07 μg/mL. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels over 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more potent than retinol palmitate. The model system will be useful for investigating antiinvasive activity of other retinoids as well as other compounds

  3. Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

    International Nuclear Information System (INIS)

    Fazely, F.

    1988-01-01

    The effects measured were the inhibition of tumor cell migration through the basement membrane (BM) and tumor cell degradative enzyme activity on 3 H-proline labeled collagenous and non collagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.09 μg/ml, and TC-106 cells at 0.08 μg/ml. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels almost 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more than retinol palmitate. Furthermore, A549 cells treated with retinol acetate, under conditions whereby an anti-invasive state was induced,showed an increase in the number of cellular retinoic acid binding proteins (CRABP), a decrease in the activity of type IV collagenase and ectosialyltransferase, and no change in the activity of transglutaminase

  4. Exposure Prophylaxis

    African Journals Online (AJOL)

    opsig

    health care workers who report exposure to HIV at work whether given PEP or not ... breast milk, amniotic fluid, cerebrospinal fluid, pericardial fluid ... or skin lesions [1]. Other body fluid like sweat, tears, saliva, urine and stool do not contain significant quantities of HIV unless there is blood mixed with them[1,2]. HIV is not ...

  5. [THE SPIRIT CHOLESTEROL, BIOLOGICA L ROLE AT STAGES OF PHYLOGENESIS, MECHANISMS OF INHIBITION OF SYNTHESIS OF STEROL BY STATINS, FACTORS OF PHARMACOGENOMICS AND DIAGNOSTIC SIGNIFICANCE OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

    Science.gov (United States)

    Titov, V N; Kotlovskii, M Yu; Pokrovskii, A A; Kotlovskaia, O S; Osedko, A V; Titova, N M; Kotlovskii, Yu V; Digaii, A M

    2015-04-01

    The hypolipidemic effect of statins is realized by inhibition of synthesis of local pool of cholesterol spirit in endoplasmic net of hepatocytes. The cholesterol spirit covers all hydrophobic medium of triglycerides with polar mono layer of phosphatidylcholines and cholesterol spirit prior to secretion of lipoproteins of very low density into hydrophilic medium. The lesser mono layer between lipase enzyme and triglycerides substrate contains of cholesterol spirit the higher are the parameters of hydrolysis of palmitic and oleic lipoproteins of very low density. The sequence of effect of statins is as follows: blocking of synthesis in hepatocytes and decreasing of content of unesterified cholesterol spirit in blood plasma; activation of hydrolysis of triglycerides in palmitic and oleic lipoproteins of very low density; formation of ligand lipoproteins of very low density and their absorption by cells by force of apoB-100 endocytosis; decreasing in blood of content of polyenoic fatty acids, equimolar esterified by cholesterol spirit, polyethers of cholesterol spirit and decreasing of level of cholesterol spirit-lipoproteins of very low density. There is no way to eliminate aphysiological effect of disordered biological function of trophology (nutrition) on metabolism of fatty acids in population by means of pharmaceuticals intake. It is necessary to eliminate aphysiological effect of environment. To decrease rate of diseases of cardiovascular system one has to decrease in food content of saturated fatty acids and in the first instance palmitic saturated fatty acid, trans-form fatty acid, palmitoleic fatty acids up to physiological values and increase to the same degree the content of polyenoic fatty acids. The saturated fatty acids block absorption of polyenoic fatty acids by cells. The atherosclerosis is a deficiency of polyenoic fatty acids under surplus of palmitic saturated fatty acid.

  6. Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants.

    Science.gov (United States)

    Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

    2016-01-08

    Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity.

  7. Exposures series

    OpenAIRE

    Stimson, Blake

    2011-01-01

    Reaktion Books’ Exposures series, edited by Peter Hamilton and Mark Haworth-Booth, is comprised of 13 volumes and counting, each less than 200 pages with 80 high-quality illustrations in color and black and white. Currently available titles include Photography and Australia, Photography and Spirit, Photography and Cinema, Photography and Literature, Photography and Flight, Photography and Egypt, Photography and Science, Photography and Africa, Photography and Italy, Photography and the USA, P...

  8. Acidolysis of terebinth fruit oil with palmitic and caprylic acids in a recirculating packed bed reactor: optimization using response surface methodology

    Directory of Open Access Journals (Sweden)

    Koçak Yanık, D.

    2016-06-01

    Full Text Available The acidolysis reaction of terebinth fruit oil with caprylic and palmitic acid has been investigated. The reaction was catalyzed by lipase (Lipozyme IM from Rhizomucormiehei and carried out in recirculating packed bed reactor. The effects of reaction parameters have been analyzed using response surface methodology. Reaction time (3.5–6.5 h, enzyme load (10–20%, substrate flow rate (4–8 mL·min-1 and substrate mole ratios (Terebinth oil : Palmitic acid : Caprylic acid, 1:1.83:1.22–1:3.07:2.05 were evaluated. The optimum reaction conditions were 5.9 h reaction time, 10% enzyme load, 4 mL·min-1 substrate flow rate and 1:3.10:2.07 substrate mole ratio. The structured lipid obtained at these optimum conditions had 52.23% desired triacylglycerols and a lower caloric value than that of terebinth fruit oil. The melting characteristics and microstructure of the structured lipid were similar to those of commercial margarine fat extracts. The results showed that the structured lipid had the highest oxidative stability among the studied fats.Se ha investigado la reacción de acidolisis del aceite de pistacho con los ácidoscaprílico y palmítico. La reacción fue catalizada por la lipasa Lipozyme IM de Rhizomucormiehei y realizada mediante recirculación del reactor de lecho compacto. Los efectos de los parámetros de la reacción han sido analizados mediante el uso de la metodología de superficie de respuesta. El tiempo de reacción (3.5 hasta 6.5 h, la carga de enzima (10–20%, el caudal de sustrato (4–8 mL·min-1 relaciones molares de los sustrato (aceite de pistacho: ácido palmítico: ácido caprílico, 1: 1,83: 1,22–1: 3,07: 2,05 fueron evaluados. Las condiciones óptimas de reacción fueron 5,9 h de tiempo de reacción, el 10% de carga de la enzima, 4 mL·min-1 de caudal de sustrato y 1: 3,10: 2,07 de relación molar de sustratos. Los lípidos estructurados obtenidos en las condiciones óptimas tenías 52,23% de triacilgliceroles

  9. Safety and efficacy of paliperidone palmitate 1-month formulation in Chinese patients with schizophrenia: a 25-week, open-label, multicenter, Phase IV study

    Directory of Open Access Journals (Sweden)

    Zhao JP

    2017-08-01

    Full Text Available Jingping Zhao,1,* Lehua Li,1,* Jianguo Shi,2 Yi Li,3 Xiufeng Xu,4 Keqing Li,5 Lili Zhang,6 Shangli Cai,6 Yu Feng,6 Jianmin Zhuo,6 Weihong Liu,6 Huafei Lu6 1Department of Psychiatry, The Mental Health Institute, The Second Xiangya Hospital of Central South University, 2Department of Psychiatry, Mental Health Center of Xi’an City, 3Department of Psychiatry, Mental Health Center of Wuhan City, 4Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, 5Department of Psychiatry, The Sixth People’s Hospital of Hebei Province, 6Department of Medical Affairs, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China *These authors contributed equally to this work Rationale: Long-acting injectable (LAI paliperidone palmitate 1-month formulation (PP1M has demonstrated acceptable tolerability and favorable clinical outcomes in Western and Asian patients with schizophrenia. Hence, analysis of the outcomes of long-term PP1M treatment specifically in Chinese patients is of interest.Objective: The aim of this study is to evaluate the long-term safety and efficacy of PP1M treatment in Chinese patients with schizophrenia.Methods: In this 25-week, open-label, Phase IV study, patients (18–65 years diagnosed with schizophrenia and having a baseline Positive and Negative Syndrome Scale (PANSS total score of 60–120 (inclusive were enrolled. All patients received injections of PP1M 150 mg eq. (day 1 and 100 mg eq. (day 8, followed by a flexible once-monthly maintenance dosing (75, 100, or 150 mg eq..Results: Of the 353 patients, 234 (66.3% completed the study treatment (mean age, 31.1 years; 52.7% men. The PANSS total score (primary end point improved significantly over the 6-month treatment period (mean [standard deviation] change from baseline to end of treatment, -27.2 [18.30]; P<0.0001. The Clinical Global Impressions-Severity and Personal and Social Performance scores (secondary end points also improved

  10. Oxidation of linoleic and palmitic acid in pre-hibernating and hibernating common noctule bats revealed by 13C breath testing.

    Science.gov (United States)

    Rosner, Elisabeth; Voigt, Christian C

    2018-02-19

    Mammals fuel hibernation by oxidizing saturated and unsaturated fatty acids from triacylglycerols in adipocytes, yet the relative importance of these two categories as an oxidative fuel may change during hibernation. We studied the selective use of fatty acids as an oxidative fuel in noctule bats ( Nyctalus noctula ). Pre-hibernating noctule bats that were fed 13 C-enriched linoleic acid (LA) showed 12 times higher tracer oxidation rates compared with conspecifics fed 13 C-enriched palmitic acid (PA). After this experiment, we supplemented the diet of bats with the same fatty acids on five subsequent days to enrich their fat depots with the respective tracer. We then compared the excess 13 C enrichment (excess atom percentage, APE) in breath of bats for torpor and arousal events during early and late hibernation. We observed higher APE values in breath of bats fed 13 C-enriched LA than in bats fed 13 C-enriched PA for both states (torpor and arousal), and also for both periods. Thus, hibernating bats selectively oxidized endogenous LA instead of PA, probably because of faster transportation rates of polyunsaturated fatty acids compared with saturated fatty acids. We did not observe changes in APE values in the breath of torpid animals between early and late hibernation. Skin temperature of torpid animals increased by 0.7°C between early and late hibernation in bats fed PA, whereas it decreased by -0.8°C in bats fed LA, highlighting that endogenous LA may fulfil two functions when available in excess: serving as an oxidative fuel and supporting cell membrane functionality. © 2018. Published by The Company of Biologists Ltd.

  11. Impact of Paliperidone Palmitate Versus Oral Atypical Antipsychotics on Health Care Resource Use and Costs in Veterans With Schizophrenia and Comorbid Substance Abuse.

    Science.gov (United States)

    Lefebvre, Patrick; Muser, Erik; Joshi, Kruti; DerSarkissian, Maral; Bhak, Rachel H; Duh, Mei Sheng; Shiner, Brian; Young-Xu, Yinong

    2017-07-01

    Almost half of all patients diagnosed with schizophrenia have a history of substance abuse (SA). However, data on treatment of schizophrenia with paliperidone palmitate (PP) among patients with comorbid SA are limited. The objective of this study was to compare all-cause and SA-related health care resource utilization and costs in veterans with schizophrenia and co-occurring SA who were treated with PP versus oral atypical antipsychotics (OAAs). Veterans Health Administration electronic health record data were used to conduct a retrospective longitudinal study in veterans with schizophrenia who initiated PP or OAA between January 1, 2010 and June 30, 2016, had ≥12 months of enrollment before treatment initiation (baseline), were diagnosed with SA, and had ≥1 Global Assessment of Functioning score during baseline. Differences in baseline characteristics were adjusted for using inverse probability of treatment weighting. Adjusted cost differences and incidence rate ratios (IRR) for the association between PP versus OAA and all-cause and SA-related health care costs and health care resource utilization in the 12 months after treatment initiation were estimated with corresponding 95% CIs using weighted linear and Poisson regression models, respectively. Of 6872 veterans in the study, 1684 (25%) and 5188 (75%) were treated with PP and OAA, respectively. After adjustment, PP was associated with fewer all-cause inpatient (IRR = 0.88; 95% CI, 0.85 to 0.90), mental health-related inpatient (IRR = 0.88; 95% CI, 0.85 to 0.91), and long-term care stays (IRR = 0.53; 95% CI, 0.44 to 0.64), but more frequent mental health intensive case management visits (IRR = 1.51; 95% CI, 1.49 to 1.53) compared with OAA (all P schizophrenia and comorbid SA. Thus, PP appears to be a valuable treatment option for patients in this subpopulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. 2-Dodecylcyclobutanone, a radiolytic product of palmitic acid, is genotoxic in primary human colon cells and in cells from preneoplastic lesions

    International Nuclear Information System (INIS)

    Knoll, Nadine; Weise, Anja; Claussen, Uwe; Sendt, Wolfgang; Marian, Brigitte; Glei, Michael; Pool-Zobel, Beatrice L.

    2006-01-01

    The irradiation of fat results in the formation of 2-alkylcyclobutanones, a new class of food contaminants. Results of previous in vitro studies with primary human colon cells and in vivo experiments with rats fed with 2-alkylcyclobutanones indicated that these radiolytic derivatives may be genotoxic and enhance the progression of colon tumors. The underlying mechanisms of these effects, however, are not clearly understood. Therefore we performed additional investigations to elucidate the genotoxic potential of 2-dodecylcyclobutanone (2dDCB) that is generated from palmitic acid. In particular, we explored the relative sensitivities of human colon cells, representing different stages of tumor development and healthy colon tissues, respectively. HT29clone19A cells, LT97 adenoma cells and primary human epithelial cells were exposed to 2dDCB (150-2097 μM). We determined cytotoxic effects using trypan blue exclusion. Genotoxicity, reflected as strand breaks, was assessed using the alkaline version of the comet assay and chromosomal abnormalities were investigated by 24-color fluorescence-in-situ-hybridization. 2dDCB was cytotoxic in a time- and dose-dependent manner in LT97 adenoma cells and in freshly isolated primary cells but not in the human colon tumor cell line. Associated with this was a marked induction of DNA damage by 2dDCB in LT97 adenoma cells and in freshly isolated colonocytes, whereas in the HT29clone19A cells no strand breaks were detectable. A long-term incubation of LT97 adenoma cells with lower concentrations of 2dDCB revealed cytogenetic effects. In summary, 2dDCB was clearly genotoxic in healthy human colon epithelial cells and in cells representing preneoplastic colon adenoma. These findings provide additional evidence that this compound may be regarded as a possible risk factor for processes in colon carcinogenesis related to initiation and progression

  13. Effects of Ghrelin on Triglyceride Accumulation and Glucose Uptake in Primary Cultured Rat Myoblasts under Palmitic Acid-Induced High Fat Conditions

    Directory of Open Access Journals (Sweden)

    Lingling Han

    2015-01-01

    Full Text Available This study aimed to study the effects of acylated ghrelin on glucose and triglyceride metabolism in rat myoblasts under palmitic acid- (PA- induced high fat conditions. Rat myoblasts were treated with 0, 10−11, 10−9, or 10−7 M acylated ghrelin and 0.3 mM PA for 12 h. Triglyceride accumulation was determined by Oil-Red-O staining and the glycerol phosphate dehydrogenase-peroxidase enzymatic method, and glucose uptake was determined by isotope tracer. The glucose transporter 4 (GLUT4, AMP-activated protein kinase (AMPK, acetyl-CoA carboxylase (ACC, and uncoupling protein 3 (UCP3 were assessed by RT-PCR and western blot. Compared to 0.3 mM PA, ghrelin at 10−9 and 10−7 M reduced triglyceride content (5.855 ± 0.352 versus 5.030 ± 0.129 and 4.158 ± 0.254 mM, P<0.05 and prevented PA-induced reduction of glucose uptake (1.717 ± 0.264 versus 2.233 ± 0.333 and 2.333 ± 0.273 10−2 pmol/g/min, P<0.05. The relative protein expression of p-AMPKα/AMPKα, UCP3, and p-ACC under 0.3 mM PA was significantly reduced compared to controls (all P<0.05, but those in the 10−9 and 10−7 M ghrelin groups were significantly protected from 0.3 mM PA (all P<0.05. In conclusion, acylated ghrelin reduced PA-induced triglyceride accumulation and prevented the PA-induced decrease in glucose uptake in rat myoblasts. These effects may involve fatty acid oxidation.

  14. Osteotoxicity after chronic dietary administration of 13-CIS-retinoic acid, retinyl palmitate or selenium in mice exposed to tumor initiation and promotion

    International Nuclear Information System (INIS)

    Forsyth, K.S.; Gensler, H.L.; Watson, R.R.

    1989-01-01

    In view of the clinical trials of retinoids as therapeutic agents for premalignant skin lesions, a radiographic study was undertaken to measure skeletal toxicities after chronic dietary administration of retinoids in mice exposed to tumor initiation and promotion. CD-1 mice were initiated with 0.15 moles of 7,12-dimethylbenz[a]anthracene and promoted twice daily with 8 nmoles of 12-O-tetradecanoylphorbol-13-acetate for 23 weeks. Diets were supplemented with 60 IU, 200 IU, or 700 IU or retinyl palmitate (RP) per g diet. After 5 weeks, the 700 IU of RP/g diet was lowered to 350 IU/g diet. Administration of these diets to mice during the 23 weeks of tumor promotion results in a 0-fold, 2-fold, or 10-fold increase in bone fractures, respectively. Osteoporotic bone lesions identified on radiographs rose 0-fold, 0-fold, and 10-fold at the respective doses, whereas metaphyseal flares increased O-fold, 1.4-fold, and 3.6-fold. Bone deformities was augmented O-fold, 1.8-fold and 2.9-fold at the respective doses. Addition of selenium did not alter the bone toxicity of RP. 13-cis-retionic acid (CRA) was less toxic at 700 IU/g diet than was RP at that dose, as evidence by the death of 12 of 70 mice by the 6th week of dietary RP and no deaths in the 35 mice fed 700 IU CRA/g diet for 23 weeks. CRA at 700 IU/g diet resulted in 3/4 as many osteoporotic bones, 1/3 as many bone fractures, 4/5 as many metaphyseal flares, and a similar number of bone deformities as mice fed 700/350 IU/g diet. At the dose of 200 IU/g food, osterotoxicities were similar in the mice fed diets supplemented with RP and CRA

  15. Relationship between response to aripiprazole once-monthly and paliperidone palmitate on work readiness and functioning in schizophrenia: A post-hoc analysis of the QUALIFY study.

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    Steven G Potkin

    Full Text Available Schizophrenia is a chronic disease with negative impact on patients' employment status and quality of life. This post-hoc analysis uses data from the QUALIFY study to elucidate the relationship between work readiness and health-related quality of life and functioning. QUALIFY was a 28-week, randomized study (NCT01795547 comparing the treatment effectiveness of aripiprazole once-monthly 400 mg and paliperidone palmitate once-monthly using the Heinrichs-Carpenter Quality-of-Life Scale as the primary endpoint. Also, patients' capacity to work and work readiness (Yes/No was assessed with the Work Readiness Questionnaire. We categorized patients, irrespective of treatment, by work readiness at baseline and week 28: No to Yes (n = 41, Yes to Yes (n = 49, or No at week 28 (n = 118. Quality-of-Life Scale total, domains, and item scores were assessed with a mixed model of repeated measures. Patients who shifted from No to Yes in work readiness showed robust improvements on Quality-of-Life Scale total scores, significantly greater than patients not ready to work at week 28 (least squares mean difference: 11.6±2.6, p<0.0001. Scores on Quality-of-Life Scale instrumental role domain and items therein-occupational role, work functioning, work levels, work satisfaction-significantly improved in patients shifting from No to Yes in work readiness (vs patients No at Week 28. Quality-of-Life Scale total scores also significantly predicted work readiness at week 28. Overall, these results highlight a strong association between improvements in health-related quality of life and work readiness, and suggest that increasing patients' capacity to work is an achievable and meaningful goal in the treatment of impaired functioning in schizophrenia.

  16. Long-acting injectable paliperidone palmitate versus oral paliperidone extended release: a comparative analysis from two placebo-controlled relapse prevention studies.

    Science.gov (United States)

    Markowitz, Michael; Fu, Dong-Jing; Levitan, Bennett; Gopal, Srihari; Turkoz, Ibrahim; Alphs, Larry

    2013-07-11

    Increasing availability and use of long-acting injectable antipsychotics have generated a need to compare these formulations with their oral equivalents; however, a paucity of relevant data is available. This post hoc comparison of the long-term efficacy, safety and tolerability of maintenance treatment with paliperidone palmitate (PP) versus oral paliperidone extended release (ER) used data from two similarly designed, randomised, double-blind (DB), placebo-controlled schizophrenia relapse prevention trials. Assessments included measures of time to relapse, symptom changes/functioning and treatment-emergent adverse events (TEAEs). Time to relapse between treatment groups was evaluated using a Cox proportional hazards model. Between-group differences for continuous variables for change scores during the DB phase were assessed using analysis of co-variance models. Categorical variables were evaluated using Chi-square and Fisher's exact tests. No adjustment was made for multiplicity. Approximately 45% of enrolled subjects in both trials were stabilised and randomised to the DB relapse prevention phase. Risk of relapse was higher in subjects treated with paliperidone ER than in those treated with PP [paliperidone ER/PP hazard ratio (HR), 2.52; 95% confidence interval (CI), 1.46-4.35; p 70, both approximately 58.5%; p = 1.000] compared with a 10.9% decrease for paliperidone ER (58.5% vs 47.6%, respectively; p = 0.048). The least squares mean change for Positive and Negative Syndrome Scale (PANSS) total score at DB end point in these previously stabilised subjects was 3.5 points in favour of PP (6.0 vs 2.5; p = 0.025). The rates of TEAEs and AEs of interest appeared similar. This analysis supports maintenance of effect with the injectable compared with the oral formulation of paliperidone in patients with schizophrenia. The safety profile of PP was similar to that of paliperidone ER. Future studies are needed to confirm these findings.

  17. Paliperidone palmitate once-monthly maintains improvement in functioning domains of the Personal and Social Performance scale compared with placebo in subjects with schizoaffective disorder.

    Science.gov (United States)

    Fu, Dong-Jing; Turkoz, Ibrahim; Walling, David; Lindenmayer, Jean-Pierre; Schooler, Nina R; Alphs, Larry

    2018-02-01

    Evaluate the effect of paliperidone palmitate once-monthly (PP1M) injectable on the specific functioning domains of the Personal and Social Performance (PSP) scale in patients with schizoaffective disorder (SCA) participating in a long-term study. This study (NCT01193153) included both in- and outpatient subjects with SCA experiencing an acute exacerbation of psychotic and mood symptoms. Subjects were treated with PP1M either as monotherapy or in combination with antidepressants or mood stabilizers during a 25-week open-label (OL) phase. Stabilized subjects were randomly assigned 1:1 (PP1M or placebo) into a 15-month double-blind (DB) relapse-prevention period. Functioning of the randomized subjects during OL and DB phases was evaluated using the PSP scale (four domains: socially useful activities, personal/social relationships, self-care, and disturbing/aggressive behaviors). Three statistical approaches were utilized to analyze PSP scores to assess robustness and consistency of findings. No adjustments were made for multiplicity. 334 of 667 enrolled subjects were stabilized with PP1M, randomly assigned to PP1M (n=164) or placebo (n=170) in the DB phase, and included in this analysis. Improvements in all PSP domain scores were observed during the OL phase and were maintained during the DB phase with PP1M, but decreased with placebo. Differences compared to placebo were significant in all four PSP domains during the DB phase (P≤0.008). The analysis in this study showed that PP1M improves functioning, as measured by the four PSP domain scores, in symptomatic subjects with SCA. Functioning was maintained compared with placebo. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Nickel Inhibits Mitochondrial Fatty Acid Oxidation

    Science.gov (United States)

    Uppala, Radha; McKinney, Richard W.; Brant, Kelly A.; Fabisiak, James P.; Goetzman, Eric S.

    2015-01-01

    Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

  19. Past exposure

    International Nuclear Information System (INIS)

    Dropkin, G.; Clark, D.

    1992-01-01

    Past Exposure uses confidential company documents, obtained by the Namibia Support Committee over several years, to draw attention to risks to workers' health and the environment at Roessing Uranium mine. Particular reference is made to discussion of dust levels, radiation hazards, uranium poisoning, environmental leaks, especially from the tailings dam, and the lack of monitoring of thorium. In relation to agreements between trades unions and mines, agreements reached by RTZ-owned Canadian in Canada, and British Nuclear Fuels in the UK, are discussed. (UK)

  20. Alkannin Inhibited Hepatic Inflammation in Diabetic Db/Db Mice

    Directory of Open Access Journals (Sweden)

    Wenhua Xue

    2018-03-01

    Full Text Available Background/Aims: The current study was designed to investigate the protective role of alkannin (ALK on liver injury in diabetic C57BL/KsJ-db/db mice and explore its potential mechanisms. Methods: An oral glucose tolerance test (OGTT was performed. The levels of insulin, alanine aminotransferase (ALT, aspartate aminotransaminase (AST, total cholesterol (TC and triglyceride (TG were determined by commercial kits. The pro-inflammatory cytokines interleukin (IL-1β, IL-6 and tumour necrosis factor (TNF-α were determined by ELISA. The levels of the ROCK/NF-κB pathway were determined by Western blotting. Results: The contents of pro-inflammatory cytokines interleukin (IL-1β, IL-6 and tumour necrosis factor (TNF-α were inhibited by ALK, metformin or fasudil in diabetic db/db mice. Further, Western blotting analysis showed that the expression of Rho, ROCK1, ROCK2, p-NF-κBp65, and p-IκBα was significantly reversed by ALK treatment. In human hepatic HepG2 cells, the hepatoprotective effects of ALK were further characterized. With response to palmitic acid-challenge, increased amounts of insulin, ALT, AST, TG, and TC were observed, whereas ALK pretreatment significantly inhibited their leakage in HepG2 cells without appreciable cytotoxic effects. The inflammation condition was recovered with ALK treatment as shown by changes of IL-1β, IL-6 and TNF-α. Further, Western blotting analysis also suggested that ALK improves hepatic inflammation in a Rho-kinase pathway. Conclusion: The present study successfully investigated the role of Rho-kinase signalling in diabetic liver injury. ALK exhibited hepatoprotective effects in diabetic db/db mice, and it might act through improving hepatic inflammation through the Rho-kinase pathway.

  1. Mechanisms of growth inhibition of Phytomonas serpens by the alkaloids tomatine and tomatidine

    Directory of Open Access Journals (Sweden)

    Jorge Mansur Medina

    2015-02-01

    Full Text Available Phytomonas serpens are flagellates in the family Trypanosomatidae that parasitise the tomato plant (Solanum lycopersicum L., which results in fruits with low commercial value. The tomato glycoalkaloid tomatine and its aglycone tomatidine inhibit the growth of P. serpens in axenic cultures. Tomatine, like many other saponins, induces permeabilisation of the cell membrane and a loss of cell content, including the cytosolic enzyme pyruvate kinase. In contrast, tomatidine does not cause permeabilisation of membranes, but instead provokes morphological changes, including vacuolisation. Phytomonas treated with tomatidine show an increased accumulation of labelled neutral lipids (BODYPY-palmitic, a notable decrease in the amount of C24-alkylated sterols and an increase in zymosterol content. These results are consistent with the inhibition of 24-sterol methyltransferase (SMT, which is an important enzyme that is responsible for the methylation of sterols at the 24 position. We propose that the main target of tomatidine is the sterols biosynthetic pathway, specifically, inhibition of the 24-SMT. Altogether, the results obtained in the present paper suggest a more general effect of alkaloids in trypanosomatids, which opens potential therapeutic possibilities for the treatment of the diseases caused by these pathogens.

  2. Ethanol exposure can inhibit red spruce ( Picea rubens ) seed germination

    Science.gov (United States)

    John R. Butnor; Brittany M. Verrico; Victor Vankus; Stephen R. Keller

    2018-01-01

    Flotation of seeds in solvents is a common means of separating unfilled and filled seeds. While a few protocols for processing red spruce (Picea rubens) seeds recommend ethanol flotation, delayed and reduced germination have been reported. We conducted an ethanol bioassay on seeds previously stored at -20°C to quantify the concentration required to separate red spruce...

  3. Inhibition of lactation.

    Science.gov (United States)

    Llewellyn-Jones, D

    1975-01-01

    The mechanism and hormonal regulation of lactation is explained and illustrated with a schematic representation. Circulating estrogen above a critical amount seems to be the inhibitory factor controlling lactation during pregnancy. Once delivery occurs, the level of estrogen falls, that of prolactin rises, and lactation begins. Nonsuckling can be used to inhibit lactation. Estrogens can also be used to inhibit lactation more quickly and with less pain. The reported association between estrogens and puerperal thromboembolism cannot be considered conclusive due to defects in the reporting studies. There is no reason not to use estrogens in lactation inhibition except for women over 35 who experienced a surgical delivery. Alternative therapy is available for these women. The recently-developed drug, brom-ergocryptine, may replace other methods of lactation inhibition.

  4. HNF-4α regulated miR-122 contributes to development of gluconeogenesis and lipid metabolism disorders in Type 2 diabetic mice and in palmitate-treated HepG2 cells.

    Science.gov (United States)

    Wei, Shengnan; Zhang, Ming; Yu, Yang; Xue, Huan; Lan, Xiaoxin; Liu, Shuping; Hatch, Grant; Chen, Li

    2016-11-15

    Hepatocyte Nuclear Factor-4α (HNF-4α) is a key nuclear receptor protein required for liver development. miR-122 is a predominant microRNA expressed in liver and is involved in the regulation of cholesterol and fatty acid metabolism. HNF-4α is know to regulate expression of miR-122 in liver. We examined how HNF-4α regulated gluconeogenesis and lipid metabolism through miR-122 in vivo and in vitro. Expression of miR-122, HNF-4α, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol response elementary binding protein-1 (SREBP-1), fatty acid synthase-1 (FAS-1), carnitine palmitoyltransferase-1 (CPT-1) and acetyl Coenzyme A carboxylase alpha (ACCα) were determined in livers of Type 2 diabetic mice and in insulin resistant palmitate-treated HepG2 cells. CPT-1 and phosphorylated ACCα expression were significantly decreased in livers of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. In contrast, expression of miR-122, HNF-4α, PEPCK, G6Pase, SREBP-1, FAS-1 and ACCα were significantly elevated in liver of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. Expression of HNF-4α increased whereas siRNA knockdown of HNF-4α decreased miR-122 levels in HepG2 cells compared to controls. In addition, expression of HNF-4α in HepG2 cells increased PEPCK, G6Pase, SREBP-1, FAS-1, ACCα mRNA and protein expression and decreased CPT-1 and p-ACCα mRNA and protein expression compared to controls. Addition of miR-122 inhibitors attenuated the HNF-4α mediated effect on expression of these gluconeogenic and lipid metabolism proteins. The results indicate that HNF-4α regulated miR-122 contributes to development of the gluconeogenic and lipid metabolism alterations observed in Type 2 diabetic mice and in palmitate-treated HepG2 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Continuous and intermittent exposure of neonatal rat calvarial cells to PTHrP (1-36 inhibits bone nodule mineralization in vitro by downregulating bone sialoprotein expression via the cAMP signaling pathway [v2; ref status: indexed, http://f1000r.es/18x

    Directory of Open Access Journals (Sweden)

    Suzan A Kamel

    2013-06-01

    Full Text Available The development and growth of the skeleton in the absence of parathyroid-hormone-related protein (PTHrP is abnormal.  The shortening of appendicular bones in PTHrP gene null mice is explained by an effect of PTHrP on endochondral bone growth.  Whether or not PTHrP influences intramembranous ossification is less clear.  The purpose of this study was to determine the effect of exogenous PTHrP on intramembranous ossification in vitro.  Neonatal rat calvarial cells maintained in primary cell culture conditions that permit spontaneous formation of woven bone nodules by intramembranous ossification were studied. The expression of PTHrP, parathyroid hormone 1 receptor (PTH1R, and alkaline phosphatase (AP by osteogenic cells in developing nodules and the effects of PTHrP (1-36 on nodule development was determined over 3-18 days. PTHrP and PTH1R were detected colonies of osteogenic cells on culture day three, and AP was detected on day six. PTHrP and its receptor were localized in pre-osteoblasts, osteoblasts, and osteocytes, and AP activity was detected in pre-osteoblasts and osteoblasts but not osteocytes. Continuous and intermittent exposure to PTHrP (1-36 decreased the number of mineralized bone nodules and bone sialoprotein (BSP mRNA and protein, but had no effect on the number of AP-positive osteogenic cell colonies, cell proliferation, apoptosis, or osteopontin (OPN mRNA. These results demonstrate that osteogenic cells that participate in the formation of woven bone nodules in vitro exhibit PTHrP and PTH1R before they demonstrate AP activity. Exogenous PTHrP (1-36 inhibits the mineralization of woven bone deposited during bone nodule formation in vitro, possibly by reducing the expression of BSP.

  6. Method of inhibiting the onset of acute radiation syndrome and also inhibiting the onset of septicemia and a composition therefor

    Energy Technology Data Exchange (ETDEWEB)

    Ribi, E E

    1986-01-14

    A method is described for inhibiting the onset of acute radiation syndrome caused by the exposure of warm-blooded animals to a whole body dose of at least 100 rads of x-radiation. Also described is a method for inhibiting the onset of septicemia. The methods comprise administering to a warm-blooded animal an effective amount of a pharmaceutical preparation containing refined detoxified endotoxin in combination with a pharmaceutically acceptable carrier.

  7. The impact assessment of anticancer drug imatinib on the feeding behavior of rotifers with an integrated perspective: Exposure, post-exposure and re-exposure.

    Science.gov (United States)

    Yan, Zhengyu; Yan, Kun; He, Xingliang; Liu, Yanhua; Zhang, Jie; Lopez Torres, Oscar; Guo, Ruixin; Chen, Jianqiu

    2017-10-01

    The anticancer drugs are getting increasing attention as an emerging contaminant in the aquatic environments. In the present study, feeding behavior of the rotifer Brachionus calyciflorus under the impact of anticancer drug imatinib was evaluated. Traditional toxicological studies usually focus on dose-effect relationship at a given exposure time, while ignore the possible impact after the exposure. Thus, how the impact varied in the post-exposure and re-exposure was also considered in the present study. The feeding depression of the rotifers was attributed to the increased concentration of imatinib. Although the filtration and ingestion rate of the rotifers recovered to a certain extent after the exposure, the significant feeding inhibition still persisted even if the exposure was ended. In the re-exposure period, the feeding behavior was less depressed than those of the exposure period, which implied that rotifers might develop a tolerance to the same toxics. The activities of acetylcholine esterase (AchE) and the levels of reactive oxygen species (ROS) in rotifers were also detected. Imatinib inhibited the activities of AchE in the exposure and re-exposure while ROS levels increased significantly in the re-exposure period. Our present study provided an integrated assessment the potential environmental risks of imatinib at a new perspective. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to beta-palmitate and contribution to softening of stools pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    2014-01-01

    Following an application from Specialised Nutrition Europe (formerly IDACE), submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked...... to deliver an opinion on the scientific substantiation of a health claim related to beta-palmitate and contribution to softening of stools. The food constituent, beta-palmitate, that is the subject of the health claim, is sufficiently characterised. Contribution to softening of stools is a beneficial...... physiological effect for infants. In weighing the evidence the Panel took into account that, out of two human intervention studies with important methodological limitations, one suggested a stool-softening effect of beta-palmitate whereas the second did not, that one animal study did not support a stool...

  9. Efficacy and safety of paliperidone palmitate three-monthly formulation in East Asian patients with schizophrenia: subgroup analysis of a global, randomized, double-blind, Phase III, noninferiority study

    Directory of Open Access Journals (Sweden)

    Savitz AJ

    2017-08-01

    Full Text Available Adam J Savitz,1 Haiyan Xu,2 Srihari Gopal,1 Isaac Nuamah,2 Paulien Ravenstijn,3 David Hough,1 Maju Mathews,4 Yu Feng,5 Lu Yu,6 Masayoshi Takahashi,7 Dennis Liu,8 Gang Wang,9 Jin-Sang Yoon,10 Jiahn-Jyh Chen11 1Department of Central Nervous System, 2Department of Clinical Biostatistics, Janssen Research & Development, LLC, Titusville, NJ, USA; 3Department of Clinical Pharmacology, Janssen Research & Development, Beerse, Belgium; 4Global Medical Affairs, Neurosciences, Janssen Research & Development, NY, USA; 5Medical Affairs, Neurosciences, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 6Department of Clinical Development, Janssen Research & Development, Beijing, China; 7Department of Central Nervous System, Janssen Pharmaceutical KK, Tokyo, Japan; 8Playford Community Team, Northern Adelaide Local Health Network, Adelaide, SA, Australia; 9National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Affiliated Capital University of Medical Science, Beijing, China; 10Department of Psychiatry, Chonnam National University Hospital, Gwangju, South Korea; 11Department of Geriatric Psychiatry, Taoyuan Mental Hospital, Taoyuan, Taiwan Objective: To demonstrate the efficacy and safety of paliperidone palmitate three-monthly (PP3M formulation in an East Asian population with schizophrenia by subgroup analysis of a double-blind (DB, multicenter, noninferiority study. Patients and methods: Of 1,429 patients who entered the open-label (OL phase, 510 were East Asian (China: 296 [58%], Japan: 175 [34%], South Korea: 19 [4%] and Taiwan: 20 [4%]. In the 17-week OL phase, patients received paliperidone palmitate once-monthly (PP1M formulation on day 1 (150 mg eq., day 8 (100 mg eq. and once-monthly thereafter (50–150 mg eq., flexible. Following the OL phase, patients (n=344 East Asian entered DB phase and were randomized (1:1 to PP1M (n=174 or PP3M (n=170. Primary efficacy endpoint was the percentage of patients who

  10. Palmitic acid induces neurotoxicity and gliatoxicity in SH-SY5Y human neuroblastoma and T98G human glioblastoma cells

    Directory of Open Access Journals (Sweden)

    Yee-Wen Ng

    2018-04-01

    Full Text Available Background Obesity-related central nervous system (CNS pathologies like neuroinflammation and reactive gliosis are associated with high-fat diet (HFD related elevation of saturated fatty acids like palmitic acid (PA in neurons and astrocytes of the brain. Methods Human neuroblastoma cells SH-SY5Y (as a neuronal model and human glioblastoma cells T98G (as an astrocytic model, were treated with 100–500 µM PA, oleic acid (OA or lauric acid (LA for 24 h or 48 h, and their cell viability was assessed by 3-(4,5-dimetylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. The effects of stable overexpression of γ-synuclein (γ-syn, a neuronal protein recently recognized as a novel regulator of lipid handling in adipocytes, and transient overexpression of Parkinson’s disease (PD α-synuclein [α-syn; wild-type (wt and its pathogenic mutants A53T, A30P and E46K] in SH-SY5Y and T98G cells, were also evaluated. The effects of co-treatment of PA with paraquat (PQ, a Parkinsonian pesticide, and leptin, a hormone involved in the brain-adipose axis, were also assessed. Cell death mode and cell cycle were analyzed by Annexin V/PI flow cytometry. Reactive oxygen species (ROS level was determined using 2′,7′-dichlorofluorescien diacetate (DCFH-DA assay and lipid peroxidation level was determined using thiobarbituric acid reactive substances (TBARS assay. Results MTT assay revealed dose- and time-dependent PA cytotoxicity on SH-SY5Y and T98G cells, but not OA and LA. The cytotoxicity was significantly lower in SH-SY5Y-γ-syn cells, while transient overexpression of wt α-syn or its PD mutants (A30P and E46K, but not A53T modestly (but still significantly rescued the cytotoxicity of PA in SH-SY5Y and T98G cells. Co-treatment of increasing concentrations of PQ exacerbated PA’s neurotoxicity. Pre-treatment of leptin, an anti-apoptotic adipokine, did not successfully rescue SH-SY5Y cells from PA-induced cytotoxicity—suggesting a mechanism of PA

  11. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  12. Quorum sensing inhibition

    DEFF Research Database (Denmark)

    Persson, T.; Givskov, Michael Christian; Nielsen, J.

    2005-01-01

    /receptor transcriptional regulator in some clinically relevant Gram-negative bacteria. The present review contains all reported compound types that are currently known to inhibit the QS transcriptional regulator in Gram-negative bacteria. These compounds are sub-divided into two main groups, one comprising structural...

  13. Cooperation for Better Inhibiting.

    Science.gov (United States)

    Novoa, Eva Maria; Ribas de Pouplana, Lluís

    2015-06-18

    Cladosporin is an antimalarial drug that acts as an ATP-mimetic to selectively inhibit Plasmodium lysyl-tRNA synthetase. Using multiple crystal structures, Fang et al. (2015) reveal in this issue of Chemistry & Biology the fascinating mechanism responsible for cladosporin selectivity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Inhibition of Fatty Acid Synthesis Induces Apoptosis of Human Pancreatic Cancer Cells.

    Science.gov (United States)

    Nishi, Koji; Suzuki, Kenta; Sawamoto, Junpei; Tokizawa, Yuma; Iwase, Yumiko; Yumita, Nagahiko; Ikeda, Toshihiko

    2016-09-01

    Cancer cells tend to have a high requirement for lipids, including fatty acids, cholesterol and triglyceride, because of their rapid proliferative rate compared to normal cells. In this study, we investigated the effects of inhibition of lipid synthesis on the proliferation and viability of human pancreatic cancer cells. Of the inhibitors of lipid synthesis that were tested, 5-(tetradecyloxy)-2-furoic acid (TOFA), which is an inhibitor of acetyl-CoA carboxylase, and the fatty acid synthase (FAS) inhibitors cerulenin and irgasan, significantly suppressed the proliferation of MiaPaCa-2 and AsPC-1 cells. Treatment of MiaPaCa-2 cells with these inhibitors significantly increased the number of apoptotic cells. In addition, TOFA increased caspase-3 activity and induced cleavage of poly (ADP-ribose) polymerase in MiaPaCa-2 cells. Moreover, addition of palmitate to MiaPaCa-2 cells treated with TOFA rescued cells from apoptotic cell death. These results suggest that TOFA induces apoptosis via depletion of fatty acids and that, among the various aspects of lipid metabolism, inhibition of fatty acid synthesis may be a notable target for the treatment of human pancreatic cancer cells. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Latent Inhibition in an Insect: The Role of Aminergic Signaling

    Science.gov (United States)

    Fernandez, Vanesa M.; Giurfa, Martin; Devaud, Jean-Marc; Farina, Walter M.

    2012-01-01

    Latent inhibition (LI) is a decrement in learning performance that results from the nonreinforced pre-exposure of the to-be-conditioned stimulus, in both vertebrates and invertebrates. In vertebrates, LI development involves dopamine and serotonin; in invertebrates there is yet no information. We studied differential olfactory conditioning of the…

  16. Plastics for corrosion inhibition

    CERN Document Server

    Goldade, Victor A; Makarevich, Anna V; Kestelman, Vladimir N

    2005-01-01

    The development of polymer composites containing inhibitors of metal corrosion is an important endeavour in modern materials science and technology. Corrosion inhibitors can be located in a polymer matrix in the solid, liquid or gaseous phase. This book details the thermodynamic principles for selecting these components, their compatibility and their effectiveness. The various mechanisms of metal protection – barrier, inhibiting and electromechanical – are considered, as are the conflicting requirements placed on the structure of the combined material. Two main classes of inhibited materials (structural and films/coatings) are described in detail. Examples are given of structural plastics used in friction units subjected to mechano-chemical wear and of polymer films/coatings for protecting metal objects against corrosion.

  17. Inhibiting the inevitable

    DEFF Research Database (Denmark)

    Shashoua, Yvonne

    2006-01-01

    conservation is to ‘buy time’ for the object. Inhibitive conservation of plastics involves the removal or reduction of factors causing or accelerating degradation including light, oxygen, acids, relative humidity and acidic breakdown products. Specific approaches to conservation have been developed......Once plastics objects are registered in museum collections, the institution becomes responsible for their long term preservation, until the end of their useful lifetime. Plastics appear to deteriorate faster than other materials in museum collections and have a useful lifetime between 5 and 25...... years. Preventive or inhibitive conservation involves controlling the environments in which objects are placed during storage and display, with the aim of slowing the major deterioration reactions. Once in progress, degradation of plastics cannot be stopped or reversed, so the aim of preventive...

  18. S-Carvone as a natural potato sprout inhibiting, fungistatic and bacteristatic compound.

    NARCIS (Netherlands)

    Oosterhaven, K.; Poolman, B.; Smid, E.J.

    1995-01-01

    S-Carvone, a common monoterpene found in caraway (Carum carvi L.), inhibits the sprouting of potatoes very efficiently at continuous low head space concentrations. The length growth of potato sprouts was inhibited within 2 days following exposure to S-carvone. Sprouts were able to convert S-carvone

  19. Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour

    DEFF Research Database (Denmark)

    Hay-Schmidt, Anders; Finkielman, Olivia T. Ejlstrup; Jensen, Benjamin Anderschou Holbech

    2017-01-01

    to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant...

  20. Medium wave exposure characterisation using exposure quotients.

    Science.gov (United States)

    Paniagua, Jesús M; Rufo, Montaña; Jiménez, Antonio; Antolín, Alicia; Pinar, Iván

    2010-06-01

    One of the aspects considered in the International Commission on Non-Ionizing Radiation Protection guidelines is that, in situations of simultaneous exposure to fields of different frequencies, exposure quotients for thermal and electrical stimulation effects should be examined. The aim of the present work was to analyse the electromagnetic radiation levels and exposure quotients for exposure to multiple-frequency sources in the vicinity of medium wave radio broadcasting antennas. The measurements were made with a spectrum analyser and a monopole antenna. Kriging interpolation was used to prepare contour maps and to estimate the levels in the towns and villages of the zone. The results showed that the exposure quotient criterion based on electrical stimulation effects to be more stringent than those based on thermal effects or power density levels. Improvement of dosimetry evaluations requires the spectral components of the radiation to be quantified, followed by application of the criteria for exposure to multiple-frequency sources.

  1. Personal exposure control system

    International Nuclear Information System (INIS)

    Tanabe, Ken-ichi; Akashi, Michio

    1994-01-01

    Nuclear power stations are under strict radiation control. Exposure control for nuclear workers is the most important operation, and so carefully thought out measures are taken. This paper introduces Fuji Electric's personal exposure control system that meets strict exposure control and rationalizes control operations. The system has a merit that it can provide required information in an optimum form using the interconnection of a super minicomputer and exposure control facilities and realizes sophisticated exposure control operations. (author)

  2. The Aggression-Inhibiting and Aggression-Facilitating Influence of Heightened Sexual Arousal.

    Science.gov (United States)

    Baron, Robert A.; Bell, Paul A.

    Eighty-six undergraduate males participated in an experiment designed to investigate the impact of various types of erotic stimuli upon aggression. On the basis of previous research, it was hypothesized that exposure to mild erotic stimuli would tend to inhibit subsequent aggression, while exposure to more arousing stimuli of this type would…

  3. Integrated toxic evaluation of sulfamethazine on zebrafish: Including two lifespan stages (embryo-larval and adult) and three exposure periods (exposure, post-exposure and re-exposure).

    Science.gov (United States)

    Yan, Zhengyu; Yang, Qiulian; Jiang, Weili; Lu, Jilai; Xiang, Zhongrun; Guo, Ruixin; Chen, Jianqiu

    2018-03-01

    Persistence of antibiotics in aquatic environment may pose a risk to the non-target aquatic organisms. This study provided an integrated evaluation to analyze the toxic stress of sulfamethazine (SMZ) on zebrafish in two lifespan stages (embryo-larval and adult) and three exposure periods (exposure, post-exposure and re-exposure). Zebrafish embryos and adult zebrafish were exposed to SMZ at 0.2, 20 and 2000 μg/L, respectively. The results showed that SMZ at any given concentration inhibited the hatching of embryos at 58-96 hpf (hours post-fertilization). Our result also indicated that two major kinds of the malformation, which was induced by the antibiotic, were edema and spinal curvature. Additionally, the antibiotic stimulated the heartbeat while reduced the body length of the embryo at 72 hpf. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents significantly increased at 120 hpf when the embryos were exposed to the lowest concentration (0.2 μg/L) of the antibiotic. On the other hand, the antibiotic induced SOD activities and MDA contents in adult zebrafish in the exposure and re-exposure periods. The MDA contents could recover while SOD activities still increased in 2 d after the exposure. Both SOD activities and MDA contents could recover in 7 d after the exposure. Levels of SOD and MDA in the re-exposure were higher than those in the first exposure. Our results suggested that SMZ had toxic effects on both embryos and adult zebrafish, and provided an integrated evaluation of the toxic effects of SMZ on zebrafish at a new perspective. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Ghrelin Attenuated Lipotoxicity via Autophagy Induction and Nuclear Factor-κB Inhibition

    Directory of Open Access Journals (Sweden)

    Yuqing Mao

    2015-09-01

    Full Text Available Background/Aims: Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease worldwide. Autophagy is associated with NAFLD. Ghrelin is a gut hormone with various functions including energy metabolism and inflammation inhibition. We investigated the therapeutic effect of ghrelin on NAFLD and its association with autophagy. Methods: C57bl/6 mice were fed a high-fat diet for 8 weeks to induce a model of chronic NAFLD, with ghrelin (10 µg/kg administrated subcutaneously twice weekly from weeks 6 to 8. LO2 cells were pretreated with ghrelin (10-8 M before stimulation with free fatty acid (palmitic and oleic acids; 1 mM. Lipid droplets were identified by hematoxylin and eosin and Red O staining and quantified by triglyceride test kits. LC3I/II, an important biomarker protein of autophagy was detected by western blotting, real-time polymerase chain reaction, immunohistochemistry and immunofluorescence. Tumor necrosis factor (TNF-a and interleukin (IL-6 were detected by ELISA and immunohistochemistry. Nuclear factor (NF-κB p65 was detected by western blotting and immunofluorescence. AMP-activated protein kinase (AMPK and mammalian target of rapamycin (mTOR were detected by western blotting. Results: Ghrelin reduced the triglyceride content in high fat diet (HFD group in vivo and free fatty acid (FFA group in vitro. TNF-a and IL-6 were significantly reduced in the ghrelin-treated mice compared with the control group. Autophagy induction was accompanied with intracellular lipid reduction in ghrelin-treated mice. Ghrelin upregulated autophagy via AMPK/mTOR restoration and inhibited translocation of NF-κB into the nucleus. Conclusions: The results indicate that ghrelin attenuates lipotoxicity by autophagy stimulation and NF-κB inhibition.

  5. Dioxin Exposure Initiative

    Science.gov (United States)

    The Dioxin Exposure Initiative (DEI) is no longer active. This page contains a summary of the dioxin exposure initiative with illustrations, contact and background information.Originally supported by scientist Matthew Lorber, who retired in Mar 2017.

  6. Exposure scenarios for workers